‫رسالة شكر وعرفان‬

Table of
CONTENTS
01 AUTONOMIC NERVOUS SYSTEM

02 AUTACOIDS

03 DIURETICS

04 CARDIOVASCULAR SYSTEM

05 RESPIRATORY SYSTEM 🫁
06 GASTROINTESTINAL SYSTEM
2nd Term
COMING
07 BLOOD SOON
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Do you know that "you look supercalifragilisticexpialidocious when you smile. wow, what a
beautiful smile." why didn't you read this word "supercalifragilisticexpialidocious"?
 Pharmacology introduction: ................................................ 1 Indirect Sympathomimetics: ................................................9
Parasympathomimetics are classified into: ..................... 4 Cholinergic Antagonists: Parasympatholytics ............... 10
Sympathomimetic drugs agonist ........................................ 6 Sympatholytic (Adrenergic antagonist) ......................... 12
Selective D1 agonist:................................................................7 Adrenergic Antagonists ....................................................... 12
Alpha & Beta agonist: ............................................................7 Alpha Blockers ....................................................................... 13
Selective α1 Agonists .............................................................. 8 Beta-Blockers......................................................................... 13
Selective β1 Agonists .............................................................. 8 Alpha & Beta Blockers ......................................................... 14
Selective β2 Agonists .............................................................. 8 Selective α1 & Nonselective β Blockers ............................. 14

Pharmacology:
is the science that deals with the study of drugs, which includes the following branches:
Pharmacodynamics
Pharmacokinetics
Pharmacotherapeutics
Toxicology

Pharmacodynamics: The effects of drugs on the body, which includes:

1. Mechanism of action (MOA): active part of the cell which forms chemical bonds with
drugs. These active parts are:
Enzymes
Ion channels
Cell membrane
Receptors
DNA synthesis
Chemical reaction (neutralization reaction), e.g., Antacid
Physical reaction (Adsorption); e.g., charcoal, which is used in toxicity
2. Clinical use (desired effects of drugs)
3. Side effects (undesired effects of drugs)

Pharmacokinetics: - is the effect of the body on drugs which includes:

Absorption: Transfer of drugs from the site of administration to blood circulation which
occurs in the small intestine
Factors affecting absorption:
A- factors related to the patient:
1. Food: The presence of food ↓ absorption with some exceptions such
as antifungal drugs.
2. Health state: either constipation (↑ absorption) or diarrhoea (↓
absorption).
B- factors related to drugs:
1. Liquid is more absorbed than solid.
2. Parenteral (injection) is more absorbed than oral
3. Particle size: small size is highly absorbed than large.

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4. Lipid-soluble is more absorbed than water-soluble.

Bioavailability: The amount of drug that reaches systemic (blood) circulation.

↑ Bioavailability means ↑ absorption (orally)

↓ Bioavailability means ↓ absorption in such case, we administer the drug other
Chapter 1

Distribution: Spread of drugs all over the body to reach different body organs.
Factors affecting distribution:
▪ Binding to plasma protein
▪ ↑ Binding to plasma proteins → inactive drugs have a long duration of action (t½).
▪ ↓ Binding to plasma proteins → active drugs

Metabolism: The first step of drug elimination in which modification in the chemical
structure of drugs.
takes place, mainly occurs by liver enzymes.
Other sites: GIT, plasma (contains esterase enzyme), kidney, and brain (10%)
Aim:
a. Conversion of drugs from active (lipid-soluble) to inactive (water-soluble) so it can
be excreted.
b. Conversion of prodrugs (inactive drugs) to active, e.g., captopril.
c. Conversion of drugs from active to active (prolongation of action).
d. Conversion of active drugs to toxic metabolites (rare cases).

Factors affecting metabolism:

1. Healthy state of the liver (most important).
2. Age.
3. Sex: Drug metabolism occurs in males more than females because androgens
[help more synthesis of enzymes].
4. Drug-drug interaction:
1. Metabolic inducer: Drugs stimulate metabolism which may inactivate
other drugs.
2. Metabolic inhibitor: Drugs inhibit metabolism which may cause
toxicity of other drugs.

Excretion: Removal of drugs outside the body.

Site: Kidney (mainly)
Other sites: GIT, sweating, lacrimation, salivation, and exhalation
Water-soluble drugs (polar) → excretion is more than non-polar drugs.
Healthy state of kidney is an important factor in excretion.

Pharmacotherapeutics:
• The art of treatment of disease (Proper choice of drugs with proper dose for each health
problem).

Toxicology: The science that deals with the study of drug toxicity, which includes:
1. Toxic dose
2. Toxic symptoms
3. Treatment of toxicity

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Drugs: Any substance of any source which can be used for treatment, diagnosis, and prevention of
diseases.

Sources of drugs:
1. Synthetic drugs
2. Natural drugs that include:
Plant (most important source) as digoxin and atropine
Animal as insulin (from horse)
Microorganism like fungus (penicillin)
Marine (cod liver oil) omega 3
Soil as Zn+2, Mg+2, Ca+2

Route of administration:
1. External: -not reach to blood
o produce local effects
2. Internal: -reach blood
o orally, parenteral, inhalation, or rectal.
Terminology

Chapter 1
Agonist: Drug which binds to sympathetic receptor to produce similar effects to the normal
neurotransmitter.
Antagonist: Drugs bind to sympathetic receptor to block or inhibit the effects of normal
neurotransmitter.
Tolerance: Loss of drug’s response in which there is a need to increase drug dose to get the
same effect (e.g., paracetamol).
Tachyphylaxis: Rapid occurrence of tolerance.
Dependence: Severe craving to drug in which sudden stop may cause central withdrawal
effects which occur as (insomnia, anxiety, and nervousness) e.g., Diazepam.
Addiction: Severe craving to drug in which sudden stop may cause peripheral and central
withdrawal effect (death may occur) e.g., Morphine, Heroin.
Potency: Strength of drugs (concentration of active constituents).
Efficacy: Maximum response produced by drug.
Onset of action: Time between drug administration and occurrence of effects.
Duration of action: Time between occurrence of effects and reoccurrence of the symptoms of
disease (effect of drug disappears).
Therapeutic index (TI): The degree of drug safety.

So, an increase in TI means a safe drug, while a decreased TI means a toxic drug.
e.g., In paracetamol, the ED50 = 500mg and TD50=20g, so:
TI= (20×1000)÷500=40
In paracetamol, TI= 40 means it’s a safe drug.

Drug monitoring:
1. Parameters such as blood glucose, BP.
2. Free of symptoms such as fever, headache.

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3. Concentration of drugs in blood.

Terminology:
1. Parasympathetic stimulators (Parasympathomimetics).
2. Parasympathetic inhibitors (parasympatholytics).
3. Sympathetic stimulator (sympathomimetic).
4. Sympathetic inhibitor (sympatholytic).
Chapter 1

Parasympathomimetics are classified into:

Parasympathomimetics (cholinergic agonist): Drugs bind to parasympathetic receptors (N, M) to
produce a similar effect to the natural neurotransmitter (ACh).
Effects:
1. ↑ Memory and learning.
2. Eye: Miosis ↓ intraocular pressure (IOP) → ↑ drainage of aqueous humour.
3. Cardiac work: ↓ Contraction, ↓ COP, ↓ HR.
4. B.C which will lead to asthma.
5. GIT: ↑ HCl secretion (hyperacidity), ↑ motility (diarrhoea).
6. Nausea and vomiting.
7. Urinary Bladder: Contraction of the wall and relaxation of sphincter → Frequency
of urination.
8. Blood vessels: V.D via ↑ NO (indirect effect) which will lead to: A) Hypotension B)
Congestion (nasal congestion, redness of eyes).
9. Uterus: ↑ Contraction of wall (abortion).
10. Saliva: ↑ Watery secretion (parasympathetic increases watery secretion and
sympathetic decreases it).
11. ↑ Sweating and lacrimation.
12. Contraction of skeletal muscle → by stimulating the nicotinic receptor.

Note: All peripheral effects are results from stimulating the muscarinic receptor (M) except in the
skeletal muscle which is by stimulating of nicotinic receptors (N).

Muscarinic receptors:
• M1: Parietal cells of the stomach → ↑ HCl secretion.
• M2: Heart → ↓ HR.
• M3: All over the body.
• M4 & M5: In the CNS.

Parasympathomimetics are classified into:

1. Direct agonist:
The drug binds to the receptor to produce effects directly.
It works on the M receptors only.
2. Indirect agonist:
The drug increases acetylcholine, then acetylcholine will bind to the receptor and
give the effect.
It works on both M and N receptors.

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Direct agonist drugs:

Sjogren’s disease
Pilocarpine (eye drops):
MOA: Stimulates all the M agonists (non-selective). is an autoimmune disease which
comes out as dry eye & dry
CU: Glaucoma, Sjogren’s disease. mouth the drug is helpful.
Bethanechol (oral and parenteral):
MOA: M agonist.
CU: Glaucoma, postoperative urine retention & paralytic ileus. (Where this drug
make contraction of UB which prevents the urine retention and increases the motility
of the GIT especially the small intestine)
Cevimeline (oral):
MOA: Selective M3 agonist.
CU: Sjogren’s disease.

Indirect agonist drugs:

MOA: Ach esterase inhibitors → so it increases the duration of Ach in the body.

Chapter 1
Types: Reversible Ach esterase inhibitors:
o Block the enzyme for a short duration.
Irreversible Ach esterase inhibitors:
o Toxic compounds.
o The body is under control of the parasympathetic (it takes the
upper-hand).
Reversible drugs:
1. Physostigmine:
o CU: a) Eye drop in glaucoma, b) I.V in acute state such as poisoning. which means
that we can use it as antidote for cholinergic antagonist.
2. Neostigmine & Pyridostigmine:
CU: Postoperative urine retention and paralytic ileus, Myasthenia gravis.
o
3. Donepezil & Rivastigmine:
o More selective on central esterase.
Notes: They differ in the type of esterase
o Used either orally or transdermal patches
which they act on:
o CU: Dementia, which may be caused by o Donepezil: More selective on Ach
degenerative diseases such as esterase in CNS.
Alzheimer’s, Parkinson’s disease, or o Rivastigmine: Inhibits both ACh
drug-induced as anticholinergic drugs. esterase and butyryl choline esterase.

Irreversible compounds:
Organophosphate Compounds (Cpd)
These are toxic compounds such as:
• Insecticides: Parathion, Malathion 🐛
• War Gases: Sarin, Soman 💣
They lead to:
Severe miosis 👁️ Severe sweating with salivation 💦
Bradycardia Convulsion 🤯
Bronchoconstriction 🫁 Decreased B.P (Blood Pressure)
Fever 🤒 Diarrhoea and increased urination 🚽

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Treatment of toxicity by organophosphate compounds:

Non-Pharmacological Treatment: 🚑
 First Aid:
o Airways 🌬️
o Breathing 🫁
o Circulation 💓
 Washing body and changing clothes 👕🚿
Chapter 1

 Artificial oxygen 🧬
 Ice bag “❄️ ”
Pharmacological Treatment: 💊

That is done by

Atropine I.V → M- Diazepam: Skeletal

Pralidoxime (PAM): I.V
antagonist used to block M muscle relaxant (for
(Ach esterase reactivator)
receptors (Reverse the effect) convulsion)

Acetylcholine-like Side Effects for Direct & Indirect Drugs:

Miosis 👁️ Congestion
Bradycardia Abortion
Bronchoconstriction 🫁 Nausea and vomiting 🤢
Hyperacidity Increased salivation and sweating 💦
Diarrhoea Frequency of urination 🚽
Hypotension Contraction of skeletal muscles 💪

Sympathomimetic drugs agonist

Sympathomimetic (Adrenergic agonists): drugs bind to sympathetic receptor to produce similar
effects to natural neurotransmitters (adrenaline, noradrenaline and dopamine)

Catecholamines synthesis.
tyrosine → dopa (dihydroxyphenylalanine) → dopamine → norepinephrine (noradrenaline) →
epinephrine (adrenaline)

Receptors of sympathetic system

Receptor Location Action
α1 Eye Mydriasis
BV Vasoconstriction (VC) → Increase BP, decongestion
Sphincter of Constriction
U Bladder
α2 Nerve Autoregulation of Sympathetic → Stimulate α2 receptors →
Terminals Decrease release of neurotransmitter
β1 Eye Production of aqueous humor → IOP
Heart Increase cardiac work (↑ Contraction, ↑ Cardiac Output, ↑ HR)

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Kidney Renin release → Conversion of angiotensinogen (released from

liver) to angiotensin I which is converted to angiotensin II by
angiotensin-converting enzyme → Increase blood pressure
β2 Bronchi Bronchodilation
(mainly)
Uterus Wall Relaxation used to prevent premature labor
Urinary Relaxation
Bladder Wall
Blood Vessels Vasodilation of BV of skeletal muscles → Increase O2 supply and
warmth sensation → Improve their work. Coronary artery →
Vasodilation to increase O2 supply to the heart
Liver Glycogenolysis → Increase blood glucose
β3 Adipose Lipolysis (no clinical use till now)
tissue
Wall of U Relaxation of detrusor muscle → Urine retention
Bladder
D1 Renal Blood Vasodilation → ↑ Renal Perfusion → ↑ Glomerular Filtration Rate

Chapter 1
Vessels (GFR) (agonist drugs clinically used in renal failure)
Alpha1 & Beta receptors agonist
CNS → anxiety and decrease in memory and learning
GIT → ↓ HCL secretion and ↓ motility → constipation , ↓ watery secretion of saliva

Adrenergic agonists drugs: divided into: Direct &indirect

Direct adrenergic agonists
Selective D1 agonist:
1) Dopamine (polar drug)
CU: acute renal failure
ROA: parenteral
SE: high dose may cause tachycardia (β1), hypertension (α1)
2) Fenoldopam (parenteral) → peripheral V.D
CU: acute hypertension
SE: hypotension
Alpha & Beta agonist:
e.g: (Adrenaline=polar drug)
ROA: P (IM, IV)
MOA: Stimulates the following receptors:
o Alpha1: Acute hypotension, vasoconstriction (VC)
▪ To prevent bleeding
▪ Used in combination with local anesthesia for prolongation of the action of
the drug, prevents bleeding and hypotension
o Beta1: Cardiac arrest (IV)
o Beta2: Acute bronchial asthma at resistant

Adrenaline is the drug of choice in case of anaphylactic shock as it stimulates α1 and β1,2
receptors. In this case, we administer it (IM) not (IV).
Anaphylactic shock: hypotension, bronchoconstriction, ↓ HR
Side Effects: Increase BP & HR.

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Selective α1 Agonists
① Phenylephrine:
Clinical use: Direct nasal decongestant orally in combination with an analgesic or flu
drug (because it will increase BP).
(IV): In case of acute hypotension.
It has a short duration of action (3 times a day).
② Midodrine:
Orally for chronic hypotension.
Chapter 1

It has a long duration of action.

③ Oxymetazoline (nasal drops):
For nasal congestion (when the cause is not flu).

SE: Reflex bradycardia, hypertension, weak mydriasis, and urine retention.

Selective β1 Agonists
Dobutamine:
CU: For acute heart failure (IV).
Note: Dopamine is used in heart failure if the patient is suffering from renal failure.
SE: Tachycardia or arrhythmia.

Selective β2 Agonists
① Salbutamol (inhalation or oral):
CU: For acute bronchial asthma and to prevent premature labor.
Note: Salbutamol is used to prevent premature labor only if it is taken from the
beginning of the pregnancy; if used late, it will delay labor for only 72 hours.
Characteristics:
a. Rapid onset (about 30 minutes).
b. Short duration (4-6 hours).
② Salmeterol (by inhalation only):
For chronic bronchial asthma.
Characteristics:
a. Slow onset (1 hour).
b. Long duration (12 hours).
③ Clenbuterol:
Has an anabolic effect.
CU.: Is illegal for athletes.
Chronic bronchial asthma (now, it is not used because of its illegal effect).
④ Ritodrine (orally):
CU.: To prevent premature labor.
SE.:
Hyperglycemia → glycogenolysis in the liver
Tachycardia: β2 → vasodilation in the coronary artery increases oxygen supply
leading to tachycardia, and also by a lesser action on β1, leads to tachycardia &
tremors.
Note: Tremors happen when picking up an object.
Contraindications: Diabetes mellitus.

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Selective β3 Agonists
① Mirabegron:
CU: Orally in case of urinary bladder over-activity in adults, not children, because in
children it is due to psychological causes.
SE: Tachycardia (β1) & Tremor (β2).

Indirect Sympathomimetics:
Effects: There are two types of effects:
Peripheral effect: (the same effects as direct sympathomimetics)
Central effects:
Alertness, euphoria, insomnia, anxiety, dysphoria, agitation, loss of appetite,
dependence.

Increases the release of catecholamines.

MOA: Decreases the re-uptake of catecholamines.

Chapter 1
Amphetamine (Oral):
EX:
a. High central and peripheral effects.
b. High dependence potential.
c. Known as a drug of abuse.
d. Previously used in attention deficit syndrome (hyperkinetic children) to
decrease movement, increase obedience, and enhance attention. Also used
for the treatment of narcolepsy and obesity.

Hypertension
SE:
Tachycardia
Psychosis, hallucinations, and drug dependence.

Cathinone and Cathine:

Active constituents of Qat with amphetamine-like effects.
Qat decreases blood glucose levels in the first two hours of chewing, then increases it,
making it not helpful for diabetic patients.

EX: Ephedrine (Plant Extract, Used Orally):

Lower central effect than amphetamine, but higher peripheral effect.
Clinical use: In combination with cough or flu preparations.
1. With cough preparations → BID (twice daily, most common)
2. With flu preparations → acts as a decongestant due to vasoconstriction
Pseudoephedrine (plant extract and used orally):
Very low central effects and peripheral effects less than Ephedrine.
Clinical use: Indirect nasal decongestant used in combination with flu preparation.

SE: Side Effects of Ephedrine and Pseudoephedrine:

1. Urine retention, constipation, increased heart rate (HR) and blood pressure (BP).
2. Loss of appetite.
3. Insomnia (if taken at night).

Note: No dependence on Ephedrine and Pseudoephedrine.

They’re classified as OTC (Over The Counter) drugs, meaning they can be taken without a
prescription and do not produce toxic effects.

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Cholinergic Antagonists: Parasympatholytics

Cholinergic antagonists are drugs that bind to parasympathetic receptors to block or inhibit the
effects of the neurotransmitter acetylcholine.
1. Decreasing memory and learning 🧠
2. Causing sedation 😴
3. Inducing mydriasis, ↑ IOP by decreasing the drainage of aqueous humor 👁️
4. Bronchodilation (BD) 🫁
Chapter 1

5. Increasing cardiac work, leading to tachycardia 💓

6. Reducing watery secretion, resulting in dry mouth and dry skin
7. Causing urine retention through contraction of sphincters and relaxation of the bladder wall
8. Decreasing HCL secretion and motility, leading to constipation
9. Relaxing the wall of the uterus 🤰
10. Relaxing skeletal muscle 💪

There is no parasympathetic innervation to the liver and blood vessels.

•
Note: BV by an “indirect effect” where decreased nitric oxide (NO) prevents its
•
vasodilation effect.
Mechanism of Action: M-receptor antagonist (non-selective)
Examples:
① Atropine (plant extract)
Duration of action: 3-4 hours
CU: IV injection
 Antidote for cholinergic agonist
 Preanesthetic medication to decrease salivation and watery secretions from
respiratory system.
 Bradycardia (Essential)
② Hyoscine (plant extract) orally & parenterally
Clinical uses:
 Drug of choice for nausea and vomiting induced by motion sickness
 Antispasmodic in gastrointestinal and urinary system spasms 🌀
③ Tropicamide (eye drop)
Clinical use as a mydriatic for retina examination and iritis 👁️
Duration of action: 4-6 hours
④ Ipratropium Bromide (inhalation)
Clinical use as a bronchodilator in acute bronchial asthma 🫁
Duration: 4-6 hours, hence called Short Acting M-Antagonist (SAMA)
⑤ Tiotropium (inhalation)
Clinical use as a bronchodilator in acute asthma 🫁
Duration: 24 hours, hence called Long Acting M-Antagonist (LAMA)
⑥ Clidinium (oral)
MOA: Selective M3 antagonist
Clinical use: GIT spasm, can be used in combination with anti-anxiety medication for
irritable bowel disease (Librax).
⑦ Tolterodine (oral)
MOA: Selective M3 antagonist
Clinical use: More selective on the urinary system for spasms and incontinence in the
elderly in case of non-infectious urgency
⑧ Glycopyrrolate (oral/parenteral)
MOA: Selective M3 antagonist

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CU: More selective on the salivary gland, used as preanesthetic medication and for
drooling of saliva in conditions like Parkinson’s disease
⑨ Oxybutynin (oral)
MOA: Non-selective M-antagonist
Clinical use: Urine incontinence in children with autonomic nervous system defects
⑩ Orphenadrine (oral/parenteral)
MOA: Blocks M-receptors and Nm receptors on skeletal muscles
CU: Skeletal muscle relaxant for muscle spasms due to local trauma, sometimes used
in combination with analgesics like paracetamol 💪
⑪ Procyclidine
MOA: Blocks M receptors and Nm receptors in skeletal muscles
Clinical use: For drug-induced parkinsonism
⑫ Benzatropine
MOA: Blocks M receptors and Nm receptors in skeletal muscles
Clinical use: Adjuvant therapy in Parkinson’s disease

Side Effects of Cholinergic Antagonists (Atropine-like SE):

Chapter 1
1. Mydriasis 👁️ 5. Constipation
2. Increased IOP 6. Urine retention 🚽
3. Dry skin and dry mouth 7. Dementia 🧠
4. Tachycardia 💓 8. Sedation 😴

Contraindications of Cholinergic Antagonists:

1. Glaucoma 👁️ 5. Prostatic enlargement
2. Sjogren’s disease 6. Myasthenia gravis
3. Tachyarrhythmia 💓 7. Elderly 👵👴
4. Intestinal obstruction
Note: Prostatic enlargement and glaucoma are age-related diseases.

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Sympatholytic (Adrenergic antagonist)

These drugs cause:
1. Relief of anxiety
2. Decrease in aqueous humor production ➟ decrease in IOP
3. Miosis
4. Decreased myocardial contraction ➟ lower cardiac output, HR, and BP.
5. Bronchoconstriction
6. Decreased renin release
Chapter 1

7. Increased urination frequency

8. Increased GIT motility ➟ diarrhoea
9. Hypoglycemia due to decreased glycogenolysis
10. Hyperlipidemia with inhibited lipolysis
11. Vasodilation ➟ congestion and hypotension (α1)
12. Inhibition of β2 receptors ➟ vasoconstriction in blood vessels of skeletal muscles and
coronary arteries, causing fatigue and cold extremities

Note: An imbalance between blood supply and required oxygen is termed angina pectoris.
Adrenergic Antagonists
The classification of adrenergic antagonists depends on their mechanism of action, which is
determined by the type of receptor they target.
Selective α2 Agonist
MOA: Inhibits the release of catecholamines, preventing sympathetic receptor binding and
subsequent effects.
Note: Stimulation of α2 receptors blocks sympathetic actions and vice versa.

Clonidine (Oral Use)

CU: Treats chronic hypertension, especially in patients with psychological issues or
addiction.
Characteristics:
Stimulates α2 receptors.
Activates the imidazoline ring in the CNS, leading to sedation.
Side Effects:
Bradycardia
Hypotension Peripheral effects
Diarrhea
Sedation Central effects

Alpha-Methyldopa (Oral Use)

Mechanisms of Action:
1. Stimulation of α2 agonists.
2. Formation of a false neurotransmitter “L-Dopa,” reducing the levels of true
dopamine.
Clinical use: Exclusive to chronic hypertension treatment in pregnant women.
Side Effects:
1. From α2 stimulation:
▪ Decreased heart rate and blood pressure (bradycardia).
▪ Diarrhoea
2. From decreased dopamine:
▪ Central effects: depression, extrapyramidal-like side effects.

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▪Peripheral effects (hormonal): hyperprolactinemia, leading to galactorrhea,

gynecomastia, and infertility.
3. Hemolytic anemia (rare).

Contraindications: Not to be used in patients with G6P dehydrogenase deficiency due to

the risk of hemolytic anemia.

Alpha Blockers
Nonselective Alpha Blockers
MOA:
Inhibit α1 → Vasodilation (VD)
Inhibit α2 → Increase in catecholamine levels; however, adrenaline will only work
with β receptors, resulting in an increased heart rate and bronchodilation (since α
receptors are blocked).
Example: Phenoxybenzamine
Use: Orally, in combination with propranolol to also block β receptors.

Chapter 1
CU: Pheochromocytoma
SE:
▪ Hypotension
▪ Tachycardia (direct effect, not reflex)

Selective Alpha 1 Blockers

Effects of Drugs:
a. Decrease in blood pressure.
b. Increase in heart rate by reflex mechanism
c. Congestion
d. Relaxation of the urinary bladder sphincter
Examples: Prazosin, Doxazosin, Terazosin, etc., used orally.
Clinical Use: Chronic hypertension in patients suffering from benign prostatic
hyperplasia (BPH)
Note: If the patients have only hypertension without BPH, this type of drug is not
given, and vice versa.

Tamsulosin
Use: Orally
MOA: Selective α1a blocker in the sphincter of the urinary bladder.
Clinical Use: Urine retention in prostatic enlargement (BPH) without hypertension

Side Effects of Alpha 1 Blockers

Postural hypotension (can be treated by Midodrine)
Reflex tachycardia
Congestion

Beta-Blockers
Nonselective β Blockers: These are very common.
① Timolol: Eye drops used for glaucoma.
② Propranolol: Oral medication that undergoes first-pass metabolism and has a short
duration, requiring dosing three times daily.

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 Clinical Uses:
1. Cardiac diseases such as hypertension, arrhythmia, all types of anginas (except
vasospastic angina), and heart failure. Administered in small or intermittent doses
to decrease mortality rates.
2. Performance anxiety as symptomatic treatment.
3. Thyrotoxicosis, as thyroxine stimulates sympathetic β receptors.
4. Migraine headaches, the only drug used prophylactically for migraines.
5. In combination with nonselective α blockers for Pheochromocytoma.
Chapter 1

6. To prevent oesophageal bleeding caused by hepatic cirrhosis or esophageal

varices.

③ Nadolol: Similar to propranolol but with a longer duration of action.

Preferred in hepatic patients and as a prophylactic for esophageal bleeding.
Doesn’t bypass first-pass metabolism.
β-Blockers Side Effects
1. β1: Decrease in heart rate ➟ hypotension.
2. β2: May cause bronchial asthma, hypoglycemia, fatigue, and cold extremities.
3. β3: Hyperlipidemia.
4. Vivid dreams ➟ dreams like reality.

Contraindications
1. Bronchial asthma.
2. Diabetes mellitus.
3. Raynaud’s disease patients.
4. Patients with hyperlipidemia.

Selective β1 Blockers
Betaxolol: Eye drops → decrease intraocular pressure, used for glaucoma.
Esmolol: (IV) administration with a short duration of action (10-20 minutes),
Clinical Use:
Emergency hypertension
Arrhythmia during surgery.

Bisoprolol & Atenolol: Oral use

Clinical Use:
1. hypertension with cardiac disease.
2. Atenolol is preferred in hypertension with angina.

Nebivolol: Used in hypertension due to its vasodilation effects, which occur by increasing
nitric oxide (NO) release.

Side Effects
1. Bradycardia.
2. Hypotension.

Alpha & Beta Blockers

Selective α1 & Nonselective β Blockers
Labetalol: Oral or parenteral.
Clinical Use:
1. Antagonizes adrenaline in cases of overdose or Pheochromocytoma.
2. Acute and chronic hypertension in pregnant women.

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1 ‫ أمساء علوان‬:‫الدكتورة‬
Pharmacology team

Carvedilol: Oral
Clinical Use: heart failure to decrease mortality rate.
Side Effects of α1 & β Blockers
1. Bradycardia.
2. Hypotension.
3. Hypoglycemia.
4. Bronchoconstriction.
5. Cold extremities (at large doses).

Chapter 1

Page 15
 Drugs Affecting Histamine ................................. 16 5HT2A Antagonists: .................................................... 19
Histamine Receptor Blockers (Anti-H) ................. 17 5HT3 Receptors: ......................................................... 20
Sedating Anti-H1 Drugs...................................... 17 5HT4 Receptors: ......................................................... 20
Non-Sedating Anti-H1 Drugs .............................. 18 Eicosanoids: ............................................................... 21
SEROTONIN (5-hydroxytryptamine) .................... 18 Drugs Affecting Prostaglandins (PG): .......................... 22
Drugs affecting 5HT2 ........................................ 19 A. PG Derivatives: ................................................................ 22

5HT2 Agonists: .................................................. 19 B. PG and TXA2 Blockers: .................................................23

5HT2 Antagonists: ............................................. 19 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): ........ 23

Autacoids
Autacoids are substances secreted by the body that have their own receptors and effects.
Unlike neurotransmitters, they do not pass through the autonomic nervous system (ANS).

Histamine
Histamine is formed in the body from the amino acid histidine and is mainly stored in
mast cells. When exposed to allergic factors, it is released and binds to its own receptors,
producing various effects.
 Allergens: These include food, drugs, dust, perfume...etc.

Histamine Receptors
1. H1 Receptors:
Found throughout the body, H1 receptors cause allergic reactions:
Itching, redness, and rash (skin)
Bronchoconstriction (respiratory system)
Vasodilation and decreased blood pressure (blood vessels)
Rhinorrhea and congestion (nose)
Stimulation of the cough center (CNS)
2. H2 Receptors:
Located in specific tissues:
Parietal cells of the stomach: Increase HCL secretion (hyperacidity).
Heart: Increases contraction (tachycardia).

Drugs Affecting Histamine

Mast Cell Stabilizers (reduce histamine release):
Example:
① Cromolyn (Na+ cromoglycate)
MOA: Mast cell stabilizer
ROA: Has 2 ROA
▪ Eye drops: Used for eye redness due to allergies.

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▪ Inhalation: Used for chronic bronchial asthma.

Onset: Slow

② Ketotifen (used orally): has two mechanisms of action.

MOA: Mast cell stabilizer
 CU: Chronic allergy
MOA: 5HT2 antagonist effect
 CU: appetizer (more effective in children)
Side Effects:
a. Atropine-like effects
b. Sedation (preferred to be used at night)
c. Weight gain

Histamine Receptor Blockers (Anti-H)

1. First-Generation H1 Blockers (sedating anti-H1):
Characteristics:

Chapter 2
Highly lipophilic
Cross the blood-brain barrier, leading to anti-cough effects and sedation
Short duration (8 hrs) due to rapid hepatic metabolism (used 3 times a day)
Most effective antiallergic drugs
2. Second-Generation H1 Blockers (non-sedating anti-H1):
Characteristics:
Less lipophilic
Cannot cross BBB (no CNS effects, no anti-cough, no sedation)
Long duration (12-24 hours), used once a day

Sedating Anti-H1 Drugs

① Chlorpheniramine:
ROA: I.V. injection, orally
CU:
 Anaphylactic shock
 All types of allergies
 Sedation
② Diphenhydramine:
ROA: Orally
CU:
 Motion sickness
 All types of allergies
 Sedation
③ Meclizine:
ROA: Orally
CU:
 Morning sickness during pregnancy (combine with Vit B6)
 All types of allergies
 Sedation
Note: Meclizine is the only drug which is safe for use during pregnancy.
④ Cyproheptadine:
ROA: Orally

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CU:
 Appetizers (in adults)
 All types of allergies
 Sedative
⑤ Cinnarizine & Betahistine:
ROA: Orally
CU:
 Meniere’s disease
 All types of allergies
Chapter 2

 Sedative

Note: Chlorpheniramine and Diphenhydramine are also used for:

1. Cough: They affect the cough center in the brain.
2. Flu: They provide sedation and decongestion (to avoid insomnia).

SE. of anti H1:

1. Sedation
2. Atropine like effects
3. Alpha 1 blocker ➟ VD ➟ 1. BP. 2.reflex tachycardia
4. Cyproheptadine may cause weight gain and sedation.

Non-Sedating Anti-H1 Drugs

EX: Loratadine & Cetirizine:
ROA: Orally
CU:
o All types of allergies
o Flu preparations
Side Effects:
o Similar to sedating drugs but less incidence (and this is because that not everyone
has the same BBB)
o Teratogenic (should be avoided in pregnant women)
o Drug-drug interactions (mainly with Azithromycin or Clarithromycin or any drug
from macrolides group which may lead to Arrhythmia)

SEROTONIN (5-hydroxytryptamine)
• Major serotonin secretion occurs from the gastrointestinal tract (chromaffin cells).
• Serotonin interacts with four types of receptors, each having different effects.

Serotonin Receptors:
A. 5HT1
Found in the (CNS) and has two subtypes:
o 5-HT1a: Anti-anxiety effects (agonist drugs include Buspirone).
o 5-HT1D/B: Agonists for cerebral vasoconstriction (e.g., sumatriptan).
Clinical Use: Acute migraine ttt.
Note: Any drug name ending in “triptan” works on 5-HT1D/B receptors.

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B. 5HT2
Found in:
1. CNS:
▪ Anxiety
▪ Psychosis
▪ Loss of appetite
2. Platelets:
▪ Promotes platelet aggregation
3. Blood vessels:
▪ Vasoconstriction (especially in cerebral vessels)
4. GIT:
▪ Causes severe contraction (leading to pain and diarrhoea)

Drugs affecting 5HT2

5HT2 Agonists:

Chapter 2
EX: Ergotamine
ROA: Orally
CU: Acute migraine (because it causes vasoconstriction in cerebral blood vessels)
Note: It may increase blood pressure ➟ severe hypertension and clot formation.

5HT2 Antagonists:
① Ketotifen:
MOA:
 5HT2 antagonist
 blocks histamine release.
② Cyproheptadine:
MOA:
 5HT2 antagonist.
 Blocks H1 receptor.
③ Pizotifen:
MOA: 5HT2 antagonist.
CU:
 Appetizer.
 Prophylactic for migraine.
 Carcinoid tumor (tumor in chromaffin cells
➟ increased serotonin secretion).
Side Effects:
 Weight gain.
 Sedation.
Note: Pizotifen is preferred as an appetizer.

5HT2A Antagonists:
Location: Found in the CNS.
CU: Antipsychotic.
Example: Risperidone.

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Side Effects:
a) Increased appetite leading to weight gain.
b) Sedation.

5HT3 Receptors:
Location: CRTZ (chemoreceptor trigger zone) induces nausea and vomiting.
MOA: 5HT3 antagonist.
Examples: Ondansetron, Granisetron.
Chapter 2

CU: Nausea and vomiting induced by chemotherapy.

5HT4 Receptors:
Location: Found in the GIT.
Function: Enhance gastric emptying and increase intestinal motility.
MOA: 5HT4 antagonist.
EX: Metoclopramide, Domperidone.
CU: Nausea and vomiting induced by food (given 20 minutes before meals).
Side Effects:
 Diarrhoea.
 Sedation.
Notes:
Metoclopramide:
o Potent D2 receptor blocker.
o Used for nausea and vomiting induced by drugs.
o Also used to induce milk formation and ejection after delivery.
Domperidone:
o Weaker D2 blocker.

Side Effects of D2 Blockers:

1. Hyperprolactemia:
o Galactorrhea.
o Gynecomastia.
o Infertility.
2. EPS (extrapyramidal-like side effects).
3. Depression.

Selective serotonin reuptake inhibitors (SSRI) → serotonin in body centrally & peripherally.
• CU: used as an antidepressant (mainly)
• e.g.: a) Fluoxetine b) Sertraline

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Eicosanoids:
Phospholipase A2 acts upon Phospholipids, resulting in the formation of arachidonic acid.

Arachidonic acid

cyclo-oxygenase lipoxygenase

COX LOX

Prostaglandin Thromboxane A2 leukotrienes(LT)

s(PG) PG actions:
Prostaglandins (PG) Actions

Chapter 2
1. Vasodilation (VD)
2. Maintenance of ductus arteriosus
3. Increased mucus and bicarbonate secretion in the stomach
4. Uterine contraction
5. Increased drainage of aqueous humor (reducing intraocular pressure)
6. Inhibition of platelet aggregation
7. Pain and fever

Leukotrienes (LT) Action: Bronchoconstriction (BC)

Drugs Affecting Leukotrienes (LT):

① LOX Inhibitors (Inhibit LT Synthesis):
EX: Zileuton (oral)
CU: Chronic bronchial asthma
SE:
▪ Gastrointestinal disturbances (nausea, vomiting, cramps with
diarrhoea, and sometimes constipation)
▪ Increased liver enzymes: GPT and GOT
Note: Zileuton is no longer used because it causes hepatic failure, marked by
elevation of liver enzymes (GOT and GPT).
② LT Receptor Blockers:
Examples:
▪ Montelukast and Zafirlukast (oral)
CU:
1. Chronic bronchial asthma
2. Combination with non-sedating anti-H1 drugs for resistant or chronic allergic
asthma
 Note: Hepatic function tests should be done before prescribing these drugs to prevent
complications (hepatic failure). Repeat the test during ttt.
SE:
▪ Gastrointestinal disturbances (take it after food to avoid this side effect).
▪ Headache.
▪ Increased liver enzymes.

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Drugs Affecting Prostaglandins (PG):
A. PG Derivatives:
a) PGE Derivatives:
① Misoprostol (P/O):
Action:
1. Increases mucus and bicarbonate secretion.
2. Contracts smooth muscles of the GIT and uterus.
Chapter 2

3. Vasodilation.
CU:
1. Drug-induced peptic ulcer.
2. For abortion.
SE:
1. Abortion.
2. Abdominal cramps and diarrhoea.
3. Hypotension.
4. Headache.
5. Reflex tachycardia (increased heart rate).
② Alprostadil (P):
Action: Vasodilation.
CU: Maintaining ductus arteriosus.
SE:
1. Hypotension.
2. Increased heart rate.
b) PGI Derivatives:
① Epoprostenol (IV):
Action: Vasodilation and inhibition of platelet aggregation.
CU:
1. Hemodialysis.
2. Pulmonary embolism (one of the causes of pulmonary hypertension).
SE:
1. Hypotension.
2. Increased heart rate.
3. Headache.
4. Flushing due to vasodilation of cutaneous blood vessels.
c) PGF Derivatives:
① Latanoprost (eye drop):
Action: Increases drainage of aqueous humor ➟ decreasing
intraocular pressure.
CU: Glaucoma.
SE:
1. Dryness of the eye.
2. Permanent brown pigmentation of eyelashes and iris.

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B. PG and TXA2 Blockers (Inhibit Synthesis via COX):

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs):
CU:
1. Anti-inflammatory.
2. Analgesic.
3. Antipyretic (reduces fever).
4. Antiplatelets.
5. Closes ductus arteriosus.
Examples:
① Aspirin: Used as an antiplatelet.
② Paracetamol: Used as an analgesic and antipyretic only.
③ Indomethacin:
a. Used to close ductus arteriosus.
b. Used for severe pain associated with gout.
④ Meloxicam: Selective COX II inhibitors.

Chapter 2
CU: Pathological PG (pain, inflammation, and fever).
SE:
a) Gastric irritation.
b) Asthma.
c) Bleeding.
d) Tolerance.

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Diuretics
Diuretics are drugs that decrease blood volume and increase urine volume. They work on nephrons
and are divided into five groups:
1. Loop Diuretics: These work in the loop of Henle.
2. Thiazide Diuretics: They operate in the early part of the distal convoluted tubule (DCT).
3. Potassium-Sparing Diuretics: These act in the last part of the DCT.
4. Carbonic Anhydrase Inhibitors (CAI): work in the proximal convoluted tubule (PCT).
5. Osmotic Diuretics: These affect various parts of the nephron.

Carbonic Anhydrase Inhibitors (CAI):

1. They are weak diuretics that increase the excretion of NaHCO₃, leading to:
Metabolic acidosis
Alkalinization of urine
2. They also increase the excretion of Na from the brain.
3. CAIs inhibit the formation of aqueous humor and are used for:
Glaucoma
Adjuvant therapy for epilepsy
Idiopathic cranial hypertension
Urine alkalinization
Prevention of mountain sickness.

SE of CAIs:
1. Metabolic acidosis
2. Steven-Johnson syndrome (hypersensitivity reaction)

Examples of CAIs:
1. Acetazolamide (oral)
2. Dorzolamide (eye drops)

Example: Mannitol (IV)

Clinical Uses:
o Increase intracranial pressure (ICP)
o Increase intraocular pressure (IOP)
SE of Osmotic Diuretics:
1. Hypotension
2. Hypo-hypernatremia
3. Diarrhoea

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TYPE SITE MOA CLINICAL USE SIDE EFFECTS CI EXAMPLES
Loop Ascending 1. Inhibit 1. Severe hypertension 1. Hypo: 1. Hypotension 1. Furosemide (O, P).
diuretic part of the reabsorptio 2. Oedema of any cause a. Hypotension 2. DM 2. Torsemide (O, P).
loop of n of water (pulmonary, CHF, renal, b. Hypokalemia 3. Gout 3. Bumetanide (O).
The most Henle and or hepatic failure) c. Hypocalcemia 4. Hypocalcemia (the most commonly used in oral
effective electrolytes 2. Hyper (occurs in 5. Hyperlipidemia preparation)
group 2. ( chronic use) 6. Hypokalemia
excretion of a. Hyperglycemia
Na⁺/K⁺/2Cl⁻ b. Hyperuricemia
/2Mg²⁺/Ca²⁺ c. Hyperlipidemia (by
and water) unknown mechanism)
3. Dehydration
4. Ototoxicity = deafness
(in chronic use or when
given as IV infusion)
Thiazide Early part Increase 1. Mild to moderate 1. Hyper: 1. Hypotension 1. Hydrochlorothiazide (O) (8-12 hrs)
of DCT excretion hypertension a. Hyperglycemia 2. DM 2. Chlorothiazide (only P)
Most of water and 2. Idiopathic b. Hyperlipidemia 3. Gout 3. Indapamide (O)
commonly Na/Cl hypercalciuria c. Hyperuricemia 4. Hypocalcemia 4. Chlorthalidone (O)
used 3. Diabetes insipidus d. Hypercalcemia 5. Hyperlipidemia - Has long duration (about 60
2. Hypo: hours).
a. Hypotension - Most commonly used
b. Hypokalemia
K- Late part Aldosterone Alone without 1. Hormonal disturbance, 1. Renal failure All of them are used orally and has
Sparing of DCT receptor combination are used for: mainly in males due to long duration of action.
diuretic antagonist a. Hyperaldosteronism because they decrease decreased 1. Spironolactone: Aldosterone and
mechanism b. Mild hypertension androgen receptors aldosterone androgen receptor inhibitor, so used
Weak c. Androgen receptor leading to): 2. Hyperkalemia for:
diuretics blocker: can be a. Gynecomastia - Hirsutism.
used for hirsutism b. Infertility - Hyperaldosteronism
in females 2. Hyperkalemia 2. Eplerenone: Selective aldosterone
Incombination with loop 3. GIT disturbance blocker (for hyperaldosteronism).
or thiazide diuretics to: 3. Amiloride: Weak diuretics
a. Increase efficacy for (increase Na and Cl excretion),
either hypertension or preferred for Liddle's syndrome or
oedema in combination with other diuretics.
b. Prevent K loss Note: Liddle's syndrome is a state
of hypertension with hypokalemia.
 Hypertension ...................................................................... 26
ANGINA PECTORIS: ........................................................... 32
Congestive Heart Failure(CHF/HF) .................................33
Cardiac Arrhythmia .........................................................36
Arterial Hypertension ..................................................... 39
Rheumatic Fever (RF) ...................................................... 40
Pulmonary Embolism ...................................................... 40
Myocardial Infarction (MI) & IEC................................ 41
Acute pulmonary oedema. ..............................................42
Stroke ..................................................................................42

Hypertension
Is the increased resistance against blood flow.

Causes of hypertension:
1- increase blood volume
2- vasoconstriction

The purpose of the treatment is either by decreasing the blood volume or dilation of blood vessels.
Normal Blood Pressure Range ⇛ Systolic: 100-120 mm Hg and Diastolic: 70-80 mm Hg
1) Note: diastole is more closely related to hypertension diagnosis because the diastole states
the heart during rest while the changing in the systolic is various according to patient status
(emotions, exercise, rest) so we don’t diagnose hypertension from it.

- The normal difference between diastole and systole pressure ranges from 20 - 50

Types of hypertensions:
a) Essential (95%) can be related to lifestyle and diet or drug induced.
b) Secondary hypertension (5%) cases related to others diseases.

Stages of hypertension:
Stage 1 140/90 = ≥135/85
➟ treatment depends on age
Stage 2 160/100 = ≥150/95
➔ treatment Should start regardless the age
Severe hypertension 180/110 emergency cases ➟ should be treated anyway quickly
➟ may cause damage to kidney or eyes

2) Note: to diagnose hypertension, BP should be measured diurnally for five days then
calculate the average to determine the stage and start according to it the treatment, but in
emergency cases the treatment should be started quickly.

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ANTI - HYPERTENSIVE DRUGS

1. Drugs that decrease blood volume:

Diuretics only
Example:
1- Thiazide
2- Loop diuretic
3- K-sparing diuretics

2. Vasodilators: - classified according to mechanisms of action:

1) Sympatholytic (Adrenoantagonist):
Examples: - 1- labetalol 2- atenolol 3- clonidine 4- propranolol 5- prazosin
6- Esmolol 7- bisoprolol 8- alpha-methyldopa

Chapter 4
2) Ca++ channels blockers (CCB): -
They’re classified according to site of action into:
1- works on the heart more than BV →↓ contraction of heart →↓ COP →↓BP + ↓HR
So may cause hypotension & bradycardia
Example: verapamil {O, P} N.B: Symptoms of the cluster headache:
Clinical Use: ▪ Severe pain in one side of the head
▪ Congestion in nose " rhinorrhoea "
1- hypertension with tachyarrhythmia
▪ Redness & tears in one eye
2- prophylactic from cluster headache
3- Angina
SE: - hypotension, bradycardia and constipation

2- Acts on BVs more than heart → relaxation of BVs (VD) → ↓BP → ↑HR (reflex
tachycardia)
Examples: -
1- Nifedipine
2- Amlodipine.
3- Nimodipine
ROA: orally
Clinical Use: - 1) chronic hypertension 2) angina
Side Effects: -
1. hypotension 5. ankle oedema
2. reflex tachycardia 6. constipation
3. headache 7. gingival hyperplasia
4. flushing
3- Acts on BV & heart → cause VD + bradycardia → ↓↓BP (strong effects)
Example: - Diltiazem
CU: - tachyarrhythmia with hypertension
SE: - hypotension, bradycardia and constipation

3. Renin Angiotensin System inhibitors

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“AgII” functions:
1- VC (40 times stronger than sympathetic nervous system), so BP will increase.
2- Stimulates sympathetic system which leads to VC then increase in Blood Pressure
3- Stimulates Aldosterone secretion which leads to Na and water retention, ➟ increase blood
volume, so blood pressure will increase.

💊Those drugs are classified into three groups:

1. Renin inhibitors
2. ACEI “Angiotensin converting enzyme inhibitors,”
Chapter 4

3. ARB “Angiotensin Receptor Blockers”

1. Renin inhibitors
EX: Aliskiren
ROA: - oral
CU: Used in resistant essential hypertension as last drug of choice.
SE: -
o Hyperkalaemia
o Dry Cough due to Bradykinin.
o Angioedema especially in Lips and Eyes 👀
C.I:
a- Diabetes mellitus
b- Renal disease
c- Heart disease

2. ACEI:
MOA: by inhibition of Angiotensin Converting Enzyme
 ACE also breakdown Bradykinin which is located mainly in: -
1- Blood Vessels (V.D)
2- Respiratory System
e.g.:
a. Captopril c. Ramipril
b. Lisinopril d. Enalapril
 All are used orally, and considered as a pro-drug.

Clinical Use:
a. oral in chronic hypertension (essential, secondary)
b. C.H.F
c. Used to prevent diabetic nephropathy by blocking aldosterone and V.C

Side Effects:
a. Hypotension
b. Hyperkalaemia
c. Dry cough
- (This side effect is caused by Bradykinin and more predominant in
female than male. Actually, it occurs in 30% of female. Its treatment is to
use Anti cough drugs not to stop the drug)
d. Angioedema
e. Proteinuria
f. Teratogenic (in all trimesters of pregnancy) N.B: creatinine levels should
be monitored for patients with
CI: 1- Hyperkaliaemic patients 2- Renal Failure renal impairment.

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3. ARBs:
most effective group (replace ACEI drugs in patients with resistance to ACEI)
e.g.:
a. Losartan
b. valsartan

Clinical Use: - (the same as ACEI drugs)

1- Chronic hypertension
2- Congestive heart failure
3- To prevent diabetic nephropathy

✓ ARBs lack the flowing effects

1- Dry cough 2- Proteinuria 3- Angioedema

Side Effects: -
1- Hypotension

Chapter 4
2- Hyperkalaemia
3- Teratogenic

Direct vasodilators: -
Hydralazine
MOA: - two MOA (it affects Ca++ channel and releasing of NO)
CU: - pre-eclampsia
SE: -
1. Hypotension
2. Reflex tachycardia
3. Headache
4. Flushing
5. Systemic Lupus Erythematosus (SLE); autoimmune disease can be reversible if there is
no organ damage.
Minoxidil
MOA: - K+ channels opener ➟ ⇡K+ influx which ➟ prevents Ca++ entrances to the smooth
muscle causing relaxation of smooth muscle➟ VD
ROA: -
1- Systemic (O, P) it is CI for female because it may cause hirsutism
2- Local (spray, shampoo, solution) ➟ increase hair growth used for (alopecia "male pattern
baldness")
SE: -
Systemic:
- ↓BP - Headache
- ⇡HR - Hirsutism
- flushing
Local: in 1st dose may occur as headache
Na++Nitroprusside (IV)
MOA: - ⇡NO ➟ ⇡ cGMP ➟ VD
CU: - Malignant hypertension
SE: -
- Hypotension
- Reflex tachycardia
- Methemoglobinemia (cellular hypoxia appears as cyanosis)
- Cyanide poisoning → cyanosis →arrhythmia → shock → death

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PHARMACOTHERAPY OF HYPERTENSION
② If BP ≤135/85 = 130/80
Not hypertension but needs monitoring & life style changes
③ If BP ≥ 135/ 85: -
a) if pts age ≥ 80 with no underlying disease ➟ No need for ttt.
b) if pts age > 80 with underlying disease as (CVS, Diabetes, Renal diseases)
or if pts age < 80 ➟ start ttt.
Chapter 4

④ Life style is important as advice for pts suffer from hypertension as: -
1. Reduce body weight = ↓10kg ➟ ↓BP 15-20 mmHg "the most important"
2. Decrease salt intake per day (maximum 6g/day) if pts intake decreased to 3g/day it will has
clinical importance.
3. Decrease caffeine intake, stop smoking.
⑤ ttt depends on age: -
Age <55 ≥55
Step 1 ACEI CCB
Step 2 ACEI + CCB CCB + ACEI
Step 3 ACEI + CCB + Diuretics CCB + ACEI + Diuretics (thiazide)
(thiazide)
Step 4 depends on K+ level for 1. if K+ < 4.5 ➟ add Spironolactone
both:- 2. if K+ > 4.5 ➟ ⇑ dose of Thiazide
3. if K+ normal ➟ add either  or  blockers
but if there is no underlying disease (resistant
essential hypertension) ➟ add Renin inhibitor.
⑥ CCB is the DOC for elderly.
⑦ ACEI is the DOC for patients suffering from hypertension + Diabetes (regardless of age)
⑧ ACEI is contraindicated for Afro-Caribbean people (black people), because they lack ACE
⑨ ACEI replace CCB in cases of hypertension + diabetes, heart failure or post-myocardial
infarction, or in oedemated patients.
⑩ α-blockers ⇒ used in cases of hypertension + BPH.
⑪ β-blockers ⇒ used in cases of hypertension + angina, heart failure or arrhythmia
⑫ Isolated systolic hypertension: in which the difference between systolic and diastolic BP is more
than 50mmHg (occurs in elderly):
☛ ttt ⇒ CCB + Thiazide (Chlorthalidone "1st choice" or Indapamide).

⑬ Hypertensive crisis = severe hypertension ⇒ BP=180/110 mmHg and has 2 types:

➊- Emergency: with organ damage e.g. (cerebral stroke or haemorrhage, CHF, renal
disease, pulmonary embolism).
➋- Urgency: with no organ damage.
☛ ttt for both cases ⇒ Labetalol (intravenously) + ttt of effects caused by emergency
hypertension.

⑭ Malignant hypertension:
BP=200/130 mmHg
multi-organ damage:
o Retinal damage
o Cerebral haemorrhage
o Renal failure
☛ ttt: I.V Sodium nitroprusside

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⑮ Hypertension in pregnancy:
Has 4 types:
1. Pre-existing hypertension:
 BP ≥ 140/90 mmHg
 Before 20 week of pregnancy (before the fourth month)
 No proteinuria
ttt: alpha-methyldopa

2. Pregnancy induced hypertension (gestational hypertension) PIH/GIH:

 BP ≥ 140/90 mmHg
 No proteinuria
 After 20 weeks of pregnancy (from the fifth month)
ttt: Labetalol

3. Pre-eclampsia:
 BP≥ 140/90 mmHg, and sometimes it may reach 170/110

Chapter 4
 After 20 weeks of pregnancy
 With proteinuria
 Oedema in some cases
ttt:
a) Labetalol (first line)
Note: In preeclampsia associated with
b) Nifedipine
premature labour we use Nifedipine as first
c) Hydralazine line of ttt
4. Eclampsia:
 BP>140/90 mmHg
 pre-eclampsia + seizure
ttt: I.V MgSo4

⑯ Hypertension and hypokalaemia occur in:

1- Conn's syndrome= (Primary hyperaldosteronism)
| The ttt is Spironolactone
2-Cushing's disease
3- Liddle's syndrome (ttt is Amiloride)
4- Drug induced: -
1. Corticosteroids
2. NSAIDs
3. Oral contraceptive
4. MAOIs
5. liquorice ingestion

⑰ The use of multidrug of antihypertensive at low doses is preferred than use of one drug at high
dose, because multidrug:
Has a synergetic effect.
Control blood pressure by different mechanisms.

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Angina pectoris: decreased oxygen supply to the heart in which there is an imbalance
between the cardiac work and O2 supply.

Types of anginas:
1) Stable angina:
 Is caused by atherosclerosis.
 Characteristics: induced by increased sympathetic activity (emotions or
Chapter 4

exercise).
2) Unstable angina:
 Caused by embolism.
 Characteristics: is more severe and more frequent and has a longer duration
than other types of anginas.
3) Variant angina (vasospastic or prinzmetal):
 Caused by VC of the Coronary Artery.
 Characteristics: occurs at rest.

The aim of treatment is:

 ⇣ the cardiac work or
 ⇡ the O2 supply of the heart (main aim).

DRUGS USED FOR THE TREATMENT OF ANGINA PECTORIS:

Main therapy of treatment:
1) Decrease the cardiac work by:
 blockers (selective or non-selective)
CCB (Verapamil or Diltiazem)
2) Increase O2 supply of the heart by vasodilators:
 Nitrates
 CCB (Nifedipine & Amlodipine)
 Nicorandil

1. Nitrates:
MOA: ⇡ NO release ➟ ⇡ cGMP➟ VD
e.g.:
Nitro-glycerine:
 ROA: sublingually, IV, transdermal patches.
 CU: acute attacks of any type of angina.

Isosorbide mononitrate:
 (Has 100% bioavailability and is excreted unchanged by the kidney)
 ROA: orally
 CU: chronic and resistant angina
This drug can’t be used as the 1st line therapy for resistant angina but used as
the last line therapy.
SE. (of Nitrates): ________________
a. Hypotension (postural).
b. Reflex tachycardia
c. Flushing & headache
d. Tolerance
e. Methemoglobinemia (can be treated by vitamin C [ascorbic acid]
or by methylene blue)
f. Sudden withdrawal causes rebound angina.

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2. Nicorandil
ROA: orally
It has 2 MOA:
 ⇡NO release ➟ ⇡cGMP➟ VD
 K+ channel opener ➟ relaxation of smooth muscles of BVs➟ VD
Clinical Use:
 Chronic use in resistant angina
 Replacement of  blockers (for patients with bronchial asthma) or Nifedipine (for
patients with oedema).
Side Effects:
1. Hypotension
2. Tachycardia
3. Headache
4. Flushing
5. Oral and anal ulcers → (so it is not used as the 1st line therapy).

Chapter 4
Adjuvant therapy: is added to the main therapy including:
1. Antiplatelet drugs.
2. Antihyperlipidemic drugs.

① Antiplatelet:
e.g.:
a. Aspirin (COX inhibitor)
b. Clopidogrel (ADP receptors inhibitor)

② Antihyperlipidemic drugs: these drugs decrease cholesterol blood levels.

e.g.: Statins
Notes:
① Nitroglycerin is used for all types of Anginas.
② for Variant Angina: the DOC is CCB while b-blockers are contraindicated.
③ The best drug used for monotherapy is CCB (Diltiazem (preferred) or Verapamil).
④ in combined therapy choose two drugs with different SE (bradycardia and tachycardia):
 Change (Diltiazem/ Verapamil) with other
CCB (Nifedipine/ Amlodipine) +  blockers
 In case of resistant: use (Nicorandil +  blockers/ Verapamil)
or use (oral nitrate +  blocker/ Verapamil)
⑤ Add antiplatelet or antihyperlipidemic drugs with any regimen.

Congestive Heart Failure(CHF/HF)

Definition: is the inability of the heart to contract.
- in this case the body activates compensatory mechanisms as:
• ⇡ sympathetic activity.
• activation of renin-angiotensin system (causing hypervolemia)
• ⇡ heart size (cardiac hypertrophy)
- Patients usually complain from:
(fatigue, palpitation, oedema, dyspnoea, cardiomegaly).
- Causes may be:
1. uncontrolled hypertension
2. valves regurgitation
3. uncontrolled myocardial infarction

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Treatment of acute CHF:

- is treated by sympathomimetic:
1. Dobutamine (IV) or
2. Dopamine (in case of renal disease) or
3. Adrenaline (if the previous 2 drugs have no effect)

Treatment of chronic CHF:

1. ACEI
Chapter 4

2. Spironolactone (K+ sparing diuretic)

3. -Blocker
4. other drugs

① ACEI:
MOA: decrease preload and afterload of the heart
it is the DOC
It can be replaced or combined with ARB
If ARB replace ACEI, Sacubitril should be combined with ARB

Sacubitril:
- is used in combination with Valsartan (ARB) for resistant cases of heart failure.
- this combination is preferred over (digoxin + hydralazine).
MOA: Neprilysin inhibitor ➟ inhibits the breakdown of ANP {natural diuretic}
SE: due to increased bradykinin ➟ dry cough & angioedema.

② K+ Sparing diuretics (decrease pre-load):

Can be replaced by Eplerenone (selective anti-aldosterone) in cases of gynecomastia, infertility but
if the patient still suffering from oedema ➟ add Thiazide or Loop diuretics

③ -blockers:
Either Propranolol or Bisoprolol are used.
Used to decrease the mortality rate.
-blockers are not used in oedemated patients
In case of resistance or CI from -blockers ➟ they are replaced with Ivabradine.

Ivabradine: (O) for chronic resistant heart failure.

MOA: I(f) blocker (inhibition of funny channel) ➟ inhibition of hyperpolarization ➟
decrease HR with No effect on the force of contraction.
SE: as the funny channels are found in the SAN and retina Ivabradine can cause:
• Bradycardia
• Visual disturbances (Luminous phenomena)

④ Other drugs: used for chronic and resistant cases:

e.g.: in severe cases:
1. Hydralazine
2. Digoxin
Digoxin:(O)
MOA
increase Ca++ intracellularly
a. positive inotropic effect (increases heart contractility)
b. negative chronotropic effect. (Decreases heart electric conductivity)

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inhibition of Na-K+ATPase.
N.B: this drug has low therapeutic index.
SE:
In GIT: nausea, vomiting, cramps, diarrhoea, anorexia.
Heart:
• Bradycardia (therapeutic dose).
• Tachyarrhythmia and ventricular fibrillation (toxic dose).
CNS: headache and confusion

*N.B: Tachycardia associated with high dose of digoxin is treated by:*

1. KCL (O) ➟ 1st line therapy
2. Lidocaine (IV) ➟ last line therapy

Chapter 4

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Cardiac Arrhythmia
Definition: Deviation from the normal pattern of cardiac rhythm is known as arrhythmia (Irregular
heartbeats).
Types: (origin of the arrhythmia)
1. Ventricular arrhythmias (Wide QRS): Includes
1- Ventricualr extrasystole
2- Ventricular Tachycardia
3- Ventricular Fibrillation.
Chapter 4

2. Supraventricular arrhythmias: Includes

o Atrial Arrhythmias (Narrow QRS)
1- Atrial extrasystoles (APC)
2- Atrial Tachycardia
3- Atrial Flutter
4- Atrial Fibrillation.
Extrasystole = premature beats= premature complexes= premature
contractions
Complications:
1. Hypoxia, cyanosis, death.
2. Cardiac arrest.

Signs:
1. Palpitations (awareness of heartbeats).
2. Syncope.

Note:
1. If the beat originates from the SA node, it’s called “Sinus rhythm.” Otherwise, it’s termed
“Arrhythmia.”
2. On an ECG:
o Many narrow QRS complexes indicate supraventricular tachycardia.
o Many wide QRS complexes indicate ventricular tachycardia.

Diagnosis: ECG (Electrocardiogram)

Specific Arrhythmias:

Supraventricular Tachycardia (SVT):

Drug of Choice: Adenosine (IV).
Avoid combining adenosine with theophylline, because, theophylline increases the
heart rate (a stimulant).
Side Effects: Decreased heart rate, blood pressure.
Contraindicated in asthma; use “Verapamil” instead.
Atrial Flutter:
Appears on ECG as sawtooth waves (4-5 P waves followed by QRS).
What's the most common cause of cardiac arrhythmia?
- It is atrial fibrillation.
Atrial Fibrillation (AF):
No P waves.
Irregular R wave intervals.
Narrow or wide QRS waves.
ttt:
Rate control (>65 years): Beta blockers (Metoprolol, bisoprolol).
Rhythm control (<65 years):
▪ First-line: Flecainide (without other heart disease).
▪ Second-line: Amiodarone (with other heart disease).

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Anti-Arrhythmic Drugs:
Examples: Amiodarone, Flecainide.
Age-based selection:
<65 years: Anti-arrhythmics.
>65 years: Selective beta blockers.
Vaughan Williams classification:
Class 1 (Na channel blockers).
Class 2 (Beta blockers).
Class 3 (K+ channel blocker - Amiodarone).
Class 4 (Ca2+ channel blockers - Verapamil, Diltiazem).
Ventricular Tachycardia:
Similar to supraventricular tachycardia.
Most dangerous: Ventricular fibrillation.
ECG: No P wave, irregular R wave intervals, narrow or wide QRS waves.
ttt: Amiodarone; lidocaine if resistant.
Ventricular Fibrillation:

Chapter 4
Chaotic ECG pattern.
Torsade de Pointes: Prolonged QT interval followed by ventricular tachycardia and
fibrillation.
Drugs causing Torsade de Pointes: Old antihistamines, Procainamide,
Azithromycin.
ttt: Defibrillation (if available); otherwise, IV magnesium sulfate (MgSO4).
Atrioventricular (A.V.) Block:
Prolonged PR interval.
ttt: Atropine for symptoms like fatigue, dizziness.
Wolff-Parkinson-White Syndrome:
Abnormal tissue connection between atrium and ventricle.
ttt: Catheter ablation; anti-arrhythmic drugs.

SHOCK
It is a decrease in blood perfusion to vital organs (brain, heart, kidneys, lungs, and liver) in this
order.
The most common type of shock is hypovolemic shock.
Common Characteristics of shock:
Hypotension
Reflex tachycardia (except in cardiogenic shock)
Sweating
Weakness

Types of shock:
A. Hypovolemic shock (most common type):
Causes:
o Hemorrhage
o Severe diarrhoea
o Vomiting
o Excessive sweating
Treatment:
o Emergent administration of fluids (e.g., normal saline) is essential. Isotonic
fluids are preferred.
o Blood transfusion may be necessary if fluids alone are insufficient.

B. Anaphylactic shock:
Also known as a type 1 hypersensitivity reaction.
Some patients may develop hypersensitivity to common foods like bananas or peanuts.

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Drug allergies, such as penicillin, can also cause this reaction.
Immunoglobulin E (IgE), an antibody, plays a key role in this type of shock.
IgE binds to and degranulates mast cells, leading to the release of inflammatory
mediators like histamine, serotonin, and prostaglandins.
This is the fastest and most life-threatening type of shock.
Treatment:
o Adrenaline (epinephrine): Life-saving drug
▪ ROA: Intramuscular
▪ Dosage: 0.3–0.5 mg
Chapter 4

o Chlorpheniramine:
▪ ROA: Intravenous
▪ Dosage: 10 mg
o Hydrocortisone (released from the adrenal cortex):
▪ ROA: Intravenous or intramuscular
▪ Dosage: 100–200 mg

C. Distributive shock (vascular shock):

Circulatory failure caused by blood pooling in the body’s extremities, leading to
dizziness.
Blood volume is normal.
Causes:
o Infection
o Certain medications
Diagnosis: Based on the medical history of recent illnesses or medications.
Treatment: Alpha-1 agonists (preferably phenylephrine over midodrine for two reasons):
o Midodrine is only available orally.
o Phenylephrine is a more selective alpha agonist, targeting blood vessels and
not the heart.

D. Cardiogenic shock:
Definition: Weakness of the heart’s pumping power.
The only type of shock with bradycardia.
Causes: -
1- Acute myocardial infraction or acute heart failure.
2- Presence of a large effusion or tamponade.
Treatment:
o Dobutamine (IV)
o Dopamine (IV)
o Adrenaline (IV)

E. Septic shock:
Caused by bacterial infection and severe fever → peripheral V.D
Treatment:
o Antibiotics
o Vasoconstrictors

F. Neurogenic shock:
Generalized vasodilation (causing diaphoresis and flushed skin).
Caused by a frightening or disgusting sight (psychological trauma).
Treatment:
o Rest
o Elevating the patient’s legs

G. Endocrine shock:
Involves the adrenal glands.

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Decreased adrenal gland secretion leads to Addison’s disease (chronic).

Acute adrenal failure can develop in Addison’s disease patients during stressful
situations.
Treatment:
o Hydrocortisone (glucocorticoid) and fludrocortisone (mineralocorticoid) – both
are used because each has a specific function.

H. Severe hypothyroidism shock:

A rare type of shock caused by very low levels of thyroxine in the blood.
Treatment: Thyroxine replacement therapy.

Pulmonary Hypertension (PHT)

Definition:- is an increase in pulmonary artery pressure exceeding 25 mmHg.
Types of PHT

Chapter 4
Pulmonary arterial hypertension: Due to pulmonary stenosis.
Pulmonary venous hypertension: Due to left-sided heart failure, leading to congestion
of the pulmonary veins.
Pulmonary embolism: Due to an embolism originating from the lower limb.
Cor pulmonale: Due to lung disease (obstructive or restrictive disease).

Treatment
• Cor pulmonale: Treat the underlying cause (chronic obstructive or restrictive pulmonary
disease).
• Pulmonary embolism: Treat the embolism.
• Pulmonary venous hypertension: Treat heart failure.

Arterial Hypertension
Definition: Arterial
hypertension involves high
blood pressure affecting the
arteries of the lungs and the
right side of the heart.

Symptoms (triad):
Acute chest pain
Dyspnea
Syncope
Diagnosis:
Catheterization
Treatment:
Vasodilator drugs
CCB
(Amlodipine)
Phosphodiesterase enzyme inhibitors (PDE)
▪ PDE is an enzyme that breaks down cAMP and cGMP
▪ Examples: Sildenafil and Tadalafil
Prostacyclin derivatives (Epoprostenol and Iloprost)
Endothelin receptor antagonists (Bosentan)
Note: Endothelin is a natural substance found in the body that causes vasoconstriction. Pregnant
women with PHT are advised against continuing the pregnancy due to the high risk of danger and
potential death.

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Rheumatic Fever (RF)
Definition: is an autoimmune
inflammatory process that develops as a
sequela of streptococcal infection. Usually
affects children (especially males) aged 5-
15 years old.

Causes: Tonsillitis caused by Group A

Streptococcus pyogenes. Children su-
Chapter 4

sceptible to chronic tonsillitis and

pharyngitis caused by Group A Strepto-
coccus bacteria. As this bacteria shares
similar proteins with glomeruli, heart
valves, and joints, the immune response
causes glomerulonephritis, carditis, and
arthritis respectively. A resistant immune
response on heart valves can cause valve
regurgitation or stenosis.

Diagnosis: Based on two major criteria or one major and two minor criteria.
Major criteria Minor criteria
Arthritis (pain with signs of inflammation), carditis, chorea Arthralgia (joint pain),
(a disease of the nervous system characterized by muscle hyperpyrexia, ASO test (anti-
spasms), subcutaneous nodules, skin rash. streptolysin O antibody).

Treatment: Antibiotics (e.g., Benzathine penicillin IM with analgesics due to pain) every month or
21-28 days to prevent chronic inflammation. Maybe used up to 5 yrs.

Pulmonary Embolism
The veins of the lower limbs are divided into superficial
veins (like the saphenous vein) and deep veins (like the
femoral and tibial veins). Congestion in superficial
veins leads to varicose veins. Congestion in deep veins
leads to thrombus formation. Large thrombi can cause
vein obstruction and leg swelling. Small thrombi can
travel to the lungs and cause pulmonary embolism.

Risk factors: Surgery (main cause), trauma, obesity,

fracture (due to immobilization).

Triad of symptoms: Acute chest pain, dyspnea, hemoptysis.

Notes:
Blood in urine or feces in patients over 50 years old suggests cancer until proven otherwise.
Patients with pulmonary edema should never be treated with fluids without diuretics.

Diagnosis: (CTPA) Computed tomo-graphy

(CT) pulmonary angiography, which uses X-
rays or CT scans to construct a 3D image of
the lungs and pulmonary tract.

Treatment: Heparin (IV for acute stage),

warfarin (oral for chronic use), fibrinolytic
drugs (to dissolve thrombus within 12 hours of formation). Heparin and warfarin are used as
prophylactic.

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Myocardial Infarction (MI)

Definition
A myocardial infarction, commonly known as a heart attack, is a complication of unstable angina
characterized by prolonged chest pain. Unlike stable and vasospastic angina, the chest pain in MI is
not relieved by Nitroglycerin.
Symptoms
Severe, central substernal chest pain, and often radiates up to the neck, shoulder, and jaw,
and down the left arm.
Feeling of impending doom.
Nausea and vomiting.
Diagnosis
Cardiac biomarkers/enzymes.
ECG showing ST segment elevation.
Treatment
Aspirin (nonenteric-coated chewable)

Chapter 4
Nitroglycerin
Morphine (for pain relief)
Metoclopramide
Oxygen supply
All drugs are administered intravenously (IV).

Infective endocarditis
Definition: Infection of the endocardial layer of the heart. Characterized by fatigue and pyrexia
(occurs in artificial valves).
Symptoms:
1. Hematuria.
2. Subconjunctival hemorrhage.
3. Septal hemorrhage (red line on finger).
4. Petechiae.
5. Heart failure.

Modified DUKE criteria for Infective Endocarditis MNEMONIC: BE TIMER

Major Minor
Blood culture Positive > Temperature > 38° C (Fever)
2 times 12 hours apart. Immunological phenomena (Osler's nodes, Roth spots)
Electrocardiographic Microbiological Evidence (Positive blood culture not meeting a major
evidence of endocardial criterion)
involvement. Embolic Phenomenon (Arterial emboli, septic emboli, conjuctival
hemorrhage & painless skin lesions.)
Risk Factors (Congenital heart condition or IV drug use)
DEFINITIVE DIAGNOSIS: Two major criteria OR one major and three minor criteria OR Five minor criteria.
POSSIBLE DIAGNOSIS: One major and one minor criteria OR Three minor criteria

Treatment
Bacteria causing endocarditis are Streptococcus and Staphylococcus.
Streptococcus is treated with Benzoyl Penicillin (Penicillin G [short duration]) or in
combination with Gentamicin.
Staphylococcus is resistant to Penicillin except for one type, Flucloxacillin.
Some types are resistant to Flucloxacillin and are treated with Vancomycin.

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Acute pulmonary oedema.

can be defined as an abnormal accumulation of extravascular fluid in the lung parenchyma. This
process leads to diminished gas exchange at the alveolar level. Fluid which maybe:
1. Pleural effusion.
2. Pericardial effusion.
3. Pulmonary edema (fluid in the alveoli).
Symptoms
Chapter 4

Difficulty breathing (dyspnea) or

extreme shortness of breath that
worsens with activity or when lying
down.
A feeling of suffocating or drowning
that worsens when lying down
Fatigue, restlessness, or confusion

Treatment:
1. Furosemide (the most important).
2. Nitroglycerin may be used.
3. Oxygen, fluid restrictions, and
positioning the patient in a sitting
position.

Stroke
A stroke occurs when blood supply to the brain is interrupted (often due to hypertension leading to
cerebral stenosis).
Ischemic stroke (85%): Blood vessel blockage. Treatment is focused on restoring blood
flow.
Hemorrhagic stroke (15%): Blood vessel rupture. Often requires surgical intervention.

Symptoms:
Dysphasia (difficulty speaking)
Weakness on one side of the body

Diagnosis:
CT scan:
 White patches indicate hemorrhagic stroke.
 No white patches suggest ischemic stroke.
Treatment for ischemic stroke:
1. Aspirin (O,P).
2. Fibrinolytic (Thrombolytic or plasminogen activators) if stroke onset is less than 4 hours.
3. Vasodilators (Gradually reduce blood pressure).
4. Oxygen.
5. IV nutrition (fluid nutrition) if the patient cannot swallow.
6. Statins → decrease blood cholesterol level.

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 Chronic Obstructive Pulmonary Disease (COPD) ............................................ 43
Tuberculosis (TB).................................................................................................... 44
Bronchial Asthma :- .............................................................................................47
Types of asthma: - ..............................................................................................47
Chronic Obstructive Pulmonary Disease COPD ............................................... 48
Cough Treatment .................................................................................................. 49

Chronic Obstructive Pulmonary Disease (COPD)

Etiology: Excessive healing ⇢ then turns to fibrosis
Characteristics of the lung in CRPD:
Small
Black
With white spots

Symptoms:
Dyspnea
Dry cough (without sputum)
Clubbing ⇢ see image
Problem in inspiration

History: The patient was exposed to a polluted environment.

Note:
Smoking ⇢ COPD ⇢ Chronic bronchitis and emphysema (more dangerous)
⇢ Death because of hypoxia and cyanosis
Diagnosis:
By spirometry that measures the [FEV1] Forced Expiratory Volume in the
first second, and [FVC] Forced Vital Capacity in both COPD and CRPD.
− FEV1 of CRPD ⇢ normal
− FEV1 of COPD ⇢ low

Treatment:
Bronchodilators
 Beta agonists (Salbutamol & Salmeterol)
 Anti-cholinergic drugs (Ipratropium & Tiotropium)
Methylxanthine derivatives (Theophylline & Aminophylline)

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Antifibrotic drugs (Pirfenidone & Nintedanib)
Corticosteroids (Suppresses immunity & healing process)
Pirfenidone (antifibrotic, can be used for ttt of idiopathic pulmonary fibrosis)

Tuberculosis (TB)
It is a multisystemic disease (mainly pulmonary disease) and is considered a third-world disease.
Cause: Mycobacterium tuberculosis infection (special stain = Ziehl-Neelsen stain)
Chapter 5

Appropriate conditions for the disease:

 Weak immunity
 Crowded places
 Poverty
 Prisons
 Abandoned places
 Malnutrition

Mode of infection: Through the air from person to person by respiratory droplets and speaking.
Pathogenesis: TB infection begins when
the mycobacteria reach the alveolar air sacs
of the lungs, where they invade and replicate
within lymphocytes and macrophages,
forming granulomas. Granulomas aggregate
to form Ghon focus. Then, Ghon focus
transfers into the lymph node to form the
primary complex of Ranke (which is
surrounded and enveloped by macrophages).
MB TB + macrophages ⇢
Granuloma
Aggregation of Granuloma ⇢
Ghon’s focus
Ghon’s focus + lymph node ⇢
Primary complex of Ranke

One-third of the world’s population carries TB, and no symptoms appear.

Note: If immunity is weak, the disease starts affecting the lungs. If the patient is asymptomatic,
don’t exclude TB.
Symptoms:
1. Pneumonia 4. Fever
2. Productive cough (mucopurulent or 5. Dyspnea
blood-stained) 6. Sweating
3. Hemoptysis 7. Kyphosis

TB starts as pulmonary and then becomes extrapulmonary, affecting:

 Brain ⇢ Meningitis
 Heart ⇢ Pericarditis

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 Kidney ⇢ Hematuria
 Spinal cord ⇢ Kyphosis
 Bone ⇢ Pott’s disease

Note: Neglected tropical diseases include Malaria, Dengue fever, Typhoid, TB, and Leishmania.
Diagnosis:
Ziehl-Neelsen stain
Mantoux test or tuberculosis sensitivity test: Place under the skin; if enlarged, the person is a
carrier or diseased.
 If positive: Diseased or carrier
 If negative: No disease, no carrier

Treatment of pulmonary TB:

Chapter 5
1. Isoniazid (INH) ⇢ 300 mg/d
2. Rifampin ⇢ 600 mg/d
3. Pyrazinamide ⇢ 25 mg/kg/d
4. Ethambutol ⇢ 20 mg/kg/d

Note: All the drugs are used at the same time. Duration of treatment: 6 months.
Drugs of pulmonary TB:
The first 2 months: Use four-drug regimen of rifampicin, isoniazid, pyrazinamide and
Ethambutol.
The last 4 months: continuation of Isoniazid and Rifampin.

TB + Meningitis:
Use all of the previous drugs at the same time (for the first 2 months).
Use Isoniazid and Rifampin (for a year).
Add Dexamethasone (anti-inflammatory to prevent loss of hearing and brain damage).

TB + Pericarditis:
Use all of the previous drugs at the same time (for the first 2 months).
Use Isoniazid and Rifampin (for a year).
Add Prednisolone (anti-inflammatory, used for 2-3 weeks).

Extrapulmonary TB:
Streptomycin ⇢ 1 gm daily for one month.

Treatment for carriers:

Isoniazid + Rifampin (with the same previous dose) for 3 months.
Or Isoniazid and Pyridoxine for 6 months.

For protection: Take Isoniazid or Rifampin on the day you go to the centre that deals with TB
patients.
Treatment of resistant TB:
Isoniazid + Rifampin + Pyrazinamide

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Add Ciprofloxacin + Gentamicin

Note: If the patient starts the treatment, they become non-infectious after two weeks.
Side Effects:
Isoniazid:
• Hepatitis
• Peripheral neuropathy (treated by vitamin B6)
Chapter 5

Rifampin:
• Hepatitis
• Orange-red urine (metabolic inducers)
• GIT disturbance
Pyrazinamide:
• Hepatitis
• Hyperuricemia (Gout)
Ethambutol:
• Optic neuritis ⇢ Colour blindness
• GIT disturbance

Cystic fibrosis
is an inherited condition that affects the lungs, pancreas, GIT and other organs. CF decreases the
watery secretion of the body, leading to saltier sweat.
Mutation – impaired Sodium-Chloride-water transport.
- Thick, viscous secretions
- Impaired mucociliary clearance in the lung
- Impaired pancreatic secretion
- Abnormal sweat 😓
Diagnosis: taken while childhood: Mother’s notice some signs and symptoms in her children like:
1. Steatorrhea (due to decreased pancreatic
secretion).
2. Pneumonia.
3. Malabsorption.
4. Malnutrition.
5. Infertility (due to decreased seminal fluid).
6. Chronic diarrhoea.
7. Mental and physical retardation in children.

Treatment: Depends on the specific problem:

- Pneumonia ⇢ Antibiotics.
- Pancreatic insufficiency ⇢ Pancreatic enzymes to aid in digestion.
- Infertility ⇢ Intracytoplasmic Sperm Injection (ICSI)

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BRONCHIAL ASTHMA :- .
It's a combination case of airway inflammation and airway hyper-responsiveness
⇢ airflow limitations
1- SABA ⇢ Short Acting Beta2 Agonist as Salbutamol
2- LABA ⇢ Long Acting Beta2 Agonist as Salmeterol
3- SAMA ⇢ Short Acting Muscarine Antagonist
4- LAMA ⇢ Long Acting Muscarine Antagonist
5- ICS ⇢ inhaled corticosteroids
1- Allergic asthma: - 6- LTRA ⇢ Leukotriene receptor antagonists
Caused by exposure to allergens which leads to IgE production that binds to mast cell ➟ histamine
release.

2- Non allergic asthma: -

Chapter 5
Caused by; stress, anxiety, exercise, cold exposure, smoking, infection

MANAGEMENT OF ASTHMA: -
1. start with SABA "Salbutamol"
2. if uncontrolled or symptoms persist for 3 weeks add ICS as "Beclomethasone"
3. if uncontrolled continue adding LTRA as "Montelukast"
4. if also uncontrolled replace LTRA by LABA so patient will take
( SABA + ICS + LABA )
5. if uncontrolled due to resistant allergy add IgE inhibitors

1- Inhaled corticosteroids: -
EX :-
NOTES

1- Beclomethasone ⇢ most useful for bronchial asthma.

2- Fluticasone ⇢ most useful for COPD due to its long duration of action 24hr
MOA :-
inhibits phospholipase A2 ⇢ inhibit synthesis of arachidonic acid ⇢ inhibit PG &
Leukotrienes production ⇢ No inflammation & No bronchoconstriction.
inhibit IgE production , so prevent histamine release.
CU: they can be used for both allergic & non allergic asthma.
SE:
A- Systemic:
1. Increase blood pressure
2. Increase blood glucose level
3. ⇡ Uric acid “gout”
4. Peptic ulcer
5. Suppress the immune system (recurrent infection)
B- Inhaled (local):
6. Oro-pharyngeal candidiasis “most important”

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To avoid Oro-pharyngeal candidiasis :-

1. Rinse with water (prophylaxis)
2. if occurs, patient should be treated with antifungal drug such as
(Nystatin)
Note: Nystatin used orally, non-absorbable, so no toxic SE.

2- IgE inhibitors: belongs to monoclonal antibodies.

Chapter 5

MOA:
Acts via binding to IgE ⇢ prevent its binding to mast cell ⇢ inhibits histamine release.
EX:-
Omalizumab
ROA :-
{P: subcutaneous} every 2-4 weeks.
SE:
a. pain at injection site d. headache.
b. swelling. e. pruritus
c. Erythema

Chronic Obstructive Pulmonary Disease COPD

Long-term condition characterized by obstruction in the air way
1. Causes :-
1. Smoking (the main cause)
2. Open fire “cooking”
3. Occupational causes (cement, coal , cadmium)
2. Symptoms:-
1. Dyspnea 2. Wheezing 3. Chest pressure 4. Chronic cough (productive)

Management: -
1- 1st line treatment: stop smoking
_start with SAMA (Ipratropium) or SABA (salbutamol)
2- 2nd line treatment: if resistant persists
A- Replace SABA and SAMA by LABA(Salmeterol) or LAMA (Tiotropium)
B- depends on FEV-1 (Force Expiration Volume within 1 second) :-
1- if FEV-1 > 50 ⇢ use only LABA or LAMA
2- if FEV-1 < 50 ⇢ add ICS to LAMA or LABA (in this case Fluticasone +
Salmeterol used as a combined drug )
3- 3rd line treatment: if pts uncontrolled
LABA + ICS + LAMA

Notes:
1. Other drugs can be added to treatment for COPD :-
o Synergistic effects: like PDE inhibitors

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Symptomatic Treatment:
o
Use anti-cough (mainly mucolytic)
2. Salbutamol can be used in combination with Ipratropium (SABA+SAMA), the
combination is called Combivent ⇢ used for acute bronchoconstriction
3. Salmeterol used in combination with Fluticasone ⇢ to maintain the duration effect of
drug.

Cough Treatment
The treatment according to the type of cough:
1. Dry cough (Antitussive)

Chapter 5
2. Wet cough (Mucolytic & Expectorant)

1. Dry cough:
- Caused by cold exposure, allergy or drug induced & CRPD.
Antitussive drugs are 2 types:
a. Peripheral Antitussive:
b. Central Antitussive:
A- Peripheral Antitussive:
MOA: coating of sensory receptors of respiratory system.
EX :
1- Lozenges (contain methanol, honey, ginger, peppermint)
2- Boiling water ( evaporated water, inhalation of evaporated water )
SE: No side effect (safe)
B- Central Antitussive:
MOA: inhibit cough centre in CNS.
EX:- opioids :
1. Codeine (natural)
2. Dextromethorphan (synthetic)
S.E:
• Tolerance
• Dependence
• Constipation ( decrease intestinal motility )
• Sedation

Adjuvant therapy to antitussive (dry cough)

1- Sedating anti H1
e.g.- Diphenhydramine
2- Plant extract: Guava
3- Indirect sympathomimetic:
e.g. - Ephedrine as (bronchodilator)

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2. Wet or productive cough (with infection) & COPD: -
a- Mucolytic:
MOA:
breaks down of S-S bond of the mucous ⇢ conversion of mucus from viscous to watery
form (usually patient swallows it )
e.g. :
1) Acetylcysteine (P) ( for acute coughing in emergency)
Chapter 5

2) Ambroxol (O)
3) Bromohexene (O)
b- Expectorant:
MOA : stimulates parasympathetic system leads to:
1. increase watery secretion
2. increase motility of cilia
e.g.
• NH4CL (O)
• Guaifenesin (O)
usually used in combination.
Notes :
1- Anti-cough drugs are preferred mixed or combined (expectorant +mucolytic)
2- Thyme (plants extract) is used for wet cough .

Phosphodiesterase inhibitors (PDEI)

1- Non selective PDEI: ⇡ cAMP & ⇡ cGMP
e.g. : Theophylline (methyl xanthine )
MOA:
a. inhibits breaking of cAMP ⇢ increases of cAMP ⇢ relaxation of bronchi
b. adenosine receptors blockers ⇢ bronchodilation, ⇡ heart rate.
S.E :
1- Tachycardia.
2- V.D ⇢ hypotension + reflex tachycardia.
3- Tachyarrhythmia by two mechanisms.
4- Insomnia (so used with Phenobarbitone)
5- Low therapeutic index.

2- Selective PDE-4 inhibitor:

MOA:
⇡ cAMP only (so no effects on the heart and blood vessels)
e.g.:
Roflumilast (O)
it has a long duration of action.
S.E:
1. GIT → nausea, vomiting, cramps, diarrhoea, loss of appetite & weight loss
2. Headache, insomnia

50 Page
 Diarrhoea ......................................................................51 Chronic Liver Diseases:............................................... 61
Constipation: .............................................................. 52 Hemochromatosis: ..................................................... 62
Peptic Ulcer .................................................................54 Wilson’s Disease: ......................................................... 62
Antibacterial Drugs: .................................................. 56 Autoimmune Hepatitis (AIH): .................................. 62
Antiemetic Drugs:....................................................... 57 Primary Biliary Cholangitis (PBC): ....................... 63
Gall Stones:..................................................................58 Primary Sclerosing Cholangitis (PSC): .................. 63
Pancreas:......................................................................58 Coeliac Disease: .......................................................... 63
Pancreatitis: ................................................................ 59 Viral Hepatitis: ........................................................... 63
Irritable Bowel Syndrome (IBS): ............................. 59 Alpha1 Anti-Trypsin Deficiency: ............................. 64
Inflammatory Bowel Disease (IBD): ...................... 60 Complications of Liver Disease: .............................. 64

Diarrhoea
Diarrhoea Definition: A condition characterized by increased motility of the small
intestine.
Types of Diarrhoea:
1. Microbial Diarrhoea
2. Non-Microbial Diarrhoea

Microbial Diarrhoea: Any infections like:

Cholera:
Symptoms: Watery diarrhoea.
Treatment: DOC is Doxycycline “oral” 100 mg twice a day for 7 to 10 days
(Antibiotic).
Side Effect: Teratogenic.

Typhoid:
Causative agent: Bacterium Salmonella.
Types: Classified according to the affected organ:
• Salmonellosis: Causes GIT symptoms like nausea, cramps, and diarrhoea (no
systemic symptoms).
• Typhoid: Causes GIT and systemic symptoms: in addition to the above →
fever, headache, and rose-red spots on the trunk, arthralgia.
Treatment:
• Salmonellosis’ DOC is Co-trimoxazole {O} “Antibacterial” for both adults
and children.
• Typhoid’s drugs depend on the age of the patient:
 In Children: Co-trimoxazole is used “oral” replacement therapy
Ceftriaxone “parenteral” antibiotics.
 In Adults: Ciprofloxacin “antibacterial” {O} the replacement
therapy is Ceftriaxone “P” “antibiotics”.

Clostridium difficile infection:

Caused by either drug-induced like “Broad Spectrum Antibiotics” or toxicity.
Resulting in: Fatal diarrhoea by PMC “Pseudomembranous Colitis”.

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Symptoms: Pus diarrhoea, severe pain.
Treatment:
• Metronidazole “oral” “Antibacterial drug”.
 Side Effects: Metallic taste, dark urine, GIT disturbances.
• Vancomycin
• Fidaxomicin (used orally, non-absorbable antibiotics, no systemic side
effects).

Amoebiasis and Giardiasis:

Treatment: The DOC is Metronidazole.
Dosage: 500-750 mg × 3 times × 7-10 days (three times daily for 10 days).
Replacement therapy: Tinidazole.
Dosage: 2 g single dose.

Non-Microbial Diarrhoea:
Causes:
o Drug-induced.
o Disorders like Irritable Bowel Syndrome and Diabetes.
o Some foods.
MOA: Decrease the intestinal motility.
Examples:
o Anticholinergic drugs: Atropine and Hyoscine (not commonly used).
o Opioids: More selective on GIT by decreasing intestinal motility.
▪ Loperamide (preferred in Diabetic and 1IBD).
▪ Diphenoxylate.
Side Effects of Opioids:
1. Sedation
2. Tolerance of dependence (not strong, doesn’t cross BBB)
3. Constipation
Notes:
1. First-line treatment of diarrhoea depends on the prevention of dehydration by using:
“ORS” Oral Rehydration Salt.
IV fluids Ringer’s lactate.
2. Rifaximin:
Best drug for Traveller’s diarrhoea.
non-absorbable drug, so it produces a local effect on GIT.
is an antibiotic drug.
3. Diabetic or IBD with diarrhoea is treated with Loperamide.
4. Diabetic or IBD with constipation is treated with Senna.

Constipation:
Constipation Constipation is not a disease but a symptom of GIT disorders. It
may be caused by:
Lifestyle factors such as decreased vegetable, fruit, and water
intake
Drug-induced

1
IBS ‫هذا قصد الدكتورة فرقو بينهم‬

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Disorders such as irritable bowel disease (IBD) or diabetes

First line of Treatment: Change lifestyle by increasing water and fiber intake.
Second line of Treatment: Laxative drugs, which are divided by MOA into four groups:

① :
It is fiber but as a drug.
MOA: It is a hydrophilic compound that absorbs water and forms a bulk complex,
increasing peristalsis.
Examples: Bran (Methylcellulose)
ROA: Orally

Chapter 6
② :
MOA: Act by easing the passage of stool in the gut and also via softening the stool.
Examples:
Glycerine: Used [supp.], preferred in children and postoperative patients.
Paraffin oil: Used [orally], preferred in pregnancy.
 SE: In chronic use, it may cause fat-soluble vitamin deficiency.
Na docusate, Na picosulfate [O]: Work as surfactants (soap), do not cause
fat-soluble vitamin deficiency (allow water to enter the stool). Can be used in
children and pregnancy (but not first-line treatment).
 SE: Abdominal cramps.

③ :
All of them are used [orally], with a short duration.
Onset of action: 3 - 6 hrs.
MOA: Transferring water from low salt concentration to high salt concentration,
increasing water in the large and small intestine by osmotic pressure.
SE: Patients start feeling flatulence, abdominal cramps, and end with diarrhoea.
Examples:
MgSO₄: Safe but contraindicated in renal failure due to increased Mg²⁺ level
in blood, which leads to decreased Ca²⁺ and K⁺ levels in blood.
Lactulose: Mainly used with hepatic disease to prevent hepatic coma
(encephalopathy) by trapping NH₃ to be excreted with stool.
Polyethylene glycol (PEG): Safe drug even in renal disease.
Note: Osmotic laxatives are used for premedical procedures.

④ :
Drugs that increase motility of both small and large intestine directly, with a slow
onset of action (6-12 hrs).
Examples:
Natural drugs:
 Castor oil: Increases motility of both small and large intestine, has
drug-drug interaction, so it is not used chronically.
Clinical Use: Premedical procedures.
 Senna: Increases motility of the large intestine, no drug-drug
interaction. Senna is the first line of treatment for patients with
chronic disease suffering from constipation.

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Clinical Use: IBD, diabetic (the best/first choice for
constipation in both).
 SE of natural drugs: More tolerance and dependence than synthetic,
cramps, and diarrhoea.
Synthetic drugs: Bisacodyl (replacement therapy to Senna).
 SE: Cramps and diarrhoea.

Peptic Ulcer
Peptic
MERCURY Increased HCl secretion affects the mucosal layer of the stomach (it
Ulcer starts as irritation then perforation).

Causes:
H. pylori
Types of food intake (citrus fruits, spicy food)
Stress
Anxiety
Smoking
Some drugs (aspirin) and alcohol consumption

Factors affecting HCl secretion:

ACH ⇢ acts on M1 receptors ⇢ increases HCl secretion
Histamine ⇢ acts on H2 receptors ⇢ increases HCl secretion
Gastrin ⇢ acts on G receptors ⇢ increases HCl secretion
H+/K+ ATPase ⇢ increases synthesis and secretion of HCl (the last step in HCl secretion)
Prostaglandin (PGE) ⇢ increases mucus and bicarbonate secretion (force against acidity)

H2 blockers (closing histamine and gastrin receptors)

M1 blockers (anticholinergic drugs)
Proton pump inhibitors (PPI) (inhibition of H+/K+ ATPase)
Antacids
Protectives
Anti-bacterial drugs (for H. pylori ulcer)
PGE derivatives

MOA: Decrease HCl secretion by H2 and Gastrin receptors inhibition.

Examples: Cimetidine (O/Parenteral), Ranitidine (O/Parenteral)
Characteristics: Metabolized and excreted by the kidney. They are metabolic inhibitors.
Side Effects: In elderly and renal impairment patients ⇢ cause hallucinations, bradycardia,
hyperprolactinemia & low androgen blood level. In GIT (diarrhoea, cramps, and flatulence).
In CNS (headache).

Example: Pirenzepine (O)

Clinical Use: Stress-induced ulcer.
Side Effects: Atropine-like side effects, so it’s rarely used.

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The most effective group.

Efficacy: 90-98%
Duration of action: 24h
They are prodrugs (cation+ active form), so contraindicated with other metabolic inhibitors.
Used twice daily in peptic ulcer and once daily in hyperacidity 1 hour before meals (food
delays absorption and activity of the drug).
They’re coated to prevent their lysis in the stomach and reach the intestine to be well
absorbed.
MOA: Irreversible binding to H+/K+ ATPase (the enzyme is synthesized after 18h). If used
for a week, H+/K+ ATPase is synthesized in 3-4 days.
Examples:
Omeprazole & Esomeprazole (same as omeprazole) (O/I.V)
Pantoprazole (O/I.V)

Chapter 6
Lansoprazole (O)
Side Effects:
Indigestion (flatulence, cramps, and diarrhoea)
Headache (hypotension or vasodilation of cerebral blood vessels)
Nutritional deficiency (chronic use may cause ↓ of vit.B12, Ca++, or Mg++
absorption)
Bacterial infection (in GIT and respiratory system).
They are category C drugs (could be or couldn’t be teratogenic, used only in the third
trimester of pregnancy if suffering from peptic ulcer).
Chronic use may cause cancer due to changes in the gastric surface (mucosa).

Notes:
Omeprazole is a metabolic inhibitor (contraindicated in patients with multidrug therapy
such as diabetic patients).
Pantoprazole and Lansoprazole are safe for multi-drug patients.
PPI is the drug of choice for any cause of gastric irritation (peptic ulcer).
PPI can be used in children after dissolution of the drug in water.

Example: Misoprostol (O) increases mucus and bicarbonate.

Side Effect: Abortion.

Reacts with HCl → salt + water (neutralization).

Acts locally.
Used after meals (1 hour).
Efficacy depends on binding of alkali to acid.
Duration: 2 hours.
To increase duration of action and decrease frequency of doses, a mixture is preferred.
Examples:
CaCO₃ → CaCl₂ + ↑CO₂ (O).
▪ Side Effect: Hypercalcemia, flatulence.
Al(OH)₃ + Mg(OH)₂.
▪ Lack flatulence effect.
▪ Al³⁺ causes severe constipation. Mg²⁺ causes severe diarrhoea.
▪ Used in combination to produce balanced effects on GIT motility and
decrease rebound of hyperacidity.

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Notes:
Simethicone is used with antacid as an antiflatulent.
Antacids are the first-line treatment for hyperacidity in pregnancy.
Antacids are contraindicated to be used with multivitamins.
• Lead to deficiency in Ca²⁺, Mg²⁺, and Fe²⁺.

:
Drugs that bind to the irritated site of the mucosa to create a protective cover for the stomach
mucosa.
Local effect and acts as a barrier between HCl and the irritated site of the mucosa.
Examples:
1. Sucralfate (gel / 1 gm × 4 times)
☺ 1 hour before meals
☺ Second-line treatment for pregnancy
☺ Side Effects: GIT upset (nausea, vomiting, black stool, and constipation)
2. Bismuth subsalicylate (O)
☺ Antibacterial effect
☺ Antidiarrheal
☺ Side Effects: Black tongue & stool (if taken in high dose), constipation, nausea, and
vomiting

Antibacterial Drugs:
Used for H. pylori ulcer.
Examples:
Amoxicillin (1g × 2 times)
Clarithromycin (500 mg × 2 times)
Metronidazole (500-750 mg × 3) or Doxycycline (100 mg × 2) (in case of Amoxicillin
resistance)

Triple Therapy:
Amoxicillin + Clarithromycin + PPI (1 × 2 × 7)
In old medical books (1 × 2 × 14), then stop the antibacterial drugs and continue treatment
with PPI for 14 days.
Replace Amoxicillin with Metronidazole or Doxycycline (1× 2×7) in case of resistance.

Quadruple Therapy:
Amoxicillin + Clarithromycin + PPI + Bismuth subsalicylate (1 × 2 × 7 days)

Bismuth subsalicylate:
Antibacterial, antidiarrheal, and protective drug.

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Antiemetic Drugs:
Drugs used for the treatment of vomiting.
Causes of Vomiting:
Drug-induced
Related to diseases ⇢ motion sickness, morning sickness, bacterial infection

Classified according MOA:

① Anticholinergic Drugs:
Example: Hyoscine
CU: Motion sickness
② Anti H1 (sedating):
Examples:
▪ Meclizine ⇢ morning sickness (with Vit B6)
▪ Diphenhydramine ⇢ motion sickness

Chapter 6
▪ Cinnarizine/Betahistine ⇢ Meniere’s disease
③ 5HT3 Antagonists:
Examples: Ondansetron / Granisetron
CU: Nausea & vomiting induced by chemotherapy and infection

④ 5HT4 Agonists:
Examples: Metoclopramide / Domperidone
CU: Nausea & vomiting induced by food
MOA: Stimulate 5HT4 ⇢ increase gastric emptying

Metoclopramide also blocks D2 receptors, so it:

1. Helps in milk formation & ejection
2. Prevents nausea & vomiting induced by drugs
⑤ Selective D2 Blocker:
Only for radiation & drug-induced nausea and vomiting
Example: Chlorpromazine (antipsychotic drug for schizophrenia)
S.E:
▪ ⇡ Prolactin ⇢ leads to galactorrhea, gynecomastia, infertility
▪ ↓ Dopamine ⇢ leads to:
▪ Depression
▪ Extrapyramidal symptoms (EPS)

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Gall Stones:
Gall Bladder (GB): An organ that stores and secretes bile acids (cholic acid and chenodeoxycholic
acid) and releases them during food ingestion for fat digestion. The synthesis of bile is the function
of the liver.
Bile is composed of:
1. Cholesterol
2. Bile acids

Risk factors for increased

cholesterol:
1. Female
2. Obesity
3. Contraceptives

Gall Stone:
Formed due to either increased cholesterol in bile or decreased bile salts.
This condition is called cholestasis.
Irregular in shape.
Small stone (asymptomatic)
Large stone (symptomatic)

When the patient eats fatty food, the stone starts moving and pressing down, causing severe pain.
This “contraction-like pain” is manifested in the center of the abdomen, extending to the right
shoulder.
Inflammation of the gall bladder is called “cholecystitis,” and the removal of the gall bladder is
called “cholecystectomy.”
Symptoms:
1. Severe abdominal pain (long term, about 6 hours) like “”‫دبابيس‬
2. Nausea
3. Vomiting

Diagnosis: By USS (Ultrasound Scan)

Treatment:
According to the size of the stone:
If the stone’s size is less than 1 cm:
IV fluids
Ursodeoxycholic acid (“The Natural bile acid") which will increase the percentage
of bile, hence decreasing the gall stones. This drug needs a long duration from 6
months to 1 year.
Antibiotics because of the bacterial infection.
If the stone’s size is more than 1 cm:
Surgical removal of the stone is required. After the removal, the patient will suffer
from steatorrhea.

Pancreas:
An organ of the digestive system with both exocrine and endocrine functions.
Function of the pancreas (as exocrine):
• Secretes pancreatic juice containing enzymes (trypsin, amylase, and lipase), which are the
most important enzymes for digestion.
Pancreatic Disorders:
Decreased pancreatic secretion → pancreatic insufficiency.
Increased pancreatic secretion → pancreatitis.

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Pancreatic Insufficiency: Caused by cystic fibrosis.

Symptoms:
Steatorrhea
Azotorrhea (increased nitrogen in the stool)
Diarrhoea
Cachexia in adults
Mental and physical retardation in children
Diagnosis:
Decreased elastase level (a protease produced by the pancreas used for protein analysis)
In the case of cystic fibrosis, the patient generally has more salt in their sweat (salty taste).
Treatment of Pancreatic Insufficiency:
• Pancreatin, as a compensatory for pancreatic enzymes (trypsin, amylase, and lipase), one
pill before eating.

Pancreatitis:

Chapter 6
Causes:
More than 90% of acute pancreatitis is caused by:
Stone → obstruction of the pancreatic duct
Alcohol → increases HCl and pancreatic juice
Excessive secretion
Scorpion venom
Diagnosis:
Blood tests to look for elevated levels of pancreatic enzymes (amylase & lipase)
Symptoms:
These symptoms are not specific. The patient typically has the same symptoms as peptic ulcers,
such as:
Acute abdominal pain
Vomiting
Anorexia
Nausea
Epigastric pain
Hypovolemia and dehydration due to accumulation of fluid around the pancreas
Treatment:
There is no specific treatment for pancreatitis, so we give the patient supportive treatment such as:
IV fluids
Analgesics (Buprenorphine)
Prevent the patient from eating
Prevent the drinking of alcohol (if the patient is addicted)

Irritable Bowel Syndrome (IBS):

IBS: Disturbances of GIT motility (diarrhoea, constipation, and cramps).
It is more common in adult females.
Diagnosis of IBS: Investigation to exclude other differential diagnoses, e.g.:
Stool examination to exclude Amoebiasis and Giardia
H. pylori examination to exclude peptic ulcer
Amylase test to exclude pancreatic disorders

Treatment depends on symptoms (symptomatic):

1. If the patient has constipation, treat with laxative drugs (tablets):
Senna
Lactulose (preferred in liver diseases)

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Castor oil
Bisacodyl
Polyethylene glycol (used for evacuation of the colon before operation)
2. If the patient has diarrhoea (non-infectious diarrhoea), treat with fluids and opioids, e.g.:
Loperamide (DOC)
Diphenoxylate
Codeine: Used as ‘antimotility, antitussive & analgesic’
This group works by decreasing motility of GIT but has side effects (dependence and
tolerance).
3. If the patient has cramps, treat with direct smooth muscle relaxation drugs, e.g., Mebeverine.
4. If the patient doesn’t benefit from all previous drugs to treat IBS, it may be due to
psychological causes such as depression. In this case, use “Amitriptyline.” This drug is also
used for:
Urinary incontinence in children
Peripheral neuropathy in diabetic patients

Inflammatory Bowel Disease (IBD):

A chronic autoimmune inflammatory disease (tissue damage).
Can be treated by: Anti-inflammatory & immune suppressant drugs
IBD can cause ulcers in the lower GIT

The difference between IBD and peptic ulcer:

1. IBD:
Autoimmune disease
Treated by corticosteroids and NSAIDs (e.g., Aspirin)
2. Peptic ulcer:
Caused by increased HCl or decreased mucus secretion or H. pylori
Corticosteroids and NSAIDs are not used (contraindicated)

Types of IBD:

Ulcerative Colitis Crohn’s Disease

Left side (sigmoid, rectum, and descending Right side (terminal ileum, cecum, and ascending
colon) colon); can occur at any site from mouth to rectum
Mucosa and submucosa only Affects all layers
- Rectal bleeding with mucus, Pain in the - Chronic diarrhoea, Occult bleeding, Oral ulcers
lower left side of the abdomen
Anemia Anemia

Diagnosis of IBD:
Colonoscopy (the most specific)
X-ray using Barium sulphate
Abdominal ultrasound
Notes
Complications of IBD: •: Increased Calprotectin in blood
1. Gangrene (degeneration of tissue) indicates GIT inflammation (not
2. Ischemia specific)
3. Peritonitis • Decreased elastase in stool indicates
4. Colorectal cancer (long period) pancreatic insufficiency
5. Perforation

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Treatment of IBD:
1. 5-Amino Salicylic Acid (5-ASA) (NSAIDs):
Note: 5-ASA is highly absorbed in the stomach & small intestine, so it doesn’t reach the
target site of inflammation in the colon. That’s why it’s used in combination with other
compounds, e.g.:
Sulfasalazine: A pro-drug converted into its active metabolites (5-ASA) in the
colon by bacteria.
− Structure: 5-ASA + Sulphapyridine.
Asacol: A modified structure of 5-ASA which depends on pH.
− MOA: The drug isn’t released until it reaches the alkaline media in the large
intestine (pH=8).
Pentasa: MOA: Delays the release of the drug until after 8 hours, which is the time
when the drug reaches the colon.
Canasa: Suppository

Chapter 6
Rowasa: Enema
2. Corticosteroids (O, P, suppository):
Examples: , ,
Increase the dose gradually and withdraw gradually.
Side Effects of corticosteroids:
Hypertension
Diabetes
Central obesity
Peptic ulcer
Glaucoma
Decreased immunity
Osteoporosis
Muscle weakness
Cataract
3. TNFα Inhibitors:
TNF alpha plays a very important role in inflammatory bowel disease.
TNF alpha inhibitor drugs end with the suffix (mab).
They are monoclonal antibodies.
Side Effects: Decreased immunity
Examples:
1. - Anti CD20

4. Cyclosporine: Used to decrease immunity, commonly in organ transplantation.

5. Rituximab (monoclonal antibodies):
Anticancer (anti CD20)

Chronic Liver Diseases:

Causes:
1. Alcoholic Fatty Liver:
The most common worldwide cause of chronic liver disease.
Diagnosis: AST is twice ALT.
Treatment: Stop alcohol consumption.
2. Non-Alcoholic Fatty Liver:
The second most common cause.

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“NAFLD” is part of metabolic syndrome.
Patients characterized by:
Hyperlipidaemia
Hyperglycemia
Hypertension
Hyperuricemia
Obesity
In females:
Polycystic ovarian diseases
Treatment:
Treat the underlying problem causing the disease.

Hemochromatosis:
Iron precipitation in the liver, skin, and pancreas associated with bronze diabetes.
Diagnosis: High ferritin in blood.
Treatment:
1. Iron Chelating Agents:
o They bind with iron and form a complex to be excreted in urine.
o Examples: Deferoxamine (also used in patients suffering from thalassemia major or
beta thalassemia)
2. Venesection: Pulling blood from the patient.

Wilson’s Disease:
Precipitation of copper in the liver and CNS.
:
Cu²⁺ chelating agents:

o (zinc salt)
Diagnosis:
If an adult patient suffers from Parkinson’s or chorea, the diagnosis is Wilson’s disease until
proven otherwise.
Ceruloplasmin is an enzyme that releases copper from the liver to the blood. Its decrease
leads to increased accumulation of copper in the liver and decreased levels in serum (so
ceruloplasmin measurement is helpful in diagnosis).

Autoimmune Hepatitis (AIH):

Liver inflammation that occurs when the immune system attacks the liver.
Diagnosis:
• Testing the elevation of immune markers in the blood:
1. ASMA (anti-smooth muscle antibody)
2. LKMA (liver kidney microsomal antibody)
3. ANA (antinuclear antibody)
Treatment:
• Immunosuppressants (steroids):
o (has Cushing’s-like side effects)
o (to reduce the side effects of Prednisolone)
Side Effects of corticosteroids: Hypertension, osteoporosis, muscle weakness, peptic ulcer,
bruising, cataract, and decreased immunity.

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Gastrointestinal system

Primary Biliary Cholangitis (PBC):

Occurs when the immune system attacks the biliary system inside the liver.
Diagnosis:
• Clinical picture: jaundice, itching, and usually associated with Sjögren’s syndrome.
• Treatment of itching: cholestyramine, rifampin, or ondansetron.
• High blood levels of alkaline phosphatase.
• Increased blood level of AMA (antimitochondrial antibody).
Treatment: (UDCA) by increasing bile flow. ‫جاي من الدب‬

Primary Sclerosing Cholangitis (PSC):

Occurs when the immune system attacks the biliary system outside and inside the liver.
Diagnosis:
• Clinical picture: jaundice, itching, and usually associated with ulcerative colitis.
• High blood levels of alkaline phosphatase.

Chapter 6
• Increased blood level of ANCA (antineutrophil cytoplasmic antibody).
Treatment: (UDCA) by increasing bile flow.

Coeliac Disease:
An inflammatory and destructive autoimmune condition of the small intestine triggered by gluten
ingestion in genetically susceptible individuals.
Diagnosis:
• By immune markers:
o EMA (anti-endomysial antibody)
o TTG (tissue transglutaminase)
Treatment: Gluten-free diet.

Viral Hepatitis:
Hepatitis A:
• Occurs in children and no need for treatment.
Hepatitis E:
• No need for treatment (only self-care and rehydration).
Hepatitis A & E:
• Transmitted by contaminated food and water only.
Hepatitis C:
• This virus spreads by contact with contaminated blood (transfusion, needles).
• Diagnosis: HCV antibody test.
• Treatment: Treated by a combination called Harvoni, which is a mixture of two drugs
( & ).

Hepatitis B:
• Transmitted like hepatitis C and by sexual contact.
• Diagnosis: HBsAg test.
• Treatment:
o For decompensated patients: Entecavir or Tenofovir.
o For compensated patients: Interferon-alpha .

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Alpha1 Anti-Trypsin Deficiency:
is a genetically inherited disorder often unrecognized in clinical practice. It results in impaired
production of alpha-1 antitrypsin protein, which plays a role in protecting the body from neutrophil
elastase, an enzyme released by white blood cells during infection. Due to defective protein
production, there is reduced activity of AAT in the blood and lungs. Additionally, abnormal
AAT levels can lead to the accumulation of AAT in the liver, leading to liver disease.
This leads to emphysema (smokers are more susceptible) and chronic liver disease.
Treatment: Supportive.

Complications of Liver Disease:

1. Oesophageal Varices:
o The most dangerous complication of liver disease.
o Cause: Increased pressure in the portal vein due to chronic liver disease leads to the
formation of anastomosis. These blood vessels are weak, so they may rupture,
causing esophageal bleeding.
o Prevention: By non-selective β blockers, e.g., Propranolol or Nadolol.
o Treatment:
Terlipressin (vasopressin derivatives): Selective V1 agonist which causes
vasoconstriction, used in acute esophageal bleeding.
Octreotide (somatostatin derivatives): Universal hormone inhibitor. It
inhibits the secretion of growth hormone, VIP, glucagon, and insulin.
2. Portal Encephalopathy (Portal Coma, Hepatic Coma):
o Caused by increased ammonia in the blood, which diffuses to the brain and causes
portal coma.
o Divided into 4 grades:
Grade 1: Confusion.
Grade 2: Drowsiness.
Grade 3: Hallucination.
Grade 4: Coma.
o Treatment (preventive treatment):
Lactulose: It is converted into lactic acid and acetic acid, both bind with
alkaline ammonia forming a non-absorbable complex ammonium which is
excreted outside the body.
Rifaximin (local reactive antibacterial drug): Not absorbed by the body, so it
kills bacteria in the GIT that produce ammonia.
3. Ascites:
o Caused by liver cirrhosis, reducing albumin, leading to ascites and edema.
o Treatment:
Aspiration
Diuretics
Spironolactone
Eplerenone (doesn’t cause gynecomastia, so it may be an alternative to
spironolactone).

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NSIADS ............................................................................................ 65 Septic Arthritis .............................................................................84
Types of Anaemia: .................................................................... 68 Temporal Arteritis (GCA) - Giant Cell Arteritis .....................84
Other Types of Anemia ............................................................72 Gout................................................................................................. 85
Drugs Affecting Blood Coagulation ......................................... 74 Anti-Phospholipid Syndrome..................................................... 85
................................................................................ 76 Fibromyalgia ................................................................................. 86
.............................................. 76 Behcet Syndrome ......................................................................... 86
Hyperlipidemia .............................................................................. 77 Rheumatoid Arthritis (R.A)........................................................ 86
Anti-Hyperlipidemic Drugs ......................................................... 77 Systemic Sclerosis (SS) ................................................................. 87
Blood Cancer................................................................................. 80 Systemic Lupus Erythematosus (SLE)........................................ 87
Classification of Anticancer Drugs.......................................... 82 Sjogren’s Syndrome ...................................................................... 88
Osteoarthritis ............................................................................... 84 Ankylosing Spondylitis 88

NSIADS
Definition: Drugs used to relieve pain.
They are divided into:
Opioid analgesics: Affect the CNS and induce addiction.
Non-opioid analgesics: Do not affect the CNS, so no induction of addiction.

Non-opioid analgesics are divided chemically into:

Steroidal anti-inflammatory drugs (SAIDs): Have hormonal effects.
Non-steroidal anti-inflammatory drugs (NSAIDs): Lack hormonal effects.

MOA: COX inhibitor ⇢ inhibits PG and Thromboxane A2 synthesis.

Pharmacological action:
Analgesic
Antipyretic (reduces raised temperature only, not the normal one)
Anti-inflammatory
Antiplatelet

CU:
Fever
Pain of any cause (headache, toothache, colic, and bone pain as in gout) except in bone
fractures because it may delay the healing process due to its vasoconstrictive effects.
Inflammation, either symptomatic or asymptomatic.
Aspirin is the only one used as an antiplatelet.
Indomethacin is used to close ductus arteriosus.

SE:
Gastric irritation (drug-induced peptic ulcer): Due to inhibition of PGE formation
(which has a role in mucosal wall formation) and because they are acidic drugs (local
effect).
Treatment of gastric irritation: PPI (proton pump inhibitor), e.g., Omeprazole,
Misoprostol (PGE derivatives). Misoprostol was used in the past but is not used
now because it causes abortion.

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Bronchial asthma (drug-induced asthma): Due to increased conversion of arachidonic
acid to leukotrienes (so increased leukotriene synthesis leads to bronchoconstriction).
Treatment of bronchial asthma: LT receptor blocker, e.g., Montelukast.
Increased bleeding tendency: Due to inhibition of TXA2 synthesis.
Chronic use of NSAIDs: Can cause renal failure due to vasoconstrictive effects of these
drugs, which decrease the blood supply to the kidney.
Chapter 7

Chronic or misuse of paracetamol: Can cause hepatotoxicity resulting from direct

metabolism of paracetamol to hepatotoxic metabolites.
Note: Paracetamol is normally metabolized indirectly by conjugation. In case of
chronic use, the conjugated substance depletes, resulting in paracetamol being
metabolized directly, which leads to hepatotoxicity (the problem is not in
paracetamol, but in the metabolic production).
Treatment: Antidote (Acetylcysteine).
Tolerance
Reye’s syndrome: If children under 12 years old use aspirin, it is contraindicated in
children.
Note: In Reye’s syndrome in children under 12 years, there is an increase in salicylic
acid in the blood, leading to severe gastric irritation, hematemesis (bloody vomiting),
tachyarrhythmia, hypotension, shock, coma, and death.

1. :
Examples: Aspirin, Ibuprofen, Ketoprofen, Indomethacin, Mefenamic acid,
Piroxicam, Diclofenac, Naproxen.
2. :
Examples: Meloxicam, Celecoxib, Etoricoxib.
Characteristics:
All are orally used.
Have a long duration of action (12-24 hrs depending on dose). For example,
Meloxicam dose 7.5 mg has a 12-hour duration, but 15 mg has a 24-hour
duration.
These compounds prevent only pathological prostaglandin, so thromboxane
A2 will not be affected, which leads to increased platelet aggregation and clot
formation. Therefore, they are contraindicated in thromboembolic disease
(TED).
Safe in patients with peptic ulcer.
Etoricoxib is preferred to be used in bone pain (not in fractures).
Selectivity (COX-2 / COX-1):
▪ Meloxicam (5:1)
▪ Celecoxib (20:1)
▪ Etoricoxib (100:1)

3. :
Analgesic & antipyretic (found in CNS).
Example: Paracetamol.
Hepatotoxic.
Safe: First-line treatment for pregnant women, lactation, children, and patients
suffering from peptic ulcer (only if the pain is without inflammation).
Used in combination with Codeine or Caffeine to:
Increase duration of action.
Increase efficacy.

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Lacks anti-inflammatory effect.

Paracetamol extra means paracetamol with caffeine.

NOTES:
1. Aspirin has 2 doses:
300 mg: Used as an analgesic, anti-inflammatory, and antipyretic.
75-150 mg: It is a selective and irreversible TXA2 inhibitor, so it’s the only NSAID
used as an antiplatelet. It is contraindicated in gouty patients (hyperuricemia)
because uric acid and salicylic acid (aspirin) compete for the same receptor in
excretion, decreasing uric acid excretion, resulting in increased blood levels and
worsening gout.
2. Ibuprofen: Second line of treatment for pregnancy, lactation, and children in case of
inflammation.
3. Ketoprofen: Strong analgesic:
Inhibits COX and LOX, so it is safe in asthmatic patients.

Chapter 7
Preferred in bone and dental pain.
4. Indomethacin: Used to:
Close ductus arteriosus.
Preferred in acute gout due to non-selective COX and phospholipase C inhibition.
Note: Phospholipase C is responsible for WBC migration, so its inhibition decreases
inflammation associated with gout.
5. Mefenamic acid:
Preferred and first line of treatment for haemorrhagia (the only one that decreases
bleeding by an unknown mechanism).
6. Piroxicam: Has a long duration of action (24 hours), used once per day, and preferred in
bone pain.
7. In renal impairment:
DOC: Naproxen is used because only <1% is excreted via the kidneys.
Diclofenac (Voltaren): 1-2% excreted via kidneys.
8. Patients with peptic ulcer suffering from inflammation:
DOC: Selective COX-II inhibitor.
9. In pregnancy, only paracetamol is used because other NSAIDs:
Delay normal delivery by inhibition of PG synthesis in the uterus, which is
responsible for contraction.
Close ductus arteriosus by inhibition of PG, which maintains ductus arteriosus.

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Iron deficiency anaemia

Anaemia of chronic diseases
Megaloblastic anaemia: vitamin B12 deficiency (pernicious anaemia) and folic acid
deficiency
Chapter 7

Spherocytosis
Autoimmune haemolytic anaemia
Favism
Paroxysmal nocturnal haemoglobinuria (PNH)
Haemoglobinopathies like sickle cell anaemia and thalassemia

Note: Around the world, the main cause of anaemia is iron deficiency anaemia.

• Females: Menstrual cycle and haemorrhage

• Older people: Cancer is the main cause. We should know the site of bleeding, which may
be:
o Rectal bleeding
o Haematuria
o Haemoptysis

Some symptoms of anaemia:

Fatigue
Dyspnea

Signs of anaemia:
Tachycardia
Pale colouration of the skin.
Cyanosis
Cirrhosis in chronic phase
Hypoxia

Diagnosis of anaemia:
By CBC (complete blood count)
By blood film
Fe²⁺
Ferritin
Total iron binding capacity
In all types of anaemia, haemoglobin, RBC, and hematocrit are low, then they vary according to type.

Types of Anaemia:
1. Iron deficiency anaemia is caused by lack of iron,
often because of blood loss or pregnancy.
Diagnosis:
CBC: Low haemoglobin, RBC, and hematocrit levels
Low ferritin level
Increased total iron binding capacity (TIBC): A blood test that measures your blood’s
ability to attach (bind) to iron and carry it.

Notes:
Ferritin test can be a single test for anaemia (means it can individually diagnose the
anaemia).

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The most common cause of iron deficiency is ancylostoma (worm).

Treatment:
Oral preparation of iron:
Ferrous sulfate
Ferrous fumarate
Ferrous gluconate
Parenteral preparation of iron: (In the past, there was a drug called Iron Dextran,
but it no longer exists)
Iron isomaltose
Iron carboxymaltose
Side Effects:
High dose ⇢ gastritis, which leads to melena (dark stool)
Haemochromatosis in daily doses of iron that are not for therapeutic reasons.
Long-term use can lead to haemosiderosis.

Chapter 7
2.
Any chronic disease is accompanied by anaemia.
Chronic diseases such as:
DM
Asthma
Rheumatoid arthritis
Chronic obstructive pulmonary disease
Pulmonary restrictive disease
Hepcidin: Regulates how your body uses iron and regulates iron absorption by decreasing
the absorption. This hormone is released when stored iron increases and sends signals to the
intestines to stop absorbing iron. In patients with chronic disease, it is also released and
elevated (although the stored iron is not high), and iron will not be absorbed, which leads to
anaemia.
Treatment: Treat the underlying cause.
Diagnosis:
Decrease in haemoglobin.
Decrease in serum iron.
Decrease in RBC.
Normal or low total iron binding capacity.
Normal or high ferritin level.
Low stored iron.

3.
Vitamin B12 deficiency anaemia (pernicious anaemia)
Folic acid deficiency anaemia

With the help of vitamin B12, methylmalonyl CoA is converted to succinyl CoA,
which has a role in myelin sheath formation. If there is no B12, the myelin sheath will
not be produced, leading to peripheral neuropathy (socks and gloves neuropathy).

• Autoimmune antibodies destroy parietal cells, decreasing HCl and the intrinsic
factor, which decreases the absorption of vitamin B12.

• Haemoglobin is low.
• RBCs are macrocytic and megaloblastic, which do not transport oxygen.

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Folic acid in folic acid deficiency anaemia.

Vitamin B12 (hydroxocobalamin and methylcobalamin) in pernicious anaemia.
In peripheral neuropathy ( Hb).
Every pregnant woman should take folic acid from the beginning of pregnancy until the end
of pregnancy; it prevents deformities and contributes to enhancing the fetus’s health.
Chapter 7

• Hydroxocobalamin, methylcobalamin, and cyanocobalamin.

• Hydroxocobalamin can be used as an antidote (in case of cyanide poisoning because it
stops cytochrome oxidase).

Glucose-6-phosphate dehydrogenase deficiency.

• Decreases the enzyme, leading to the destruction of RBCs.
Note: Glutathione (GSH) is a very strong antioxidant. It needs G-6-P dehydrogenase to change from
inactive (oxidized) to active (reduced). G-6-P dehydrogenase deficiency decreases the activation of
glutathione, leading to the accumulation of oxidizing agents that cause the destruction of RBCs.
• Low RBCs, hematocrit, and Hb.
• Increased unconjugated bilirubin and lactate dehydrogenase.
• Increased number of reticulocytes.
Treatment:
1. Prevention (avoid certain types of food and drugs such as legumes and primaquine).
2. In severe hemolysis: Blood transfusions.

• Whole blood in case of hemorrhage.

• RBC concentrates if RBCs < 7.
• Platelet concentrates if platelets < 50,000.
• Fresh frozen plasma in warfarin overdose toxicity.

Decrease in protein (glycophosphatidyl inositol GPI), which prevents RBC breakdown (by
protecting blood cells against C5).
• May be accompanied by brown urine, thrombosis, and pancytopenia.
Treatment:
• Eculizumab (anti-C5).
• Blood transfusion.
• Sometimes anticoagulants.

(Heme + globin 2 Alpha, 2 Beta)

• Common in South Africa.

• 20% of African people have the sickle cell trait, which provides protection from malaria
(Plasmodium falciparum).

Every gene consists of 2 alleles (one from the mother and one from the father). If there is a defect in
both alleles, the patient has sickle cell disease. If only one allele is defective, it results in the sickle
cell trait. RBCs are sickle-shaped.

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The causes of SCA include:

Hypoxia
Infection
Dehydration
Acidosis

These causes lead to thrombosis all over the body due to the abnormal shape of RBCs, resulting in
five types of crises as complications:
Stroke crisis
Acute chest syndrome (sickle chest crisis)
Vaso-occlusive crisis
Hemolytic anemia due to aplastic crisis
Splenic sequestration

It also leads to pain in the extremities.

Chapter 7
Treatment: Hydroxyurea (hydroxycarbamide).

Defect in alpha globin → alpha thalassemia.

Defect in beta globin → beta thalassemia.

Beta globin has 2 alleles. If there is a defect in both alleles, it’s called beta thalassemia major
(dangerous).

Treatment:
• Blood transfusion with iron chelating agents such as deferoxamine.
• Bone marrow transplantation.

If there is a defect in one allele → beta thalassemia minor.

Treatment:
• Supportive therapy (iron and folic acid).
• Rare blood transfusion.
Note: In beta thalassemia major, there is decreased HbA and increased HbF.

Has 4 alleles.
• Defect in 1 allele → alpha thalassemia trait (silent carrier).
o Treatment: No need for treatment, asymptomatic.
• Defect in 2 alleles → alpha thalassemia minor (mild anemia).
o Treatment: Folic acid supplements.
• Defect in 3 alleles → Hemoglobin H (sometimes needs blood transfusion).
o Treatment: Blood transfusion from time to time.
• Defect in 4 alleles → born dead (hydrops fetalis).
o Treatment: The baby is already dead.

Note: Diagnosis of hemoglobinopathies: Hb electrophoresis.

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(Hereditary blood disorder)

RBCs become rounded in shape, leading to splenomegaly.
Diagnosis: By microscope.
Treatment: Partial or total splenectomy.
Chapter 7

The immune system attacks and destroys red blood cells faster than your bone marrow can make
new ones.
Diagnosis: By Coombs test.
Treatment: Corticosteroids, Prednisolone with Azathioprine (immune suppressor).

Hemolytic Uremic Syndrome (HUS)

Definition:
HUS is a triad condition characterized by:
• Anemia (Hemolysis)
• Uremia (increased urea in the blood) as a result of renal failure
• Thrombocytopenia (decrease in platelets), leading to bleeding

Causes:
It may occur after infection by a strain of Escherichia coli. HUS can also be caused by Shigella. It
mainly affects children.
Treatment:
• In most cases, it is self-limiting.
• Severe hemolysis (hemoglobin < 7g) is treated with red blood cell concentrate.
• Severe renal failure is treated with hemodialysis.
• Severe HUS is treated with plasma exchange.

Thrombotic Thrombocytopenic Purpura (TTP)

Definition:
TTP is characterized by the following pentad of Symptoms:
Hemolysis
Thrombocytopenia
Renal failure
Fever
Neurological disorders

Bleeding Types:
• Petechiae: Small, pinpoint hemorrhages
• Purpura: 2 cm hemorrhages
• Ecchymoses: 3-4 cm hemorrhages
• Hematoma: Clotted blood

Treatment:
Plasma exchange.

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Disseminated Intravascular Coagulation (DIC)

Definition:
DIC is a state of excessive consumption of coagulation factors, causing a severe decrease in these
factors, leading to:
• Thrombosis: Due to excessive consumption of coagulation factors
• Bleeding: Due to a decrease in coagulation factor numbers

Causes:
This occurs in patients suffering from:
• Cancer (lymphoma)
• COVID-19
• Some infections
• Prolonged hospital stays

Diagnosis:

Chapter 7
• Decreased fibrin levels
• Decreased platelet count
• Increased D-dimer levels
• Increased fibrin degradation products (FDPs)

Treatment:
• Fresh frozen plasma for patients with bleeding
• Heparin & Warfarin for patients with thrombosis

Von Willebrand Disease (VWD)

Definition:
VWD is the most common inherited bleeding disorder caused by missing or defective von
Willebrand factor (VWF), a clotting protein that activates platelets aggregation and forms a platelet
plug.
Symptoms:
• Epistaxis (nosebleeds)
• Menorrhagia (heavy menstrual bleeding)
• Easy bruising
• Gum bleeding
• Excessive bleeding from injuries

Treatment:
Tranexamic acid (plasminogen inhibitor) to prevent the conversion of plasminogen to plasmin. It
may also be used as an antidote for fibrinolytic drugs.

Immune Thrombocytopenic Purpura (ITP)

Definition:
ITP is an autoimmune bleeding disorder where the immune system destroys platelets.
Diagnosis:
• Low platelet level in the peripheral blood
• High number of megakaryocytes in the bone marrow
• Purpura rash on the skin
Treatment:
• Prednisolone
• Azathioprine to reduce the severity of prednisolone

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Hemophilia A
Cause:
Decrease in coagulation factor VIII (anti-hemophilic factor).
Treatment:
Chapter 7

Administer anti-hemophilic factor.

Hemophilia B
Cause:
Decrease in coagulation factor IX (Christmas factor).
Treatment:
Administer Christmas factor (factor IX).

Hemophilia C
Cause:
Factor XI deficiency.
Treatment:
Administer plasma thromboplastin (factor XI).

Drugs Affecting Blood Coagulation

1. Oral Anticoagulants
Warfarin
MOA: Vitamin K antagonist (inhibition of factors II, VII, IX, X)
CU:
1. Deep Venous Thrombosis (DVT)
2. Pulmonary Embolism
SE:
1. Bleeding, very dangerous especially cerebral bleeding
2. Teratogenic
CI: Pregnancy
Dosage Control: Via INR (International Normalized Ratio)
1. INR = Prothrombin time of the patient / Prothrombin time of the standard
2. INR = 2-3

Important Drug-Drug Interactions:

Drugs that increase Warfarin action:
o Broad-spectrum antibiotics (due to the killing of normal flora, hence
decreasing Vitamin K)
o Metabolic inhibitors like Erythromycin
Drugs that decrease Warfarin action:
o Cholestyramine (used for itching with chronic liver disease, decreases the
absorption of Warfarin from the intestine)
o Metabolic inducers like Rifampin
Antidotes:
1. Vitamin K
2. Fresh Frozen Plasma

Notes: The usage of Warfarin without a reason (as a prophylactic drug) is very dangerous, unlike
Aspirin.

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2. Parenteral Anticoagulants
 Heparin
MOA: Stimulation of antithrombin III
Forms:
1. UFH (Un-Fractionated Heparin)
Natural Heparin
ROA: Intravenous, Subcutaneous (never intramuscular due to the risk
of hematoma)
Duration: Short-acting
DOC: In renal failure patients because it decomposes in the liver
Cost: Cheaper
2. LMWH (Low Molecular Weight Heparin)
Synthetic Heparin
Other Names: Enoxaparin, Dalteparin, Fondaparinux
ROA: Subcutaneous

Chapter 7
Duration: Long-acting
Cost: More expensive
CU: In DVT, preventing future thrombi (prophylactic)
Dosage Control: Through APTT (Activated Partial Thromboplastin Time)
1. APTT = PTTp / PTTc
2. PTT stands for Partial Thromboplastin Time
3. P stands for patient
4. C stands for control (normal person)
5. PTT must be 2 to 3
Side Effects:
1. Bleeding
2. HIT (Heparin-Induced Thrombocytopenia) due to the accumulation of
thrombocytes in specific regions in the body
Treatment for HIT:
1. Stop Heparin immediately
2. Administer Argatroban (IV)
Antidote for Heparin: Protamine Sulfate

 Argatroban
 MOA: Direct thrombin inhibitor
 ROA: Parenteral
 CU: HIT

In Case of Pulmonary Embolism:

 Warfarin:
o Oral
o Cheap
o Slow onset of action
 Heparin:
o IV
o Expensive
o Rapid onset of action (IV immediately, SC after 1 hour)
Treatment Strategy: Start with Heparin, then continue with Warfarin.

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1. Fresh Frozen Plasma (FFP):

o Contains all clotting factors
o Used as an antidote for Warfarin
2. Prothrombin Complex Concentrate (PPC):
Chapter 7

o Contains prothrombin
o Useful for Warfarin overdose
3. Cryoprecipitate:
o Contains high fibrinogen

Aspirin
Family: NSAID
CU: Prevention of stroke and myocardial infarction
SE: Gastric irritation (peptic ulcer in overdose)
Antidote: Theoretically, Ethamsylate is considered an antidote because it increases
platelet aggregation
Usage: For a lifetime

Clopidogrel
MOA: Inhibits ADP (adenosine diphosphate)
CU: Does not replace aspirin but enhances its work

Other Names: Thrombolytics / Plasminogen Activators

Examples:
1. Streptokinase (IV) - from Streptococcus
2. Urokinase (IV)
3. Alteplase & Tenecteplase - synthetic drugs, thromboselective, specialized for pulmonary
embolism (IV)

MOA: Plasminogen activator

CU: They are the only drugs that lyse thrombus provided it has not lasted for a long time
o Myocardial infarction: less than 12 hours
o Pulmonary embolism: less than 12 hours
o Ischemic stroke: less than 4 hours
SE: Bleeding
Antidote: Tranexamic Acid

Example:
Dabigatran (oral) - Replacement for Warfarin

Uses of Dabigatran:
Deep venous thrombosis

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Hyperlipidemia
Definition: Hyperlipidemia is the increase of lipids in the blood (Cholesterol & TG). It’s carried in
the blood by lipoproteins and is classified as:
1. Chylomicron: If the patient consumes a meal with high lipid content.
2. LDL: Cholesterol.
3. VLDL: TG.
4. HDL: Good lipid carrier.

Causes of Hyperlipidemia:
• Genetic (mostly in VLDL).
• Obesity (mostly cholesterol).
• Drugs that cause hyperlipidemia, such as:
o B-blockers (chronic use).
o Chronic use of diuretics.

Chapter 7
o Hormones such as corticosteroids & estrogen.

Results of Hyperlipidemia:
1. Atherosclerosis.
2. Hypertension.
3. Clot.
4. Stroke.

The ttt of Hyperlipidemia depends on the type of disorders.

Disorder LP Increased Elevated Elevated Risk of Treatment
TG CH Atherosclerosis
I CM + + No Diet
IIa LDL + +++ High Statins
IIb VLDL, LDL +++ +++ High Statins, fibrates,
nicotinic acid
III VLDL(B) +++ ++ Moderate Fibrates
genetic disorder
IV VLDL +++ + Moderate Fibrates, nicotinic
acid
V VLDL, CM +++ + Weak Diet + adjuvant

Note:
• Increased cholesterol leads to cardiac diseases (atherosclerosis, stroke, angina).
• Increase in TG has a lower risk than an increase in cholesterol.

Anti-Hyperlipidemic Drugs
1. Main Therapy:
Statins:
MOA: Inhibits cholesterol synthesis by inhibiting HMG CoA reductase.
CU: Orally, once daily at night for type IIa & IIb (long DOA).

Note: should be taken at night because:

1. Cholesterol synthesis is high at night (the enzyme works more at night).
2. Decreases the incidence of side effects.

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SE of Statins:
1) Severe GIT disturbance (so used after meals).
2) Elevated liver enzymes (GOT, GPT) leading to hepatotoxicity, especially if the patient
has liver diseases.
3) Myopathy/myositis (myalgia) due to inflammation of skeletal muscle, leading to
increased myoglobin release from skeletal muscles, which can cause acute renal failure.
Chapter 7

4) Teratogenic (contraindicated in pregnancy).

Examples:
① Simvastatin.
② Atorvastatin.
③ Rosuvastatin.

Notes:
1. Rosuvastatin has the least incidence of Side Effects (myositis and renal failure).
2. Simvastatin has the highest incidence of Side Effects (myositis and renal failure).

Fibrates:
MOA: Inhibit VLDL production via stimulation of PPAR alpha receptor.
CU: Orally, once daily at night for type III, IV, and V.

SE: Similar to statins but with less incidence:

• GIT disturbances.
• Myositis (myalgia).
• Acute renal failure.
• Increased liver enzymes.
• Teratogenic (contraindicated in pregnant women).
• Gallstones (increased cholesterol).

Examples:
1. Fenofibrate.
2. Gemfibrozil.
3. Bezafibrate.

Notes:
• Fenofibrate is a uricosuric, increasing renal excretion of uric acid, so it is preferred for gouty
and hyperlipidemic patients.
• Uricosuric drugs increase renal excretion of uric acid.

2. Adjuvant Therapy:
Use:
1. With main therapy to increase efficacy (maximum 30%).
2. Alone when main therapy is contraindicated or when the case isn’t severe (no
need for main therapy).

Resins:
Examples: Cholestyramine, colestipol (drugs with a positive charge that bind with
bile acid, which has a negative charge).
MOA:
1. Inhibit intestinal absorption of cholesterol and fat-soluble vitamins by binding to
bile acid, forming a non-absorbable complex.

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2. Increase conversion of cholesterol to bile acid.

CU:
1. Adjuvant therapy for type IIa and IIb hyperlipidemia.
2. To prevent pruritus due to liver disease (increased bilirubin in blood).
SE:
1. GIT disturbances.
2. Steatorrhea (fatty diarrhoea).
3. Fat-soluble vitamin deficiency (A, K, E, D).
4. Drug-drug interaction mainly with warfarin (inhibits vitamin K synthesis),
leading to increased toxicity of warfarin.

Beta-Lactam:
Example: Ezetimibe (O).
MOA: Decreases absorption of cholesterol by inhibiting protein cotransporter in the
intestine.

Chapter 7
CU:
1. Adjuvant therapy for type IIa and IIb (adjuvant therapy to statin).
2. Main therapy for type IIa and IIb in case statins are contraindicated (pregnancy,
chronic renal failure, hepatic failure).
SE: Less incidence and include:
1. GIT disturbances.
2. Steatorrhea.

Note:
Occurrence of SE is less than with resins.
No drug-drug interaction.
No effect on fat-soluble vitamin absorption.

Vitamin: Nicotinic Acid/Niacin (Vitamin B3):

MOA:
1. Decreases LDL and VLDL production, leading to decreased cholesterol and TG
(mainly added to statins).
2. Increases HDL production.

CU:
1. Orally, in combination with statins for type IIa (to increase efficacy) and IIb (to
increase efficacy and to eliminate TG).
2. Can be used for hypertriglyceridemia.

SE:
VD: headache, flushing, hypotension, reflex tachycardia.

Note: All the previous antihyperlipidemic drugs are prophylactic drugs (meaning they don’t treat
hyperlipidemia; they only prevent the effects of it).

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A. Leukemias: Increased WBC numbers.

B. Myeloproliferative Disorders
C. Lymphoma: Cancer in lymphoid glands.
D. Myelomas: Cancer in bone marrow.
Chapter 7

Causes of Cancer (in general):

1. X-ray
2. Electrophoresis
3. Bacteria
4. Smoking
5. Viruses
6. CT scan

A. Leukemias
Types:
ALL: Acute lymphoblastic leukemia
AML: Acute myeloid or myeloblastic leukemia
CLL: Chronic lymphocytic leukemia
CML: Chronic myelocytic leukemia

1. ALL (Acute Lymphoblastic Leukemia)

Definition: A cancer of the lymphoid line of blood cells characterized by an increased number of
immature lymphocytes.
Characterized by: Mutations that inhibit enzymes responsible for forming mature WBCs
(lymphocytes and myelocytes), leading to severe depression in the number of mature WBCs
(possibly down to 300). This results in a huge increase in the number of immature cells
(lymphoblasts or myeloblasts).
Prevalence: 4 times more common in children than adults.
Prognosis: Good prognosis.
Diagnosis:
1. Via bone marrow biopsy, which will show blast cells making up more than 25% of the
bone marrow.
o Note: In a normal person, bone marrow is hypercellular (filled with different
immature cells), but in this case, the bone marrow is semi-empty and filled with
immature lymphoblasts or myeloblasts.
2. Via samples from peripheral blood vessels.

Treatment:
Chemotherapy:
1. Vincristine (Oncovin)
2. Prednisolone
3. Daunorubicin
4. Methotrexate

2. AML (Acute Myeloid Leukemia)

Similar to ALL but differs in:
Prevalence: 4 times more common in adults than children.
Prognosis: Bad prognosis.

Treatment: Chemotherapy similar to ALL treatment.

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Note: Auer rods are used to differentiate between AML and ALL. They are present in the
cytoplasm of AML and absent in ALL.

3. CLL (Chronic Lymphocytic Leukemia)

Characteristics: Immunity is severely decreased for unknown reasons. It may transform into
ALL, which is a dangerous situation.
Treatment: FCR

4. CML (Chronic Myelocytic Leukemia)

Characteristics: It may transform into ALL, which is a dangerous situation.
Treatment: Imatinib

B. Lymphoma
Types:

Chapter 7
1. Hodgkin’s Lymphoma
o Treatment: ABDD
2. Non-Hodgkin’s Lymphoma: More dangerous and spreads rapidly.
o Treatment: RCHOP

C. Multiple Myeloma (MM)

Characteristics: Increased numbers of plasma cells lead to increased synthesis of immunoglobulins,
which attack bone tissue, leading to osteoporosis and hypercalcemia.
Treatment: Chemotherapy with drugs for osteoporosis, such as the bisphosphonate group
(hypocalcemic drugs).
Notes:
• Most of these drugs are teratogenic.
• Azathioprine and methotrexate are taken orally, while the rest are taken parenterally.

D. Myeloproliferative Diseases
Types:
Polycythemia Rubra Vera
Essential Thrombocythemia
Myelofibrosis
Common Drug: Hydroxyurea

1. Polycythemia Rubra Vera (PRV)

Definition: Huge increase in RBC numbers.
Symptoms: Increased hypertension due to increased RBC numbers.
Treatment:
1. Aspirin
2. Blood donation
3. Venesection (removal of blood from the body to treat an underlying disorder or
complication)
4. Patients are advised to drink large quantities of water.

2. Essential Thrombocythemia
Definition: Increased platelet count.
Treatment: Aspirin

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3. Myelofibrosis
Characteristics: Fibrosis in bone marrow leads to the inhibition of RBC synthesis.
Treatment: RBC concentrate
Chapter 7

Common Side Effects for All Anticancer Drugs:

1. Nausea and vomiting
2. Bone marrow degradation
3. Infertility
4. Alopecia: hair loss all over the body

Alkylating Agents
Cyclophosphamide:
CU: Cancer and autoimmune diseases
MOA: Forms additional connections in the DNA strands
SE: May cause cancers

Antimetabolic Drugs
Examples:
Methotrexate:
MOA: Competes with folic acid due to similar structure
5-Fluorouracil:
MOA: Competes with uracil due to similar structure
SE: Megaloblastic anemia

Antibiotic Anticancer Drugs

Examples:
1. Doxorubicin (DXR)
2. Daunorubicin (DNP)
3. Bleomycin

MOA: Cross-links between adjacent guanine bases

SE:
1. Doxorubicin and Daunorubicin:
o Cardiac myopathy and cardiac toxicity, which may lead to heart failure
2. Bleomycin:
o Pulmonary fibrosis

Plant Alkaloids Anticancer Drugs

Example: Vincristine: Also known as Oncovin
Origin: Sunflower
MOA: Blocks mitosis in phases of the cell cycle
SE: Neurotoxicity, peripheral neuropathy, numbness, and paresthesia
Notes:
• Numbness: Loss of feeling
• Paresthesia: An abnormal sensation with no apparent physical cause

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Others
• Imatinib
• FCR

Chapter 7

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These diseases have extra-articular manifestations which may cause death.

Definition: Degenerative joint disease, degeneration of the articular cartilage.

Risk Factors:
Obesity
Chapter 7

Occurs in the elderly

Overuse of some joints related to patients’ work

Pathology: Degenerative disease affecting synovial joints (large joints), which over time leads to:
Decreased synovial fluid
Decreased space between cartilage, leading to crepitus

Symptoms: Pain increases with movement and crepitus.

Diagnosis:
History
X-ray

Treatment:
Glucosamine and Chondroitin: Substances that help in the synthesis of synovial fluid, but
should be used for a long duration to help the patient.
NSAIDs to relieve pain only.

Definition: Inflammation of joints due to bacterial infection.

Risk Factors:
Immunocompromised conditions such as malnutrition, diabetes, TB, HIV patients, and
children
Trauma to the joint, allowing bacteria (Staphylococcus aureus) to enter
Signs (Presentation):
Fever (pyrexia)
Septicemia
Patients look ill

Cause: Staphylococcus aureus.

Diagnosis:
Aspiration
Culture

Treatment:
If it’s Staphylococcus aureus: Flucloxacillin
If the bacteria is MRSA: Vancomycin

Definition: An autoimmune disease that affects people over 60 years old.

Pathogenesis: Inflammation of the temporal artery (vasculitis) affecting the ophthalmic artery,
which may cause blindness if not treated immediately.
Symptoms:
Headache
Jaw claudication and tenderness
Joint pain

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Visual disturbance

Treatment: Prednisolone (high dose about 1mg/kg). Should be taken before investigation to prevent
blindness. As soon as possible
Note: If the patient doesn’t take the drug, they will suffer from irreversible blindness.

Definition: Accumulation of uric acid in the blood, which may form crystals that deposit in joints.
Cause: Increased uric acid is mainly a result of decreased excretion by the kidney (due to renal
failure and drug competition).
Diagnosis:
Aspiration and microscope (urate crystals):
o Uric Acid crystals appear needle shape and blue.
Serum uric acid level is elevated.

Chapter 7
Treatment:
Allopurinol (Oral)
Febuxostat (Oral)
Rasburicase (Injection)

Notes:
Allopurinol and Febuxostat: Xanthine oxidase inhibitors.
Rasburicase: Breaks down uric acid.
NSAIDs and Colchicine are used to relieve pain.

Uric Acid Formation:

• Purine ⇢ hypoxanthine ⇢ xanthine (by xanthine oxidase) ⇢ uric acid.

Additional Notes:
• Colchicine decreases pain by reducing WBC synthesis and migration, leading to no
inflammation and no pain.
• Allopurinol: 90% is excreted via the kidney, so it is used if there is hepatic disease.
• Febuxostat: 90% is metabolized in the liver, so it is used if there is renal insufficiency.

Definition: Increase of Ca++ pyrophosphate dehydrate salt (⇡CPPD).

 Calcium pyrophosphate dihydrate crystals in the synovial fluid
 Calcium Pyrophosphate Appears yellow with rhomboid shape
 most commonly affects the KNEE
Treatment:
• NSAIDs
• Colchicine

Definition: Considered a type of rheumatology, autoimmune disease, and vasculitis.

Characteristics: Associated with thrombosis and recurrent abortion.
Treatment:
• Anticoagulants: Heparin, Warfarin

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Note: Causes of recurrent abortion include:

1. Toxoplasmosis
2. Cytomegalovirus
3. Anti-phospholipid syndrome
Chapter 7

4. Rh Factor (Erythematosus fetalis)

Definition: Fibromyalgia is a chronic (long-lasting) disorder that causes pain and tenderness
throughout the body, as well as fatigue and trouble sleeping. Commonly Occurs in older females.
Treatment: Amitriptyline (antidepressant).

Definition: Behcet's disease is a multisystem, chronic-relapsing inflammatory disorder.

Its target is predominantly the venous system.
Triad of Behcet’s Syndrome:
Oral and genital ulcers
Uveitis (inflammation of the uvea, including anterior and posterior)
Arthritis

Treatment:
DOC: Colchicine
Topical steroids for uveitis

Note: If not treated, it may cause blindness.

Definition: The typical type of arthritis, an autoimmune disease that affects the small joints. It affects
females more than males and is symmetrical (bilateral).
Symptoms:
• Deformity in hands or feet
• Extra-articular manifestations: Pulmonary fibrosis, scleritis, pericarditis, anemia

Diagnosis:
• Rheumatoid factor (RF)
• ACPA

Treatment:
DMARDs (Disease Modifying Anti-Rheumatic Drugs):
Methotrexate (the most important): Anti-folate, decreases DNA synthesis, decreases
WBCs
Hydroxychloroquine (anti-malarial drug) or sulfasalazine (one of them, not both)

SE of Anti-Malarial Drugs (Cinchonism):

• Tinnitus
• Headache
• Nausea and vomiting
• Dizziness

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Corticosteroids: If the previous ones were not helpful

• Prednisolone

TNF Inhibitors: If the previous ones were not helpful

• Infliximab
• Adalimumab
• Etanercept

Note: These drugs should not be used if the patient suffers from TB or is a carrier of TB.
Additional Note: Rituximab has magical effects on autoimmune diseases but is very expensive.

Definition: An autoimmune disease associated with the following Symptoms:

• Raynaud’s syndrome (cold extremities)
• Skin tightness

Chapter 7
• Pulmonary hypertension
• Proteinuria

Types:
• Scleroderma: Skin tightness only
• Limited Cutaneous Systemic Sclerosis: Pulmonary hypertension, joint pain, Raynaud’s
syndrome
• Diffuse Cutaneous Systemic Sclerosis

Treatment:
 Using vasodilator drugs:
 Calcium channel blockers (Amlodipine, Nifedipine)
 Phosphodiesterase inhibitors (Sildenafil)
 Prostacyclin derivatives (Epoprostenol)

Note: Avoid cold exposure because it may lead to gangrene.

Systemic Lupus (SLE)

Definition: A generalized autoimmune disorder with a specific antibody called Anti-dsDNA
antibodies.
Criteria: If four of the following 11 criteria are present, it is considered :
1. Butterfly skin rash
2. Photosensitivity
3. Oral ulcer
4. Pancytopenia
5. Arthritis
6. Proteinuria
7. Gangrene in extremities
8. Myalgia
9. …

Treatment:
 Avoid sun exposure
 NSAIDs and corticosteroids
 Pulse therapy (given in dangerous situations, e.g., risk of losing an organ):
o High dose of Methylprednisolone (1g IV for three days)

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o High dose of Cyclophosphamide (1g every two weeks)
 Vasodilators for peripheral vasoconstriction that may occur

Sjogren’s Syndrome
Definition: An autoimmune disease affecting salivary and lacrimal glands (dry eye, dry mouth).
Chapter 7

Symptoms:
 Dry mouth
 Dry eye
 Dry vagina
 Arthritis

Note: Sjogren’s syndrome may cause lymphoma 40 times more than in normal persons.
Treatment:
 Pilocarpine (direct cholinergic): Increases secretion
 Artificial tears

Ankylosing Spondylitis
Definition: Affects the vertebral column (autoimmune), making it immobile as one piece.
Advice: Patients should do a lot of exercises.

NOTES
 A type of arthritis that needs to avoid sun exposure: SLE
 A type of arthritis that needs to avoid cold exposure: SS
 A type of arthritis that needs vasodilators: SS

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Appendix
Drug/Substance Antidote 6. Spherocytosis:
Alteplase No Antidote
o Treatment: Partial or total
Aspirin Ethamsylate
splenectomy
overdose
7. Wilson’s Disease:
Beta-blocker Glucagon
overdose Treatment:
o
Cyanide Hydroxycobalamin ▪ Penicillamine
poisoning ▪ If unavailable, use
Dabigatran Idarucizumab Trientine
Digoxin Digibind ▪ Zinc chloride (salt) is
overdose the last choice
Digoxin Digibind 8. Hemochromatosis:
Heparin Protamine sulphate
overdose o Treatment: Deferoxamine
Iron overdose Deferoxamine and venesection as
Paracetamol Acetylcysteine replacement therapy
Paracetamol N-acetylcysteine
toxicity Coagulation Disorders
Rivaroxaban Andexanet alpha 1. Antiphospholipid Syndrome:
Thrombolytic Tranexamic acid
Warfarin - Prothrombin o Treatment: Heparin and
Complex Warfarin
Concentrate (PCC) 2. Factor X Inhibitors (e.g.,
- Fresh Frozen Rivaroxaban, Apixaban, Idoxaban):
Plasma (FFP)
o Antidote: Alpha-Andexanet
- Vitamin K
3. Fibrinolytics / Plasminogen
Blood Disorders and Anticoagulants Activators (e.g., Streptokinase,
1. Heparin-Induced Urokinase, Alteplase, Tenecteplase):
Thrombocytopenia (HIT):
o Antidote: Tranexamic Acid
o Treatment: Argatroban
(direct thrombin inhibitor) IV Cardiovascular Disorders
o Antidote for Dabigatran 1. Supra-Ventricular Tachycardia:
(oral direct thrombin o Treatment: Adenosine (if
inhibitor): Idarucizumab associated with asthma, use
2. Beta Thalassemia Major: Verapamil)
o Treatment: Deferoxamine 2. Ventricular Tachycardia:
o Treatment: Amiodarone
3. Sickle Cell Anemia:
3. Pulmonary Embolism:
o Treatment: Hydroxyurea o Treatment: Heparin followed
4. Autoimmune Hemolytic Anemia: by Warfarin
o Treatment: Corticosteroids, Gastrointestinal Disorders
Prednisolone with 1. Inflammatory Bowel Disease (IBD):
Azathioprine
o Treatment: 5-Amino
5. Paroxysmal Nocturnal
Salicylic Acids (5-ASAs)
Hemoglobinuria (PNH):
o Specific 5-ASAs:
o Treatment: Eculizumab
 ▪Sulfasalazine: Autoimmune and Rheumatic Disorders
Combined 1. Systemic Sclerosis:
▪ Asacol: pH-dependent
o Treatment: Avoiding cold
▪ Pentasa: Delayed
exposure
release
2. Systemic Lupus Erythematosus
▪ Rowasa: Enema
(SLE):
▪ Canasa: Suppository
2. Autoimmune Hepatitis: o Treatment: Avoiding sun
exposure
o Treatment: Prednisolone with
3. Fibromyalgia:
Azathioprine
3. Coeliac Disease: o Treatment: Amitriptyline
4. Osteoarthritis:
o Treatment: Diet modification
(gluten-free diet) o Treatment: Glucosamine and
4. Primary Biliary and Sclerosing Chondroitin
Cholangitis (PBC & PSC): 5. Septic Arthritis:
o Treatment: Ursodeoxycholic o Treatment: According to the
Acid (UDCA) septic agent (e.g.,
5. Preventive Treatment of Portal Flucloxacillin, Vancomycin)
Encephalopathy (Coma): 6. Sjogren’s Syndrome:
o Treatment: Lactulose, o Treatment: Pilocarpine
Rifaximin
 Team leaders
Team Members Noah_Al-haj
Aia Al-Hassani Hend_Alaghbary
Alaa Al-ghassaly Huda_Al-omari
Amjed Shehab Ansam _Mohammed
Bra’ah Al-hershi
Esmail Bahlol
Esmail Khurim
Ekram Sabah
Ghadeer Rajeh
Hamza Al-moliky
Hamza Elshekeil
Heba Al-hamadi
Hesham Dhafer
Lamees Alwajeeh
Mazin Al-qaini
Mousa Mohammed
Moheeb Al-khwlani
Mohmmad Al-ameri
Mohammed Abdu
Mohanad aqlan
Nadia sallam
Nada Al-shami
Omaima
Abdulrazaq
Osama Omer
Radwan Dghaish
Suhilla Muharram
Wael Al-samawi

Abdurrhman Hidra
Edited by:
Abdurrhman Hidra