Information Sheet-2 Drug acting on Autonomic nervous system (ANS)

Drugs acting on autonomic nervous system can be

classified as

i. Drugs acting on peripheral nervous system

a.Parasympathomimetics (Cholinomimetics)
b.Parasympatholytics ( Cholinergic antagonist)
ii. Drugs acting on somatic nervous system
a.Sympathomimetics ( Adrenomimetics)
b.Sympatholytics ( Adreno-recepeter antagonist,
Sympathoplegic)
2.2.1. Cholinergic drugs

Cholinergic agonists can be divided into directly and

indirectly acting drugs.
 Direct-acting (agonist)
Bind to cholinergic receptors, causing stimulation
 Indirect-acting
Acetyl cholinesterase enzyme cholinesterase.
These drugs physiologically released and
acetylcholine.
• inhibitors (AchEIs) also called anti- act primarily
where acetylcholine is are thus amplifiers of
endogenous
Directly acting cholinergic agonists
 Cholinergic agonists mimic the effects of ACh by binding
directly to muscarinic or nicotinic.
 These agents may be broadly classified into two groups:
o choline esters which include Ach and synthetic esters
of choline, such as carbachol and bethanechol, and
o naturally occurring alkaloids, such as nicotine and
pilocarpine
Pilocarpine
 Is a directly acting muscarinic agonist and used for the treatment of
glaucoma (a disease with enhanced pressure of fluid in the eyeball).
 Pilocarpine constricts the ciliary muscle in the eye, which promotes
the outflow of intraocular fluid through the canal of Schlemn
 used for topical uses b/c of muscarinic systemic toxicity

Used in the treatment of

1.Glaucoma
2.To reverse mydriatic (dilating) effects of atropine ( Anti-cholinergic
drug)
3.Xerostomia (dry mouth)
4.Fever : Works by increasing sweating
Bethanecol

 has mainly muscarinic actions

 Relaxes sphincters in bladder and GI tract, allowing them to empty
 Helpful for postsurgical atony of the bladder and GI tract
 Dose:10-40 mg oral, 2.5-5.0 mg SC

Carbachol

 is a direct agonist of both muscarinic and nicotinic receptors

 It is useful only as an eye drop to treatment of glaucoma as second line
drug next topilocarpine.
Adverse effects

Adverse effects of cholinergic agonists are practically muscarinic types:

Bronchoconstriction, bradycardia, increased gastric acid secretion,

sweating, difficulty in visual accommodation, increased salivation.
Indirectly acting cholinergic agonists
Indirectly acting drugs, logically, do not directly act on the
receptor. They inhibit the acetylcholine esterase enzyme
(AchE) and thus, these drugs do not mimic but increase
both the level and duration of the neurotransmitter.

According to the mode of action, AChE inhibitors can be

divided into two groups: irreversible and reversible.
Reversible inhibitors
Edrophonium

 It is used for diagnosis of Myasthenia gravis

 Since it has a very short duration of action not for the treatment of
myasthenia gravis
Neostigmine: is a reversible AchE inhibitor and used for the treatment of:

 Myasthenia gravis treatment (nicotinic action).

 Paralytic ileus (like bethanechol which is direct drug)
 Urinary retention
 Competitive (non-depolarizing) neuromuscular blockers intoxication
Physostigmine
 Is lipid soluble (non-polar) reversible AchE inhibitor used for the treatment
of Glaucomaand Atropine toxicity (anti-muscarinic drug).

Donepezil, Rivastigmine, and Galantamine: used in treatment of

Dementia of Alzheimer‘s d.
Irreversible inhibitors
 The result is a long-lasting increase in ACh at all sites where it is
released
 Many of these drugs are extremely toxic and were developed by the
military as nerve agents.
 Related compounds, such as parathion and Malathion, are used as
insecticides.
 Ecothiopate: are topical eye drops only for the treatment of severe
glaucoma.is ease
Adverse effects: (same for both direct and indirect cholinomimetic)
  Diarrhea (Diaphoresis), Urination, Miosis, Bronchospasm
(secretion) Bradycardia, exciteskeletal muscle and CNS (Emesis),
Lacrimation, Lethargy, and Salivate
Contraindications: (same for both direct and indirect cholinomimetics)

Both direct and indirect cholinomimetic drug should not be given for
those patients with the following clinical problem:

 Bronchial asthma
 Peptic ulcer
 Angina pectoris
 urine incontinence
 Intestinal obstruction
2.2.2 Anticholinergic (Cholinergic
antagonists)
• Cholinergic antagonist is a general term for agents that bind
to cholinoceptors (muscarinic or nicotinic) and prevent the effects
of acetylcholine (ACh) and other cholinergic agonists.
• Nicotinic receptor blockers are ganglionic blocking drugs or
neuromuscular blockers (skeletal muscle relaxants) depending on
the location of the nicotinic type acetylcholine receptors.

Antimuscarinic agents

 Antimuscarinic are drugs which block ACh at the muscarinic

receptorsin the PSNS
 Drugs include: Atropine, Scopolamine (Hyoscine), Ipratropium
bromide, Benztropine,Trihexyphenidyl
Therapeutic uses
 Parkinson‘s disease: Benztropine, Biperiden, Procyclidine &
Trihexyphenidyl used asadjunctive therapy
 Motion sickness: Scopolamine (oral or transdermal prophylactically 4
hrs. before journey)
 As Anti-secretory and Preanesthetic medication: Atropine used
for this purpose
 Urinary incontinence: Tolterodine is M3 selective drugs used to
relieve urinary frequency,and urgency and Enuresis in children
 Asthma: Ipratropium bromide is used as inhalational drug in asthma.
 Chronic obstructive pulmonary disease (COPD) patients –
Chronic smokers, older patients:Tiotropium bromide a long acting
quaternary anti-muscarinic drug and can be given once daily.
 Bradycardia and partial heart block: Atropine is useful if these
cases are occurred
 Abdominal cramp and intestinal colic: Dicyclomine is good drug for
this purpose
 Non- infectious, traveler and drug induced diarrhea: atropine
(usually used in combinationwith diphenoxylate)
 To reverse the toxicity of organophosphate (irreversible
cholinesterase
inhibitors)poisoning: IV atropine sulfate every 5-15 min until signs
Adverse effects
 Dry mouth, mydriasis, blurred vision tachycardia, dry eyes, hot &
flushed skin, bodytemperature increases, constipation,
hallucinations, agitation, delirium which may progressto
depression, collapse of circulatory and respiratory system, coma
and death.
 Simply the adverse effects of muscarinic blocker are anti-
DUMBBELLS.

Contraindication of Antimuscarinic drugs

 Avoid the use of anti-muscarinic drug in glaucoma patients

especially angle closure, and with a history of prostatic
hyperplasia and use in elderly men with caution.
Anti-nicotinic drugs
 Two types: ganglion blockers and neuromuscular

blockers Ganglionic blockers

 Ganglionic blockers act on the nicotinic receptors of both

parasympathetic and sympathetic autonomic ganglia.

 These drugs show no selectivity toward the parasympathetic or

sympathetic ganglia.

 Thus, these drugs block the entire output of the autonomic nervous
system at the nicotinic receptor.

 Since responses observed are complex and unpredictable they are

rarely used therapeutically.
Neuromuscular blockers

• These drugs block cholinergic transmission between

motor nerve endings and the nicotinic receptors on the
neuromuscular end plate of skeletal muscle.

• These Nm blockers are structural analogs of acetylcholine,

and act either as antagonists (non- depolarizing type) or,
as agonists (depolarizing type) receptors on the end plate
of the Nm junction.
i.Non-depolarizing (competitive) blockers
 E.g. tubocurarine, cisatracurium, pancuronium, rocuronium,
and vecuronium
 Used during surgery to relax muscles combined with
anesthetics
 Increase safety of anaesthetics by reducing the dose
of anesthetics required
 Injected intravenously, as oral absorption is minimal
 Penetrate the membrane very poorly and do not enter cells
or cross the BBB
 Depolarizing blocking agents work by depolarizing the plasma
membrane of the muscle fiber, similar to the action of ACh.
 However, these agents are more resistant to degradation by
Acetylcholinesterase and can thus more persistently
depolarize the muscle.

E.g. Succinylcholine

 Therapeutic uses: Because of its rapid onset of action,

succinylcholine is useful when rapid endotracheal intubation is
required during the induction of anesthesia

 Adverse effects: Malignant Hyperthermia (caused by abnormal

release of calcium from stores in skeletal muscle), apnea and
hyperkalemia.
 ii. Depolarizing blockers
3. Adrenergic drugs
 Drugs that stimulate the sympathetic nervous system (SNS)

 Also known as adrenergic agonists or sympathomimetics

 Mimic the effects of the SNS neurotransmitters: nor-epinephrine
(NE) and epinephrine(EPI)
The sympathomimetic classified by mode of action into three groups
Direct acting

 Act directly interact with and activate one or more of the adrenergic receptors
 e.g., nor-epinephrine and epinephrine
Indirect acting
 Increase the availability of nor-epinephrine or epinephrine to stimulate
adrenergic receptors by
o causing displacement of stored catecholamines from adrenergic nerve
endings (e.g.,Amphetamine and tyramine) or
o inhibition of reuptake of already released catecholamines from the
synapse (e.g., Cocaine and tricyclic antidepressants (TCADs))
o Blocking the metabolizing enzymes: e.g. Monoamine oxidase (MAO) is
inhibited by pargyline while catechol-O-methyltransferase (COMT) is
inhibited byentacapone
Mixed acting sympathomimetics

Refers drugs that indirectly release norepinephrine and also directly

activate adrenoreceptors. e.g., ephedrine, dopamine
Epinephrine (adrenaline)

 Epinephrine interacts with both α and β receptors.

 At low doses, β effects (vasodilation) on the vascular system
predominate, whereas at highdoses, α effect (vasoconstriction) is the
strongest.

Therapeutic uses of epinephrine

 Bronchospasm: in treatment of acute asthma and

anaphylactic shock, epinephrine is the drug of choice and can be
lifesaving in this setting. Within a few minutes after subcutaneous
administration, respiratory function greatly improves.
 Anaphylactic shock: Epinephrine is the drug of choice for the
treatment of typesI hypersensitivity reactions (including anaphylaxis)
in response to allergens.
 Cardiac arrest: Epinephrine may be used to restore cardiac rhythm
in patients
with cardiacarrest.
 Anesthetics: Local anesthetic solutions may contain low
concentrations Epinephrine greatly increases the duration of local
anesthesia by producing vasoconstriction at the site of injection.
 This allows the local anesthetic to persist at the injection site
before being absorbed into the systemic circulation

Epinephrine Side Effects

 Nervousness, tremor, insomnia Paradoxical bronchospasm,

Angina, arrhythmias, Hypertension, Tachycardia Nausea/Vomiting
and Hyperglycemia
Dopamine
 At low rates of infusion
o D1-mediated vasodilation in renal, coronary vessels with little
effect on other bloodvessels or on the heart.
 At higher rates of infusion
o It causes Bet1-mediated increased force of heart contraction
and alpha 1- mediatedgeneralized vasoconstriction
 Indications
o Treatment of severe congestive failure
o Treatment of cardiogenic and septic shock.
Selective alpha 1 agonists
 E.g. Phenylephrine
 Phenylephrine causes marked arterial vasoconstriction during
intravenous infusion.
 Phenylephrine is used as a nasal decongestant and as a mydriasis
in various
nasal andophthalmic formulations.
Alpha 2 selective agonists: methyldopa and clonidine

Methyldopa

 Centrally acting antihypertensive agent (it is the preferred

agent during pregnancy)
 Causes activation of central alpha2 receptors
 Inhibits SNS activity and leads to a fall in Blood pressure
 Adverse effects: sedation, dry mouth, bradycardia,
hepatotoxicity, hemolytic anemia

Beta 1-selective agonists E.g. Dobutamine

 Dobutamine injection is used for treatment of heart failure, shock

and atrioventricular heartblock
 Adverse Effects of Beta1Activation:tachycardia (excessive heart
rate), dysrhythmias(irregular heartbeat) and Angina Pectoris.
Beta 2 selective agonists
Used for treatment of asthma
Classified into two based on the duration of action
Short acting: Albuterol and terbutaline are short-acting β2 agonists.
 Albuterol is the short acting β2 agonist of choice for the
management ofacute asthma symptoms.
Long acting: Salmeterol and formoterol are long acting β agonists
(LABAs) thatare β2 selective.
 Salmeterol and formoterol are the agents of choice for treating
nocturnalasthma in symptomatic patients taking other asthma
medications.
Adverse Effects
o Tremor is a relatively common adverse effect
 o Can be minimized by starting oral therapy with a low dose of
drug and progressively increasing the dose as tolerance to the
tremor develops.
o Feelings of restlessness, apprehension, and anxiety
o Tachycardia is a common adverse effect with systemic
administration

4. Adrenergic blockers

 The adrenergic antagonists (also called adrenergic blockers or

Sympatholytic) bind to adrenoceptors but do not trigger the usual
receptor-mediated intracellular effects. These drugs act by either
reversibly or irreversibly attaching to the adrenoceptors, thus
preventing activation by endogenous catecholamines
Alpha-adrenergic blocking agents
 The adrenergic antagonists (also called adrenergic blockers or
sympatholytic) bind to adrenoceptors but do not trigger the usual
receptor-mediated intracellular effects.
 As indicated inthe flow chart above adrenergic blockers are classified
into selective and non-selective based on their affinity toward either
beta1 or beta 2 receptors.

Non-Selective alpha-Adrenergic Receptor Antagonists:

 Non-selective Alpha-receptor antagonists may be reversible
(Phentolamine) or irreversible (Phenoxybenzamine) in their
interaction with these receptors.
Therapeutic Uses: both drugs are used in the following condition

 Treatment of pheochromocytoma
 Treat patients in preparation for surgery
 Prolonged treatment in patients with inoperable or malignant
pheochromocytoma
 Erectile dysfunction

Toxicity and adverse effects

 Postural hypotension accompanied by reflex tachycardia, reversible

inhibition ofejaculation
Alpha1-Adrenergic Receptor Selective Antagonists
 Prazosin, terazosin, doxazosin, tamsulosin, and alfuzosin are
selective competitive blockers of the α1 receptor
o Inhibits vasoconstriction induced by endogenous
catecholamines; vasodilation may occur in both arteriolar
resistance vessels and veins,
o Resulting in a fall in blood pressure due to decreased
peripheral resistance.
 Therapeutic use:
o Treatment of hypertension (prazosin, terazosin, doxazosin)
o Congestive heart failure
 o Benign prostatic hyperplasia (especially Tamsulosine)
 Adverse effects
o Most common side effect is postural hypotension and
syncope when administered for the first time (―first- dose
phenomenon‖).
 This disappears with continued therapy,
tolerance develops and
cardiovascular reflexes are not impaired appreciably by
chronic therapy.
o Other side effects: - headache, drowsiness, dry mouth,
blurred vision, stress incontinence
Beta-adrenergic blocking agents
 Block stimulation of beta receptors in the SNS
 Two types
o Non-selective beta blockers: Propranolol, timolol, nadolol, pindolol
o Cardioselective (Beta1) blockers: atenolol, esmolol, metoprolol
 Therapeutic use:
o Angina and Certain tachyarrhythmia
o Myocardial infarction
o Heart failure
o Hypertension
o Glaucoma (topical use): reduce production of aqueous humor
 E.g. Timolol
o Hyperthyroidism, migraine headache, anxiety: propranolol
Adverse effects
 Bronchoconstriction: non-selective beta blockers like propranolol
 Bradycardia
 Hypoglycemia Contraindication
 Asthma is an absolute contraindication
 Insulin-dependent diabetes
o Masking of hypoglycemia in insulin-dependent diabetes
because ofblunting of sympathetic nervous activation.
Information Sheet-3 Central nervous system drugs

2.3.1. Definition of terms

 Addiction: a chronic, relapsing brain disease that is characterized
by compulsive drug seeking and use, despite harmful consequences.

 Analgesics: medicines that are used to relieve pain (provide

analgesia).

 Anesthesia: a way to control pain during a surgery or procedure

by using medicine called anesthetics.

 Anxiety: a feeling of worry, nervousness, or unease about

something with an uncertain outcome.

 Chemical synapses: are biological junctions through which signals

from neurons can be exchanged to each other and to non-neuronal
cells such as those in muscles or glands.
 Dependence: is an adaptive state that develops from repeated
drug administration, and which results in withdrawal upon cessation
of drug use.

 The limbic system: a group of cortical and subcortical structures

involved in memory formation and emotional responses. The
major parts of limbic system are the hypothalamus, the basal
ganglia, and the hippocampus

 Narcotic: an addictive drug affecting mood or behavior.

 Neuron or nerve cell: is an electrically excitable cell that

receives, processes, and transmits information through electrical
and chemical signals. A typical neuron consists of a cell body
(soma), dendrites, and an axon
 Opioids: are substances that act on opioid receptors to produce
morphine-like effects. Medically they are primarily used for pain relief,
including anesthesia.
 Pain: is an unpleasant sensory and emotional experience
associated with actual or potential tissue damage
 Psychotropic: drugs that affect a person's mental state. Tolerance:
reduced reaction to a drug following its repeated use.
 Extrapyramidal system: is involved in the regulation of gross
voluntary movements, thus it complements the function of the
pyramidal system. The ―basal ganglia‖ constitute an essential part of
this system.
 The pyramidal system: originates from the motor area of the
cerebral cortex and passes through the spinal cord, therefore it is
also known as the ―corticospinal tract‖. It is responsible for the
regulation of the fine voluntary movements.
 Bipolar disorder (manic-depressive illness): a brain disorder
that causes unusual shifts in mood between depression and mania.

 Mania: excitement manifested by mental and physical

hyperactivity, disorganization of behavior, and elevation of mood

 Drugs acting on CNS were among the first to be discovered by

primitive humans and are still the most widely used group of
pharmacologic agents.

 In addition to their use in therapy, many drugs acting on the CNS

are used without prescription to increase the sense of well-being.

 The mechanisms by which various drugs act in the CNS have not
always been clearly understood.

 Generally, most drugs act on specific receptors that modulate

synaptic transmission
 Drugs that act on CNS include sedative-hypnotics (anxiolytics),
antidepressants, mood stabilizers, antipsychotics, anti-seizures,
anesthetics, muscle relaxants, analgesics and antiparkinsonian agents.
2.3.2. Sedatives and Hypnotics (Anxiolytics)
 Often these drugs are referred to as sleeping pills. Their effects range
from calming down anxious people to promoting sleep.
 The most important drug classes are benzodiazepines and barbiturates.

• Benzodiazepines: chlordiazepoxide, diazepam, alprazolam,

lorazepam
• Benzodiazepines are a class of drugs primarily used for treating
anxiety and insomnia, but they also are effective in treating several
other conditions such as epilepsy and muscle disorder.
• They are also as part of anesthesia due to their amnesiatic properties.
 Benzodiazepines enhance the activity of GABA, effectively
slowing nerve impulses throughout the body. This
neurotransmitter has an inhibitory effect on motor neurons,
thus the presence of GABA slows or stops neuronal activity.
 Due to their sedative properties, benzodiazepines have a
high potential for abuse, especially when used with other
depressants such as alcohol or opiates.
 Common side effects include: Lightheadedness, Drowsiness,
Confusion, Sedation, Memory impairment, Tolerance,
Dependence
B.Barbiturates: Thiopental, Phenobarbitone
• The effects of barbiturates are, in many ways, similar to the
effects of alcohol. Small amounts produce calmness and relax
muscles. Larger doses can cause slurred speech, memory loss,
and irritability (bad temper/impatience), changes in alertness,
decreased interpersonal functioning, staggering gait, poor
judgment, and slow, uncertain reflexes. These effects make it
dangerous to drive a car or operate machinery.
• Large doses can cause unconsciousness and death.
• Barbiturates may also pass through the placenta, creating birth
defects and behavioral problems in babies.
• They cause dependence
2.3.3 Anti-psychotic drugs

• Anti-psychotics are drugs used to treat schizophrenia.

 Schizophrenia is characterized by thoughts or experiences that
seem out of touch with reality, disorganized speech or behavior
and decreased participation in daily activities. Difficulty with
concentration and memory may also be present. People with
schizophrenia may have difficulty distinguishing between what is
real and what is imaginary.
 Symptoms typically come on gradually, begin in young adulthood,
and last a long time.
 Common symptoms include false beliefs (delusion), unclear or
confused thinking, hearing voices that others do not hear
(hallucination), reduced social engagement and emotional
expression, and a lack of motivation
 The exact cause of schizophrenia is not known, but a
combination of genetics and drug abuse may play a role.
 The "dopamine theory of schizophrenia" states that
schizophrenia is caused by an overactive dopamine system in the
brain. There is another theory, ―serotonin theory‖, which states
that schizophrenia is caused by overactive serotonin. The two
theories are compatible. Thus, drugs used to treat schizophrenia
act, by reducing the activity of either dopamine or serotonin.
 The mainstay of treatment is antipsychotic medication, along with
counseling, job training and social rehabilitation.
 Antipsychotics, also known as neuroleptics or major tranquilizers,
are a class of medication primarily used to manage psychosis,
principally in schizophrenia and bipolar disorder. Antipsychotics
are classified into two:
1.Typical Antipsychotics (neuroleptics or 1st
generation antipsychotics)
 Act by inhibiting the activity of the neurotransmitter dopamine
 Examples: Chlorpromazine, Thioridazine, Fluphenazine, Haloperidol
 Possible Adverse reactions of 1st generation anti-psychotic drugs
include:
A.Extrapyramidal side-effects
a.Parkinson's disease-like symptoms - tremor, muscle rigidity,
loss of facialexpression
b.Dystonia - contraction of muscles
c.Akathisia: -Restlessness
d.Tardive dyskinesia - involuntary, abnormal movements of the
face, mouth,and/or body. This includes lip smacking and
chewing movements.
B.anticholinergic side effects (blurred vision, dryness of mouth,
constipation, urinaryretention and tachycardia)
C.Sedation, orthostatic hypotension, weight gain
D.Neuroleptic malignant syndrome: rare but a serious.
1.Atypical antipsychotics (2nd generation
antipsychotics):
clozapine, olanzapine, risperidone,
 Act by inhibiting the neurotransmitters serotonin and dopamine

 Atypical antipsychotics are less likely to produce extrapyramidal side

effects (such as tremor and Parkinson's-like symptoms) and tardive
dyskinesia (abnormal, repetitive facial movements).Atypical
antipsychotics are also more likely to improve cognitive function.
 Adverse effects include: hyperglycemia, weight gain, hyperlipidemia,
sexual and cardiac dysfunction. Clozapine can cause agranulocytosis.
Anti-parkinsonism
 Parkinson Disease: characterized tremor, rigidity and difficulty in
the coordination of fine muscle movements. The other important
feature is Bradykinesia/hypokinesia.

 The main problem is in the basal ganglia portion of the midbrain.

 Loss of Dopamine
 High activity of Acetylcholine

Treatment strategies:

1.Decreasing the Muscarinic Activity: help to control tremors and

rigidity though theyare not of much help in hypokinesia.e.g.
Benzotropine, Trihexyphenidyl
1.Increasing the dopaminergic activity: help control bradykinesiae.g.
Sinemet (Levodopa + carbidopa), Bromocriptine
Levodopa plus carbidopa

⚫ More effective than levodopa alone

⚫ Carbidopa enhances effects of levodopa by inhibiting
decraboxylases in periphery so levodopa available for CNS increases

⚫ Advantages of carbidopa - Combination superior in 3 ways

⚫ Increases fraction of levodopa available for CNS

⚫ Levodopa dose can be reduced by 75%

⚫ Decreases cardiovascular response.

 Drugs affecting brain
dopaminergic system

 Dopamine precursors: levodopa

 Peripheral decarboxylase inhibitors: carbidopa & benserazide
 Dopaminergic agonists: bromocriptine, lisuride, pergolide,
ropinirole, cabergoline & pramipexole
 MAO-B inhibitors : Selegiline
 COMT inhibitors: Entacapone, tolcapone
 Dopamine facilitator: Amantidine

Drugs affecting brain cholinergic system

 Anticholinergics: Benzatropine, biperiden
 Antihistaminics: promethazine
 Trihexyphenidyl (benzhexol), Procyclidine,
2.3.5 Antidepressants
 Depression: a mood disorder that causes a persistent feeling of
sadness and
loss of interest.
 Antidepressants are a broad group of drugs that are used in the
treatment of depression.Although they do not cure depression,
they are usually effective at improving mood andrelieving
symptoms such as restlessness, anxiety, sleep problems, and
suicidal thoughts.
 Antidepressants are also sometimes used to treat people with long-
term (chronic) pain.
 A decrease in the level of norepinephrine, 5-HT (serotonin) and
dopamine causesdepression. Antidepressants relieve depression by
increasing the level of norepinephrine,serotonin and dopamine.
The following are commonly used antidepressant classes:
1.Tricyclic antidepressants (TCA): imipramine, amitriptyline
2.Selective serotonin reuptake inhibitors (SSRI): fluoxetine,
sertraline, citalopram.
Adverse effects
 In general, the most common side effects of antidepressants are
usually mild. Side effects should improve within a few days or
weeks of treatment, as the body gets used to the medication.
 Side effects like loss of sexual desire, erectile dysfunction and
decreased orgasm may last longer
 Common side effects of antidepressants include:
Both TCA and SSRI side effects
Increased appetite and weight gain
Sexual dysfunction: loss of sexual desire, erectile dysfunction and
decreased orgasm
TCA only side effects
Anticholinergic side effects (dry mouth, blurred vision,
constipation) Hypotension
 2.3.6 Anti-epileptics
 A seizure happens when abnormal patterns of electrical activity arise in
the brain. It may cause thebody to move in an uncontrolled way,
and can also cause loss of consciousness for a short period.
 Seizures are also known as convulsions when there are uncontrollable
muscle contractions.
 But not all seizures produce convulsive behavior, e.g. Absence
seizures involve only brief periods of staring and have no convulsion.
 The symptoms produced by a seizure are dependent on which part
of the brain is experiencing the abnormal electrical activity.
 Seizures are generally short-lived – from 15 seconds to 15
minutes – however; there is a life-threatening type of seizure,
status epilepticus, in which the seizure continues for longer
period of time.
 A variety of conditions and substances can trigger seizures.
Common causes include congenital abnormalities of the brain,
illicit drug use, fever, brain tumors and metabolic imbalances,
such as high levels of glucose or sodium.
 Epilepsy is a condition in which a person experiences
repeated seizure, due to an overall electrical disturbance in the
brain. It usually begins in childhood, but can start at any age.
 Anti-seizure drugs help control seizures in about 70% of
people. They work by increasing the level of GABA and
decreasing the levels of sodium and calcium in brain. They don't
cure epilepsy, but can stop seizures happening.
 The most common anti-seizure drugs
include:
 Phenytoin Ethosuximide (forabsence
 Sodium valproate seizure only)
 Carbamazepine  Phenobarbitone
 Lamotrigine  Diazepam

 Both seizures and medications are associated with some risks.

Seizure control is critical because the risks from seizures are
greater than the risks from medications.
 For example, generalized tonic-clonic seizures are associated with
increased risk to both the mother and baby:

 Trauma from falls or burns Increased

risk of premature labor Miscarriages

 Lowering of the baby's heart rate

Change in seizures
  The most common malformations include cleft lip and clef
palate (which can be surgically corrected), problems with the
heart, urinary or genital systems.

Common adverse effects of anti-seizure drugs include:

 Drowsiness, A lack of energy, Blurred vision, headaches, Tremor,

Hair loss or unwanted, air growth, Rashes
 Phenytoin only side effects
o Swollen gums (Gingival hyperplasia)
o Long-term use may lead to development of peripheral
neuropathies and osteoporosis
 Sodium valproate only side effects
o Rare hepatotoxicity may cause a rise in liver enzymes, which
should be monitored frequently
Anesthetic agents
 Anesthesia is defined as ―loss of sensation"
 Medications that cause anesthesia are called anesthetics
 Anesthetics are used during tests and surgical operations to numb
sensation in certain areas of the body or induce sleep. This prevents
pain and discomfort, and enables a wide range of medical procedures
to be carried out.
 Anesthetics work by stopping the nerve signals that keep you awake
and aware from reaching your brain.
 During this state of induced sleep, procedures can be carried
outwithout you feeling anything. After the anesthetic has worn
off, the nerve signals will beable to reach your brain, and
consciousness and feeling will return
Anesthetics are classified into two:
a.Local anesthetic: used during minor procedures where a small area
of the body is numbed and you remain fully conscious.
Two basic classes of local anesthetics exist
Amino amides: lidocaine, bupivacaine
Amino esters: procaine, tetracaine
 Amino esters are much more likely than amino amides to
cause allergic hypersensitivity reactions.

b. General anesthetic: used for more serious operations where

you're totally unconscious andunaware of the procedure.
General anesthetics are classified in to injectable and
inhalation type Injectable: propofol, ketamine, Thiopental
Inhalation: nitrous oxide, halothane, enflurane
  The purpose of general anesthetic is to induce:

 Analgesia - remove natural response to

pain

 Amnesia - memory loss

 Immobility - removal of motor
reflexes
 Unconsciousness
 Skeletal muscle relaxation.

Common adverse effects of general

anesthetics include

 Nausea and vomiting

 Shivering and feeling cold
 Confusion and memory loss
 Urinary retention
Opioid analgesics
 Drugs: Morphine, Codeine, Meperidine (pethidine),
Methadone, Tramadol
 When you have a mild headache, an over-the-counter pain
reliever (e.g. Paracetamol) is usually enough to make you feel
better. But if your pain is more severe, stronger analgesics like
opioids are needed.
 Opioids are used to treat moderate to severe pain that may not
respond well to other pain medications. Opioids are among the most
effective pain medications.
 Opioids are also used to treat dry cough (antitussive effects)

 Opioid drugs work by binding to opioid receptors ( read as mu)

in the brain, spinalcord, and other areas of the body. They reduce
the sending of pain messages to the brain and reduce feelings of
pain.
  Common side effects of opioid include:
o Sedation
o Dizziness
o Nausea and vomiting
o Constipation
o Dependence and tolerance
o Respiratory depression
 Naloxone is specific antidote for opioid poisoning

Muscle relaxants
 The goal with these medications is a reduction of skeletal
muscle spasms, muscle spasticity, relief of pain.
 Muscle spasms or cramps are sudden, involuntary contractions
of a muscle or group of muscles.
 They can be caused by too much muscle strain and lead to pain.
 They‘ are associated with conditions such as lower back pain,
neck pain, and fibromyalgia.
 Muscle spasticity, on the other hand, is a continuous muscle spasm that
causes stiffness,rigidity, or tightness that can interfere with normal
walking, talking, or movement. Musclespasticity is caused by injury to
parts of the brain or spinal cord involved with movement.
 Anti-spastics are used to treat muscle spasticity and include the
following
o Baclofen
o Dantrolene
o Diazepam
 Anti-spasms are used to treat muscle spasm and include the following.
o Chlorzoxazone
o Methocarbamol
o Orphenadrine
 Neuromuscular blockers are used in conjunction with an anesthetic to
provide skeletalmuscle relaxation during surgery
o D-Tubocurarine, vecuronium, mivacurium
o `Succinylcholine
Information Sheet-4 Drug Acting on Cardiovascular system

1. Diuretics
 Diuretics are drugs that increase the rate of urine flow and
sodium excretion
– Used to adjust the volume/ composition of body fluids in
various clinical situations
–Used in patients with Hypertension, Heart failure, renal
failure Classes of Diuretics
1.Carbonic Anhydrase Inhibitors (CAIs)
2.Osmotic Diuretics
3.Loop diuretics, High-ceiling Diuretics
4.Thiazide and Thiazide-like Diuretics
5.Potassium-Sparing Diuretics
 Fig. Tubule transport systems and sites of action of diuretics.

1.Carbonic Anhydrase Inhibitors(CAIs)

 CAIs were the prototype of modern diuretics. They includes
 Acetazolamide, Dichlorphenamide, Methazolamide
 Inhibit carbonic anhydrase in all body parts
 Kidney – Proximal tubule
 Reduce HCO3- reabsorption and Na+ uptake
 Decrease the rate of formation of aqueous humor → decrease
intraocular pressure
 Increased urinary pH & metabolic acidosis
Therapeutic uses of CAIs
Diuretics (rarely used) Glaucoma
Acetazolamide 250mg PO QID
Prophylaxis and treatment of acute mountain sickness
To correct metabolic alkalosis
Epilepsy Adverse effects of CAIs
 Metabolic acidosis
 Renal stones (due to precipitation of calcium phosphate salts—in
an alkaline urine)
 Renal potassium wasting
 Drowsiness and paresthesias
 Hypersensitivity reactions (fever, rashes, bone marrow
suppression and interstitial nephritis)
2.Osmotic Diuretics
 Includes: Glycerin, Isosorbide, Mannitol, Urea
 Easily filtered
  Poorly reabsorbed
 Alter the diffusion of water relative to Na+
 Causes water to be retained
This stimulate urine flow → Mild diuresis
Therapeutic uses of Osmotic Diuretics
 To increase urine volume
 Mannitol - decrease Cerebral edema and intraocular pressure
 Mannitol, IV, 1.5–2 g/kg as a 20% solution over 30–60 minutes
Glycerol, oral, 1 g/kg of 50% solution as a single dose
immediately Side effects ofOsmotic Diuretics
– Nausea
– Vomiting
– Dehydration
– Electrolyte imbalances (Hyperkalemia, Hypernatremia
3. Loop (High-ceiling) Diuretics
 Loop diuretics include drugs like Furosemide, Torsemide, Ethacrynic
acid
 Selectively inhibit NaCl reabsorption in the thick ascending limb of
the loop of Henle by blocking the Na/K/2Cl transport
 Due to the large NaCl absorptive capacity of this segment, loop
diuretics are among the most efficacious diuretic
 Increaseded urinary excretion of Na+& Cl- (25% of filtered), Ca++,
Mg++,
Therapeutic use Loop Diuretics
 Loop Diuretics are used in the treatment of the following clinical
conditions 3

 Acute pulmonary edema and other edematous conditions

Congestive Heart Failure
 To treat hypertension
 Facilitate excretion during poisoning
 Furosemide, 40-80mg, P.O., BID is the most commonly prescribed
Side effects of Loop diuretics
 Hypokalemia, Hyperuricemia and Hypomagnesemia
 Ototoxicity
 Allergic reactions
 Nausea, anorexia, vomiting
 Fatigue
 Weakness and Muscle cramps
 Drowsiness and Dizziness
4.Thiazides and thiazide like diuretics
4.Thiazide diuretics includes: Chlorothiazide,
Hydrochlorothiazide, Indapamide
 Inhibit NaCl reabsorption in the distal convoluted tubel by blocking the
Na+/Cl- transporter
– Increase Na+& Cl- excretion /only 5% filtered Na+ load/
– Also possess carbonic anhydrase inhibition
– Increase HCO3 & Phosphate excretion
– Increase Excretion of K+
–Decrease Uric acid excretion Therapeutic uses of Thiazide
-
diuretics
Thiazide diuretics are used in the management of
 Hypertension
 Heart failure
 Edema associated with CHF, Hepatic cirrhosis, Nephrotic syndrome
 Nephrogenic diabetes inspidus
 Hydrochlorothiazide 12.5-100mg/day is the most commonly used
thiazide diuretics
Side effects of thiazide diuretics
Hypokalemic, metabolic alkalosis
Hyperuricemia and Hyponatremia
Hyperglycaemia and Hyperlipidaemia
Allergic reactions
Weakness, fatigability and paraesthesia
Impotence
Epigastric distress, nausea and vomiting
Visual disturbance
 5.Potassium-sparing diuretics
 Potassium-sparing diuretics includes: - Spironolactone, triamterene,
amiloride – known to cause mild diuresis
 Primarily used in combination with thiazides or loop diuretics in
edema
 Act distally in the collecting duct to either inhibit binding of
aldosterone to mineralocorticoid receptors or inhibit epithelial
Na+ channel (ENaC)
 Increase excretion of Na+, Ca++ and HCO3 but decrease
excretion of K+
Clinical uses of Potassium-sparing diuretics
 Potassium-sparing diuretics are used in the treatment of
Hypertension
 Heart failure
 Acne - 50–100 mg daily for up to six months
 Hirsutisim, aldosteronism
 Side effects of Potassium-sparing
diuretics
 Hyperkalemia
 Metabolic acidosis
 Gynecomastia
 G.I. disturbances
 Dry mouth
 Rashes
 Confusion
 Orthostatic hypotension
 2.4.2 Antihypertensive agents
What is Hypertension?
Hypertension is defined as systolic BP above 140 mm Hg or diastolic
BP above 90 mm Hg
Classification of hypertension

Classification Blood pressure (mmHg)

Systolic Diastolic
Normal <120 And <80
Pre-hypertension 120-139 Or 80-89
Hypertension stage1 140-159 Or 90-99
Hypertension stage2 >160 Or
>100
There are 2 general types of Hypertension:
Essential Hypertension
 There is an absence of identifiable secondary cause.
 This accounts for ~95% of all cases of hypertension.
 Also referred to as primary or idiopathic hypertension.
 It is a heterogeneous disorder with numerous risk factors including
sedentary life style, obesity, insulin resistance (metabolic
syndrome), salt/sodium sensitivity,
alcohol intake, age, family history.
Secondary Hypertension
 Where hypertension can be attributed to an identifiable cause (e.g.
aldosteronism, hyperthyroidism, glucocorticoid excess, reno-
vascular disease, renal failure, pheochromocytoma)
 Treatment is targeted to the underlying cause

Why should we treat hypertension?

 Sustained arterial hypertension damages blood vessels in kidney,

heart and brain and leads to an increased incidence of renal failure,
cardiac failure, and stroke.

 Effective pharmacologic lowering of blood pressure prevents the

damage to blood vessels and reduces the morbidity and mortality
rate.
Treatment of hypertension
Two therapeutic Interventions
 Non-pharmacologic
Non- pharmacological therapy of
hypertension include
 Low sodium chloride diet
 Weight reduction
 Exercise
 Cessation of smoking
 Decrease in excessive consumption
of alcohol
 Avoid stress
 Pharmacological therapy of
hypertension

 Currently available drugs lower blood pressure by decreasing

either cardiac output (CO)or total peripheral vascular resistance
(PVR) or both
 Anti-hypertensive drugs are classified according to the principal
regulatory site ormechanism on which they act into:
o Alpha blockers: e.g. Prazosin
o Centrally acting anti-hypertensive e.g.
Methyldopa
o Diuretics
o Direct vasodilators
o Angiotensin converting enzyme inhibitors
o Angiotensin II receptor blocckers
o Calcium channel blockers
Diuretics
 Diuretics are drugs that increase the rate of urine formation and
Sodium (salt) excretion. The kidneys play a major role in
regulating blood pressure, and diuretics exert their effects on the
kidneys.

 The diuretics increase the elimination of water, sodium, and

selected electrolytes (K+,Cl-, HCO3−), depending on their location
of action in the kidney, in the nephrons (see figure below).

 They reduce blood pressure by reducing blood volume and cardiac

output as a result of a pronounced increase in urinary water and
electrolyte particularly sodium excretion.

 Commonly used diuretic classes include: Loop diuretics,

thiazide diuretics, and potassium sparing diuretics.
Loop diuretics
Example: Furosemide, Ethacrynic acid
Effective in patients with decreased renal and cardiac
thiazides)
Adverse effects
anorexia, nausea, vomiting, dizziness, rash, postural
hypotension
Hypokalemia (may cause arrythmia if given with
digoxin)
Ototoxicity (electrolyte imbalance in the inner ear)
Hyperuricemia (may precipitate gout)
Thiazide diuretics

Chlorothiazide, Hydrochlorothiazide
hydrochlorothiazide is the most widely used thiazide
diuretic for hypertension

Potassium sparing diuretics

 e.g. spironolactone
 The diuretic action of these drugs is weak when
administered alone
 used as adjuncts with thiazides or loop diuretics to
avoid excessive potassium depletion(hypokalemia)
Direct vasodilators: E.g. hydralazine, sodium
nitroprusside

Hydralazine:
 Dilates arterioles but not veins.
 Is used particularly in severe hypertension
 The most common adverse effects are headache, nausea, anorexia,
palpitations, sweatingand flushing
Sodium nitroprusside:
 It is a powerful vasodilator that is used in treating hypertensive
emergencies
 It dilates both arterial and venous vessels, resulting in reduced
peripheral vascularresistance and venous return.
 Nitroprusside rapidly lowers blood pressure and it is given by
intravenous infusion.
 The most serious toxicities include metabolic acidosis,
arrhythmias, excessivehypotension and death.
Angiotensin converting enzyme inhibitors:
Captopril, enalapril, etc
 They lower blood pressure principally by decreasing
peripheral vascular resistance
 The common adverse effects include

 The main adverse effect on chronic use is cough;

 angioedema, cough, first-dose hypotension, and hyperkalemia

 Are contra-indicated during pregnancy

Angiotensin II receptor blockers (ARBs), e.g.
losartan, candesartan, irbesartan etc
 They lower blood pressure by blocking the binding of angiotensin
II. ARBs also inhibitangiotensin II–stimulated growth of smooth
muscle, reducing ventricular and arterialhypertrophy that is
associated with chronic hypertension.
 The ARBs are similar to ACE inhibitors in effectiveness but
produce less dry cough,perhaps because they do not increase
bradykinin levels like the ACE inhibitors.
 The ARBs are first-line therapy for treatment of hypertension,
especially in
patients withdiabetes and coronary artery disease who cannot
tolerate ACE inhibitors.
Calcium channel blockers e.g. nifedipine,
Amlodipine, verapamil

 Lower blood pressure because of their ability to relax blood vessels

 The main adverse effect in chronic use is ankle swelling.

 The most important toxic effects for calcium channel blockers

are cardiac
arrest, bradycardia, atrioventricular block and congestive heart
failure and are contraindicated in such scenarios
 Beta-blockers; reduce the risk of vascular events, but are
contraindicated in patients with obstructive pulmonary disease.
 Adverse events (dose-related) include
 fatigue and cold extremities.
 Heart failure,
 heart block or claudication can be exacerbated in predisposed
patients.
3. Drug for Angina pectoris
Angina pectoris
 Is a sudden, severe, pressing chest pain radiating to the neck, jaw,
back, and arms
 Occurs when oxygen supply to the heart is insufficient to meet
oxygen demand
 When the increase in coronary blood flow is unable to match the
increased oxygen demand
o angina develops

 Oxygen supply to the heart is reduced by thrombus and

vasospasm
 Oxygen demand is increased when heart rate and contractility
increase
 Angina can be treated by drugs that can either increase oxygen
supply to the heart or drugs that can decrease oxygen demand of
 There are three families of anti-anginal agents: organic nitrates,
Beta blockers, and calcium channel blockers.

Organic nitrates
 Include nitroglycerine, isosorbide dinitrate

 are most frequently used antianginal drugs

 Work by causing vasodilation and thereby increase oxygen supply

 Adverse effects: headache, postural hypotension, facial
flushing, Reflex tachycardia
Beta blockers: - propranolol, atenolol
 decrease the oxygen demands of the myocardium by lowering
both the rate and the force
of contraction of the heart

Calcium channel blockers: - verapamil, nifedipine

 Cause relaxation of the coronary arteries and thereby increase

oxygen supply
 Verapamil can produce modest additional reductions in
oxygen demand by suppressing heart rate and contractility
4. Drugs for heart failure
 Heart failure is a syndrome in which the heart is unable to pump
sufficient blood to meet the metabolic needs of tissues.

 It is a highly lethal condition, with a 5-year mortality rate

conventionally said to be about 50%. Presenting symptoms are
weakness, dyspnea, orthopnea and body swelling.

Drug classes used for heart failure include:

 Diuretics: furosemide, hydrochlorothiazide, spironolactone

 furosemide is drug of choice for patients with severe HF
  Cardiac glycosides-digoxin
 Beta - adrenergic stimulants e.g. dopamine, dobutamine
 Angiotensin converting enzyme inhibitors e.g. captopril,
enalapril
Digoxin
 Digoxin increases myocardial contractile force thereby increase
cardiac output
 Is dangerous drug because, at doses close to therapeutic, it
can cause severe dysrhythmias
Adverse effects:

 Anorexia, nausea, and vomiting, Confusion, dysrhythmia

 Decreased K+ increases the potential for cardio toxicity
o Reduction of serum potassium levels is most frequently
observed in
patientsreceiving thiazide or loop diuretics which can
usually be prevented by useof a potassium-sparing diuretic
or supplementation with potassium chloride
5. Anti-arithmetic drugs
 Normally, the electrical system of the heart causes it
to contract (or beat) in a regular and organized rhythm
that can be graphed by an electrocardiogram (EKG).
 An arrhythmia is an abnormal heart rhythm that can
interfere with the heart‘s ability to pump in an
effective, organized manner.
 Familiar arrhythmias include tachycardia,
bradycardia, flutter and fibrillation.
 Antiarrhythmic drugs are used to prevent or correct
cardiac arrhythmias
Drugs used in the treatment of cardiac arrhythmias are
traditionally classified into:
 Class (I): Sodium channel blockers which
include quinidine, lidocaine, phenytion, etc.
 Class (II): Beta adrenergic blockers which
include propranolol, atenolol, etc.
 Class (III): Potassium channel blockers e.g.
amiodarone, bretylium.
 Class (IV): Calcium channel blockers e.g.
verapamil, etc.
 Others: Digitalis e.g. digoxin, atropine
2.4.6 Drugs used in vascular shock
(Adrenaline)
 Cardiogenic shock (CS) is a state of impaired end-
organ perfusion caused by a decrease in cardiac output
despite adequate intravascular volume, and is usually
associated with systolic blood pressure of less than 90
mmHg for more than 30 min (in the absence of inotropic
or vasopressor support).
 The most frequent cause of CS is acute myocardial
infarction (AMI) Drugs used in cardiogenic shock.
 Drug Drug class
Epinephrine, Catecholamine

Dobutamine Catecholamine ( β1-

agonist
Dopamine Catecholamine

Milrinone Phosphodiesterase
inhibitor
Norepinephrine Catecholamine
Vasopressin Vasopressor
Epinephrine (Adrenalin)

 Epinephrine is a sympathomimetic hormone and drug

that binds to α- and β-adrenergic receptors.

 It increases mean arterial pressure by increasing
cardiac output and peripheral vascular tone, and is thus
used to treat shock.
 Its effects in septic shock have been tested in clinical

trials, in which it showed similar efficacy and impact on

mortality to norepinephrine
7. Cholesterol and lipid lowering agents

 Anti-hyperlipidemics are used to lower high levels of

cholesterol that can lead to blood vessel blockade and
cause coronary heart disease (CHD).

 Cholesterol is a lipid normally present in the body that is

essential for healthy cell function.

 Cholesterol levels are measured as total cholesterol, LDL

(low density lipoprotein), and HDL (high density lipoprotein).

 Excess amounts of LDL can lead to blocked blood

vessels and cardiovascular problems.
 Drug therapy to lower plasma lipids is only one
approach to treatment & is used in addition to dietary
management & correction of other modifiable CV risk
factors
 The main classes of drug used clinically are:
– Statins: HMG-CoA reductase inhibitors
– Fibrates :
– Bile acid-binding resins: Colestipol, Cholestrymaine &
Colesevelam
– Niacin (Nicotinic acid)
– Cholesterol absorption inhibitors: Ezetimibe
Statins
 Potent competitive inhibitors of the enzyme 3-hydroxy-3-
methylglutaryl coenzyme Areductase (HMG CoA reductase)
othe rate-limiting enzyme in cholesterol biosynthesis
HMG-CoA reductase inhibition result in:
o Reduces intracellular cholesterol levels
o↑LDL-receptor expression
o↓Plasma LDL-C
o↓Hepatic VLDL synthesis & ↑clearance of VLDL
remnant particles by LDL receptors→↓TG (20-40 %)
 Are the most effective drugs for lowering LDL
 Cause small increases in HDL
 Drugs include: Lovastatin, simvastatin, atorvastatin,
pravastatin and rosuvastatin
Use:
• Commonly used inthe treatment of
hypercholesterolemia & mixed hyperlipidemia
• The major use of Statins is in the primary & secondary
prevention of CVD
Side effects

oMyalgia, myopathy: Pravastatin & fluvastatin appear to

have less intrinsic muscle toxicity, Rhabdomyolysis
(rare), Hepatotoxicity
Drug interactions

 Gemfibrozil (↑ Rhabdomyolysis)

 CYP 450 inhibitors enhance toxicity of statins

 oThe risk is substantially ↑ed for most statins extensively
metabolized by CYP 3A4 with concurrent therapy
with drugs that interfere with CYP3A4

oPravastatin, fluvastatin & rosuvastatin are preferred

when concurrent therapy with a strong inhibitor of
CYP3A4 cannot be avoided
Contraindications

oHepatic dysfunction & concomitant use of Fibrates,

cyclosporin, other cytotoxic drugs, & macrolide
antibiotics
oContraindicated in pregnancy, in women of childbearing
age & during lactation
Fibric acid derivatives (Fibrates)

Drugs: colfibrate- proto type and the 1st

 Gemfibrozil:- Nonhalogenated; commonly used

 Fenofibrate, bezafibrate, ciprefibrate

MOA: not clear;

Reduce TG by Interacting with PPAR (peroxisome
Receptors) and proliferator-activated
• activating

Stimulation of fatty acid synthesis

Increased LPL synthesis

Enhanced clearance of VLDL

Increase in HDL levels

LDL-C levels may 🡣 o r Not affected or 🢁 e d

• Absorption: rapid & almost complete - given with a meal

• Highly protein bound

• Elimination; mainly renal: unmodified

• Contraindicated in Renal failure.

• Adverse effects:
• GI distress, Cholestasis, mypothy, Muscle
toxicity (pronounced in pts also treated with a
statin)
• hepatitis

Clinical use:
• In hypertriglyceridemia (alone)
• Combined hypercholestrolemia &
Bile acid Sequestrants (BAS)
• Includes: Colestipol, Cholestrymaine & Colesevelam
• They are not absorbed in the GIT& act by binding bile salts in the
intestine→ prevent reabsorption of bile acids
• ↑Hepatic bile acid synthesis
• Deplete hepatic cholesterol content
• Stimulate the production of LDL-receptors
• ↑ LDL Clearance & lowers LDL-C level
• Side effects
• Major adverse reactions are GIT, including
• Nausea, bloating, cramping
• Colesevelam, is better tolerated & less likely to cause GI side
effects
• They can bind to & impair the absorption of other drugs, such as
• Digoxin, warfarin & fat soluble vitamins
• This effect can be minimized by administering the other drugs
1 hr before or 4 hrs after the BA
 Information Drug Acting on Respiratory System
Sheet-5

1. Antitussives/Expectorant (Drugs for cough)

• Are drug used to relive coughing.

• Cough is an important physiological protective

mechanism, but may also occur as a symptom of an
underlying disorder such as asthma, gastro-oesophageal
reflux disease (GERD).

 It is a protective reflex, which serves the purpose of

expelling sputum and other irritant materials from the
respiratory airway.
Types of Cough
 Useful productive Cough-Effectively expels secretions and
1.The useful cough:

 It‘s useful when it expel secretion or foreign material

effectively from the respiratory tract. i.e when it‘s
productive.
 The useful cough suppressed only when it‘s exhausting
the patient or it‘s dangerous. i.e eye surgery
2.The useless cough:
It‘s useless when it‘s not productive & persistent.

It may prevent rest& sleep, should be stopped.

Chronic cough contribute to fatigue especially in elderly

patient.
Asthma, rhino sinusitis, esophageal reflux is the
commonest reason for persistent cough.
Drug classes used for treatment of cough
include
 Antitussives
 Expectorants
 Mucolytics and
 Decongestants
Antitussives
 Antitussives are drugs used to suppress the intensity and
frequency of coughing.
 Mechanism of action: Depression of the cough center or
suppression of nerve receptors in respiratory system
 May be divided into two groups:
 Opoid antitussive e.g. codeine, hydrocodeine, etc
 Opioid derivatives without addiction liabilities:
dextromethorphan
Codeine

 Codeine is a narcotic relatively less addicting drug and central

antitussive agent
 Nausea, vomiting, constipation, tolerance to antitussive as well
as analgesic effects,and physical dependence can occur, but
potential for abuse is low.
Dextrometrophan

 Dextromethorphan is an opoid synthetic antitussive,

essentially free of analgesic and addictive properties
Expectorants
 Is a drug that aid in removing thick tenacious mucus from
respiratory passages by decreasing their viscosity, thus facilitating
removal
 Guaifenesin is the most commonly used expectorant in OTC cough
remedies.
 Adverse reactions: Nausea and vomiting, drowsiness, GI distress
Mucolytics

 Are agents that liquefy mucus and facilitate

expectoration
 MOA: Break apart glycoprotein, resulting in a
reduction of viscosity and easier movement and
removal of secretions.
 Drugs: Acetylcysteine, bromhexine
 Acetylcysteine has an unpleasant odor and taste that
may cause noncompliance
Decongestants
 Decongestants are the drugs that reduce congestion of
nasal passages, which in turn open clogged nasal passages
and enhance drainages of the sinuses.
 Indications: Temporary relief of nasal congestion from the
common cold, sinusitis, and upper respiratory allergies.
 MOA: Stimulation of the a-adrenergic receptors, resulting in
constriction of the dilated arteries within the nasal mucosa
e.g phenylephrine, oxymetazoline and pseudo ephedrine

 Adverse reactions: CNS stimulation, increased blood

pressure, increased heart rate
2.5.2 Anti-asthmatics
 Asthma is a chronic inflammatory disease of the
airways characterized by increased responsiveness
of the tracheabronchial tree to allergens and
physical stimuli.

 Clinically it is characterized by episodic shortness of

breath, usually accompanied by wheezing and
coughing.

 Common precipitating factors include exposure to

cold weather, upper respiratory tract infections, bad
smells, exercise, ingestion of drugs like aspirin and
beta-blockers etc.
Characterized by:

1.Reversible air way obstruction

2.Inflammation of air way

3.Bronchial hyperactivity/ Hyper responsiveness to

stimuli such as irritant chemical, cold air, stimulant
drug in w/c all result Broncho-constriction

1.Asthma associated with specific allergic reaction

Are extrinsic/ classical, the commonest type of asthma.

Occur in patient who develop allergy to inhaled

antigenic substance.

Allergen avoidance is relevant to manage this type of

asthma.
2. Asthma not associated with known allergy
Intrinsic/ less common
Caused by chronic or recurrent respiratory infection,
emotional upset & exercise
Patient experience wheezing, breathlessness in the
absence of allergen.
Allergen avoidance have no value in the management.

• In both type of asthma there is airway

inflammation. Once asthma attack established it
triggered by various stimuli such as viral infection,
exercise, atmospheric pollutant.
 Acute sever asthma(status Asthmatics)

Is not easily reversed, cause hypoxemia

Require hospitalization, oxygen therapy.

Exercise induced Asthma

Some patient develop wheeze within few minutes of

exercise similar response occur during cold air.

It appear due to air way drying.

 Overall objectives of therapy are to return lung function

to as near normal as possible and to prevent acute
exacerbations of the disease.
Strategies for asthma management
 Avoid allergen exposure
 Reduce amount of IgE production bound to mast cell( Anti
IgE).
 Prevent mast cell degranulation( cromolyn,
nedocromolyn.
 Block the action of release mediator( Leukotriene
receptor antagonist).

 Inhibit the effect of Acetylcholine release from vagal

motor nerve( Muscarinic antagonist)
 Direct relax air way smooth muscle( symptomatic agent).
 Increase responsiveness through anti inflammatory
agent( Inhaled corticosteroid) Primary classes of
 Bronchodilators are used both in maintenance therapy
and as needed to reverse acuteattacks
 Anti-inflammatory therapy must be used in conjunction
with bronchodilators in all but the mildest asthmatics
 Commonly used anti-inflammatory agents
predinisolone , include
 hydrocortisone,beclomethasone, triamcinolone
 Bronchodilators include:
o β- Adrenergic agonists
o Methylxanthines; theophylline
  The theophylline preparations most commonly
used for therapeutic purposes is aminophylline
(theophylline plus diethylamine)
 Contraindications/cautions: Peptic ulcer
disease, seizure disorders, arrhythmias
o Muscranic receptor antagonists e.g. Ipratropium
bromide
β- Adrenergic agonists
 Non-selective β- agonists eg. Adrenaline (epinephrine)
o Cause more cardiac stimulation (mediated by a β1
receptor), they should bereserved for special situation
o Administered by inhalation or subcutaneously.
o Side effects include arrhythmia and worsening of angina
pectoris, increase blood pressure, tremors
Β2- selective agonists
 Largely replaced non-selective β2- agonists
 are effective after inhaled or oral administration and
have got longer duration ofaction
 Commonly used drugs both by oral and inhalation are

o Salbutamol, terbutaline, metaproterenol

  Salmeterol and formeterol are long acting β2- selective agonists
(with duration ofaction 12 hrs or more)
 Side effects
o Tremors, anxiety, insomnia, tachycardia, headache,
hypertension and etc
Methylxanthines; theophylline, aminophylline

 The theophylline preparations most commonly used for

therapeutic purposes is aminophylline (theophylline plus
diethylamine)

 Used to treat lung disease that is unresponsive to other

medications; used as a bronchodilator in reversible airway
obstruction caused by asthma, chronic bronchitis, or
emphysema

 MOA: Reverse bronchospasm associated with antigens and

irritants; improve contractility of diaphragm

 Contraindications/cautions: Peptic ulcer disease, seizure

disorders, arrhythmias
Anti-inflammatory
 Anti-inflammatory drugs are used both for treatment and
prophylactic purposes.
 They decrease bronchial reactivity and frequency of
asthma exacerbation and severity of symptoms.
 These classes of anti-asthmatic drugs include
corticosteroids (which will be discussed under endocne
drugs) and leukotriene inhibitors.
 Leukotriene modifiers (Zafirlukast, Montelukast) are a class of
biologically active compounds that occur naturally in leukocytes and
produce allergic and inflammatory reactions similar to thoseof
histamine. They are thought to play a role in the development of
allergic and auto allergic diseases such as asthma, rheumatoid arthritis,
inflammatory bowel disease, and psoriasis.
 Indications: - Leukotriene modifiers are used for prophylaxis and chronic
asthma in adults and children older than 12 years. Zafirlukast is
prescribed as maintenance therapy for patients with chronic asthma.
Montelukast is prescribed prophylactically for asthma attacks.
Adverse effect

 Montelukast and zafirlukast may produce cough, hoarseness or sore

throat, headache, indigestion, heartburn or stomach upset, and runny
nose. Montelukast may also produce difficulty sleeping, dizziness,
drowsiness, muscle aches or cramps, or unusual dreams.