H2 blockers can inhibit certain liver enzymes, particularly cytochrome P450 enzymes, which are involved in the Sulfonylureas:

as: These drugs, like glibenclamide,

metabolism of sulfonylureas. As a result, when patients take both sulfonylureas and H2 blockers concurrently, the gliclazide, glimepiride, and glipizide, are commonly
Drug
metabolism interaction
of sulfonylureas – Sections
is slowed & midterm
down. This – Menna
leads to higher Hazem of sulfonylureas and a
serum concentrations ‫زتونة‬work by
used to treat type 2 diabetes mellitus. They
prolonged duration of action. stimulating the release of insulin from pancreatic
Asthma Shift to LOX beta cells, thereby lowering blood glucose levels.
Sulfonylureas are metabolized in the liver and
SSRI (citalopram) excreted via the kidneys.
↑ risk of bleeding H2 Blockers: H2 blockers, such as ranitidine
Phenprocoumon (Zantac) or cimetidine (Tagamet), are medications
Glucocorticoids ↑ risk of GIT bleeding & Ulcer commonly used to reduce gastric acid secretion in
conditions like peptic ulcer disease and
Diuretics ↓ antihypertensive effect of loop diuretics
gastroesophageal reflux disease (GERD). They
work by blocking histamine H2 receptors on the
NSAIDs • Fluid retention (edema) parietal cells in the stomach, which reduces the
Thiazolidinedione production of gastric acid.
• heart failure (Thiazolidinedione's cause cardiotoxicity)
↓ blood pressure lowering effect (antagonism the antihypertensive effects):

ACE inhibitors reduction in glomerular perfusion through reduction of local

prostaglandin E2 synthesis with corresponding reactive secretion of renin
lithium ↓lithium elimination, ↑ lithium levels. (inhibit PGs → ↓ GFR of Lithium)
• Fluid retention (edema)
Thiazolidinedione
• heart failure (Thiazolidinedione's cause cardiotoxicity)
β blockers Potential effects include bradycardia 29%, heart block/arrhythmia 17%
CCBs
Change in first pass metabolism- ↑ dofetilide conc through increased
dofetilide
hepatic blood flow and risk of ǪT prolongation
digoxin ↑ digoxin bioavailability → toxicity (inhibit P-glycoprotein)
Kill microflora → ↑ digoxin bioavailability (by ↓ bacterial inactivation of
digoxin In the gut, some bacteria help inactivating digoxin. When antibiotics eliminate these bacteria, there are fewer of them available to inactivate digoxin.
digoxin)
This results in an increased bioavailability of digoxin in the body.

antibiotics warfarin Kill microflora → causes vitamin K deficiency → ↑ effects of anticoagulants

Kill microflora → efficacy ↓ (intestinal flora produces an enzyme essential
oral contraceptives
for absorption of estrogens).
azole Azole antifungals, such as fluconazole or ketoconazole, inhibit CYP3A4, leading to decreased metabolism of atorvastatin.

Verapamil, diltiazem causes severe muscle damage (rhabdomyolysis).

atorvastatin
clarithromycin Avoid use of macrolides and azoles, use rosuvastatin
cyclosporine Cyclosporine is an immunosuppressant used to prevent organ rejection in transplant patients by inhibiting T-cell activation.

diuretics Beneficial effects

potassium sparing
↑ potassium retention so strong → life-threatening hyperkalemia ensues.
(amiloride, Spironolactone )
ACE inhibitors
↓ blood pressure lowering effect (antagonism the antihypertensive effects):

NSAIDs reduction in glomerular perfusion through reduction of local

prostaglandin E2 synthesis with corresponding reactive secretion of renin
ACEIs + DIURETIC + NSAIDs = Renal failure reduction in glomerular perfusion
ibuprofen reversible bind to COX-1 which prevent acetylsalicylic acid
ibuprofen
from acetylation of serine residue at position of 529 of COX-1 protein.
Acetazolamide inhibit tubular excretion of ASA
Thiazide Diuretics ↑ blood uric acid level
Aspirin is heavily bound to plasma proteins and displace anticoagulants
warfarin
Aspirin as warfarin → ↑ its levels and ↑bleeding.
Aspirin and NSAIDs inhibit secretion of methotrexate into urine, as well as
methotrexate displacing it from protein-binding sites (↑ free form of MTX) →
methotrexate toxicity
Antacid ↑ urine pH and renal excretion (analgesic dose of aspirin)
paracetamol additive
Page 1 of 7
 Drug interaction – Sections & midterm – Menna Hazem ‫زتونة‬
Verapamil and diltiazem are calcium channel blockers that slow conduction through the AV node and reduce myocardial contractility.

Verapamil – Diltiazem bradycardia, AV block

Antidiabetic drugs Suppression of Neuroglycopenic symptoms (tremors, sweating,
This can lead to hypoglycemia unawareness, where
β blockers (insulin - sulfonylurea) palpitations) hypoglycemia unawareness patients do not recognize or respond to low blood
sugar levels appropriately.

↓bronchodilator activity, bronchial spasm : Propranolol (beta blocker)

Bronchodilators
opposes bronchodilator effect of salbutamol (beta agonist)
digoxin Chemical & Pharmacokinetic - ↓ absorption
warfarin
T4 (levothyroxine)
Cholestyramine propranolol Pharmacokinetic interactions - Chelation - ↓ absorption
ciclosporin
tricyclic antidepressants
mycophenolate ↓ enterohepatic recirculation by binding free mycophenolic acid in GIT
Natural Black Licorice
↑ effects of digoxin by ↓ K levels and ↑ Na → Digoxin toxicity
(Glycyrrhiza)
40% or more digoxin dose is metabolized by the intestinal flora.
Verapamil and Antibiotics Antibiotics kill a large number of normal flora of the intestine ↑ digoxin
diltiazem inhibit
P-glycoprotein toxicity
(P-gp), a drug
transporter that Verapamil, Diltiazem ↑ digoxin levels, digoxin toxicity (P-gp inhibitors) → ↓ digoxin excretion
mediates the
excretion of ↑ digoxin toxicity due to hypokalemia (hypokalemia caused by thiazide or
digoxin from the Diuretics
intestines and loop diuretics sensitize the heart to digoxin therapy)
kidneys.
spironolactone ↓ digoxin excretion
Corticosteroids cause hypokalemia → ↑ digoxin toxicity
digoxin
Amiodarone
Clarithromycin
↑ digoxin toxicity
cyclosporine
itraconazole
↓ effects of digoxin by ↑ K from salt substitutes → Lack of digoxin efficacy,
Salt Substitutes
exacerbation of CHF
Rifampin Modulation of drug transporter - Induction of P-glycoprotein
cholestyramine Chemical & Pharmacokinetic - ↓ absorption
Atropine ↓ motility → ↑ absorption slowly
Metoclopramide prokinetic drug → ↓ absorption disintegrated
Atropine ↓ motility → ↓absorption
prokinetic drug → ↑ absorption rapidly
↑ gastric emptying and ↑ the absorption rate of disintegrated
Metoclopramide
Paracetamol paracetamol --> therapeutic advantage in the treatment in stomach
of migraine to ensure rapid analgesic effect.
Opioids (diamorphine ↓ the absorption rate, without affecting the extent of absorption
and pethidine) (note: not occur with Codeine)
↑ cyclosporine exposure when given with metoclopramide because of
metoclopramide cyclosporine
enhanced gut motility by metoclopramide

Acetylcholine and noradrenaline have opposing effects on heart rate. Acetylcholine acts on muscarinic receptors
to decrease heart rate, while noradrenaline acts on adrenergic receptors to increase heart rate. When these
neurotransmitters are present together, their effects counteract each other, resulting in a modulation of heart rate.
Page 2 of 7
 SSRIs inhibit the activity of the cytochrome P450 enzyme system, particularly CYP2D6, which metabolizes metoprolol
Drug interaction – Sections & midterm – Menna Hazem ‫زتونة‬
Metoprolol inhibit the metabolism of metoprolol → ↓ blood pressure, bradycardia
NSAIDs ↑ risk of bleeding
Triptans (For migraine) SSRIs and NSAIDs both increase the risk of bleeding, but through different
Triptans are serotonin receptor agonists
(SSRIs) Phenelzine (MAOIs) mechanisms. SSRIs inhibit the reuptake of serotonin, which plays a role in
platelet aggregation and clot formation. NSAIDs inhibit the activity of
Fluoxetine and Tramadol (atypical opioid) cyclooxygenase (COX) enzymes, which are involved in the synthesis of
paroxetine, tricyclic antidepressants prostaglandins, substances that promote platelet aggregation.
serotonin syndrome
citalopram (amitriptyline)
opioids Omeprazole can inhibit the conversion of clopidogrel to its active form,
reducing its antiplatelet effect.
linezolid
Linezolid is an antibiotic that inhibits monoamine oxidaseThis interaction may lead to diminished efficacy of clopidogrel in preventing
5HT1-agonists thrombotic events.
Adrenaline procaine Dentist injection Synergism – adrenaline is vasodilator ↑ duration of procaine
Acetylcholine Noradrenaline Antagonism - have opposing effects on heart rate
H2 blocker
sulfonamide
↑ efficacy of sulfonylureas,hypoglycemia glucose monitoring.
clarithromycin
Phenelzine is a monoamine oxidase inhibitor (MAOI) that inhibits the activity
verapamil of monoamine oxidase enzymes, leading to increased levels of
sulfonylurea Rifampicin neurotransmitters such as serotonin, norepinephrine, and dopamine
phenytoin beta blockers, particularly nonselective ones, can interfere with the normal physiological response
to hypoglycemia by inhibiting the release of glucagon from pancreatic -cells.
carbamazepine ↓ efficacy of sulfonylureas,hyperglycemia glucose monitoring
Nonselective tricyclic antidepressants, like amitriptyline, inhibit the reuptake of serotonin and
norepinephrine, leading to increased levels of these neurotransmitters in the
β blockers synaptic cleft
Antagonism- Blood glucose-lowering effects of antidiabetics
corticosteroid antidiabetics
are opposed by corticosteroid-induced hyperglycemia
Steroid ↓ effect of antihypertensive due to Na+ retention
Interactions from actions at separate sites - the potassium-sparing
spironolactone effects of spironolactone tend to balance the potassium-wasting effects
of Hydrochlorothiazide
Aminoglycoside ototoxicity (when used with loop diuretics)
Diuretics
Digoxin ↑ digoxin toxicity due to hypokalemia
Aspirin ↑ blood uric acid level
NSAIDs ↓ antihypertensive effect of loop diuretics
Thiazide ↓ lithium elimination, ↑ lithium levels.
Lithium
(Competition at tubular site reabsorption. )
sulfonylurea ↓ efficacy of sulfonylureas,hyperglycemia glucose monitoring
Oral contraceptives Loss of contraceptive efficacy
↓ warfarin efficacy, Lower INR
Warfarin ‫ بقلل الجرعة‬3 ‫ بزود الجرعة ولو زادت عن‬2 ‫ لو قلت عن‬3-2 ‫الل بياخد وارفارين بتوصل ل‬
‫ ي‬1.09 ‫الطبيع‬
‫ي‬ ‫بيعرفن سيولة الدم‬
‫ي‬ ‫تحليل‬
With phenytoin: Un predictable effect, INR may ↑ or ↓
cortisol, dexamethasone,
Phenytoin & hydrocortisone, ↓ serum conc. of steroids
carbamazepine methylprednisolone,
prednisolone
Amiodarone,
Atorvastatin, Digoxin, ↓ serum conc. of interacting drugs
Metoprolol, nifedipine,
verapamil
Clarithromycin ↑ blood levels of Anti-epileptic drugs (AEDs)
Page 3 of 7
which reduces blood flow and slows the systemic absorption of procaine, thereby prolonging its local anesthetic effect.
 Drug interaction – Sections & midterm – Menna Hazem ‫زتونة‬
5 % dextrose Pharmaceutical drug-drug interactions
phenytoin
lorazepam Chemical DDI - ineffective if mixed in same IV bag or syringe.
TCA (Amitriptyline) ↑ serum conc. of interacting drugs
↑ risk of supratherapeutic concentrations because of displacement of
Valproic acid
metabolic inhibitor. warfarin warfarin from protein binding sites (and CYP2C9-mediated warfarin
metabolism inhibition)
digoxin ↑ digoxin toxicity
Atorvastatin Risk of rhabdomyolysis
Clarithromycin warfarin ↑ INR bleeding
inhibitor of the P-450
enzyme system Phenytoin,
↑ blood levels of Anti-epileptic drugs (AEDs)
carbamazepine
Methotrexate Methotrexate toxicity
Trimethoprim and
Amiodarone ↑ risk of arrhythmia Trimethoprim and sulfamethoxazole
co-trimoxazole
warfarin ↑ INR bleeding are selective inhibitors.
Sulfamethoxazole Trimethoprim treat bacterial infection
Clarithromycin ↑ INR bleeding Clarithromycin is an antibiotic that inhibits the activity of cytochrome P450 enzymes

Reduction in vitamin
Cholestyramine Pharmacokinetic interactions → Chelation - ↓ absorption
K levels can
potentiate the
antibiotics Kill microflora → vitamin K deficiency → ↑ effects of anticoagulants
Antibiotics can disrupt the normal flora of the intestine, leading to a decrease in vitamin K production by gut bacteria.
effects of warfarin,
leading to an Phenytoin Un predictable effect, INR may ↑ or ↓
induce the activity of cytochrome P450 enzymes, including CYP2C9, which metabolizes warfarin.
increased risk of
bleeding and carbamazepine ↓ warfarin efficacy, Lower INR
elevated INR. Induction of CYP2C9 by carbamazepine can enhance the metabolism of warfarin, leading to decreased plasma concentrations
↑ risk of supratherapeutic concentrations because of displacement of
valproic acid warfarin from protein binding sites (and CYP2C9-mediated warfarin
warfarin
metabolism inhibition)
Warfarin produces its Valproic acid can displace warfarin from its plasma protein binding sites, increasing the fraction of free (unbound)
therapeutic effect by Trimethoprim and warfarin in the bloodstream.

inhibiting the action of ↑ INR bleeding

vitamin K epoxide co-trimoxazole can inhibit the metabolism of warfarin by inhibiting the activity of vitamin K epoxide reductase, an enzyme involved in
the recycling of vitamin K.
reductase complex 1 Aspirin is heavily bound to plasma proteins and displace anticoagulants
(VKORC1) that is Aspirin
necessary to produce as warfarin → ↑levels and ↑bleeding.
aspirin can displace warfarin from its plasma protein binding sites, leading to increased plasma concentrations and an increased risk of bleeding.
the clotting factors II
(prothrombin), VII, IX, NSAIDs ↑ risk of bleeding (inhibit platelet aggregation)
and X.
Green Leafy Vegetables antagonism → ↓ effects of warfarin by ↑ Vit. K enriched contents → ↓ INR
heparin gentamicin Chemical DDI - Inactivation
When heparin and gentamicin are combined, heparin molecules may bind to the positively charged amino groups present in gentamicin molecules, forming
heparin-gentamicin complexes. additive drug interaction. Most tricyclic antidepressants, phenothiazines,
antihistaminic and older antihistaminic drugs are blockers of muscarinic receptors.
(diphenhydramine) Used concomitantly, any pair of these agents will demonstrate a
Tricyclic It also has anticholinergic
properties, similar to TCAs. predictable increase in atropine-like adverse effects
antidepressant
dicoumarol ↑ time available for its dissolution and absorption
(imipramine)
It works by inhibiting the TCAs inhibit reuptake of norepinephrine at adrenergic neurons, leading to
reuptake of Norepinephrine
neurotransmitters such hypertension
as serotonin and
norepinephrine in the
SSRIs fluoxetine and paroxetine Serotonin syndrome
brain Physical DPI - Diazepam destabilizes the propofol emulsion, causing it to
emulsion propofol Dicoumarol is an
benzodiazepines “oil out” →dangerous to administer IV anticoagulant medication that
prolongs the time required for
(Temazepam) atypical antipsychotics blood clotting by interfering
commonly used for the treatment of insomnia and anxiety enhanced sedative effect/drowsiness 22%
disorders (risperidone) used primarily for the treatment of schizophrenia and bipolar disorder.
with the synthesis of vitamin
K-dependent clotting factors.
Warfarin and vitamin K have an antagonistic relationship. Warfarin works by inhibiting the action of vitamin K, thereby reducing blood clotting.
However, if a person consumes large amounts of vitamin K-rich foods, such as green leafy vegetables, it can counteract the effects of warfarin.
The increased intake of vitamin K leads to enhanced synthesis of clotting factors in the liver, potentially overriding the anticoagulant effects of
warfarin. Page 4 of 7
 Propofol is an intravenous anesthetic agent commonly used for induction and maintenance of anesthesia during surgical procedures or sedation in critical
care settings. It acts by enhancing
Drug interaction the activity
– Sections of GABA receptors
& midterm – MennainHazem
the central nervous system, leading to potent sedative and hypnotic effects. ‫زتونة‬
Azathioprine is metabolized to mercaptopurine, which is
further metabolized by xanthine oxidase. Azathioprine is metabolised to mercaptopurine and then converted to an
Allopurinol inhibits xanthine oxidase, leading to the
accumulation of mercaptopurine. inactive metabolite by xanthine oxidase. Allopurinol is an inhibitor of
Azathioprine Allopurinol xanthine oxidase and will lead to the accumulation of mercaptopurine
which can cause bone marrow suppression and haematological
abnormalities such as neutropenia and thrombocytopenia
slow your reaction and make driving a car or operating machinery
anti histamine
Sedative drug dangerous
Clonidine Additive sedative Effects
Synergism - Excessive dryness of mouth, blurred vision and urinary
Antihistamines anticholinergic
retention
Tyramine Products: wine, ↑ effects of MAO inhibitors by inhibiting breakdown of tyramine →
MAOIs chocolate, cheese, hotdogs, ↑ hypertension
draft beer (bottle or canned ok) Tyramine-containing products, such as wine, cheese, and chocolate, can cause hypertensive
Ca, iron, vitamins, crisis when consumed with MAOIs due to the inhibition of tyramine breakdown.

alendronate antacids, coffee, tea, food can decrease the absorption of alendronate
soda, mineral water Calcium, iron, and other divalent cations can chelate with alendronate, reducing its absorption.
Quinolone Ca, Mg, iron Complexation Co-administration of quinolones with calcium, magnesium, or iron
supplements can decrease the absorption of both the quinolone and the
(-floxacin) Macrolides, citalopram QT Prolongation mineral supplement.

Clopidogrel omeprazole Reduction effect, but you can use pantoprazole

ceftriaxone Ringer solution Pharmaceutical interaction due to the risk of forming insoluble
precipitates, which can lead to
anti-infective drugs pain killer synergistic effect embolism if administered
Metformin Iodinated contrast media contrast induced nephropathy intravenously.

Synergism - ↑ hypotension nitrates or sodium nitroprusside

nitrates or sodium
(act by NO-dependent elevation of cGMP) with sildenafil (inhibits
Sildenafil nitroprusside
5-phosphodiesterase enzyme responsible for inactivation of cGMP)
ritonavir Enzyme inhibitor - ↑ risk of hypotension
Modulation of drug transporter - ketoconazole induced-inhibition of
ritonavir ketoconazole
P-glycoprotein → ↓ transport out of the CNS
Antacids or H2 change in PH - cause ↓ the tablet dissolution of ketoconazole
ketoconazole
antagonists (Antifungal absorbed in acidic medium)
ciprofloxacin ↓ absorption of ciprofloxacin by 85% due to chelation
tetracycline Pharmacokinetic interactions - Chelation
Antacid (Al or
iron Chemical DDI - Complexation
Mg(OH)2)
Azoles ↓ the bioavailability ( note: not occur with fluconazole )
aspirin ↑ urine pH and renal excretion (analgesic dose of aspirin)
Tetracycline Milk Reduction effect - Complexation
cholestyramine Pharmacokinetic interactions - ↓ absorption
Levothyroxine is a synthetic thyroid hormone used to treat hypothyroidism.
IV tubing and bags Physical DPI - sticking
levothyroxine
anti-epileptic drugs ↓ absorption
(valproate, lamotrigine)
↓ bioavailability by 50%, as a result of ↑ metabolism in the intestinal
Anticholinergic
mucosa.
levodopa its absorption can be hindered by anticholinergic drugs, which inhibit the activity of the neurotransmitter acetylcholine.
Carbidopa Potentiation effect
Carbidopa is often co-administered with levodopa in Parkinson's disease therapy to enhance its effectiveness.
Antipsychotic Antipsychotic work on dopaminergic receptors → antagonism
Antipsychotic drugs exert their effects by antagonizing dopamine receptors, primarily dopamine D2 receptors, in the central nervous .
Carbidopa does not directly affect dopamine levels but acts as a peripheral dopa decarboxylase inhibitor. It inhibits the conversion of levodopa to dopamine
outside the central nervous system, particularly in the gastrointestinal tract and peripheral tissues. Page 5 of 7
 Drug interaction – Sections & midterm – Menna Hazem ‫زتونة‬
Fentanyl Heating Physical DPI - ↑ release from transdermal patches
Fentanyl patches are transdermal delivery systems for continuous pain relief.
potassium Chemical DDI - form calcium phosphate, which will result in a precipitate
calcium chloride
phosphate (“snow”) in the (IV) fluid bag
Orlistat is a specific long-acting inhibitor of gastric and pancreatic
Orlistat fat-soluble drugs lipases, thereby preventing the hydrolysis of dietary fat to free fatty acids
Orlistat is a lipase inhibitor that prevents
the absorption of dietary fat by inhibiting and triglycerides, ↓absorption of fat-soluble drugs
gastric and pancreatic lipases. Pharmacokinetics interaction - share a common transport mechanism in
Probenecid
penicillin the proximal tubules and ↓ penicillin excretion by competition.
Clavulanic acid Potentiation effect
↓ the absorption rate, without affecting the extent of absorption
paracetamol
(note: not occur with Codeine)
Opioids Benzodiazepines Synergism - ↑ risk of drowsiness, respiratory depression
naloxone results in failure of narcotic-based analgesia) but could be
naloxone
indicated in management of opioid toxicity)
Probenecid inhibits the renal tubular secretion of penicillin by competing for the same transport mechanism in the proximal tubules of the kidneys.
As a result, probenecid can increase the serum levels and prolong the half-life of penicillin, enhancing its therapeutic effects and potentially increasing the risk
of adverse reactions.
P glycoprotein
substrates inducer inhibitor
• Morphine • Carbamazepine • Ketoconazole
• Carvedilol • Phenytoin • Diltiazem, felodipine,
• Digoxin • phenobarbital. nifedipine, verapamil
• Dabigatran (β3 agonist) • Rifampicin • Erythromycin, clarithromycin
• Ciclosporin, tacrolimus (immunosuppressant) not azithromycin
• Atorvastatin, lovastatin, simvastatin • Amiodarone, quinidine
• Vinca alkaloid

CYP Inhibition
substrates Inducers
3A4 2D6 2C9 1A2
• Warfarin • Amiodarone (CYP: 2C9, 3A4, 1A2) • Barbiturates
• Statin (3A4) • Cimetidine • Carbamazepine
(pravastatin not affected) • Omeprazole • Phenytoin
• Phenytoin (2C9) • Ciprofloxacin • Rifampin (3A4)
• Cyclosporine (3A4) • macrolide as (erythromycin • SSRIs SSRIs
• Caffeine and clarithromycin) (fluoxetine- (fluvoxamine)
• Clozapine • CCBs (verapamil, diltiazem) Paroxetine)
• Theophylline • Azole
• Methadone • Grapefruit
• Contraceptive
(failure with inducers)
• Corticosteroid This delay is primarily attributed to changes in gastrointestinal motility and absorption kinetics caused by
paracetamol.
(failure with inducers) Paracetamol has been shown to slow gastric emptying and gastrointestinal transit time. As a result, when opioids
• Codeine (↓ conversion to are co-administered with paracetamol, they may spend more time in the gastrointestinal tract before being
morphine by CYP2D6 ) absorbed into the bloodstream.
• Ritonavir
valproate is known to inhibit various drug transporters, including organic anion transporting polypeptides (OATPs)
• Methadone and P-glycoprotein (P-gp), which play roles in drug absorption and disposition.
• Amlodipine Valproate and lamotrigine can influence gastric pH, which in turn can impact the dissolution and absorption of
levothyroxine tablets.
• Alprazolam Alterations in gastric pH may affect the solubility of levothyroxine, as it is primarily absorbed in the acidic
• Cyclosporine environment of the stomach.
• diltiazem Slowed gastrointestinal transit time may lead to prolonged exposure of levothyroxine to the absorptive surfaces,
potentially enhancing absorption.
• warfarin Conversely, accelerated gastrointestinal transit time may reduce the contact time between levothyroxine tablets
• Digoxin ( ↓ excretion ) and absorptive surfaces, diminishing absorption.

Clavulanic acid inhibits bacterial -lactamase enzymes, which would otherwise degrade -lactam antibiotics, such as penicillins and cephalosporins.
Page 6 of 7
 Drug interaction – Sections & midterm – Menna Hazem ‫زتونة‬

Notes
• Alcohol + some drugs → cause you to feel tired or slow your reaction
• High blood pressure + nasal decongestant → HTN crisis
• antidiarrheal components as smecta, kapect (Kaolin) can adsorb drugs when given together and reduce their
effect.
• paracetamol rapidly disintegrated in stomach, digoxin slowly disintegrated drugs,
• drugs that highly bound to plasma protein as phenytoin (90%), tolbutamide (96%) and warfarin (99%) can be
displaced with aspirin or sulfonamide
• Sulfa (displace bilirubin) and neonates cause Kernicterus (brain retardation)
• Urinary Alkalizers: ↑ acidic drug elimination (ASA ) + ↓ elimination of weak base drug (cocaine)
• Typically inhibition of CYP3A4 by clarithromycin and erythromycin does not occur immediately, as these
agents are mechanism-based inhibitors.
• Tramadol is an atypical opioid analgesic with partial µ antagonism and central reuptake inhibition of
serotonin (5HT) and noradrenaline. At high doses it may also induce serotonin release.
• single-nucleotide polymorphism (SNP)
‫ده عبارة عن مشكلة بيغير نيوكليوتيدة من كل جين بالتالي الجين بيطلع فيه مشكلة ألنه مش هيتترجم صح‬
• Atorvastatin is a substrate for OATP1B1 hepatic uptake transporte . Therefore, the patient’s SNP in OATP1B1
may have contributed to the adverse event by decreasing the hepatic uptake of atorvastatin, thereby
increasing the circulating levels of atorvastatin.
• Glasgow Coma Scale ‫بعرف بيه هو في انهي مرحلة من االغماء‬
Clarithromycin ‫ والعكس مع الـ‬،‫ مش كويس‬rosuvastatin ‫ مع‬،‫كويس‬Warfarin + Atorvastatin •
Anti epileptics ‫أحسن مع الـ‬azithromycin ‫• الـ‬
• Serotonin syndrome: clinical triad of
1. mental status changes 5. muscle & neuromuscular 9. rhabdomyolysis
2. autonomic hyperactivity rigidity 10. hyperthermia in life-threatening cases.
3. neuromuscular 6. seizures 11. Disturbance of electrolytes,
abnormalities 7. diarrhea transaminases and creatine kinase.
4. Agitation 8. tremor in mild cases to 12. Clonus is the most important finding in
delirium establishing the diagnosis
• The 5HT2A-antagonist cyproheptadine (Antihistamine) and atypical antipsychotic agents with 5HT2A-
antagonist activity, such as olanzapine, have been used to treat serotonin syndrome, although their efficacy
has not been conclusively established.
• salicylates, are better absorbed at low pH because the non-ionized form predominates the excretion of
salicylate (acidic) is ↑ in an alkaline urine
• absorption of some drugs may be ↓ if they are given with adsorbents as charcoal or kaolin, or anionic
exchange resins as cholestyramine or colestipol.
• Albumin is the main plasma protein to which acidic drugs such as warfarin are bound
• basic drugs such as tricyclic anti-depressants, lidocaine, disopyramide and propranolol are bound to α1-
acid glycoprotein.
• Hyperkalemia produced by combination of potassium supplements with potassium sparing diuretics, ACE
inhibitors and angiotensin receptor blockers
Ketoconazole, an antifungal medication, requires an acidic environment for optimal absorption in the gastrointestinal tract.
Antacids or H2 antagonists, which decrease gastric acidity, can reduce the absorption of ketoconazole by raising the gastric pH.
Penicillin and Probenecid:
Probenecid inhibits the renal tubular secretion of penicillin by competing for the same transport mechanism in the proximal tubules of
the kidneys.
As a result, probenecid can increase the serum levels and prolong the half-life of penicillin, enhancing its therapeutic effects and
potentially increasing the risk of adverse reactions.

Mechanism of Action: Paracetamol works centrally and peripherally to inhibit prostaglandin synthesis, thereby exerting its analgesic
and antipyretic effects. Opioids, on the other hand, bind to opioid receptors in the central nervous system to produce analgesia. When
combined, they work through different mechanisms to provide synergistic pain relief. Page 7 of 7