DRUG INTERACTIONS

PROPANOLOL & INSULIN

• Propanolol is a Non-selective type beta-blocker.

• Insulin is a hormone secreted from Pancreatic beta cells which primarily

controls carbohydrate metabolism.

• Type of Interactions:- Pharmacodynamic.

• Mechanism of Interactions:-
Insulin can cause hypoglycemia characterized by
adrenergic hyperactivity symptoms like tachycardia, palpitation, tremor,
and sweating. Propanolol makes these symptoms making a diagnosis of
hypoglycemia difficult.
• Propanolol inhibits glycogenolysis resulting in delayed recovery from
hypoglycemia.

• Unopposed activity of Adrenaline on the Alpha receptor can increase

blood pressure.

• Result of interactions:- Masked insulin-induced hypoglycemic symptoms

and delayed recovery from hypoglycemia.

• Conclusion:- Concurrent administration should be avoided.

• Cardiovascular beta-blockers should be used if necessary.

 DIGOXIN & HYDROCHLORTHIAZIDE
• Digoxin is a Cardiac Glycoside mainly used in CCF with or without AF.

• Hydrochlorothiazide is a moderately potent potassium depleting diuretic.

• Type of interaction:- Pharmacodynamic.

• Mechanism of actions:- Digoxin inhibits myocardial Na+K+ ATPase. So exit of

Na from the cell and entry of K+ into the cell is inhibited. There is secondary
rise of intracellular Ca++.
• Hydrochlorthiazide causes, kaliuresis, hypercalcemia, The effect of
Digoxin is increased in presence of hypokalemia because there is
increased availability of Digoxin to the cardiac cell and increased
binding of Digoxin with Na+K+ ATP ase.

• Hypokalemia is also responsible for cardiac arrhythmia.

Hypercalcemia and hypomagnesemia can also increase Digoxin-
induced cardiac arrhythmia.

• Result:- Increased incidence of Digoxin-induced Cardiac arrhythmia.

• Remarks:- During co-therapy, potassium supplementation should be

done either in the form of diet, fruit juice, or in the form of
Potassium containing salt. ( KCl oral solution)
 ENALAPRIL & SPIRONOLACTONE
• Enalapril is an ACE Inhibitor.
• Spironolactone is a Potassium-sparing diuretic.
• Type of interaction:- Pharmacodynamic.
Mechanism of action:- Enalapril inhibits the formation of Angiotensin II.
Subsequently, aldosterone release from the adrenal cortex is reduced leading
to decreased secretion of K+ in the distal tubule & collecting duct.
Spironolactone being an aldosterone receptor
antagonist reduces the secretion of K+ in the Distal tubule and Collecting duct.

• Result:- Increased incidence of hyperkalemia & arrhythmia.

• Remarks:- Enalapril & Spironolactone should not be co-administered.

 LITHIUM & THIAZIDE
• Lithium is a mood stabilizer used in patients with Bipolar disorder.
• Thiazide is a moderately potent diuretics.
• Type of Interactions:- Pharmacokinetic.
• Mechanism of interaction:- Lithium is eliminated unchanged via the
kidney. After glomerular filtration, a fraction of lithium is
reabsorbed from PCT.
• Diuretics such as thiazides induce a
natriuresis that leads to a compensatory increase in the absorption
of Na + as well as Lithium from the PCT.
• There is about 25% decrease in Lithium
clearance with concomitant thiazide therapy.

• Result of interactions:- Increased toxicity of Lithium.

• Conclusion:- Concurrent administration should be avoided.

 LEVODOPA & PYRIDOXINE
• Levodopa is a precursor of Dopamine used as an anti-parkinsonian drug.
• Pyridoxine is Vitamin B6 & acts as a cofactor of the DOPA decarboxylase
enzyme.
• Type of interactions:- Pharmacokinetic.
• Mechanism of Interaction:- Dopamine can’t cross BBB, so its precursor
Levodopa is used as an antiparkinsonian drug. Levodopa is converted to
Dopamine by peripheral DOPA decarboxylase. Pyridoxine being a
cofactor of DOPA decarboxylase enhances the peripheral conversion and
ultimately reduces the availability of Dopamine in the basal ganglia.

• Result:- Antiparkinsonian effect of Levodopa is reduced when

administered along with pyridoxine.

• Remarks:- Levodopa & Pyridoxine should not be co-administered.

 ASPIRIN & WARFARIN
• Aspirin is a proto-type NSAID used as antipyretic, analgesic & anti-
platelet agent.

• Warfarin sodium is the most commonly used oral anti-coagulant.

• Type of interaction:- Pharmacokinetic and Pharmacodynamic.

• Mechanism of interaction:- Aspirin may displace Warfarin from

Protein binding site and thus increasing the free warfarin level in
plasma.

• Aspirin displaces platelet activation & aggregation by inhibiting

production of Thromboxane A2.
• It causes increased bleeding time whereas as an oral anticoagulant
Warfarin inhibits synthesis of Vitamin K dependent coagulation factors
( II,VII, IX,X) and increases prothrombin time.

• So concomitant use of both drugs increases bleeding tendency.

• Moreover, Aspirin is ulcerogenic in the stomach and duodenum.

• Result of Interaction:- Increased bleeding tendencies from various sites.

• Conclusion:- It is better to avoid Warfarin along with aspirin.

 CLOPIDOGREL & OMEPRAZOLE
• Clopidogrel is an oral Antiplatelet drug used to prevent clot formation in
blood vessels.
• Omeprazole is a proton pump inhibitor used to prevent GERD, peptic
ulcer disease, etc.
• Type of Interactions:-Pharmacokinetic
• Mechanism of Interaction:- Clopidogrel is a prodrug that is converted to
its active form by drug-metabolizing enzymes CYP3A, CYP2C19 etc. Its
active form irreversibly inhibits the P2Y12 subtype of the ADP receptor
which is present on platelet cell membranes. This results in inhibition of
platelet aggregation. Omeprazole is an inhibitor of CYP3A, CYP2C19. Thus
concurrent use of omeprazole with clopidogrel prevents the formation of
active form of clopidogrel.
• Result:- Decreased antiplatelet efficacy of Clopidogrel, increased
myocardial infarction after placement of Coronary Stents.
• Remarks:- Concurrent administration should be avoided. It is better to
use Pantoprazole or H1 blocker.
 ETHANOL & METRONIDAZOLE
• Ethanol is a commonly used beverage.
• Metronidazole is used as a chemotherapeutic agent in amoebiasis &
anaerobic bacterial infections.
• Type of Interaction:- Pharmacokinetic.
• Mechanism of Interaction:- Ethanol is metabolized largely by sequential
hepatic oxidation, first to acetaldehyde by alcohol dehydrogenase and then
to acetic acid by aldehyde dehydrogenase. Metronidazole inhibits Aldehyde
dehydrogenase which leads to the accumulation of Acetaldehyde.
• Result of Interaction:- Alcohol consumption during metronidazole therapy
can result in a typical reaction (Disulfiram-like reaction) characterized by
nausea, palpitation, hypotension, agitation, etc. The severity of the reaction
depends on the amount of alcohol consumed and may even cause death.
• Conclusion:- Alcohol consumption should be avoided with metronidazole
therapy.
 THEOPHYLLINE & CIPROFLOXACIN
• Theophylline is a methylxanthine used in Bronchial Asthma.
• Ciprofloxacin is a fluroquinolone antibacterial agent.
• Type of Interaction:- Pharmacokinetic
• Mechanism of Interactions:- Theophylline is metabolized largely (60-
80%) by 8 –hydroxylation into 1,3 dimethyl uric acid via hepatic
microsomal enzymes especially CYP1A2, CYP 2E1. Ciprofloxacin
inhibits this 8 –hydroxylation leading to increased theophylline
concentration in plasma.
• Result of interaction:- Theophylline is a drug with a narrow
therapeutic window. At 20-30 mcg/ml it can cause arrhythmia,
seizure, delirium. At higher concentrations, it is more fatal to
patients. As ciprofloxacin increases the level of theophylline, the
chances of ADR are more.
• Conclusuon:- Concurrent administration should be avoided.
 VERAPAMIL & PROPANOLOL
• Verapamil is a calcium channel blocker.
• Propanolol is a non-selective blocker.
• Type of Interaction:- Pharmacodynamic.
• Mechanism of interaction:- Both propranolol and verapamil reduce
myocardial contractility, heart rate, and impulse conduction. In
addition, verapamil inhibits the hepatic metabolism of propranolol
to some extent. Propanolol blocks beta 2 adrenergic receptors of
the smooth muscle of the tracheobronchial tree and increases
airway resistance. Verapamil by preventing calcium entry can cause
bronchoconstriction.
• Result:- Possibility of precipitation of heart failure, AV block, severe
bradycardia, and compensation of bronchoconstrictor effect of
propranolol by verapamil.
• Remarks:- Co-therapy should be done cautiously particularly in
paroxysmal supraventricular tachycardia.
 CHLORPROPAMIDE & DICOUMAROL
• Chlorpropamide is an oral hypoglycemic agent.
• Dicoumarol is an oral anticoagulant acting only in vivo.
• Type of interaction:- Pharmacokinetic.

• Mechanism of Interaction:- Dicoumarol prolongs the half-life of

chlorpropamide by inhibiting its hepatic metabolism and/or
reducing renal clearance of chlorpropamide.

• Result of interaction:- Hypoglycemic effect of chlorpropamide is

increased.

• Remarks:- During co-therapy of these two drugs the dose of

chlorpropamide has to be adjusted.
 RIFAMPICIN & OCP
• Rifampicin is a semisynthetic, bactericidal agent effective against
mycobacterial infection.
• Combined female OCP is an example of a fixed-dose combination of
mainly ethinyloestradiol ( a semisynthetic estrogen) and
norethindrone acetate (synthetic progesterone).
• Type of Interaction:- Pharmacokinetic
• Mechanism of interaction:- Rifampicin is a hepatic microsomal enzyme
inducer. So the metabolism of both estrogen and progestational
components is increased and the effectiveness of OCP is reduced.
• Result:- Failure of contraception, menstrual irregularities in the form of
breakthrough bleeding, spotting, etc.
• Remarks:- This type of interaction may happen when the OCP contains
less amount of estrogen and progesterone. The patient should be
asked to take OCP at high hormone content or they can adopt other
types of contraceptive methods.