Drug interactions for MBBS students.

1. Tetracycline and Aluminium hydroxide/Magnesium hydroxide.

It is an example of pharmacokinetic type of drug interaction at the level of absorption in
the stomach.

Tetracycline is a bacteriostatic broad spectrum antibiotic

Aluminium hydroxide gel (Trivalent) or Magnesium hydroxide (Divalent) is non-systemic
antacid Results of interaction: Absorption of tetracycline from the stomach will be reduced.
So, antibacterial effect will be reduced.

Mechanism of interaction:
Aluminium or magnesium is heavy metal. Tetracycline forms a chelate complex with these
compounds. The product is insoluble and non-absorbable,
Remarks: Condition may arise when these antacids and tetracycline are to be administered
simultaneously. In that case, tetracycline should be administered 1-2 hrs before or after the
administration of antacid. (The absorption of tetracycline is reduced when it is administered
with milk and egg. This is an example of drug-food interaction.)

2. Aspirin and Warfarin sodium

It is an example of both pharmacodynamic and pharmacokinetic drug interaction. Aspirin is a

prototype example of non-steroidal anti-inflammatory drug.
Warfarin sodium is an in vivo acting mostly used oral anticoagulant.
Result of interaction: Increased bleeding tendencies from various sites.

Mechanism of interaction.
a) Pharmacodynamic. Warfarin sodium increases prothombin time (PT) by inhibiting the
synthesis of vit K dependent coagulant factors. Aspirin increases bleeding time and interferes
in the normal haemostasis by inhibiting the platelet aggregation. So, there is increased
bleeding tendenciesMoreover, aspirin is ulcerogenic stomach and duodenum.
b) Pharmacokinetic. Aspirin may displace warfarin from plasma protein binding sites resulting
inincreased level of free warfarin in plasma.
Clinical significance is conflicting. This type of interaction may occur in patient of post
myocardial infarction when warfarin and aspirin are given together after initial heparin
therapy.
Remarks: It is better to avoid warfarin along with aspirin. If at all antiplatelet drugs are to be
given along with warfarin, dipyridamole, ticlopidine may be preferred.
3. Metronidazole and Alcohol

It is a pharmacokinetic type of drug interaction at the level of metabolism Metronidazole is a

potentchemotherapeutic agent used for multiple infections
Alcohol is a common beverage.
Result of interaction: Precipitation of antabuse/disulfiram like reactions characterised
vomiting, abdominal cramps, hypotension and uneasiness.

Mechanism : Alcohol is metabolised by two steps. In the first step, alcohol is converted into
acetaldehyde by alcohol dehydrogenase. In the second step, acetaldehyde is converted to
acetic acid by the enzyme aldehyde dehydrogenase. Acetic acid is eliminated from the body
in the form of CO, and water Metronidazole inhibits the enzyme aldehyde dehydrogenase
resulting in accumulation of acetaldehyde responsible for antabuse like manifestation
Remarks: During metronidazole therapy alcohol should be avoided. (Other drugs causing this
type of reaction with alcohol are cephalosporins, oral hypoglycemic agents, chloramphenicol,
griseofulvin)

4.Chloroquine and Alkali mixture

It is a pharmacokinetic type of drug interaction at the level of renal excretion.
Chlorquine is an antimalarial drug Alkali mixture is a commonly used mixture in fever to
counteract pyrexia induced actions.

Result of interaction : Increased side effect of chloroquine such as hypotension,

vasodilatation,
suppressed myocardial function, ECG changes, cardiac arrest, visual disturbances, headache
lichenoidskin eruptions, bleaching of hair etc.

Mechanism of interaction : Chloroquine is a basic drug. It is excreted as unchanged (50%) and

as its metabolite mono-desethylchloroquine (20%) in urine Alkali mixture makes the urine
alkaline Se, there is less ionisation of chlomquine in the alkaline urine and hence extensive
tubular reabsorption of chloroquine leads to side effect.

Remarks: Avoid This Combination.

5.Amoxycillin and Clavulanic acid.
It is an example of pharmacodynamic type of drug interaction. Cotherapy or fixed dose
combination of these two drugs benefits the patient.
Amoxycillin is an extended spectrum beta lactam aminopenicillin.
Clavulanic acid is a beta lactamase inhibitor obtained from Streptomyces claviligerus
Result of interaction: Amoxycillin becomes effective against penicillinase/betalactamase
producing strains of Shphylococci, H. influenza, Gonococci and E. coli.
Mechanism: The antibacterial action of amoxycillin is due to the presence of beta lactam ring
in theirstructure. Penicillinase breaks the beta lactam ring with the reduction of antibacterial
action of amoxycillin.. Clavulanic acid has a beta lactam ring that binds to beta lactamase and
inactivates them (Suicide inhibitor) Thus clavulanic acid prevents the destruction of beta
lactam antibiotics and potentiates the action ofamoxycillin.
(Fixed dose combination: Amoxycillin 250 mg + Clavulanic acid 125 mg; Ticarcillin 3g+
Clavulanic acid 100 mg: Ampicillin 250 mg + Sulbactam 125 mg).
6. Ampicillin and Tetracycline.
It is a pharmacodynamic type of drug interaction. Ampicillin is a broad spectrum bactericidal
aminopenicillin. Tetracycline is a broad spectrum bacteriostatic antibiotic.

Result of interaction: The antibacterial effect of ampicillin is reduced.

Mechanism: Ampicillin is effective against only on rapidly multiplying micro-organisms. It
inhibits cell wall synthesis. Once the cells wall is formed, it is no more effective.
Tetracycline arrests the growth of micro-organisms by acting on the 305 ribosome. So, the
number ofrapidly multiplying organisms is diminished. So, ampicillin becomes ineffective.
7. Levodopa and Pyridoxine.
This is an example of pharmacodynamic drug interaction at the level of decarboxylation of
levodopa.Levodopa is used for the treatment of idiopathic parkinsonism.
Pyridoxine is a vit B, and acts as cofactor of DOPA decarboxylase enzyme Result of interaction:
The availability of dopamine in the CNS is reduced. The anti-parkinsonianeffect of levodopa
is reduced.
Mechanism of interaction :
Peripheral conversion of levodopa to dopamine by DOPA decarboxylase is enhanced by
pyridoxine. Dopamine (a catecholamine) cannot cross BBB. Less amount of levodopa is
available to enter the CNS and so, the amount of dopamine in the basal ganglia to produce
beneficial effect in parkinsonism is reduced.
Remarks: Levodopa and pyridoxine should not be co-administered.

8. Chlorpropamide and Dicoumarol.

This is an example of pharmacokinetic drug interaction at the level of metabolism (hepatic
microsomal).

Chlorpropamide is an oral hypoglycemic agent.

Dicoumarol is an oral anticoagulant acting only in vivo.
Result of interaction :
Hypoglycaemic effect of chlorpropamide is increased.
Mechanism : Dicoumarol prolongs the half-life of chlorpropamide by inhibiting its
hepaticmetabolism and /or reduced renal clearance of chlorpropamide.
Remarks: During co-therapy, the dose of chlorpropamide has to be adjusted.
9. Propranolol and Insulin
It is an example of pharmacodynamic type of drug interaction.

Propranolol is a non-selective beta blocker.

Insulin is the hypoglycaemic hormone released from the pancreatic beta cells
Results of interaction: (a) Symptoms of insulin-induced hypoglycaemia might be masked, (b)
Potentiation of insulin induced hypoglycaemia. (c) Delayed recovery from hypoglycaemia and
(d) Possibility of increased B.P. and precipitation of angina pectoris.
Mechanism:
(a) Insulin can cause hypoglycaemia in diabetic patient particularly when there is
unaccustomed exercise after insulin administration. Hypoglycaemia causes adrenergic
hyperactivity. So, there will be tachycardia, palpitation, tremor and sweating. Propranolol
blocks these effects by blockingthe adrenergic receptors. Diagnosis of hypoglycaemia may be
difficult. (b) Propranolol itself causes hypoglycaemia. (c) Insulin induced hypoglycaemia is
compensated by hepatic glycogenolysis. Propranolol prevents this. So, recovery from
hypoglycaemia is delayed. (d) Unopposed activity of adrenaline on alphaadrenergic receptors
can increase the peripheral resistance and rise of B.P.
Remarks : Administration of propranolol in diabetic patients with insulin therapy is a relative
contraindication of propranolol. This type of drug interaction is less with cardio-selective beta
blocker.

10. Enalapril and Spironolactone.

This is an example of pharmacodynamic drug interaction
Enalapril is an ACE-inhibitor
Spironolactone is a potassium-sparing diuretic. Result of interaction: Increased incidence of
hyperkalemia and arrhythmias
Mechanism of interaction:
Enalapril, being an ACE inhibitor, inhibits the formation of angiotensin II. Subsequently,
aldosterone release from adrenal cortex is reduced leading to decreased secretion of
potassium in distal tubules and collecting ducts. Spironolactone, being an aldosterone
receptor antagonist, reduces the secretion of potassium in late distal tubules and collecting
ducts. So, when enalapril is combined with spironolactone, there may be dangerous
hyperkalemia and cardiac arrhythmias.
Remarks: Enalapril should not be combined with spironolactone during the treatment of
hypertensionor Heart failure.
 11. Gentamicin and Gallmine.
This is an example of pharmacodynamic drug interaction.
Gentamicin is an Aminoglycoside antibiotic.

Gallamine is a non-depolarizing neuromuscular blocking agents.

Result of interaction: Muscle relaxant effect of Gallamine. increased.
Mechanism : Gallamine and ACh (released from motor nerve terminal) compete for N
receptor of motor end plate and relaxant effect of Gallamine is reduced. Gentamicin inhibits
ACh release from motor end plate and increases the relaxant effect of Gallamine.
Remarks: (1) Avoid the use of Aminoglycoside antibiotic.(2) Reduction of dose of non-
depolarizing neuromuscular blocking agents.(3) Gallamine is no longer a popular NMBA. This
type of drug interaction of Gentamicin can happen with other non depolarizing NMBA

12. Antacid and Sucralfate.

It is an example of pharmacodynamic drug interaction.
Antacids are the drugs which neutralise the gastric HCI and raise the pH of the gastric
contents. Sucralfate is an ulcer protective agent which strongly adheres to ulcer base and
protects it from pepticdigestion.
Result of interaction: The cytoprotective effect of Sucralfate is reduced.
Mechanism: The Sucralfate complex is formed by sucrose octasulfate & polyaluminium
hydroxide. In acidic pH (below 4), there occurs extensive polymerisation and cross-linking of
Sucralfate to form a sticky. Viscid, yellow-white gel, which adheres strongly to the base of
ulcer crater & protects it from peptic digestion. It adheres to the ulcer base for more than 6
hrs & helps in healing of ulcer.Antacids by neutralising gastric HCI, raise the pH of gastric
contents and prevent polymerisation of Sucralfate and gel formation. So, the ulcer healing
effect of Sucralfate is reduced.
Remarks: Antacids & Sucralfate should not be administered simultaneously. Sucralfate should
be administered at least half an hr after antacid administration or it is better to avoid this
combination.