DRUG INTERACTIONS

If a second drug is given and the response

to the first drug is altered
Drug interactions may be desired and
undesired, beneficial or harmful
 Pharmacological basis of drug interactions
1. Pharmacodynamic interaction
- Both drug act on the target site of
clinical effect, exerting synergism or
antagonism
- The drug may act on the same or
different receptors or processes,
mediating similar biological
consequences
 Example: Alcohol + Benzodiazepine
(to produce sedation)
Morphine + naloxone (reverse
opioid overdose)
Rifampin + isoniazid (effective
antituberculosis combination)
2. Pharmacokinetic interaction
The drugs interact remotely from the
target site to altered (and other tissue)
concentrations so that the amount of the
drug. The target site of clinical effect is
altered (example enzyme induction by
rifampin will reduce the plasma
concentration of warfarin, enzyme
inhibition by ciprofloxacin will elevate the
concentration of theophylline
 Interaction my result antagonism or
synergism

Antagonism : occur when the action of one

drug opposen the action of another.
Physiological or functional antagonism,
histamin and adrenalin on the bronchi
Competitive antagonism, atropine and
acetylcholine
 Synergism is of two sorts :
Summation or addition occur when the
effects of two drugs having the same
action are additive (2+2=4)
Example beta blocker + thiazide diuretic
on antihypertensive
Potentiation
(to make more popowwerful) occurs when
one drug increses the action of another
(2+2=5)
Example sulphonamide + trimethoprim
 Interactions outside the body
Intravenous fluids special scope for
interactions when drug added
(incompatibilities), precipitation
Example : Protamine zinc insulin,
protamine binds with added soluble insulin
and reduced effect of the dose
 Interactions at site of absorption
- Direct chemical interactin
Example : Antacids contain aluminium and
magnesium form insuloble complexes with
tetracyclin
- Gut motility may alter by drugs
Example : Atropine may delay and reduce
absorption other drugs
- Alteration in gut flora
Example : Antimicrobial may potentiate oral
anticoagulant by reducing bacterial synthesis of
vitamin K
 Interaction during distribution
- Displacement from plasma protein
binding site
Example: Bilirubin is displaced from its
binding protein by sulphonamides, in the
neonate cause kern icterus
- Displacement from tissue binding
Example : quinidine + digoxin, the plasma
concentration of free digoxin may double
because quinidine displaces digoxin from
binding sites in tissue
Interactions directly on receptors or on body
system
- Action on receptors
Example : naloxone + morphine (opioid
receptor)
Atropine + anticholinesterase
(acetylcholine receptor)
- Action on body systems
Example : Digoxin + thiazide. More toxic in the
presence hypokalemia, caused by thiazide
Benzodiazepine + antihistamine or alcohol to
augment sedative effects
Theophylline + salbutamol potentiate beta
adrenergic effects may result cardiac arrhytmia
 Interaction during metabolism
Enzyme induction
drugs accelerates metabolism and cause
therapeutic failure
Example : Oral contraceptive + rifampin
(enzyme inducer) metabolised of
contraceptive more rapidly
Warfarin + enzyme induction, loss of
anticoagulant and danger of thrombosis
Enzyme inhibition
Potentiate other drugs that are inactivated
by metabolism
Example : Cimetidine potentiate effect of
theophylline
Erythromycin potentiate effect of warfarin
 Interactions during excretion
Both beneficial and harmful occur in the
kydney
- Interference with active diffusion
Reabsorption of a drug by renal tubule can
be reduced and its excretion increased by
altering urine pH
Example : Acidification urine by arginine
Hcl and ammonium chloride for poisoning
of amphetamine caused increased
excretion of amphetamine
 Interference with active trasport
-Example : Penicillin + probenecid
Penicillin are passed from the blood into
urine by active transport across the renal
tubular epithelium and mostly excreted in
this way. Probenecid that competes with
penicillin for this trasport system may
result prolong the action of penicillin
- Methotrexate + aspirin
 Important drug interactions
- Acetaminophen or paracetamol with
alcohol increased formation of hepatotoxic
acetaminophen metabolites
- Anticoagulants oral with alcohol
increased hypoprothrombinemic efect
- Anticoagulants oral with erythromycin :
increased effect of anticoagulants oral
(erythromycin is enzyme inhibitor)
- Metronidazole with alcohol disulfiram-like
reactions
-
- Antacid with iron : Decreased
gastrointestinal absorption of iron
- Antacid with digoxin decreased
gastrointestinal absorption of digoxin
- Antacid with tetracyclin : decreased
gastrointestinal absorption of tetracyclin
- Anticagulants oral with sulfonamide :
increased effect of anticoagulants oral
- Anticoagulants oral with barbiturate
decreased effect of anticoagulants oral
- Antidepressants with cimetidine :
Decreased antidepressants metabolism,
increased effect of antidepressants
- Antidepressants with rifampicin or
rifampin : increased antidepressants
metabolism
- Azole antifungals with phenytoin :
decreased metabolism of phenytoin with
fluconazole
- Azole antifungals with rifampicin :
increased metabolism ketoconazole
- Chloramphenicol with phenytoin :
Decreased phenytoin metabolism
- Nonsteroid antiinflammatory drugs with
antihypertension (ACE inhibitor) :
Decreased antihypertension response of
ACE inhibitor