FACTORS MODIFYING DRUG ACTION
GROUP 5
BPHARM/2019/55449 MAKOKHA M SAMMY
BPHARM/2019/56037 ESTHER N NJOKI
BPHARM/36775/2015 AARON CHERUIYOT
BPHARM/2019/49208 SALIMA K CHEBII
Introduction
Individuals drug response varies from:
Person to person,
Race and also
Pharmacokinetic drug handling.
Some show less than usual response,
Most show unusual and
Some more than usual response.
Physiological factors
Age : infants underdeveloped liver, kidney,
G.F.R,
Aminoglycosides toxicity enhanced,
Enzyme glucuronyltransferase causes
chlorampenical gray baby syndrome,
sulphonamides kernicterus: gastric acid
secretion increases absorption of amoxicillin
(accumulates)
Tetracycline's stain teeth, corticosteroids retard
growth.
Immature BBB, decreased plasma protein
binding
Elderly:
Hepatic microsomal enzymes activity reduction
Causing Benzodiazepines t½ prolongation cumulating with
repeated administration.
G.F.R drugs accumulates, GI motility reduces GI blood flow
slowing absorption, compliance challenge (memory fails).
Sex
Females susceptible to autonomic drugs (estrogen inhibit
Choline esterase).
Ketoconazole causes gynaecomastia in Males,anti-HTN
interfere with male sexual function.
Body weight: the more the weight and larger surface area,
the more dose requirements.
Pathological factors
GI diseases alter oral drug absorption
Drug absorption incomplete in pancreatic insufficiency
Nephrotic syndrome reduces albumin altering disposition and
protein binding.
Chronic renal failure alters plasma protein binding of
phenytoin.
Liver disease decreases metabolism increasing toxicity
Pathological factors (Cont’d)
• Liver disease impedes prodrug activation of
Omeprazole to active omeprazole
sulphanilamide albumin drug free form.
• Acute and chronic renal failure alters drugs
concentration.
• Hypothermia drug clearance in elderly.
• Hyperthyroidism sensitivity to adrenergics.
Pregnancy
Reduces volume of distribution and metabolic rates thus dose adjustments.
Maternal albumin excretion causing drug accumulation. Cardiac output, renal blood flow,
G.F.R excreting more drugs thus requiring dose adjustments.
Lipophilic drug distribution transversing placenta and slowly eliminated.
Genetic factors
Fast and slow acetylators to isoniazid,
Liver toxicity in fast acetylators.
G6PD def. Causes haemolysis with primaquine of
RBCs.
Pseudocholine esterase def. causes failure to rapidly
inactive suxamethonium causing muscle paralysis.
Environmental and diet actors
Hydrocarbons in tobacco induce CYP450
enzmes (CYP1A).
Polychlorinated biphenyls induce CYPIA,
Grapefruit juice induce CYP3A.
Alcohol arrests metronidazole at disulfiram.
Alcoholics require large
anaesthesia/anticonvulsant doses.
Tetracyclines form chelates when
administered with iron.
Route of drug administration
Drugs administered orally exposed to first effect thus require
upward dose adjustment.
MgSo4 administered IV as anticonvulsant, topically anti
inflammatory, orally as purgative.
Intravenous bypases first pass effect thus require dose
reduction.
Drug-drug interaction
Phenobarbitone induces liver metabolism of COCs abolishing
efficacy.
Interactions may potentiate:
Synergistic activity:
morphine+naloxone,
rifampicin+INH,
Alcohol+benzodiazepines,or
Antagonistic countering activity:
atropine on acetylcholine receptors, (Antacids+tetracyclines Cimetidine inhibits
microsomal enzymes)
Psychological factors
Beliefs and attitudes affect
drug effect particularly
CNS drugs,
Placebo working by
psychodynamic sometimes
produces response
equivalent to API for a
person who believes that
he must be given an
injection to get well.
Tolerance
Natural: inherent and less sensitivity to atropine and beta blockers
Acquired with repeated use of alcohol or CNS depresants.
Cross tolerance to pharmacological related drugs including
Barbiturates+GA, morphine and pethidine.
Tachyphlaxis
Rapid development of tolerance when a drug is repeated in
quick succession usually indirectly acting drugs Like ephedrine.
Cumulation through repeated administration in short Intervals
causing toxicity as clearance is less.
