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.