dr. shabana ali (associate professor) factors modifying drug actons
TRANSCRIPT
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DR. SHABANA ALI
(Associate Professor)
FACTORS MODIFYING DRUG ACTONS
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FACTORS MODIFYING DRUG ACTIONS
Individuals vary in drug effect from time to time & from other individuals
Nature of systemic effects of drugs depends on following factors:Physiological factors (age, sex, pregnancy, lactation, body wt., food)Pathological state (kidney or liver disease)Environmental factors
cont.
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Psychological /emotional state
Interaction with other drugs (drug-drug interactions)
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I. Physiological factors
i) Age Extreme of age show extreme drug
sensitivity Newborn babies & elderly= greater &
more prolonged effect of drugs b/c of less efficient drug metabolism & renal functions
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InfantsPremature infants= poor renal & hepatic
functions more sensitive to various drugs
E.g., Chloramphenicol = Gray baby syndrome
(inadequate metabolism) Ampicillin & morphine = GIT
absorption (less acidity) Tetrycycline = staining of teeth Corticosteroids = retardation of growth in
children
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ElderlyRenal & hepatic function decline
slowly after middle ageActivity of hepatic microsomal
enzymes decline with ageVd of lipid soluble drugs increasesElderly require less due to
degenerative changes in kidney, liver, brain, heart
Cont.,
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E.g., Diazepam & benzodiazepines = t1/2 Digoxin = Vd
Benzodiazepines= more confusion & less sedation in elderly
Hypotensive dugs= postural hypotension in elderly
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ii) Sex/GenderResponse & dose= d/f in men &
womenMetabolism of some drugs= less in
women (more adipose tissues)E.g., alcohol, diazepam Women require lesser dose than
male
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iii) PregnancyAvoid drugs during pregnancy due to
teratogenic effectsReasonsLipophilic drugs cross placental barrier CO GFR & renal elimination VdMetabolism of some drugs
E.g., pregnant uterus becomes more sensitive to oxytocin
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iv) LactationAvoid drugs during lactation due to harm to
babyDrugs easily appear in milk but <
therapeutic dose
E.g., tetracycline, sedatives, hypnotics, opoids
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V) Body wt./surface area & sizeConc. Of drug at site of action=ratio b/w
body wt. & amount of drug
D/f quantity of drug for light & heavier persons
D/f quantity of drug for smaller & larger persons
Low amount of drug for smaller perosns
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vi) foodSome drugs have interaction with food and
they alter the response of drug
E.g., toxic symptoms appear after eating of cheese, red wine & chicken liver if patient is taking MAOI (more release of NA=fatal cerebral hemorrhage)
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Pathological condition modify drug action
E.g., impaired renal function = drug excretion = drug accumulation
Liver disease= metabolism of drug=accumulation
Cont.
II. Pathological state
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Disease can cause pharmacokinetic or pharmacodynamic variation
a) PK variation Variation in absorption
Gastric statis –in migraineMalbsorption ---ileal or pancreatic disease
Cont.
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Variation in distributionAlterd PPB of phenytoin in chronic renal
failure (binding of phenytoin to PPB
Variation in metabolismHepatic cirrhosis & portal HTN
Variation in excretionAcute and /or chronic renal failure
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Pharmacodynamic alterationsVariation in receptorsIn mysthania gravis, nephrogenic
diabetes inspidus, familial hypercholesterolemia
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III. Genetic factors It affects drug action due to genetic differences
among the races & certain persons in same population
Genetic variation is an important source of PK variability
Examples:
a) Genetic polymorphism= fast/slow acetylators (hydralazine, procainamide, isoniazid)
Cont.
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Plasma choline estrase variant (suxamethonium)
Hydrooxylase polymorphism (extensive or poor metabolism of debrisoquine)
Ethnic differences in drug metabolism = propranolol, hemolytic anemia due to some oxidizing agents (primaquine, sulphonamides)
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IV. Environmental factorsMicrosomal enzyme inducers
e.g., Hydrocarbons in tobacco smoke, charcoal broiled meat induce CYP1A
Smokers metabolize drugs more rapidly than non smokers
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V) Psychological stateGeneral anesthetics required in
dose for nervous & anxious patients
Higher doses of chlorpromazine needed in schizophrenics
Placebos (inert dosage form) produce therapeutic benefits in psychomotor angina pectoris & bronchitis in asthma
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VI) Interaction with other drugs
Administration of one drug (A) can alter action of another drug (B) by
PK or PD mechanismsThis is c/d drug-drug interactionMay be desired or beneficial like
multidrug treatment of tuberculosisOr undesirable or harmful