Factors modifying drug action Dr Deepasree

Factors modifying drug action Dr Deepasree Ma’am

1. Factors modifying drug action Dr Deepasree Sukumaran Assistant Professor, Pharmacology AIIMS Kalyani

2. Variation in response to the same dose of a drug between different patients or same patients on different occasions can happen. REASONS Differences in PK :- different plasma /target site concentration of the drug Variations in the number or state of receptors , coupling proteins or other components for response production. Variations in the neurogenic/hormonal tone (atropine tachycardia depends on vagal tone, propranolol bradycardia depends on sympathetic tone) or concentrations of specific constituents (captopril hypotension depends on Na+ status. Genetic Non genetic factors

3. Non genetic factors Body size Age Sex Species and race Route of administration Environmental factors and time of administration Psychological factors Pathological states Other drugs – PK and PD interaction Cumulation Tolerance

4. 1. Body size Influences the concentration of drug at the site of action. Average adult dose – refers to individuals of medium built. For very obese and or lean individuals and children  dose may be calculated on BODY WEIGHT (BW) basis. Individual dose = BW (kg) × average adult dose 70 Body surface area (BSA) provides a more accurate basis for dose calculation.( TBW, ECF volume and metabolic activity better correlate with BSA) Individual dose = BSA (m2) × average adult dose 1.7

5. Dose recommendation based on BSA is available only for anticancer and very few drugs.

6. 3. Sex Females – smaller body size  doses required  lower side of the range Eg : Digoxin therapy  higher mortality in women. Antihypertensives (clonidine, beta blockers etc )  sexual dysfunction only in men.

7. 4. Species and Race Rabbits are resistant to Atropine Rats and mice are resistant to Digitalis These are important while extrapolating animal study results to humans. Blacks and Mongols require lower concentration of atropine and ephedrine to dilate their pupil. Beta blockers are less effective as antihypertensive in Afro - Caribbeans .

8. 5. Genetics Pharmacogenetics  study of the genetic basis for variation in drug response Pharmacogenomics  study of larger numbers of genetic variants in an individual or across a population , to explain the genetic component of variable drug responses. Eg . Atypical pseudocholinesterase results in prolonged succinyl choline apnoea . G6PD deficiency – causes hemolysis with Primaquine and other oxidizing drugs

9. 6. Route of administration It decides the speed and intensity of drug response . Parenteral drug administration  more rapid, more pronounced and more predictable drug action Eg : Magnesium sulphate oral  purgation applied on sprained joints  reduced swelling given IV  CNS depression and hypotension

10. 7. Environmental factors and time of administration Exposure to insecticides, carcinogens, tobacco smoke and consumption of charcoal broiled meat  induce drug metabolism . Type of diet and temporal relation of meals and drug intake can alter drug absorption. Eg : Food interferes with absorption of ampicillin. Fatty meal enhances absorption of albendazole . Statins cause greater inhibition of cholesterol synthesis when taken at bed time Corticosteroids taken as a single morning dose cause less pituitary – adrenal suppression.

11. 8. Psychological factors Eg : Nervous and anxious patients require more dose of general anaesthestics . Placebo (Latin: I shall please) – pharmacologically inert substance. Used in clinical trials (dummy medication) to differentiate between actual effect and placebo effects (placebo responders)

12. 11. Cumulation Slowly eliminated drugs (Chloroquine) accumulates causing retinal damage