Factors Affecting Drug Action

FACTORS AFFECTING
DRUG ACTION
Dr.Bagiyalakshmi V
1st year-PG
Factors
1. Body Size
2. Age
3. Sex
4. Species and Race
5. Genetics
6. Route of Drug Administration
7. Diet & Environmental factors
8. Psychological Factor
9. Pathological States
10. Drug Interactions
11. Cumulation
12. Tolerance
Individual variations
1. Alteration in Concentration of Drug that reaches the
receptor
2. Variation in Concentration of Endogenous receptor
Ligand
3. Alteration in Number or Function of receptors
4. Changes in components of response distal to the
receptor
Factors Modify drug action are either
• Quantitative- The plasma concentration / action of drug is increased or
decreased
• Qualitative- Type of response is altered eg. Drug allergy or idiosyncrasy

Body Size
• Average adult dose –medium built
• For obese/lean adults and children dose calculated based on Body wt
and Body surface area
Individual dose based on BW= Body wt(Kg)x Avg Adult dose

70
Individual dose based on BSA= BSA(m2 )x Avg Adult dose
1.7
BSA is calculated using Dubois Formula
= BW (Kg) 0.425 x Ht (cm) 0.725 x 0.007184
Age
Infants Elderly
• Low GFR, Immature Tubular • Renal Function
transport • Hepatic microsomal drug
• Inadequate drug metabolizing metabolizing activity
system
• metabolism and excretion
• BBB- highly permeable
(Cumulative toxicity)
• Low gastric acidity and slow
Intestinal transit • Gut motility
• Rectal and Transdermal absorption is • Albumin- Low Plasma Protein
fast binding
Sex, Species & Race
Sex Species & Race
• Small body size in females- • Certain animal Species are sensitive or
Requires less dose compared to resistant to certain drugs.
males • Important while extrapolating results
• Special Consideration to be given from experimental animals to humans
during Pregnancy and Lactation • Humans- Blacks require higher and

Mongols require lower concentrations of
atropine and ephedrine to dilate their
pupil
Genetics
• All determinants of drug response i.e., transporters, receptors, ion channels and metabolizing
enzymes are controlled genetically.
• Genetic variability in drug response could be due to single gene mutation or polygenic
• Gene polymorphisms are due to substitution of a single base pair by another
• When found in a population at a frequency >1% , these are called Single nucleotide polymorphisms
Pharmacogenetics Pharmacogenomics
• The study of Genetic basis for Use of genetic information to
variability in drug response guide the choice of drug and dose
• Deals with genetic influences on on an individual basis
drug action as well as on drug
handling by the body.
• Eg. Atypical Pseudocholinesterase- Prolonged succinylcholine apneoa

• G-6PD deficiency – hemolysis with primaquine , Dapsone , Sulfonamides
Route of Drug Administration Diet & Environmental factors
• Governs the speed and • Type of Diet

intensity of Drug response • Drug Ingestion and meals
• Different uses through alters absorption
different route • Exposure to insecticide,
Eg MgSO4 Tobacco and Consumption
of charcoal broiled foods
induces drug metabolism
Psychological Factors
• Applicable to centrally acting drugs
• Placebo- An inert substance which is given in the garb of a medicine and works by
psycho dynamic means
• Uses- 1. Control device in clinical trial of drugs
2. To treat a patient who does not require active drug
• Substances used as Placebo – Lactose tablets, Multivitamin Tab
• Nocebo- Converse of placebo, refers to negative psychodynamic effect by the

attitude of the patient or by loss of faith in medication or the physician.
Pathological States
Congestive Heart Failure

Gastrointestinal Diseases
Decreased
.
Alters the Achlorhydria GIT mucosal Alteration in Vd – elimination due

absorption of absorption of edema and Increased in Expansion
to reduced GFR.
orally of ECF volume and
acidic drugs by sphlanchnic reduced due to Eg
administered ionizing it vasoconstriction Procainamide,
drugs decreased tissue
perfusion Lidocaine
Liver Diseases
Increased Prodrugs Action of certain

bioavailability of Metabolism and requiring Serum Albumin- drugs are altered Eg.
drugs with high 1st excretion of hepatic Binding of acidic Oral anticoagulants
pass metabolism due some drugs is metabolism for drugs and free prolong PT time as
to low hepato reduced activation to be form clotting factors are
cellular function avoided low
Pathological States
Kidney diseases
Decrease in Creatinine
Maintenance dose Permeability of
Clearance and decrease
should be reduced BBB is increased Certain drugs worsen
in clearance of drugs
or dosing interval in Renal failure renal failure Eg.
that are excreted
should be prolonged ( Opiates, Aminoglycosides,
unchanged
Benzodiazepines, Tetracyclines
( Aminoglycosides,
Barbiturates)
Phenobarbitone)
Drug Interactions
• Drugs can modify response to each other by pharmacokinetic or pharmacodynamic
interaction ( Drug-Drug Interaction/ drug food interaction/ drug disease interaction)
• Between concurrently ingested drugs

Absorption • Eg Tetracyclines and calcium/Iron salts
• Displacement of one drug from its binding site on plasma
Distribution proteins by another drug
• Eg Oral anticoagulants, sulfonylureas , antiepileptics
• Certain drugs reduce or enhance the rate of metabolism of
others
Metabolism • Eg. Macrolides, azole antifungals, chloramphenicol
• Ciprofloxacin and Metronidazole are inhibitors of metabolism
of many drugs
• Drugs selectively secreted by tubular transport
Excretion • Eg. Probenecid inhibits tubular secretion of Penicillins and
Cephalosporins and prolongs their plasma t 1/2. `
Cumulation
• Any drug will cumulate in the body if rate of administration is
more than the rate of elimination
• Slowly eliminated drugs are liable to cause cumulative toxicity
• Eg. Prolonged use of chloroquine causes retinal damage.

Tolerance
• Requirement of higher dose of drug to produce a given response
• Natural/ Acquired / Cross Tolerance
Natural- The individual is inherently less sensitive to the drug
Acquired- Repeated use of drug in an individual who was initially responsive.

Tolerance does not develop for all actions
Cross Tolerance- Development of Tolerance to pharmacologically related drugs.

Closer the two drugs , more complete is the cross tolerance Eg. Morphine and
Pethidine.
Tachyphylaxis- rapid development of Tolerance when a drug is given in quick

succession resulting in marked reduce in response
Thanks all for the tolerance

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FACTORS AFFECTING

1. Alteration in Concentration of Drug that reaches the

2. Variation in Concentration of Endogenous receptor

3. Alteration in Number or Function of receptors

4. Changes in components of response distal to the

• Qualitative- Type of response is altered eg. Drug allergy or idiosyncrasy

Individual dose based on BW= Body wt(Kg)x Avg Adult dose

• Small body size in females- • Certain animal Species are sensitive or

Requires less dose compared to resistant to certain drugs.

males • Important while extrapolating results

• Special Consideration to be given from experimental animals to humans

during Pregnancy and Lactation • Humans- Blacks require higher and

• Eg. Atypical Pseudocholinesterase- Prolonged succinylcholine apneoa

• Governs the speed and • Type of Diet

• Uses- 1. Control device in clinical trial of drugs

2. To treat a patient who does not require active drug

• Substances used as Placebo – Lactose tablets, Multivitamin Tab

• Nocebo- Converse of placebo, refers to negative psychodynamic effect by the

Congestive Heart Failure

Alters the Achlorhydria GIT mucosal Alteration in Vd – elimination due

Increased Prodrugs Action of certain

• Between concurrently ingested drugs

more than the rate of elimination

• Slowly eliminated drugs are liable to cause cumulative toxicity

• Eg. Prolonged use of chloroquine causes retinal damage.

Natural- The individual is inherently less sensitive to the drug

Acquired- Repeated use of drug in an individual who was initially responsive.

Cross Tolerance- Development of Tolerance to pharmacologically related drugs.

Tachyphylaxis- rapid development of Tolerance when a drug is given in quick

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