www.linkedin.com/in/dr-aboobecker-siddique-p-a-200783a0 Factors Modifying Drug Action Drug Factors Route of administration Presence of other drugs Cumulation Placebo Patient Factors Age Body Wt. Sex Species & race Psychological Diseases Diet & Environment Genetic factor Tachyphylaxis &Tolerance

1. Pharmacodynamics
Dr. Ab.Siddique.P.A
Associate Professor
Pharmacology & Therapeutics

2. Factors Modifying Drug Action
Drug Factors Patient Factors
• Route of
administration
• Presence of other
drugs
• Cumulation
• Placebo
• Age
• Body Wt.
• Sex
• Species & race
• Psychological
• Diseases
• Diet & Environment
• Genetic factor
• Tachyphylaxis &Tolerance

3. DRUG FACTORS

4. Route of administration
Governs speed & intensity of drug
response
Quantitative- Oral dose more than i.v. dose
Qualitative: MgSO4
Locally orally IV
Reduces
edema Purgative
CNS
Depressant

5. Presence of other drugs
Drug interactions
• Alteration in the duration or magnitude
of pharmacological effects of one drug
by another drug
• In vitro
• In vivo
– Pharmacokinetic
– Pharmacodynamic

6. Drug Interactions
• Two drugs Combined: Synergism,
Antagonism etc.
• Pharmacokinetic:
Delivery of a drug to its site of action is
altered by a second drug
Eg. Antacids and tetracyclines
• Pharmacodynamic:
Response of a drug target is modified by
a second drug
Eg. NSAIDs and ACE inhibitors
Nitrates and Sildenafil

7. Cumulation
• Drugs accumulate if rate of administration
> rate of elimination
• Slowly eliminated drugs liable for toxicity
– Prolonged use of chloroquine causes retinal
toxicity
– If patient has a previous dose of digoxin in the
past week full loading dose should not be given
– Emetine course should not be repeated before
6 weeks

8. Placebo-Psychological factors
 Emotional:
• Personality of the Doctor[Placebo] and
Patient
– Neurotics require higher dose of diazepam

9. PATIENT FACTORS

10. Age
• Child dose= Age x Adult dose
Age + 12
• Child dose = Age x adult dose
20

11. AGE
• Infants:
 Low GFR and immature tubular transport
Penicillin G is given BID
Inadequate hepatic metabolizing system
Chloramphenicol – gray baby syndrome
Blood brain barrier is more permeable –
kernicterus
Lower gastric acidity & slower intestinal
transit
Skin is more permeable-transdermal
absorption is faster
Susceptible to special adverse effects
Suppression of growth with steroids

13. Age
 Elderly:
-decline in renal function
-reduced hepatic activity
-reduced intestinal motility
-altered volume of distribution
-drug interactions
-prostatic hypertrophy - urinary retention
• ADE effects more
• Dose to be lowered

14. Body Wt. And Surface Area
Influences conc. Of drug attained at the
site of action
Individual = Body weight (kg) X Adult dose
Dose 70
BSA
Individual dose = ------x Average adult dose
1.7

15. Sex
• Smaller body size⇛ lower dose
• Interference with sexual function in
males not females
– Clonidine, beta blockers, methyldopa
• Gynaecomastia
• Loss of libido in men
– Ketoconazole
• Hormones

16. Pregnancy
• Delayed absorption due to⇩ GI motility
• Volume of distribution ⇪ due to
expansion of ECF & plasma volume
• Plasma albumin⇩; α acid glycoprotein⇧
• Renal blood flow⇧
• Induction of hepatic microsomal
enzymes

17. Species & Race
• Rabbits: resistant to atropine
• Rats & mice: resistant to digitalis
• Rats more sensitive to curare
• Blacks require higher &
mongols require lower conc of atropine
• Beta blockers: less effective in blacks
• Quiniodochlor toxicity reported in
Japan; no cases in India

18. Diet & Environment
• Pollutants like DDT, Cigarette smoke,
Insecticides, Alcohol-Enzyme inducers-
Affects OCP
• Hypnotics taken at night
• Corticosteroids in the morning
Time of administration

19. Genetic factors
• Differences in amount & isoforms of
drug metabolizing enzymes
– Atypical pseudocholinesterase: prolonged
succinyl choline apnoea
– G-6 PD deficiency: haemolysis with
primaquine
– Acetylator polymorphism: INH toxicity
– Acute intermittent porphyria: precipitated
by barbiturates
– Malignant hyperthermia after halothane

20. Pathological States-Diseases
Gastrointestinal diseases:
Malabsorption syndrome
Achlorhydria: Decreases aspirin
absorption

21. Liver disease:
↓First pass metabolism
• B.A of Lidocaine, Propranalol
Reduced serum albumin
Metabolism & elimination
• Morphine, lidocaine, pentobarbitone
Prodrugs needing hepatic metabolism for
activation
• Prednisone, Bacampicillin
Pathological States-Diseases

22. Kidney disease :
↓Clearance of drugs that are excreted in
unchanged form
• Aminoglycosides
Low plasma albumin in renal disease
Permeability of blood brain barrier ⇪
Opiates, barbiturates,benzodiazepines produce
more CNS depression
Avoid pethidine: nor pethidine metabolite
accumulates ⇛toxicity
⇪Postural hypotension with antihypertensives
Pathological States-
Diseases

23. Pathological States-Diseases
• Congestive cardiac failure:
– Decreased drug absorption due tomucosal
edema & splanchnic vasoconstriction
– Modifies volume of distribution
– Retards drug elimination due to⇩ perfusion
& ⇩GFR
– Decompensated heart more sensitive to
digitalis

24. Pathological States-Diseases
• Thyroid disease:
–Hypothyroid patients: more sensitive
to digoxin, morphine
–Hyperthyroid patients: resistant to
inotropic action of digoxin

25. Tolerance
• Tolerance occurs when the person no
longer responds to the drug in the way
that person initially responded.
• A state in which higher dose is required
to achieve the same effect
Nitrates in Angina
Morphine in pain relief

26. Types of Tolerance
Acquired
Tolerance
Natural
SPECIES
Rabbits
are
resistant
to
Atropine
RACE
In Afro –
Carribeans
β blockers
Less
effective
•On
repeated
exposure
•May be
only to
some
effects of
a drug
Morphine
Not to
Constipation and
Mydriatic
actions

27. Tolerance: Mechanism
• Pharmacokinetic:
Increased Metabolism, reduced
absorption
• Pharmacodynamic
Cells of the target organ become
less sensitive
Morphine, Barbiturates,
Nitrates, Alcohol

28. • Tachyphylaxis (acute tolerance):
Rapid development of tolerance
Amphetamine, Nicotine
• Cross tolerance:
Development of tolerance to
pharmacologically related drugs
Eg.
Alcohol and Barbiturates
Morphine and Barbiturates
Morphine and Pethidine