Q7:

PHARMACODYNAMICS

Types of Doses
1. Standard dose - The same dose is appropriate for most patients.
2. Regulated dose- The drug modifies a finely regulated body function which can be
easily measured.
3. Target level dose- The response is not easily measurable but has been
demonstrated to be obtained at a certain range of drug concentration in plasma.
4. Titrated dose- The dose needed to produce maximal therapeutic effect cannot be
given because of intolerable adverse effect.
Drug Potency and Efficacy

Drug Potency- The amount of drug needed to produce a certain response.

Drug Efficacy- The maximal response that can be elicited by the drug.

Dose Response Relationship (curve)

When a drug is administered systematically, the dose-response relationship has

two components: 1.Dose-plasma concentration relationship
2.Plasma concentration-response relationship.

Emax D
KD D

Response
100%

Dose

70%
30%

log.Dose

Dose

Combined Effects of Drugs. Give Example

Combined effect of drugs may increase (synergism) or decrease (antagonism) in

combined drug usage.

Drug interactions are 2 kind:

A. Pharmacodynamic interaction: both drugs act on the target side of clinical
effect, exerting synergism or antagonism. These drugs act on the same or
different receptors or processes, mediating similar biological consequence.
B. Pharmacokinetic interaction: the drugs interact from the target cell to alter
plasma (and other tissue) concentration of the active drug at its site of
action.

Drugs antagonism. Effect of drugs A+B< effect of drug A + effect of drug B.

Depending on the mech. involved, antagonism may be:
1. Pharmacological antagonism (receptor):
Antagonist binds to receptor preventing an agonist from interacting w its
receptor to produce an effect.
I. Competitive
when 2 drugs compete for the same receptor site. Here the action of one
drug can be reversed by increasing concentration of another drug, coz.
the drug molecules are loosely bound w receptor by weak and reversible
bonds. Eg hydrogen ,Van der Waals
II. Noncompetitive (irreversible)
when antagonist produces certain changes in the receptor and abolishes
the reaction of agonist. here the action of antagonist cannot be reversed
by increasing the concentration of agonist due to strong covalent bonds
bet. Receptor and antagonist. Eg. adrenaline + phentolamine alpha
adrenoceptors.
2. Physiologic antagonism (functional)
When 2 drugs at a time inf. a physiological system. In opposite direction here
both drugs effects are cancelled by each other. Eg. glucagons d insulin
opposite effect on blood sugar level.
3.

Chemical antagonism
When 2 drugs react chemically and neutralize each other to form an inactive
substance. Eg. heparin+protamine sulphate

4. Pharmacokinetic antagonism.
When one drug can reduce the potency of another drug by:
Alteration of absorption from. GIT
Reducing binding to plasma protein
Alteration of renal excretion

Inhibition of metabolic degradation

Drug synergism (syn-together, ergon-work)
Additive drugs effect: if two drugs w same effect are given together, they produce
the sum of their effects. E (A+B) = E (A) + E (B) egg. aspirin+paracetomol
Potentiation (supraadditive): the effect of combination is greater than the ind.
Effects of the components. E (A+B)> E (A) + E (B=0)
eg.sulfonamide+trimetoprim

Factors Modifying Drug Action

These factors modify drug action either:
a) Quantitatively. Plasma concentration & or the action of the drug is increased @r
decreased. Most of the factors introduce this type of change & can be dealt by adjustment
of drug dosage.
b) Qualitatively. This type of response is altered (drug allergy or idiosyncrasy). Less
common but often precludes further use of that drug in affected patient. The various
factors are discussed below:
1. Body size. Influences the concentration of drug attained at site of action. Average adult
dose refers to individuals at the site of action.
Individual dose = (BW / 70) x average adult dose BW=Body weight (kg)
Individual dose = (BSA / 1.7) x average adult dose BSA=Body surface area (m2)
2. Age. Transport is immature as such t of drugs is prolonged. Hepatic drug
metabolizing system is inadequate in newborns, blood brain barrier is more permeable
drug attains higher concentration in CNS. Drug absorption may be altered in infants. In
elderly, incidence of adverse drug reactions is much higher.
Child dose = Age / (Age + 12) x adult dose (Youngs formula)
Child dose = (Age/20) x adult dose (Dillings formula)
3. Sex. Females have smaller body size & require doses that are on lower side of the
range. Ketoconazole causes loss of libido in men but not in women. Obviously androgens
are unacceptable to women & estrogens to men. Drugs given during pregnancy can affect
the fetus.
4. Species & race. Rabbits are resistant to atropine & mice are resistant to digitalis. blockers are less effective as antihypertensive in blacks. Indians tolerate thioacetazone
better than whites.

5. Genetics. This is because of differing rates of drug metabolism as the amount of

microsomal enzymes is genetically controlled. There are also differences in target organ
sensitivity.
6. Route of administration. Drug may have entirely different uses through different
routes.
7. Environment & time of administration. Several environmental factors affect drug
responses.
8. Psychological state (nervous & anxious patient, alcohol). Efficacy of a drug can be
affected by patients beliefs, attitudes & expectations.
9. Pathological state (GIT diseases, liver disease, kidney disease, thyroid disease).
Several diseases can influence drug disposition & drug action.
10.Other drugs (drug interactions). Drugs may modify response to each other by
pharmacokinetic @ pharmacodynamic interaction between them.
11. Cumulation. Drug will cumulate in the body if rate of administration is more than rate
of elimination.
12. Tolerance (tachyphylaxis, drug resistance, cross tolerance). It means requirement of
higher dose of drug to produce given response.