What are the Factors Affecting the Dose and Action of Drugs?

The term posology (Greek posos, how much; and logos, science) is the science of doses. All Pharmacopoeias prescribe the doses of drugs for internal use.

The dose is usually expressed as a range. The minimum dose or the lower limit of the dose is essential for eliciting an intended therapeutic response whereas the maximum dose or the higher limit of the dose is the amount of the drug substance that can be tolerated by an average individual.

These doses are prescribed for the guidance of the prescriber. The pharmacist is much concerned with the maximum limit of the doses which, if exceeded, may cause untoward effects in the patient. The actual dose of a drug is to be decided by the prescriber depending on patient's age, sex, symptoms, his medication history and the factors like tolerance, idiosyncrasy, route of administration etc.

Factors Affecting the Dose and Action of Drugs

These factors are discussed below:

1. Age

In general, children require smaller doses than adults. Either Young's formula (based on age) or Clark's formula (based on weight) can be used for calculating the doses for children but the formula based on body surface area is more reliable.

2. Sex

This is particularly important in the case of treatment with sex hormones. Female adults generally require smaller doses than males due to the presence of more body fat.

3. Body weight

The usual doses for drugs are mentioned generally for 70 kg adult. The drug concentration at site of action is based on the ratio between the amount of drug administered and size of the body. The dose calculations for abnormally thin or obese patients are required to calculate on the basis of body weight.

4. Severity of disease

It is a common experience that dull headache may be relieved by a single tablet of aspirin whereas severe headache may necessitate administration of 2-3 tablets of the same drug. But this is no true in all cases. For example, in case of iron deficiency anemia, the dose of iron salt administered orally remains the same irrespective of severity because there is a limit to which iron can be absorbed from the intestine daily and incorporated in haemoglobin.

5. Health and nutrition

Debilitated and anaemic patients are, in general, more sensitive to the toxic effects of drugs and hence they are given smaller doses. Persons with severe anaemia associated with hookworm infestation are more susceptible to the toxic effects of tetrachloroethylene. Myxoedematous patients are known to show less response to drugs like amphetamine because of low cellular metabolism.

6. Pathological state

If the organs, through which biotransformation or excretion takes place, are diseased then smaller dose is indicated. For example, in case of renal insufficiency, phenobarbitone (mainly excreted by the kidneys) should be given in smaller dose and in case of patients suffering from liver diseases, morphine should be given in smaller dose (morphine is mainly inactivated in liver). Aspirin has no effect on normal body temperature but lowers the body temperature in fevered patients. Quinine precipitates black water fever more often with falciparum malaria than otherwise.

7. Tolerance

Some children can tolerate relatively large doses of arsenic, belladonna and calomel. Tolerance can be acquired as a result of repeated administration of some drugs e.g., morphine, heroin and cocaine.

8. Simultaneous administration of two or more drugs

(a) Addition : When two or more drugs given together produce the same resulting effect is the algebric sum of their individual effects e.g., carbachol and acetycholine.

(b) Synergism : In synergism, the effect produced is greater than the algebric sum of the effects due to individual drugs e.g., adrenaline and cocaine.

(c) Antagonism : When two drugs having opposite effect e.g. the use of amphetamine to correct partially the sedation caused by anticonvulsant doses of phenobarbital and the administration of ephedrine to correct hypotension resulting from spinal anesthesia.

9. Route of administration

In general, the rapidity of absorption of a drug decreases with route of administration in the following order:

Intravenous > Intramuscular > Subcutaneous > Oral

Thus, in general, intravenous (intravenous) dose of a drug is smaller than its intramuscular (intramuscular) or subcutaneous or oral dose.

Example : Doses of ergotamine for various routes are as follows.

Oral : 2 to 5 mg

Intramuscular : 1 mg (about to 1/2 of oral dose)

Intravenous : 0.25 mg (about to 1/8 of oral dose and % of IM dose)

10. Time and frequency of drug administration

Biological half-life of a drug i.e. the time required for the blood level to drop down to 50 % of the initial peak level, is the main factor governing frequency of drug administration. For example, if the biological half-life of sulphadiazine is 4 hours, 1 g of the drug has to be given every 4 hours after initial dose of 2 g. But in certain instances e.g., reserpine as a tranquiliser, biological half-life of a drug has no relation to frequency of administration.

11. Idiosyncracy

Morphine normally depresses central nervous system but may produce excitation in some individuals, specially women.

12. Allergy

Penicillin may produce anaphylactic shock (sudden fall of blood pressure) in allergic patient! but not in normal patients.

The doses of commonly used drugs are given in the Indian Pharmacopoeia.