Posology & Factors affecting of the dose | Pharmacy Notes

Age, Sex, Body Weigh, Tachyphylaxis, Route of Administration, Metabolic disturbance, Time of Administration, Environmental Factors, Emotional factors, Presence of disease, Accumulation, Additive effects, Synergism ,Antagonism , Idiosyncrasy, Tolerance

Posology is derived from the Greek word posos meaning how much and logos meaning science. So posology is the branch of medicine dealing with doses.

Dose of the drug:  appropriate amount of a drug needed to produce certain degree of response in a patient.

Dose of drug is governed by:

  • It’s potency
  • Pharmacokinetics property
  • Concentrate at which it present at the target site

The optimum dose of a drug varies from patient to patient. The following are some of the factors that influence the dose of a drug.

  1. Age
  2. Sex
  3. Body Weigh 15. Tachyphylaxis
  4. Route of Administration
  5. Metabolic disturbance
  6. Time of Administration
  7. Environmental Factors
  8. Emotional factors
  9. Presence of disease
  10. Accumulation
  11. Additive effects
  12. Synergism
  13. Antagonism
  14. Idiosyncrasy
  15. Tolerance

 1. Age: Human beings can be categorized into the following age groups:

  • 1.       Neonate:       From birth up to 30days.
  • 2.       Infant:            Up to 1 year age
  • 3.       Child in between 1 to 4 years
  • 4.       Child in between 5 to 12 years.
  • 5.       Adult
  • 6.       Geriatric (elderly) patients

In children the enzyme systems in the liver and renal excretion remain less developed. So all the dose should be less than that of an adult. In elderly patients the renal functions decline. Metabolism rate in the liver also decreases. Drug absorption from the intestine becomes slower in elderly patients. So in geriatric patients the dose is less and should be judiciously administered.

2. Sex: Special care should be taken while administering any drug to a women during menstruation, pregnancy and lactation. Strong purgatives should not be given in menstruation and pregnancy. Antimalarials, ergot alkaloids should not be taken during pregnancy to avoid deformation of foetus. Antihistaminic and sedative drugs are not taken during breast feeding because these drugs are secreted in the milk and the child may consume them.

Female also have small body size

 3. Body size: It influences the concentration of drug in the body. The average adult dose is calculated for a person with 70kg body weight (BW). For exceptionally obese (fat) or lean (thin) patient the dose may be calculated on body weight basis.

Another method of dose calculation is according to the body surface area (BSA). This method is more accurate than the body weight method.

The body surface area (BSA) of an individual can be obtained from the following formula:

BSA (m2) = BW(kg)0.425  x  Height (cm)0.725  x  0.007184

4. Route of administration

In  case of intravenous injection the total drugs reaches immediately to the systemic circulation hence the dose is less in i.v. injection than through oral route or any other route.

For example MgSO4 is used

  • orally-purgation
  • Joints-decrease swelling
  • Intravenous: CNS depression

5. Time of administration

The drugs are most quickly absorbed from empty stomach. The presence of food in the stomach delays the absorption of drugs. Hence a potent drug is given before meal. An irritant drug is given after meal so that the drug is diluted with food and thus produce less irritation.

6. Environmental factors

Stimulant types of drug are taken at day time and sedative types of drugs are taken at night. So the dose of a sedative required in day time will be much higher than at night.

Alcohol is better tolerated in winter than in summer.

7. Psychological state

Psychological state of mind can affect the response of a drug, e.g. a nervous and anxious patient requires more general anaesthetics. Placebo is an inert substance that does not contain any drug. Commonly used placebos are lactose tablets and distilled water injections. Some time patients often get some psychological effects from this placebo. Placebos are more often used in clinical trials of drugs.

8. Pathological states (i.e. Presence of disease)

Several diseases may affect the dose of drugs:

In gastrointestinal disease like achlorhydria (reduced secretion of HCl acid in the stomach) the absorption of aspirin decreases.

In liver disease (like liver cirrhosis) metabolism of some drugs (like morphine, pentobarbitone etc.) decreases.

In kidney diseases excretion of drugs (like aminoglycosides, digoxin, phenobarbitone) are reduced, so less dose of the drugs should be administered.

Thyroid disease

9. Accumulation

Any drug will accumulate in the body if the rate of absorption is more than the rate of elimination. Slowly eliminated drugs are often accumulated in the body and often causes toxicity e.g. prolonged use of chloroquine causes damage to retina.

10. Drug interactions

Simultaneous administration of two drugs may result in same or increased or decrease effects.

Drug administration with dosePharmacological effect
Drug AEffect A
Drug BEffect B
Drug A + Drug BEffect AB
RelationshipName of the effectExamples
Effect AB = Effect A + Effect BAdditive effectAspirin + Paracetamol
Effect AB > Effect A + Effect BSynergistic (or potentiation)Sulfamethaxazole + Trimethoprim
Effect AB < Effect A + Effect BAntagonismHistamine + Adrenaline
Drug Interaction

11. Idiosyncrasy

This an abnormal response to a drug in few individual patients. For example, in some patients, aspirin may cause asthma, penicillin causes irritating rashes on the skin etc.

12.    Genetic diseases

Some patients may have genetic defects. They lack some enzymes. In those cases some drugs are contraindicated.

e.g. Patients lacking Glucose-6-phosphate dehydrogenase enzyme should not be given primaquin (an antimalarial drug) because it will cause hemolysis. Sulfonamide, dapsone, quinine,  nalidixic acid, nitrofurantoin, meenadione etc

13. Tolerance

Some time higher dose of a drug is required to produce a given response (previously less dose was required).

Natural Tolerance: Some races are inherently less sensitive to some drugs, e.g. rabbits and black race (Africans) are more tolerant to atropine.

Acquired Tolerance: By repeated use of a drug in an individual for a long time require larger dose to produce the same effect that was obtained with normal dose previously.

Cross tolerance: It is the development of tolerance to pharmacologically related drugs e.g. alcoholics are relatively more tolerant to sedative drugs.

Tachyphylaxis: (Tachy = fast, phylaxis = protection) is rapid development of tolerance. When doses of a drug is repeated in quick succession an reduction in response occurs – this is called tachyphylaxis. This is usually seen in ephedrine, nicotine.

Drug resistance: It refers to tolerance of microorganisms to inhibitory action of antimicrobials e.g. Staphylococci  to penicillin.

14. Species & Race:

  • Rabbit-resistance to atropine
  • Rat and mice-resistance to digitalis

Racial

  • Black require a higher dose of atropine
  • Mongols required a lower dose of atropine

Dose: 

  1. Standard dose
  2. Regulated dose
  3. Target level dose
  4. Titrated dose

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