Factors affecting Posology - Pharmaceutics - I B. Pharma 1st Semester

Factors affecting Posology

Objective

At the end of this lecture, student will be able to:

• List out the factors affecting dose selection

• Explain factors influencing dose selection- age, body weight, gender, route of administration, time of administration, pathological factors

Factors Affecting Dose Selection

1.  Age

2.  Body weight

3.  Gender

4.  Route of administration

5.  Time of administration

6.  Pathological conditions

7.  Environmental factors

8.  Genetic makeup

9.  Rate of elimination

10. Idiosyncrasy

11. Tachyphylaxis

12. Species and race

13. Synergism

14. Antagonism

15. Psychological factors

Age - Newborns

• Infants and children

• The organs liver and kidney which are responsible for biotransformation and excretion are immature and still in the generative stage.

• The blood brain barrier is more permeable

• Drug absorption may be altered in infants because of lower gastric acidity and slower intestinal transit.

Age - Pediatric

• The hepatic drug metabolizing system is inadequate in newborns-

• Chloramphenicol can produce gray baby syndrome

• Occurs in neonates or immature babies below the age of 2 months, between 2-9 days after administration of large    dose of Chloramphenicol (over 70mg/kg/day).

• Growing children are more vulnerable to special adverse effects of drugs.

• E.g. Corticosteroids affected growth suppression, discoloration of teeth due to accumulation of tetracycline.

Age - Geriatrics

• In case of geriatrics (elderly patients)

-  The liver and kidney function progressively declines

-  Renal and metabolic clearance will be low

- The organs exhibit impaired ability to inactivate or excrete drugs

- Develop cumulative toxicity while receiving prolonged medication

• Absorption will be slower due to reduced blood flow and motility of intestines.

• Multiple drug therapy for hypertension, ischaemic heart disease, diabetes, arthritis etc.

• increased chances of drug interactions

Body Weight

Is dose same for everyone?

The recommended adult dose is based on the normal body weight of 70kg

Child doses are calculated on the basis of body weight (mg/kg body weight)

 

Gender 

Male

• Muscular

• More dose

• Less responsive and sensitive

• Estrogens are unacceptable to men.

• Gynaecomastia occurs only in men.

Female 

• Less muscular

• Lesser dose

• More responsive and sensitive

• Androgens are unacceptable to women.

• Gynaecomastia is not seen in women.

Precautions while calculating Women Dose 

1. Strong purgatives should be avoided during menstruation.

2. Drugs which induce contraction of uterus must be avoided during pregnancy

3. During pregnancy, drugs like barbiturates, narcotics, anesthetics and alcohol which readily crosses the fetal circulation should be avoided.

4. In lactating mothers, drugs like tetracycline, antihistamines, and morphine should be carefully prescribed.

Route of Administration

• Influence the efficacy of drug.

• A single drug may exhibit varied uses through different routes.

Oral Route

• Absorption of drugs is less

• More dose

• Magnesium sulphate à purgative action

Parentral Route

• Absorption of drugs is rapid

• Lesser dose

• Magnesium sulphate à CNS depression hypotension

Time of Administration

• Drugs which are absorbed rapidly should be given on empty stomach.

E.g. Food interferes with absorption of Ampicillin.

• Drugs which are irritant to the GIT should be given after meals.

E.g. Fatty meals enhance absorption of Griseofulvin.

Presence of Disease/Pathological Conditions

• Drugs influences disease conditions.

Example -

Stomach diseases                    decreases the absorption.

Liver diseases                          increase the bioavailability.

                                                 Decreases 1st pass metabolism.

Kidney diseases                       alter the clearance of drugs.

Environmental Factors

• Alcohol is better tolerated in cold environment

• The dose of sedative required to produce sleep during the day is more than the dose required to produce sleep in the night.

• Hypnotics taken at night and in quiet, familiar surroundings may work more easily.

Genetic Makeup

Personalized medicine - PHARACOGENOMICS

• The genetic makeup of an organism is known as its genotype

• The genotype refers to the set of traits found within the cells of living organisms

• These traits, known as the genetic code, are passed from one generation to the another during cell division and reproduction

Rate of Elimination

• Age

• Disease

• Impaired liver function delays the breakdown of drugs.

• Both situations cause greater and prolonged activity of medicaments with a risk of toxic reactions.                                                                                              

Summary

• Paediatrics - liver and kidney will be in the generative stage

• Geriatrics - liver and kidney function progressively declines

• Child doses are calculated on the basis of age, body weight (mg/kg body weight) and body surface area.

• Time of administration is vital because some drugs are absorbed rapidly on empty stomach others in presence of food.

• Drug will also be influenced by the disease conditions and environmental factors.

• Variations in response of different individuals to the same dose of a drug are sometimes due to differences in genetic makeup