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