Posology

Posology means study of dose of drug. Various factors affecting on dose of drug in humans & animals. Dose calculation by using various formulae.

1. Posology Prepared & presented by Ms. Nisha S. Mhaske Lecturer, PRES’s COPD, Chincholi. Email : [email protected] Loknete Dr.Balasaheb Vikhe Patil ( Padmabhushan Awardee ) Pravara Rural Education Society’s College of Pharmacy (D.Pharm) Nashik.

2. Learning outcomes Learner will be able to understand What do you mean by dose & dosage form? What is Posology ? Various factors effect on dose of drug in human & animals Various formulae to calculate dose of drug.

3. Content Posology Factors affecting on dose of drug in humans Calculation of child dose Factors affecting on dose of drug in animals

4. posology Branch of science which deals with study of Doses of drug. Posology is derived from Greek word; Posos-How Much & Logus-Science or study . Dose- it is quantity of a drug administered into the body to produce desired therapeutic effect. Dosage form- any suitable physical form of a drug in which it is administered in a prescribed quantity is referred as a dosage form of a drug. The dosage form may be solid- tablets, capsules, powders Liquid- syrup, suspension, emulsion, mixture Semisolid- ointment, cream, paste Gaseous- aerosols.

5. Various factors affecting on dose of drug in Human Body weight Presence of disease Age Metabolic disturbances Sex Cummulative effect Route of administration Additive effect Time of administration Synergism (Potentiation) Diet and environmental factor Antagonism Genetic factor Drug Tolerance Emotional factor Drug Dependence

6. Body weight The dose of drug is related to body weight. The dose of drug is usually expressed as mg/kg of body weight. Body weight based formula Clarks formula Child dose = Weight of child in Kg X Adult Dose 70 Clarks rule for infants Dose for infant = Weight in pound X Adult Dose 150 1 kg=2.205 pounds (lbs) Pound is a Latin word meaning Weight. Lbs has been derived from a roman word Libra, it is represented by “lb” or “lbs” international term.

7. age Infants and old patients need dose different from adults. In Infants, the metabolizing enzymes and excretory organs and processes are not fully developed. Hence doses of children should be smaller than adults. Age based formula 1. Young’s formula- for children 2 to 12 year age. Child dose = Age in years X Adult Dose Age in Years +12 2. WJ Dilling formula Child dose = Age in years X Adult Dose 20 3. Frieds rule for Infant Infant dose = Age in months X Adult Dose 150

8. 4. Cowling’s rule Child dose = Age at next Birthday (in Years) X Adult Dose 24

9. sex Drug responses differs according to sex. Females requires smaller doses of drugs due to their lesser body weight. Drugs must be administered with due care in females as they have to pass through delicate periods of life like menstruation, pregnancy, lactation. Examples Morphine crosses placental barrier and depress foetal respiration are avoided in pregnant women. Many drugs are excreted in milk and either discourage breast feeding or innocently appears in foetal circulation and produce toxicity. Drugs producing pelvic congestion like drastic purgatives should be avoided during menstruation.

10. Route of administration As the route of administration changes, the dose required for same pharmacological action varies. Hence IV dose is smaller than SC dose which is also smaller than oral dose. IV Dose < SC Dose < Oral Dose

11. Time of Administration of drugs When the drugs are taken before meals, the absorption is Greater, but there is irritation to GIT due to direct contact of drug with walls of GIT. Some drugs are advised to be taken in an empty stomach:- To get quick action To avoid interference of food To prevent destruction of drugs by digestive enzymes. Eg -Anti-motion sickness agent & Antibiotics-Penicillin, tetracycline When the drugs taken after meals, the absorption is poor but there is no irritation to GIT. This is because drug is mixed with food material hence direct contact of drugs with walls of GIT is avoided. So, most of drugs are advised to be taken after meal, so as to reduce risk of gastric irritation, nausea, & vomiting. Eg - Salicylates & derivatives- Aspirin And

12. Diet and environmental factor In the presence of diet, the absorption of drug is poor. Environmental factor also affects the variation in the doses of drugs. Example The alcohol is well tolerated in cold environment than in summer. During day time central nervous system is highly active. Hence dose of barbiturate ( Phenobarbitone ) required to produce a sleep during day time is larger than the dose required during night.

13. Genetic factor The patients with hereditary metabolic disorders rarely show a disturbance in the metabolism of drugs. This is because of microsomal enzyme systems involved in the metabolism of drugs. Thus the genetic factor gives individual variations in response to drugs. Some drugs pass through genes and modify drug response from generation to generation. Eg - Diabetes mellitus.

14. Emotional factor The personality of the physician may influence the drug effect particularly in psychic patients. Hence nervous patients require smaller dose of drugs as compared to normal patients. The inert dosage forms, which resemble the actual medicament only in physical properties like color, size, shape, smell is called as Placebo. Placebos are effective in conditions like angina pectoris, bronchial asthma and psychic disorder to avoid aggravation of condition due to emotional factors.

15. Presence of disease Drug responses are altered in presence of diseases. Eg - in Liver cirrhosis, drugs like barbiturate and chlorpromazine may produce prolonged effects. Drugs which are excreted mainly by the kidney may prove toxic if administered during kidney impairment.

16. Metabolic disturbances The changes in water balance, electrolyte balance, acid-base balance, body temperature and other physiological factors may affect drug response. Eg - salicylate reduce body temperature only in case of pyrexia. Absorption of Iron from GIT is more in iron deficient anaemia.

17. Cumulative Effect When excretion of drug is slow, repeated administration of drug accumulates in the body and may lead to toxicity. This is known as cumulation & the phenomenon is known as cumulative effect. Examples Digitalis, emetine, heavy metals, chloramphenicol show cumulation. Cumulation can be avoided by following ways:- Stop the administration of drug at the appearance of first warning symptoms. It must be known that the drug is eliminated slowly or rapidly. Carefully select the dosage form in which the drug is to be administered. Check the liver and kidney function before and during drug administration.

18. Additive Effect When two or more drugs administered, act on same physiological system. The total pharmacological action is equivalent to sum of their individual pharmacological actions. This phenomenon is termed as “Additive effect.” Eg - Combination of ephedrine and aminophylline shows additive effect in the treatment of bronchial asthma. 1+1 = 2

19. Synergism (Potentiation) When two or more drugs are used in combination form, their action is increased, the phenomenon is called as synergism. Examples Aspirin + codeine as analgesic Where Syn means With & Ergo means Work. 1+1 = 3

20. Sulphamethoxazole + trimethoprim as antibacterial

21. Antagonism When the action of one drug is opposed by the other drugs on the same physiological system is known as drug antagonism. Opposite actions of two drugs on the same physiological system. Eg - when adrenaline and acetylcholine are given together, they neutralize the effect of each other due to antagonism because adrenaline is vasoconstrictor and acetylcholine is vasodilator.

22. Importance of Antagonism Antagonism is useful in poisoning cases to block the actions of poison. Antagonism is useful to control the adverse effects of the drugs. Antagonism is useful to adjust the doses of the drugs combined.

23. Drug Tolerance When larger dose of drug is required to get an effect, which is produced by the normal therapeutic dose of a drug, the phenomenon is known as drug tolerance.

24. 1. True Tolerance True tolerance is seen on both oral and parenteral administration. a. Species Tolerance Some animal species can tolerate large amount of particular drug which may prove to be lethal (Toxic) to man. Eg - Rabbits can tolerate large amounts of belladonna due to presence of atropine esterase in liver. i . Natural Tolerance

25. b. Racial Tolerance- In humans When Ephedrine is instilled into the conjunctiva sac of the Caucasians, it produces prompt dilation of pupils but in Negros ephedrine does not produce any dilation at all as they are tolerant to sympathomimetic amines. Eskimos can tolerate high fat diet and carbohydrates. Caucasians White skin, European origin Negros Black skin, Spanish, Portuguese Eskimos Indigenous- Canada, Greenland, Siberia

26. ii. Acquired tolerance Repeated administration or consumption of a drug results in slow development of resistance to its effect. Due to this, to achieve same therapeutic response, it is essential to increase the dose of drug. This phenomenon is called as acquired tolerance. Eg - morphine, cocaine, heroin, alcohol, nicotine, barbiturates etc. a. Tissue Tolerance b. Cross Tolerance Tolerance is developed to the certain tissue, organ or systems. Tolerance is developed to the different drugs of same group or category. Morphine produces tolerance for its euphoria effect but pupil and GIT never become tolerated. Tolerance to Vasodilator effect of Glyceryl trinitrite and pentaerythriol tetra nitrite.

27. 2. Pseudo Tolerance / False tolerance /Apparent tolerance It is observed only by Oral route. When small dose of poison is taken orally, tolerance is developed to that poisons by the GIT. This is possible after repeated administration of small quantity by oral route in the individual immune to such poison. This tolerance to the oral administration of drug is probably due to local changes developed by GIT which prevent poison from getting absorbed into the systemic circulation.

28. 3.Tachyphylaxis or Acute tolerance The repeated administration of drug within a short interval of time, decreases the pharmacological response progressively. This phenomenon is known as tachyphylaxis or acute tolerance. Tachyphylaxis probably can occur if the drug dissociates only slowly from its combination with receptor and thus continuing receptor blockade, while loosing its intrinsic activity, i.e. looses its pharmacological effects. Eg - Ephedrine in the treatment of bronchial asthma.

29. Tolerance Tachyphylaixs Reduces responsiveness to drug. It is also called acute tolerance. It develops slowly It develops quickly In this phenomenon original effect may be obtained by increasing the dose Original effect may not be obtained by increasing the dose. Eg - Barbiturates, vasodilators Eg - Ephedrine

30. Drug Dependence It is a psychic or physical condition of the person due to interaction between living organism and drug, which includes a compulsion to take the drug and tendency to increase the dose at the cost of health. Example- morphine, heroin, alcohol, tobacco etc. Physical dependence Psychic dependence It is the condition in which the body shows dependant stage on the drug. If the drug is withdrawn, the intense physical disturbances occur. A condition in which a drug produces a feeling of satisfaction and a psychic drive that requires periodic or continuous administration of the drug to produce pleasure and to avoid discomfort is called as psychic dependence.

31. Methods of calculation

32. Proportion to body Surface area 1. Catzel’s formula Dose for patient= Surface are of patient (m² ) X Adult dose Average adult surface area(1.73 m² )

33. Calculation of doses Dose proportionate to surface area Percentage of adult dose = Surface are of child X 100 Surface area of adult The body surface area is calculate from the height and weight of the child. Determination of Child dose from adult dose on the basis of Body Surface area Sr. No. Weight (Kg) Approx. surface area in square meters Approx. percentage of adult dose 1 2 0.15 9 2 4 0.25 14 3 6 0.33 19 4 8 0.40 23 5 10 0.46 27 6 15 0.63 36 7 20 0.80 46 8 25 0.95 55 9 30 1.08 62 10 35 1.20 70

34. Veterinary doses Pharmacist should have complete knowledge of posology which pertains to animal medication. The doses required for animals are more or in higher side in comparison to human beings beacause the weights and surface area of animals is normally more than that of human beings. Doses for animals are normally mentioned on body weights.

35. Various factors affecting on dose of drug in animals Age Habit Sex Rate of elimination Body weight & size The e ffect of drug Time of administration Purpose of medication Route of administration Species Environmental conditions Character of drug

36. Age Young animals need less dose of drug as compared to adults, because young animals are more susceptible than adults. Sex Female require less dose than the male animals. Certain drugs are contraindicated in pregnant animals because of hazards of inducing abortion. Some drugs have tendency to pass into milk which becomes unfit for human consumption. Such drugs must be used carefully when administered in milch animals.

37. Body weight & Size Dose of drug in animals depend on their body weight & size. The size of animals varies according to its breeds. Eg - In case of dogs, a dose which may be harmless for a heavy breed of dog may be dangerous to dogs of lighter breed. Time of administration A small dose of a drug may be more effective if given in an empty stomach rather than the same when given after meals. Purgatives and anthelmintics are more effective when given in empty stomach. Hypnotics are more effective when given after sunset than given early in the morning.

38. Route of administration Maximum dose of drug is required when the drug is given orally. Minimum dose is required when drug is given by Intravenous route. Environmental conditions In rainy season, when the climate is quite humid & hot, less dose is required than in winter when climate is dry & cold. Atmospheric moisture and temperature have a great influence on dose of drug in animals. Habit In animals, drug tolerance can develop when animal constantly under the influence of a drug. In that case, normal dose fail to produce the desired effect, hence larger doses are required to produce the required effect. Oral > SC > IM > IV

39. Rate of elimination Those drugs which excreted at a faster rate require larger dose of the drug. Those drugs which excreted at a slower rate require smaller dose of the drug. The effect of drug Synergistic & antagonistic effect may occur in animal doses. Purpose of medication Dose of drug varies with the purpose for which it is used. Eg - magnesium sulphate acts as purgatives in large doses but in smaller doses it acts as antacid and laxative.

40. Species Dose of drug varies from species to species. The dose of drug for a cow will be different from horse, sheep, pig, cat etc. Eg - opium is a narcotic even than it produces excitement in horse and cattle but it shows narcosis in dog. These differences in action are due to anatomical and physiological peculiarities. Character of the drug Larger doses of drug are required if it given in crude form to the animals. Eg - nux vomica powder is required in larger doses, but its active constituent strychnine alkaloid is required in smaller dose.

41. Assignment no- 3 Define posology. Define dose & dosage form. Enlist and describe factors affecting on dose of drug in human. Give the formulae for the calculation of pediatric doses. Calculate the dose of phenacetin for 8 years child using WJ Dilling’s formula. Adult dose-600 mg (Ans-240 mg) Calculate dose of aspirin for a child of 6 yrs age. Adult dose is 1 gm. (Ans-0.5 gm) Calculate the dose of ferrous fumerate for 3 months old infant. Adult dose 0.6 gm ( Ans - 0.012 gm)