Posology

1. Posology Prepared by Dr. SUBHASHIS DEBNATH Department of Pharmaceutics Seven Hills College of Pharmacy Accredited “A” Grade by NAAC Tirupati 517561

2. Posology: (Derived from the Greek posos - how much, and logos - science) is the branch of medicine/pharmacy dealing with doses. • Posology is a branch of medical science which deals with dose quantity of drug which can be administered to a patient to get the desirable pharmacological action. • Dose:is the quantitative amount administered or taken by a patient for the intended medicinal effect. How much Quantity of drug To get desirable Pharmacological Action Posology

3. On administration of a drug ,a predicted response is obtained but some times´ Individuals may vary considerably in their responsiveness´ Such as: 1. Respond differently to drugs both from time to time and from other individuals. 2. Some would show less than the usual response , and some may show more than usual response 3. Occasionally individuals exhibit unusual response-IDIOSYNCRACY

4. Factors affecting drug dosage: 1- Age: • Age is the most common factor that influences the amount of drug to be given. An infant would require much less dose than an adult. Elderly patients may require more or less than the average dose, depending upon the action of the drug and the condition of the patient. • Newborn infants have high total body water, low fat, immature renal & hepatic function, different protein binding. Hence required less dose. • Elderly patients mostly suffers from renal & hepatic dysfunction, which decreases elimination of drug from the body. Due to that drug will stay in the body for longer period of time (half life of the drug increases). • Hence less dose is required.

5. Tetracyclines produce teeth staining in children Corticosteroids cause growth and developmental retardation Certain drugs may lead to serious consequences e.g. Chloramphenicol causing gray baby syndrome. Sulphonamides causing kernicterus These are all different responses than adults Drug elimination is less efficient in new born babies , and in old people so that drug produces greater and more prolonged effects at extremes of age .especially drugs which are excreted through kidneys as there is decrease in G.F.R Generally children and old people due to their less capacity of metabolism and excretion requires less dose of drug than an adult requires. This is not true in all the cases because children can tolerate relatively large dose of digitalis and belladonna on the basis of higher rate of metabolism. Elderly patients are more sensitive to some drug effects eg. Hypnotics and tranquillizers which may produce confusion states in them.

6. Immature renal & hepatic function • Different protein binding Required less dose Newborn infants Suffers from renal & hepatic dysfunction, which decreases elimination of drug from the body Less dose is required Elderly patients

8. Various rules of dosage in which the pediatric dose was a fraction of the adult dose: 1- Young’s rule, based on age: • For calculating doses for children 12 years of age. Dose for child = Adult dose x Eg: If the adult dose of a drug is 30 mg than for a child of 6 years dose can be calculated as following Dose for the child= 6/6+12 X 30 = 10mg Age Age + 12

9. 2- Cowling’s Rule: For calculating doses for children two years of age or older. Dose for child = Adult dose x 3- Fried’s Rule for infants: For calculating doses for infants younger than one year of age. Dose for infant = Adult dose x Age at next birthday (in years) Age + 12 Age (in months) 150

10. Dillings Formula: This formula is most useful for the calculating the dose for children in between 4 to 20 years of age. Formula: Dose for the children = Adult dose X Bastedo’s Formula: Dose for the child = Adult dose X Age in Years 20 Age in Years + 3 30

11. 2- Body weight: In the calculation of dosages, weight has a more direct bearing on the dose than any other factor, especially in the calculation of pediatric doses. The rule governing calculation of pediatric doses based on weight is Clark’s Rule shown below: Clark’s Rule: Dose for child = Adult dose x Weight in pounds 150 (average weight of adult in lb)

12. The official usual doses for drugs are considered suitable for 70 kg (150 pounds) individuals. • The ratio between the amount of drug administered and the size of the body influences the drug concentration at the site of action. • Therefore, drug dosage may require adjustment from the usual adult dose for abnormally lean or obese patients.

13. 3- Body surface area: • A close relation exists between a large number of physiological processes and body surface area (BSA). • Many physiological factors such as plasma volume, oxygen consumption, body electrolyte are proportional to the surface area. • The surface area used to calculate dose. • Eg. Anticancer drug methotrexate is administered on mg per sq.mm of body surface. • Average body surface area of a 70kg adult is 1.7 to 1.8 sq.meters

14. To calculate the dose of a drug for children based on body surface area as related to weight: Many physicians believe that doses for children should be based upon body surface area, since the correct dosage of drugs seems more proportional to the surface area. Approximate dose = Adultx for child dose BSA of child (in m2) 1.8 m2 (average adult BSA)

15. 4-Sex: • Women are more susceptible to the effects of certain drugs than are men. • On the basis of body weight female adults generally requires smaller doses than males. • Because % of adipose tissue is greater and % of water is lower in adult females as compared to adult males • Pregnant women and nursing mothers should use medications only with the advise and under the guidance of their physician.

16. Less Body weight • % of adipose tissue is greater and • % of water is lower Required less dose or altered dose than male Females

17. Examples of drugs that are transported from the maternal to the fetal circulation e.g. alcohol, anesthetic gases, barbiturates, anticoagulants, etc. • Because of the undeveloped drug detoxification and excretion mechanisms present in the fetus, concentrations of drugs may reach a higher level in the fetus than in the maternal circulation.

18. The transfer of drugs from the mother to the nursing infant through human milk may occur with various drugs with the drug effects becoming manifest in the infant. 5- Pathological state: • Because of pathological conditions like renal function impairement or liver disease many drugs remain in the body for longer period of time. • This leads to accumulation of drug in the body. • The drug with their higher concentration in the body shows toxic effects, eg: Digitalis, Heavy Metals etc. • If such condition takes place, dose of the drug should be adjusted.

19. Kidney or Liver disease Elimination / Metabolism of drug decreases Dose must be adjusted to avoid toxicity

20. 6- Route of administration: • Drugs administered intravenously enter the blood stream directly and thus the full amount administered is present in the blood. • In contrast, drugs administered orally are rarely fully absorbed due to the various physical, chemical and biologic barriers to their absorption, including interactions with the gastric and intestinal contents. • Thus, a lesser parentral dose of a drug is required than the oral dose to achieve the same blood levels of drug. • Eg: • TriflupromazineHCl : Oral Dose: 30 to 150 mg / day, IV dose 1 to 3 mg /day. • Route of administration is selected based on the severity of the disease.

21. Directly enters into systemic circulation Require small dose IV Dose Cross biological barrier, chemical interactions, metabolism Enters into systemic circulation Extra Vascular Dose Require large dose then IV Rate of drug absorption increases Oral Subcutaneous Intramuscular Rectal Intravenous Dose of Drug increases

22. 7- Time of administration: • The time at which a drug is administered sometimes influences dosage. This is specially true for oral therapy in relation to meals. • Absorption proceeds more rapidly if the stomach and upper portions of the intestinal tract are free of food, and an amount of a drug that is effective when taken before a meal may be ineffective if administered during or after eating. • Gastric emptying rate affect dose. • Irritating drugs ( eg iron, aspirin)are better tolerated by the patient if food is present in the stomach to dilute the drug’s concentration. • Appetizers should be given before meal, digestants given after meal. • Several physiological functions are altered during bed rest like reduction in gastric emptying rate, increase in cardiac output and renal flow. It changes absorption, distribution and elimination of drug.

23. 8. Frequency of administration • Drugs having short half life gets rapidly excreted from the body. In such case, to maintain steady state plasma concentration it requires frequent dosing. • Hence controlled or sustained release formulations are developed.

24. 9. Tolerance: Drug tolerance: When usually large dose of drug is required to elicit a normal pharmacological action is knows as Tolerance. • Tolerance occurs commonly in such drugs • e.g. anti-histaminics, narcotic analgesics (morphine, heroin, cocaine). • Types Of Tolerance : • True tolerance – Produced by oral and parenteral administration of drugs. In this type of tolerance receptors of drug are decreased. • Pseudo tolerance – Produced only to the oral route of administration. In pseudo tolerance receptors are alive but absorption of drug is decreased or excretion is increased.

25. The development of tolerance can be minimized by: • Initiating therapy with the lowest effective dose. • Avoiding prolonged administration. • Eg. Smokers can tolerate more nicotine. • Alcoholics can tolerate more alcohol . To elicit a normal pharmacological action Large Dose required Tolerance

26. Produced by oral and parenteral administration of drugs Receptors of drug are decreased True Tolerance Receptors of drug are alive but absorption may decrease or excretion may increase for drug Produced by oral administration of drugs PseudoTolerance

27. 10. Elimination Of drug • Body considers drugs as foreign substances and continuously works at eliminating them. • Hydrophilic Drug – Dissolve in water, Easily eliminated • Hydrophobic drug – Dissolved in fat & lipoidal membrane, difficult to remove by body. • Hence doses of hyrdophilic drug requires more than that of hyrophobic drugs.

28. 11. Idiosyncrasy & Hypersensitivity • Idiosyncrasy is defined as “Genetically determined abnormal or unusual response to a drug.” • Eg: In some people aspirin causes asthma, penicillin produces irritating rash, small dose of quinine may produce ringing in the ears etc. • Hypersensitivity or drug allergy is an adverse to particular chemical resulting from a previous exposure to the substance, occurring in only a small fraction of all people receiving the particular drug. • eg . Skin rashes,edema,anaphylactic shock, broncho-spasm etc.

29. 12. Tachyphylaxis • When certain drugs are administered repeatedly at short interval , the cell response get blocked & pharmacological response to that particular drug is decreased. • The decreased response can not be reversed by increasing dose. • Eg. Ephidrine in treatment of bronchial asthma at short intervals may produce very less response due to tachyphylaxis. • Some other drugs like amphetamine, cocaine and nitrates also behave like this.

30. 13. Drug interactions 1. Synergism : When two or more drugs given together results in a total effect greater than the sum of their independent effect is called as synergism. Eg. Aspirin & paracetamol, Procaine & adrenaline combination increases the duration of action of procaine. 2. Additive Effect : When the total pharmacological action of two or more drug administered together is equivalent to sum of their individual pharmacological action. Eg: Combination of epherdine and aminophylline in the treatment of bronchial asthma. 3. Antagonism : When action of one drug is opposed by the other drug on the same physiological system is knows as antagonism. • Eg. Adrenaline – Vasoconstrictor Acetylcholine – Vasodilator It is also useful in the treatment of poisoning. Like milk of magnesia is given in acidic poisoning, where alkaline effect of the milk of magnesia neutralise the effect of acid poisoning