2 Principles of Clinical Pharmacology and Therapeutics Principles of Clinical Pharmacology and Therapeutics 3 and the maximum dosage whereby no toxic symptoms occur is called the therapeutic width. Finally, administration of a substance can also induce a number of effects which have nothing whatsoever to do with the pharmacological properties of the substance; these are the placebo 1 effects. GENERAL PHARMACOLOGY Nomenclature Pharmacology deals with the knowledge of drugs. Drugs are Pharmacology chemical substances which affect living organisms and are used by the clinician to diagnose, prevent or cure diseases. So the safe use of drugs needs sound knowledge of their various aspects such as INTRODUCTION mechanism of action, doses, routes of administration, adverse affects, From the fact mentioned that pharmacon can mean both toxicity, drug interactions etc. medicine and poison, it follows that what we ingest does not always A health professional is also interested to know the chemical result in the desired effect, the primary effect, but can also result in agents that are commonly responsible for household and industrial unwanted side effects on the basis of which we classify that substance poisoning as well as environmental pollution so that he may prevent, as toxic (poisonous). recognize and treat such toxicity or pollution. The primary effect is, therefore, understood to be the desired The word pharmacology is derived from the Greek words effect, the effect intended. Side effects are those effects which are not pharmakon (drug) and logos (study). The word drug has also a French intended, but do occur. Every healing or pleasure substance has side- origin— ‘drouge’ (dry herb). In clinical practice, drug is a chemical effects. That this distinction is relative can be illustrated by the substance that is used for the diagnosis, prevention and treatment of substance promethazine, better known under the trade name diseases in appropriate doses. WHO (1966) definition of a drug is Phenergan. This drug is used to counteract allergies such as hay fever, any substance or product that is used or intended to be used to modify but it also induces drowsiness. If the doctor prescribes it for hay fever, or to explore physiological system or pathological states for the benefit its drowsiness effect is the sideeffect. However, if Phenergan is used of the recipient. as a tranquilizer, drowsiness is the primary effect and the antiallergic Following are the major subdivisions of pharmacology: effect is the sideeffect. • Pharmacy is a branch of pharmacology that deals with When taking medicine we must always ask ourselves if its identification, selection, preservation, combining, analyzing, healing properties outweigh its sideeffects or the risk of possible standardization, preparing, compounding and dispensing of sideeffects. Take, for example, aspirin. Does its use as a painkiller, medicines for administration to the patient. A pharmacist almost always effective, outweigh the risk of gastric hemorrhage, a prepares compounds and dispenses medicines to the patient sideeffect in one out of every thousand users. upon a written order of a licensed medical practitioner. It is possible to administer a substance at such a small dosage • Pharmacognosy is a term derived from the Greek word that no effect whatsoever occurs. A larger dosage will bring about ‘gnosis’ which means knowledge. It is a branch of the effect wanted, while an even larger dosage will bring about a pharmacology that deals with the sources of drugs derived toxic effect. The difference between the minimum effective dosage from plants and animals. It is also a study of physical and 4 Principles of Clinical Pharmacology and Therapeutics Principles of Clinical Pharmacology and Therapeutics 5 chemical properties of such substances. useful data about the potency, usefulness, doses and toxicity • Pharmacokinetics is a term derived from the Greek word of new drugs for their safe clinical use. ‘kinesis’ meaning a movement. It deals with the time course • Biopharmaceutics deals with the development of new drug of drug absorption, distribution, metabolism and excretion. delivery systems and new dosage forms. It also provides In other words, it means “What the body does to the drug”. information how these dosage forms can influence the It provides a rational basis for doses of a drug and helps in pharmacodynamic and pharmacokinetic properties of a drug. dosage adjustment in altered physiological and pathological • Medicinal Chemistry is the science of designing and synthesis states like aging, renal or hepatic impairment. of a new drug. It is based on the structure activity relationship • Pharmacodynamics (Greek ‘dynamics’ means force) is the data of existing drugs belonging to one generic group. study of physiological and biochemical effects of drugs, mechanisms of action and the relationship of the plasma DRUG INFORMATION SOURCES concentration of the drug with its response and the duration Most useful drug information sources are textbooks, drug of action. In other words, it means “What the drug does to reference books, drug compendia and journal articles. They provide the body”. information about established drugs and furnish information for • Pharmacotherapeutics (Greek ‘therapia’ means medical understanding newer ones. treatment) deals with the use of drugs in the diagnosis, However, they do not include many other details such as trade treatment or prevention of a disease or their purposeful use names, physical and chemical properties, identification criteria, in alteration of physiological functions for the benefit of the standards of purity and strength, methods of storage and dosage recipient. In other words, it is the clinical application of the range for therapeutic use which are necessary from a legal point of pharma-cokinetic and pharmacodynamic knowledge of the view for drug control. drug. All these details of drugs are provided by Pharmacopoeias and • Therapeutics deals with the science and art of treatment of Formulary. They are collectively known as Drug Compendia. diseases. When therapy is based on clinical evidence it is Pharmacopoeias are prepared by a committee, which usually has called Empirical Therapeutics. It means the drug is effective, predominance of physicians. Formulary is prepared by a committee, although its mode of action is unknown. which usually has predominance of pharmacists. Then there are non- • Chemotherapy deals with the use of chemothera-peutic agents official sources of information. to inhibit or destroy invading microbes, parasites or cancer • Pharmacopoeia: It is an official code containing a selected list cells with minimal effect on healthy living tissues. of the established drugs and medicinal preparations with • Toxicology (Greek ‘toxicon’ means poison) is the science of descriptions of their physical properties, identification, purity, poisons. It deals with the adverse effects of drugs and potency and the minimum standard required and the average poisonous effects of various chemicals (household, dose for adults. Each country has its own pharmacopeia. environmental, industrial or homicidal). It is also concerned For example: with their source, chemical composition, action, tests for – British Pharmacopeia detection and antidotes.. Clinical toxicology is the science of detection, diagnosis and treatment of poisoning. – United States Pharmacopeia • Pharmacogenetics is a relatively new field. It deals with – Indian Pharmacopeia genetically mediated variations in drug responses. – European Pharmacopeia • Clinical Pharmacology is a branch of pharmacology that deals with the pharmacological effects of drugs in man. It gives – Russian Pharmacopeia 6 Principles of Clinical Pharmacology and Therapeutics Principles of Clinical Pharmacology and Therapeutics 7 – International Pharmacopeia • Maintenance of optimal health. • Formulary: It includes information on drugs, other Sources of drugs pharmaceutical products and formulated products in the respective countries. Synthetic Sources – British National Formulary is published by the At present majority of drugs used in clinical practice are prepared British Medical Association synthetically, such as aspirin, oral antidiabetics, antihi-stamines, – National Formulary is published by American amphetamine, chloroquine, chlorpromazine, general and local anaesthetics, paracetamol, phenytoin, synthetic corticosteroids, Pharmaceutical Association. sulphonamides and thiazide diuretics. – National Formulary of India is published by the Advantages of synthetic drugs are: Government of India. • They are chemically pure. Non- Official Compendia • The process of preparing them is easier and cheaper. • Control on the quality of the drug is excellent. They are secondary sources of drug information which give • Since the pharmacological activity of a drug depends on its useful and miscellaneous information about drugs for pharmacists chemical structure and physical properties, more effective and and medical practitioners. They include both generic and trade names safer drugs can be prepared by modifying the chemical of the drugs. The information is not limited to drugs which are structure of the prototype drug. approved for use by legally constituted committee of that country. Some examples of non-official compendia are: Natural Sources • AMA Drug Evaluation: By American Medical Association. Drugs are obtained from the following natural sources. • Drug Information for the Health Care Profession: By United States Plants: