L. 1 Dr. Mohammed AL-Zobaidy Basic Principles in Pharmacology Learning objectives: by the end of this lecture you should Understand the possible uses of drugs. Explain why a drug has different names. Identify the criteria of an ideal drug. Recognise the factors that determine the intensity of drug action. Define OTC drugs and list the criteria for selecting them. Recognise the definitions of some basic pharmacological terms. 1
Introduction Pharmacology can be defined as the study of the effects of substances on living systems through chemical processes, especially by binding to receptors and activating or inhibiting normal body processes. The precursor of pharmacology is material medica which is the science that deals with preparation and medical uses of drugs (Figure 1.1). Figure 1.1 History of pharmacology 2
Uses of the drugs Prevention of disease. This could be primary prevention or secondary prevention. Treatment of disease with or without other modalities of treatment. Diagnosis of disease. Sources of drugs A drug is any substance that causes a change in biological function through its chemical actions. In most cases, the drug molecule interacts with a receptor in the biological system that has a regulatory function. In general drugs could be: Endogenous substances that are synthesised within the body such as Hormones (thyroxine, insulin, testosterone, oestrogen). Chemicals that are synthesised outside the body (Xenobiotics). For example, antimicrobial agents (antibiotics). Chemicals that have almost exclusively harmful effects (Poisons). Those synthesised by plants and animals are called organic poisons (Toxins) in contrast to the inorganic poisons such as lead and arsenic. Drugs names Chemical name: it describes the chemical structure of the substance. For example, 1, 25- dihydroxy cholecalciferol is the chemical name of Vitamin D3. The disadvantage of the chemical name of a drug is that it is too long and difficult to use while prescribing. Nonproprietary name: it is also known as a generic name and it describes the pharmaceutical substances or active pharmaceutical components of a drug. In other word, it represents the scientific name of the drug. For example, captopril (generic name) while Capoten (trade name). Sometimes, there are pharmaceutically related substances and this relationship is described by using a common stem in their generic names. For example, captopril, enalapril, lisinopril, ramipril. Proprietary (brand) name: this is the trade name of the drug that is chosen by the manufacturer or the company that produces the drug. This name should be simple, easy to remember (Capoten for captopril) and suggestive of the clinical use (Flu-out) or the active components of the formulation (Paracetol). Properties of ideal drugs 1. Effectiveness: a drug that produces the therapeutic effect aimed for. 2. Safety: safe even at high concentrations and for long periods of administration. 3. Selectivity: selective for specific action with no side effects such as cramps, fever, nausea, depression, anaemia, etc. 4. Reversible action: the drug can be removed from the body within specific time (short half life). 3
5. Predictability: the patient's response to drug is already anticipated. 6. Ease of administration: reduced number of doses and easy of administration. 7. Freedom from drug interactions: does not enhance or inhibit the effectiveness of other drugs. 8. Low cost: especially for drugs used for treatment of chronic diseases. 9. Chemical stability: a drug that does not become ineffective when stored. 10. Possession of a simple generic name that can be easily remembered and pronounced.. Factors that determine the intensity of drug action 1. Age: infants and elderly patient require special consideration, because of altered body weight, renal function, hepatic drug metabolism as well as stage of body development. 2. Body size: drug dosage should be modified according to body weight, body surface area. 3. Gender: although there are no major differences between males and females in their responses to drugs, special care is needed when prescribing drugs during pregnancy and lactation. 4. Race: some drug effects are seen more frequently in certain races than others. For example, the Japanese are more susceptible than Indians to the side effects of hydroxyquinolone. 5. Genetic influences: variations in drug response could be attributed to the genetic makeup of the patient. For example, the development of haemolytic anaemia after treatment with nitrofurantoin or primaquine in patients with G6PD deficiency. 6. Route of administration: drug response is greatly affected by the route of drug administration. 7. Time of administration: the time of the day at which drug is administered may affect response to some drugs. For example, the best time for administration of corticosteroids is in the morning. 8. Psychological state: alterations in the psychological state of the patient may affect his/ her response to drugs. For example, people who have anxiety will require higher dose of a general anaesthetic drug. 9. Disease state: drug responses are greatly influenced by pathological conditions affecting the heart, kidney, liver and GIT. 10. The concurrent use of other drugs: administration of two or more drugs at the same time may increase or decrease the action of administered drug(s). 11. Tolerance: it means that a drug must be administered with progressively higher doses to get the desired effect. It could due to natural or acquired. The latter could be acute or chronic. 4
Over the counter drugs Drugs can be divided into prescription drugs (those and those sold by prescription only) and nonprescription or Over-The-Counter drugs (OTC). Examples include: analgesics, nasal decongestants, antacids, cold preparations, topical agents, antitussive agents. You should be familiar with OTC drugs because: Many of these OTC drugs are useful in the treatment of common illnesses. For example, antihistamines in the treatment of common cold and allergy. Many of the active constituents of the OTC drugs may interact with other prescription drugs or they may worsen existing illnesses. For example, Cimetidine (H2 blocker) may inhibit the hepatic metabolism of other drugs such as phenytoin, theophylline and warfarin. This inhibition results in increased plasma concentration and toxicity of these drugs. Another example is that aspirin and other NSAIDs may worsen already present peptic ulcer. The inappropriate use of the OTC drugs may cause important clinical problems for patients. For example, aspirin should not be prescribed for children with viral infection even when they have fever because of the risk of Reye's syndrome. Also, inappropriate use of antacids such as aluminium hydroxide may cause constipation. Criteria for selection of OTC drugs Select an OTC product that contains as few as possible ingredients. Those with a single ingredient are preferable. Be aware of the active ingredients in each product to avoid possible overdose and toxicity. Be aware of the effective doses and duration of action of all ingredients in the OTC product. Select the product that contains a therapeutically effective dose. Select the product that is suitable for the patient s clinical condition. In case of children, select the product with the appropriate dose and formulation. Basic terms Medical pharmacology: is the science that deals with substances used for the prevention, diagnosis and treatment of disease. Drug receptors: the component of a cell or an organism that interacts with a drug and initiates the chain of events that lead to the drugs observed effects. Pharmacogenetics: is the study of the relation between the individual s genetic makeup and his/ her response to specific drugs. Toxicology: is the branch of pharmacology that studies the unwanted effects of drugs on living systems, from cell level to the complex living body. Pharmacokinetics: is the study of the effects of the body on drugs. 5
Pharmacodynamics: is the study of the effects of drugs on the body. Chemotherapy: it refers to the use of drugs in the eradication of microbial agents (bacteria, viruses or parasites), but without causing injury to the patient. Also, it includes treatment of cancer cells. Pharmacy: it is the science that deals with preparing, compounding and dispensing drugs. It is independent from pharmacology. Teratogenicity: it is a kind of unwanted drug effects that result in foetal abnormalities when the drug is administered in the first trimester of pregnancy. For example, thalidomide, anticancer agents, antiepileptic drugs. Immunopharmacology: it deals with the effects of drugs on the immune response and the formation of antibodies in response to drug therapy. Pharmacotherapeutics: it means that drug therapy involves selection of a drug for a specific disease and it also involves knowledge, skills, wisdom and responsibility for the use of this drug. Placebo: it is an inactive substance that is used for its nonspecific, psychological or psychophysiological effects on a patient, on symptoms, or on a disease. It is mostly used as a control in controlled clinical studies. Iatrogenic diseases: are diseases caused by drugs or medical procedures. All drugs have the potential to cause iatrogenic diseases; therefore, a careful risk-benefit ratio assessment must be done before using a drug or carrying out a medical procedure. For example, peripheral neuropathy cause by INH, aplastic anaemia caused by chloramphenicol. 6