Introduction to Pharmacology PDF

# Introduction to Pharmacology ## Principles of Drugs ### THE HISTORY OF PHARMACOLOGY: * Prehistoric people recognized the beneficial or toxic effects of many plant and animal materials. Early written records from Iraq, China and from Egypt list remedies, including a few still recognized as usefu...

# Introduction to Pharmacology ## Principles of Drugs ### THE HISTORY OF PHARMACOLOGY: * Prehistoric people recognized the beneficial or toxic effects of many plant and animal materials. Early written records from Iraq, China and from Egypt list remedies, including a few still recognized as useful drugs today. However, many were worthless or actually harmful. * In the 1500 years ago, rational methods were introduced into medicine. However, none was successful owing to the dominance of systems of thought that purported to explain all of biology and disease without the need for experimentation and observation. This idea that disease was caused by excesses of bile or blood in the body, and that wounds could be healed by applying a saliva to the weapon that caused the wound. * Around the end of the 17th century, reliance on observation and experimentation began to replace theorizing in medicine. As the value of these methods in the study of disease became clear, physicians began to apply them to the effects of traditional drugs used in their own practices. * In the late 18th and early 19th centuries, methods of experimental animal physiology and pharmacology began to develop. * Advances in chemistry and the further development of physiology therapeutics, only about 50 years ago it became possible to evaluate therapeutic claims. Around the same time, a major expansion of research efforts in all areas of biology began. As new concepts and new techniques were introduced, information accumulated about drug action. ### Approximate Dates | Time | Description | | ----------------------- | ---------------------------------------------------- | | ~ 3000 BC | Therapeutics, magical potions, herbal remedies. | | ~ 1600 AD | Commerce, Apothecaries | | ~ 1800 | Chemistry, natural products, chemical structure | | ~ 1900 | Synthetic chemistry, synthetic drugs | | ~ 1970 | Biomedical Sciences, Pharmacology, Pathology, Physiology, Pharmaceutical Industry, Biochemistry, Molecular biology,Biopharmaceuticals | | 2000 | Pharmacology | ## Pharmacology: Defined as the study of substances (Drugs) that interact with living systems through binding to regulatory molecules and activating or inhibiting normal body processes. These drugs may be administered to achieve a beneficial therapeutic effect on some process or for their toxic effects on regulatory processes in the patient. ### Medical Pharmacology The science of substances used to prevent, diagnose, and treat disease. ### Molecular Pharmacology The scientific study of the biochemical and biophysical characteristics of drugs at the molecular level and their interaction with, and effects on, biological macromolecules and cellular structures and processes. ### Pharmacotherapy Treatment of health conditions by using pharmaceutical products (drugs) as medication ### Therapeutics The treatment and care of patient for the purpose of both preventing and combating disease or alleviating pain or injury. ### Pharmacogenetics Which branches of pharmacology deal with genetic basis for difference drug responsiveness among population? ### Pharmacogenomics The relation of the individual's genetic makeup to his or her response to specific drugs ### Pharmacoeconomy Branch of health economics evaluates the costs, outcomes of drugs and services ### Pharmacoepidemiology Study of interactions between drugs and human populations, investigating, in real conditions of life, benefits, risks and use of drugs. ### Pharmacometrics Science concerned with mathematical models of pharmacology, biology, disease, and physiology used to describe and quantify interactions between drugs and patients, including beneficial, and side effects resultant from such interfaces. ### Toxicology The branch of pharmacology which deals with the undesirable effects of chemicals on living systems, from individual cells to complex systems. ### Side Effects of Drugs The unwanted effects that are possibly related to a drug. Vary from minor to life-threatening events (may be useful). ### Adverse drug reaction (ADR) or event (ADE) An harmful unintended response occurring in certain susceptible patients include intolerance, idiosyncrasy (frequently genetic in origin), and allergy (usually immunologically mediated), all. ### Pharmacovigilance The science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine related problem. ## Drug Drug may be defined as any substance that produce a change in biologic function through its actions. In the great majority of cases, the drug molecule interact with a specific molecule in the biologic system that plays a regulatory role. Molecules called a Receptor. Drugs may be synthesized within the body (e.g., Hormones) or may be chemicals not synthesized in the body. Drugs to interact chemically with its receptor, a drug molecule must have: - Appropriate size - Electrical charge - Shape - Atomic composition Furthermore, a drug is often administered at a location distant from its intended site of action, e.g., a pill given orally to relieve a headache. Therefore, a useful drug must have the necessary properties to be transported from its site of administration to its site of action. Finally, a practical drug should be inactivated or excreted from the body at a reasonable rate so that its actions will be of appropriate duration. Drugs may be solid at room temperature (e.g., aspirin, atropine), liquid (e.g., nicotine), or gaseous (nitrous oxide). These factors determine the best administration routes. ### Xenobiotics Chemicals which are not natural and therefore are foreign to living organisms and ecosystems, such as chemically synthesized compounds (including drugs, pesticides, and carcinogens) ### Orphan Drugs and Treatment of Rare Diseases Drugs for rare diseases—so-called orphan drugs—can be difficult to research, develop, and market. ## Classification of Drugs Drugs may be classified by: 1. Body system, e.g., alimentary, cardiovascular 2. Therapeutic use, receptor blockers, enzyme inhibitors, ion channels 3. Mode or site of action. Loop diuretic 4. Molecular structure, e.g., glycoside, alkaloid, steroid ## Pharmacodynamics ### What Drugs do to the Body (Mechanisms of Drug Action) 1. **Drugs Act on the Cell Membrane by:** - *Action on specific receptors:* e.g., histamine receptors - *Interference with selective passage of ions across membranes:* e.g., calcium entry (or channel) blockers. - *Inhibition of membrane-bound enzymes and pumps:* e.g., membrane-bound ATPase by cardiac glycoside 2. **Drugs Act on Metabolic Processes within the Cell:** - *Enzyme inhibition* - *Inhibition of transport processes* - *Incorporation into larger molecules* - *Altering metabolic processes* 3. **Drugs Act Outside the Cell by:** - *Direct chemical interaction:* e.g., antacids - *Osmosis:* as with purgatives, e.g., magnesium sulphate, and diuretics, e.g., mannitol. ## Nomenclature (Names) of Drugs Any drug may have names in all three of the following classes: 1. The full chemical name 2. A nonproprietary (official, approved, generic) name 3. A proprietary (brand) name **Example: One Drug - Three Names** 1. 3-(10, 11-dihydro-5H-dibenz (b, f)-azepin-5-yl) propyldimethylamine 2. Imipramine 3. Tofranil (UK), Prodepress, Surplix, Deprinol, etc (various countries) ## Receptors Most receptors are protein macro-molecules. When the natural transmitter or hormone (endogenous ligands) binds to the receptor, the proteins undergo an alteration in conformation which induces changes in systems. ### Types of Drug-receptors Interaction 1. **Agonists.** Drugs that activate receptors do so because they resemble the natural transmitter or hormone (endogenous ligands). 2. **Antagonists (blockers)** of receptors are sufficiently similar to the natural agonists to be “recognized” by the receptor and to occupy it without activating a response, thereby preventing (blocking) the natural agonist from exerting its effect. 3. **Partial agonists.** Some drugs, in addition to blocking access of the natural agonist to the receptor, are capable of a low degree of activation, i.e., they have both antagonist and agonist action. 4. **Inverse agonists.** Some substances produce effects that are specifically opposite to those of the agonist. 5. **Physiological (functional) antagonism:** Mechanism by which one drug may oppose the effect of another drugs. ## Enzymes Interaction between drug and enzyme is in many respects similar to that between drug and receptor. Drugs may alter enzyme activity because they resemble a natural substrate and hence compete with it for the enzyme. ## Potency and Efficacy **Potency** is the amount (weight) of drug in relation to its effect, e.g., if weight-for-weight drug A has a greater effect than drug B, then drug Ais more potent than drug B. **Pharmacological efficacy** refers to the strength of response induced by occupancy of a receptor by an agonist. **Therapeutic efficacy** effectiveness, is the capacity of a drug to produce an effect and refers to the maximum such effect, e.g., if drug A can produce a therapeutic effect that cannot be obtained with drug B, however much of drug B is given, then drug A has the higher therapeutic efficacy. ## Tolerance Continuous or repeated administration of a drug is often accompanied by a gradual diminution of the effect it produces. ## Drug Passage Across Cell Membranes 1. Passive diffusion 2. Filtration and bulk flow 3. Endocytosis 4. Ion-pairing 5. Active transport ## Pharmacokinetics is What the Body Does to Drugs The individual processes (Absorption, Distribution, (Metabolism (biotransformation), Execration) Elimination. ### Absorption Considerations of anatomy, physiology, pathology, pharmacology, therapeutics and convenience determine the routes by which drugs are administered. Usually these are: 1. Interal: by mouth (swallowed) or by sublingual or by rectum2. 2. Parenteral: by injection to intravenous or, intramuscular, subcutaneous or infusion, 3. Other routes, e.g., inhalation, topical application for local (skin, eye, lung) or for systemic (transdermal) effect intrathecal, intradermal, intranasal, intratracheal, intrapleural, are used when appropriate. ### Presystemic (First-pass) Elimination Drugs are metabolized in a single passage through the gut wall and (principally) the liver. ### Dose - Sub Therapeutic dose - Therapeutic dose: - Minimum dose: - Maximum dose: - Toxic dose: - Fatal dose: - **Median effective dose (ED50):** the dose at which 50% of individuals exhibit the specified effect. - **Median toxic dose (TD50):** the dose required to produce a particular toxic effect in 50% of animals - **Median lethal dose (LD50):** the dose required to produce death in 50% of animal - **Duration of action:** Time from beginning of drug action to end. - **Onset of drug action:** Time from drug administration to appearance of action. - **T1/2:** Time required to decrease drug amount in blood to half. - **Bioavailability:** Fraction of unchanged drug in blood to dose administered. ### Elimination Removed of drug from body by Renal, hepatic, pulmonary elimination