Introduction to Pharmacology PDF

‌‫المحاضره‌االولی‬ ‌ Introduction to Pharmacology Learning Objectives At the end of this chapter the student will be able to: 1. Define various terminologies used in pharmacology. 2. Know about nature and sou...

‌‫المحاضره‌االولی‬ ‌ Introduction to Pharmacology Learning Objectives At the end of this chapter the student will be able to: 1. Define various terminologies used in pharmacology. 2. Know about nature and sources of drugs. 3. Understand pharmacokinetics like absorption, distribution, metabolism and excretion (ADME) of drugs. Understand theoretical pharmacokinetics like half-life. 4. Pharmacodynamics like mechanism of drug action, dose relationship. A. Definitions: 1. Drugs: chemical substances that, when introduced into the body, alters the body's function by interactions at the molecular level. 2. Prodrug: a chemical that is readily absorbed and distributed and then converted to the active drug by biologic processes — inside the body. 3. Pharmacology: Pharmacology is the study of interaction of drugs with living organisms. Pharmacol : medicine; Logia: study 4. Clinical Pharmacology: It evaluate the pharmacological action of drug preferred route of administration and safe dosage range in human by clinical trails. 5. Pharmacy: It is the science of identification, selection, preservation, standardisation, compounding and dispensing of medical substances. 6. Pharmacotherapeutics: It deals with the proper selection and use of drugs for the prevention and treatment of disease. 7. Toxicology: It’s the science of poisons. Many drugs in larger doses may act as poisons. Poisons are substances that cause harmful, dangerous or fatal symptoms in living substances. 8. Chemotherapy: It’s the effect of drugs upon microorganisms, parasites and neoplastic cells living and multiplying in living organisms. 9. Pharmacopoeia: An official code containing a selected list of the established drugs and medical preparations with descriptions of their physical properties and tests for their identity, purity and potency e.g. Indian Pharmacopoeia (I.P), British Pharmacopoeia (B.P). 10. Pharmacokinetics: Study of the absorption, distribution metabolism and excretion (ADME) of drugs (―i.e what the body does to the drug‖) 11. Pharmacodynamics: The study of the biological and therapeutic effects of drugs (i.e, ―what the drug does to the body‖). B. Drugs are obtained from: 1. Minerals: Liquid paraffin, magnesium sulfate, magnesium trisilicate, 2. Animals: Insulin, thyroid extract, heparin and antitoxin sera, etc. 3. Plants: Morphine, digoxin, atropine, castor oil, etc. 4. Synthetic source: Aspirin, sulphonamides, paracetamol, zidovudine, etc. 5. Micro organisms: Penicillin, streptomycin and many other antibiotics. 6. Genetic engineering: Human insulin, human growth hormone etc. Out of all the above sources, majority of the drugs currently used in therapeutics are from synthetic source. How are Drugs Administered? (Routes of Administration) ENTERAL(GI route) (i) Buccal cavity: e.g. nitrates (ii) Stomach: e.g. aspirin, alcohol (iii) Intestine: e.g. most of non ionized and ionized drugs. (iv) Rectum: e.g. rectal suppositories, bisacodyl laxatives. Parenteral route: IV, IM, SC most common – IV provides immediate availability – IM/SC-must rely on vascular system perfusion to site to be absorbed. Others routes: - Intrathecal: Injected into subarachnoid space of spinal cord e.g. spinal anaesthetics. - Intraperitonial: Injections given into the abdominal cavity e.g. infant saline, glucose. - Intra-articular: Injected directly into a joint e.g. hydrocortisone - Transcutanoeus, - Topical/ local route - Inhalation  Pharmacokinetics Pharmacokinetics deals with the absorption, distribution, metabolism and excretion drugs in the body (ADME). Drug absorption: Absorption is the process by which the drug enters in to the systemic circulation from the site of administration through biological barrier. In case of intravenous or intra-arterial administration the drug bypasses absorption processes and it enters into the circulation directly. A. Biotransport of drug: It is translocation of a solute from one side of the biological barrier to the other. Passage of drug across membrane. 1) Simple diffusion ( Passive transfer). 2) Filtration 3) Facilitated diffusion 4) Specialized transport ii) Active transport 5 ) Endocytosis. 1. Simple diffusion: Movement of a solute through a biological barrier from the phase of higher concentration to phase of lower concentration. No need of energy e.g. highly lipid soluble drugs. 2. Filtration: Is the process by which water soluble drug of relatively low molecular weight crosses the plasma membrane through pores as a result of hydrodynamic pressure gradient across the membrane e.g. urea and ethylene glycol. 3.Facilitated diffusion: It means the passage of drug across the biological membrane along the concentration gradient by the protein carrier mediated system also called as carrier mediated diffusion. It depends on number of carrier e.g. tetracycline, pyrimidine. 4. Active transport: The process by which drugs pass across the biological membrane most often against their concentration gradient with the help of carriers along with the expenditure of energy e.g. alpha methyl dopa, levodopa, 5-fluoro-uracil, 5 bromouracil. ATP Active transport Higher Low concentration concentration Intestinal Apical cell membrane Cell interior lumen Drug + Carrier Drug Carrier Carrier Drug Carrier Examples: 5-fluorouracil, levodopa, riboflavine, body nutrients, l - amino acids, thiamine, nicotinic acid, vit B6, etc. 5. Endocytosis: It is the process by which the large molecules are engulfed by the cell membrane and releases them intracellularly e.g. protein, toxins (botulinum, diphtheria). E- Pinocytosis High Lower concentration concentration Intestinal Apical cell membrane Cell interior lumen Drug Drug vacoule Not important for drug absorption 2. Bioavailability: It is the rate and amount of drug that is absorbed from a given dosage form and reaches the systemic circulation following non-vascular administration. When the drug is given IV, the bioavailability is 100%. It is important to know the manner in which a drug is absorbed. The route of administration largely determines the latent period between administration and onset of action. Drugs given by mouth may be inactive for the following reasons: a) Enzymatic degradation of polypeptides within the lumen of the gastrointestinal tract e.g. insulin. b) Poor absorption through gastrointestinal tract e.g. aminoglycoside antibiotic. c) Inactivation by liver e.g. testosterone during first passage through the liver before it reaches systemic circulation. Bioavailability curves Single dose bioavailability test involves an analysis of plasma or serum concentration of the drug at various time intervals after its oral administration and plotting a serum concentration time curve. AUC after oral dose Bioavailability (F) = --------------------. AUC after I.V. dose Factors affecting drug absorption and bioavailability: a) Physico-chemical properties of drug b) Nature of the dosage form c) Physiological factors d) Pharmacogenetic factors e) Disease states. a ) Physico-chemical properties of drug: i) Physical state: Liquids are absorbed better than solids and crystalloids absorbed better than colloids. ii) Lipid or water solubility: Drugs in aqueous solution mix more readily than those in oily solution. However at the cell surface, the lipid soluble drugs penetrate into the cell more rapidly than the water soluble drugs. iii) Ionization: Most of the drugs are organic compounds. Unlike inorganic compounds, the organic drugs are not completely ionized in the fluid. Unionized component is predominantly lipid soluble and is absorbed rapidly and an ionized is often water soluble component which is absorbed poorly. Most of the drugs are weak acids or weak bases. It may be assumed for all practical purposes, that the mucosal lining of the G.I.T is impermeable to the ionized form of a weak organic acid or a weak organic base. Acidic drugs: rapidly absorbed from the stomach e.g. salicylates and barbiturates. Basic drugs: Not absorbed until they reach to the alkaline environment i.e. small intestine when administered orally e.g. pethidine and ephedrine. b) Dosage forms: i) Particle size: Small particle size is important for drug absorption. Drugs given in a dispersed or emulsified state are absorbed better e.g. vitamin D and vitamin A. ii) Disintegration time and dissolution rate. Disintegration time: The rate of breakup of the tablet or capsule into the drug granules. Dissolution rate: The rate at which the drug goes into solution. iii) Formulation: Usually substances like lactose, sucrose, starch and calcium phosphate are used as inert diluents in formulating powders or tablets. Fillers may not be totally inert but may affect the absorption as well as stability of the medicament. Thus a faulty formulation can render a useful drug totally useless therapeutically. c) Physiological factors: i) Gastrointestinal transit time: Rapid absorption occurs when the drug is given on empty stomach. However certain irritant drugs like salicylates and iron preparations are deliberately administred after food to minimize the gastrointestinal irritation. But sometimes the presence of food in the G.I tract aids the absorption of certain drugs e.g. griseofulvin, propranolol and riboflavin. ii) Presence of other agents: Vitamin C enhances the absorption of iron from the G.I.T. Calcium present in milk and in antacids forms insoluble complexes with the tetracycline antibiotics and reduces their absorption. iii) Area of the absorbing surface and local circulation: Drugs can be absorbed better from the small intestine than from the stomach because of the larger surface area of the former. Increased vascular supply can increase the absorption. iv) Enterohepatic cycling: Some drugs move in between intestines and liver before they reach the site of action. This increases the bioavailability e.g. phenolphthalein. v) Metabolism of drug/first pass effect: Rapid degradation of a drug by the liver during the first pass (propranolol) or by the gut wall (isoprenaline) also affects the bioavailability. Thus a drug though absorbed well when given orally may not be effective because of its extensive first pass metabolism. d) Pharmacogenetic factors: Individual variations occur due to the genetically mediated reason in drug absorption and response. e) Disease states: Absorption and first pass metabolism may be affected in conditions like malabsorption, thyrotoxicosis, achlorhydria and liver cirrhosis.