General Pharmacology

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 GENERAL PHARMACOLOGY

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By, Md. Habibur Rahman, M. Pharm. (PhD), Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Definition of Pharmacology and its various branches Brief history of Pharmacology Various sources of drug information: official and non-official Sources of drugs Dosage forms and various routes of administration Mechanism of drug actions Factors modifying drug actions BRIEF OUTLINES

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Pharmacology deals with the knowledge of drugs. The word pharmacology is derived from the Greek words pharmakon (drug) and logos (study). Pharmacology is the branch of medicine which deals with drugs. Pharmacology is the study of how drugs exert their effects on living systems. Pharmacologists work to identify drug targets in order to learn how drugs work. Pharmacologists also study the ways in which drugs are modified within organisms. In most of the pharmacologic specialties, drugs are also used today as tools to gain insight into both normal and abnormal function. INTRODUCTION

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 MAJOR BRANCHES OF PHARMACOLOGY

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Clinical Pharmacology is a branch of pharmacology that deals with the pharmacological effects of drugs in human. It gives useful data about the potency, usefulness, doses and toxicity of new drugs for their safe clinical use. Experimental Pharmacology is a branch of pharmacology which deals with the study of drug effects in laboratory animals. In vitro – Isolated tissue. In vivo – Intact organism. Pharmacokinetics is a term derived from the Greek word 'kinesis' meaning a movement. It deals with the time course of drug absorption, distribution, metabolism and excretion. In other words, it means "What the body does to the drug". It provides a rational basis for doses of a drug and helps in dosage adjustment in altered physiological and pathological states like aging, renal or hepatic impairment.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Pharmacodynamics (Greek 'dynamics' means force) is the study of physiological and biochemical effects of drugs, mechanisms of action and the relationship of the plasma concentration of the drug with its response and the duration of action. In other words, it means "What the drug does to the body". Pharmacotherapeutics (Greek ' therapia ' means medical treatment) deals with the use of drugs in the diagnosis, treatment or prevention of a disease or their purposeful use in alteration of physiological functions for the benefit of the recipient. In other words, it is the clinical application of the pharmacokinetic and pharmacodynamic knowledge of the drug. Therapeutics deals with the science and art of treatment of diseases. When therapy is based on clinical evidence it is called Empirical Therapeutics. It means the drug is effective, although its mode of action is unknown. Chemotherapy deals with the use of chemotherapeutic agents to inhibit or destroy invading microbes, parasites or cancer cells with minimal effect on healthy living tissues.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Toxicology (Greek ' toxicon ' means poison) is the science of poisons. It deals with the adverse effects of drugs and poisonous effects of various chemicals (household, environmental, industrial or homicidal). It is also concerned with their source, chemical composition, action, tests for detection and antidotes.. Clinical toxicology is the science of detection, diagnosis and treatment of poisoning. Pharmacogenetics is a relatively new field. It deals with genetically mediated variations in drug responses. Biopharmaceutics deals with the development of new drug delivery systems and new dosage forms. It also provides information how these dosage forms can influence the pharmacodynamic and pharmacokinetic properties of a drug.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 BRIEF HISTORY OF PHARMACOLOGY Since the dawn of civilization, herbal drugs and other natural source materials have been used for the alleviation of human suffering. " Traditional " systems of medicine were developed by all civilizations. Pan Tsao is the great herbal "materia medica" of China. Sken Ming probably wrote it in 2735 B.C. Ayurveda contains the earliest Indian records of "traditional“ medicine. It dates back to 2500 BC. " Dravyaguna " is the first Ayurvedic "materia medica". Eber's Papyrus is the first written account of medical experiences from Egypt in 1600 B.C. Hippocrates (a Greek physician of 5th century B.C.) is known as the Father of Modern Medicine. Theophrastus (300 BC) is called the Father of Pharmacognosy because of his accurate observations of medicinal plants

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Pharmacology is a relatively recent branch of medical science. In fact, pharmacology originated as a branch of Physiology. Early half of the 19th century Samuel Haneman wrote the first edition of his book "Pharmacologia Sen Manuchitio ad Materiam Medicam " which gave birth to the discipline of Pharmacology. Oswald Schmiedeberg (1838-1921) is considered the Father of Pharmacology because he became the first University Professor of Pharmacology at Strausbergin 1872. In India, Col. Sir Ram Nath Chopra((1882-1973) initiated, promoted and established pharmacology as a teaching and research discipline. He was the first to be appointed as Professor of Pharmacology (1921) in the newly established Calcutta School of Tropical Medicine and was simultaneously head of the Department of Pharmacology at the Calcutta Medical College. He is known as the Father of Pharmacology in India.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 SOURCES OF DRUGS Drug is a substance which is used for the following purposes: Diagnosis of the disease Prevention of the disease Treatment or palliation (relief of symptoms) of disease Prevention of pregnancy (i.e. contraception) Maintenance of optimal health Drugs may be obtained from: Plants Animals Mineral / Earth Synthetic / Semi-synthetic sources Microbiological sources Recombinant DNA technology /Genetic engineering.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 SYNTHETIC SOURCES At present majority of drugs used in clinical practice are prepared synthetically. E.g.: aspirin, oral antidiabetics, antihistamines, amphetamine, chloroquine, chlorpromazine, general and local anaesthetics, paracetamol, phenytoin, synthetic corticosteroids, sulphonamides and thiazide diuretics. Advantages of synthetic drugs are: They are chemically pure. The process of preparing them is easier and cheaper. Control on the quality of the drug is excellent. Since the pharmacological activity of a drug depends on its chemical structure and physical properties, more effective and safer drugs can be prepared by modifying the chemical structure of the prototype drug.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 II. NATURAL SOURCES Drugs are obtained from the following natural sources: A- PLANTS: Following categories of drugs are derived from roots, leaves or barks of plants: a) Alkaloids These are nitrogenous heterocyclic bases, which are pharmacologically active principles of plants. They are composed of carbon, hydrogen, nitrogen and oxygen. They are bitter in taste and are often poisonous. These are, therefore, used in small doses. They are insoluble in water. However, they form salts with acids which are soluble in water.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 ALKALOID SOURCE Atropine Atropa belladonna Quinine Cinchona bark Morphine Papavarum somniferum Reserpine Rauwolfia serpentina Nicotine Tobacco Digoxin Digitalis lanata Caffeine Coffee, Tea, Cocoa Some examples of alkaloids and their sources are listed in the table:

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 b) Glycosides They are ether-like combination of sugar moiety with non-sugar moiety. They are called glucosides, if the sugar moiety is glucose. Sugar moiety is not essential for the pharmacological activity but it governs the pharmacokinetic properties of the glycoside. In the body it may be removed to liberate aglycone. Pharmacological activity resides in the non-sugar moiety that is called aglycone (or genin). Some examples are digitoxin, digoxin and ouabain.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 c) Oils . They are liquids which are insoluble in water. They are of three types and are used for various medicinal purposes. i ) Essential Oils (or volatile oils): Essential oils are obtained from leaves or flower petals by steam distillation, and have an aroma. They have no caloric or food value. They do not form soaps with alkalies . They do not leave greasy stain after evaporation. On prolonged stay, they do not become rancid (foul smell). They are frequently used as carminatives and astringents in mouth-washes. Some of these oils are solid at room temperature and sublime on heating e.g. menthol and camphor. Other example s are clove oil, peppermint oil, eucalyptus oil and ginger oil.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 ii) Fixed oils are glycerides of stearic , oleic and palmitic acid. They are obtained from the seeds that are present within the cells as crystals or droplets. They are non-volatile and leave greasy stains on evaporation. They have caloric or food value. They form soaps with alkalies . On prolonged stay, they become rancid. They do not have marked pharmacological activity and have little pharmacological use except castor oil (purgative) or arachis oil (demulcent). They may be of vegetable origin e.g. olive oil, castor oil, croton oil and peanut oil or of animal origin e.g. cod liver oil, shark liver oil and lard . iii) Mineral Oils are mostly petroleum products and extracted by fractional distillation. These are mixtures of hydrocarbons of the methane and related aliphatic series. These are extracted in various consistencies - hard paraffin, soft paraffin and liquid paraffin. Hard and soft paraffins are used as vehicles for preparation of ointments while liquid paraffin is employed as a purgative.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 d) Gums are colloidal exudates from plants which are polysaccharides chemically and yield simple sugars on hydrolysis. Upon addition of water, some of them swell or dissolve or form adhesive mucilage or remain unchanged. Uses: - In gut agar and psyllium seeds act as hydrophilic colloids and function as bulk purgatives. Gum acacia and gum tragacanth are used as suspending agents in making emulsions and mixtures.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 e) Resins are ill-defined solid substances found in plants, and are polymers of volatile oil. They are produced by oxidation and polymerization of volatile oils. They are insoluble in water but soluble in alcohol, chloroform and ether. Examples: oleoresins (aspidium); gum resins (asafoetida); oleogum resin (myrrh); balsams (benzoin, tolu, peru); benzoin shellac, podophyllum. Uses: Benzoin is used as inhalation in common cold. Tincture benzoin is applied as antiseptic protective sealing over bruises. Colophony (an oleoresin) is used as an ingredient in various plasters. Shellac (from Lucifer lacca) is used for enteric coating of tablets. Balsams are used in the treatment of cough and bronchitis for their antiseptic and protective properties. Podophyllum is used as an irritant purgative.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 f) Tannins are non-nitrogenous phenolic plant constituents which have an astringent action. Pyrogallol tannins are glycosides of glucose that occur in oak galls. Pyrocatechol tannins are sugar-free derivatives of catechol that are present in catechu and eucalyptus. Tannic acid is a tannin that is obtained from oak galls and is used for treating burns and diarrhoea .

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 B-ANIMAL SOURCES Some animal sources continue to be used to procure some modern drugs because of cumbersome and expensive procedures for the synthesis of such chemicals. For example: Insulin, extracted from pork and beef pancreas, is used for the treatment of diabetes mellitus. Thyroid powder for treating hypothyroidism. Heparin is used as an anticoagulant. Hormones and vitamins are used as replacement therapy. Vaccines (cholera, T.B., smallpox, polio and antirabic) and sera (antidiptheria and antitetanus) are used for prophylaxis/treatment.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 C-MICROBIOLOGICAL SOURCES Many life-saving drugs are obtained from fungi, moulds and bacteria e.g. penicillin from Penicillium notatum, chloramphenicol from Streptomyces venezuelae, grisofulvin (an anti-fungal drug) from Penicillium griseofulvum, neomycin from Streptomyces fradiae and streptomycin from Streptomyces griseus. D-MINERAL SOURCES Minerals or their salts are useful pharmacotherapeutic agents. For example: Ferrous sulfate is used in iron deficiency anaemia. Magnesium sulfate is employed as purgative. Magnesium trisilicate, aluminium hydroxide and sodium bicarbonate are used as antacids for hyperacidity and peptic ulcer. Kaolin (aluminium silicate) is used as adsorbent in antidiarrheal mixtures. Radioactive isotopes of iodine, phosphorus, gold are employed for the diagnosis/ treatment of diseases particularly malignant conditions.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Recombinant DNA Technology The new technique for preparing certain drugs e.g. Human insulin insulin analog , Erythropoietin. Human Insulin & insulin analogs may be prepared by inserting human or modified pro-insulin gene into E-coli or yeast & treating the extracted pro-insulin to form the insulin or insulin analog molecules. Advantages: Mass production. Cost effective Less immunological reactions.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 DOSAGE FORMS A. Classification of dosage forms of a drug according to physical properties Gaseous dosage forms Medicinal gases, Aerosols Liquid dosage forms Solutions, Emulsions, Suspensions Semisolid dosage forms Ointments, creams Pastes, Suppositories, Pessaries , Gels, Lotion Solid dosage forms Powders, Tablets, Capsules, Patches, Implants, Lozenges,

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 B. Classification of dosage forms according to the route of administration For systemic administration Peroral ( p .o) Sublingual (S.L) and buccal . Rectal Parenteral ( i.V , I.M, I.A) T ransdermal Inhalation For local administration Topical (on the skin or mucosa) Into/onto - the eye, nose, ear - the oral cavity - the vagina, rectum - the brochi - the skin Local parenteral ( viz Parenteral above) Oral (local effect within GIT; antacids, adsorbents)

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 ROUTES OF DRUG ADMINISTRATIONS Routes of Drug Administration 1. Oral (per os , p.o .) 2. Inhalation vapors, gases, smoke 3. Mucous membranes intranasal (sniffing) sublingual rectal suppositories 3. Injection ( parenteral ) intravenous (IV) intramuscular (IM) subcutaneous (SC) intraperitoneal (IP; nonhumans only) 4. Transdermal

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 oral – the most convenient and most commonly used route of administration Advantages 1. examples are tablets, capsules, and liquids 2. patients with dysphagia can usually swallow liquids without problems 3. infants may be given drugs in liquid form mixed with some formula or juice in a nipple 4. unconscious patients can receive liquid medications via NG tube (nasogastric) 5. oral route usually abbreviated as p.o. or PO (Latin per os, meaning through the mouth.) Disadvantages 1. some drugs, especially certain penicillins, cannot be administered orally as they become inactivated by the stomach acid, therefore must be administered via intramuscular or intravenous injection. 2. some drugs are so quickly metabolized by the liver after oral administration that as they pass through the portal circulation that therapeutic levels cannot be reached in the systemic circulation. These drugs must be administered via intravenous injection, e.g. lidocaine (Xylocaine) for cardiac dysrhythmias 3. some drugs combine chemically with certain foods or beverages to form an insoluble complex or interact to produce adverse side effects, e.g. tetracycline cannot be taken with dairy products

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Parenteral - any route of administration other than the oral route A. intradermal – injection of a liquid into the dermis, just below the epidermis; when correctly administered the tip of the needle is still visible through the skin, e.g. Mantoux test for TB B. subcutaneous – injection of a liquid into the fatty layer of tissue just below the dermis of the skin but above the muscle layer 1. slower absorption of the drug because only few blood vessels in this layer as compared to intramuscular injection, e.g. insulin, heparin, allergy shots 2. no official abbreviation but commonly accepted are: s.q., SQ, subQ, s.c., S.C., or subc.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 C. intramuscular – injection of liquid into the belly (area of greatest mass) of a large muscle 1. large muscles well supplied with blood vessels 2. provides for more rapid absorption than via subcutaneous injection 3. only five intramuscular injection sites that allow for administration with lowest risk of damage to adjacent nerves and blood vessels a. deltoid – located on upper arm, lateral aspect b. vastus lateralis – located on midthigh, lateral aspect c. rectus femoris – located on midthigh, anterior aspect d. . ventrogluteal – located on the side of the hip over gluteus muscle between anterior and superior spines of the iliac crest e. dorsogluteal – located over gluteus minimus and edge of gluteus maximus muscles in upper outer quadrant 4. some drugs are not water soluble and would precipitate out in muscular tissue, therefore are not acceptable to be administered intramuscularly, e.g. Valium, Librium

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 D. intravenous – injection of drug directly into the vein 1. therapeutic effect can be seen immediately 2. drug does not need to be absorbed 3. examples a. Pantothal for induction of general anesthesia b. Valium for control of continuous epileptic seizures c. chemotherapy drugs for cancer treatment d. antibiotics in high dosages

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 4. i.v . or IV injection can be accomplished in three ways a. I.V. push - the administration of a drug bolus by injecting a single dose of drug directly into the vein or through a port (rubber stopper) into an existing intravenous line in a very short time b. I.V. drip - mixing the drug with fluid in an I.V. bag or bottle to be administered continuously over several hours c. I.V. piggyback – mixing the drug in a very small I.V. bag or bottle connected through tubing to a port in the existing primary I.V

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 E. sublingual – the drug, usually in tablet form, is placed under the tongue and allowed to dissolve slowly. 1. the tablet is NOT swallowed. 2. the drug is absorbed quickly through oral mucous membranes into the large blood vessels under the tongue. 3. sublingual application provides a faster therapeutic effect than the oral route, e.g. nitroglycerin tablets and spray for angina.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 F. rectal – reserved for certain clinical situations, such as a vomiting patient and medication not available in injectable form, e.g. Tylenol. 1. preferred route when drugs are administered to relieve constipation or hemorrhoids 2. absorption via rectal route slow and often unpredictable in effectiveness G. vaginal – used to treat vaginal infections and vaginitis with creams and suppositories, e.g. Monistat suppositories, Premarin vaginal cream; also route of administration for vaginal contraceptive foams and gels

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 H. topical – applied directly to the skin or the mucous membranes of the eye, ear, nose, or mouth • effect usually local, not systemic, e.g. bacitracin antibiotic ointment, Sudafed nasal decongestant, Timoptic eye drops I. transdermal – applied to the skin via physical delivery through a porous membrane, e.g. nitroglycerin transdermal patch 1. therapeutic effects felt systemically 2. usually releases drug slowly over time, providing sustained therapeutic blood levels

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 J. inhalation – administration involves inhaling of a drug in gas or liquid form; drug is absorbed through alveoli of the lungs, e.g. nitrous oxide for general anesthesia, Proventil (albuterol) bronchodilator

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 FACTORS MODIFYING/AFFECTING DRUG ACTIONS Physiological Factors. Age Sex Pregnancy Race / Species Body weight Lactation Food II. Pathological Factors (Diseases). Liver Disease Renal Disease Malnutrition III. Genetic Factors. IV Psychological State V. Environmental Factors. VI. Drug related factors Dose of a drug (drug dosage) Form of a drug Route of drug administration Time of drug administration Drug combinations Drug cumulation (cumulative action) Drug tolerance

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 1. AGE Newborn Lower gastric acid secretion. Lower liver microsomal enzymes (glucuronyl transferase). Lower Plasma protein binding. Lower GFR & tubular secretion.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Immaturity of BBB in neonates. GIT absorption of ampicillin and amoxicillin is greater in neonatesdue to decreased gastric acidity. Chloramphenicol ---Grey baby syndrome (Inadequate glucouronidation of chloramphenicol with drug accumulation). Sulfonamides ------Hyperbilirubinemia & Kernicterus

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 CHILDREN • Tetracyclines Permanent teeth staining • Corticosteroids Growth & development retardation • Antihistaminics Hyperactivity.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Old Age Decrease Liver function. diazepam, theophylline . Decrease Kidney function. Digoxin, lithium. Decrease Plasma protein binding Increase sensitivity to CNS depressants. diazepam, morphine

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 SEX. •Testosterone increases the rate of biotransformation of drugs. •Decreased metabolism of some drugs in female (Diazepam). •Females are more susceptible to autonomic drugs ( estrogen inhibits choline estrase).

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 3. Pregnancy •Increase Cardiac output • Increase GFR and renal elimination of drugs. • Increase Vd • Increase Metabolic rate of some drugs. • Lipophilic drugs cross placental barrier & slowly excreted.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 4. Plasma Protein Binding – Malnutrition. – Drug Interaction.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 II. Pathological Factors Diseases cause individual variation in drug response (A) Liver Disease – Prolong duration of action = ↑ (t1/2). –decrease Plasma protein binding for warfarin, tolbutamide and cause more adverse effects. –decrease Hepatic blood flow and thus decrease clearance of morphine-propanolol. – Impaired liver microsomal enzymes Decrease Diazepam-rifampicin-theophylline

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 (B) Renal Disease –Decrease GFR. –Decrease tabular function. –Decrease Plasma albumin digoxin-lithium-gentamycin-penicillin. (C) Malnutrition – Decrease plasma protein binding of drugs. –Decrease amount of microsomal enzymes. – ↑Increases portion of free, unbound drug – warfarin

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 III. Genetic Factors Pharmacogenetics is the study of the relationship b/w genetic factors and drug response. Idiosyncrasy -abnormal drug reaction due to genetic disorder . –Acetylation. –Oxidation. –Succinylcholine apnea. –Glucose 6-phosphate dehydrogenase deficiency. GENETIC POLYMORPHISM The existence in a population of two or more phenotype with respect to the effect of a drug.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Acetylation enzymes deficiency • acetyl transferase (non-microsomal). • Isoniazid, sulphonamides, etc. • Slowacetylator phenotype -peripheral neuropathy . • Rapidacetylator phenotype -hepatitis. Pseudocholinesterase deficiency. • Succinyl choline ( Sk.muscle relaxant ) Succinylcholine apneadue to paralysis of respiratory muscles. Malignant hyperthermia • By succinyl choline due to inherited inability to chelate calcium by sarcoplasmic reticulum. • Carelease, muscle spasm, Temp.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Deficiency of Glucose–6 phosphate dehydrogenase (G-6-PD). G-6-PD Deficiency in RBCs increase hemolytic anemia upon exposure to some oxidizing drugs. – Antimalarial drug, primaquine. – Long acting sulphonamides. – Fava beans ( favism).

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 IV. Environmental FactorsMicrosomal Enzyme Inducers – Tobacco Smoke – Smokers metabolize drugs more rapidly than non smoker.

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Psychological State • More general anesthetics needed in nervous and anxious patients • Higher doses of chlorpromazine 500- 1000mg/day in schizophrenics • Placebos ( inert dosage forms) produce therapeutics benefits in psychomotor angina pectoris and bronchial asthma- Placebo reactors

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Regulated Dose Dose which is accurately adjusted by repeated measurement of affected physiological parameter.e.g :- Antihypertensives Anticoagulants Hypoglycemics Diuretics Dosage Forms & Time • Injectables rapidly absorbed and efficacious • Mixtures & powders rapidly absorbed than oral tablets and capsules for rapid effects • Hypnotics at night have better efficacy than daytime • Corticosteroid in single morning doses

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Route of drug Administration • Oral magnesium sulphate acts as purgative, Rectally it lowers intracranial tension, IV it depress CNS & CVS • Inhalation N-acetylcystyeine is mucolytic, IV it is drug of choice in acute paracetamol poisoning • Insulin and adrenaline not efficacious orally. Drug combinations • Drug synergism: Syn = Together ergon = Work • Additive effects: total effect of combination is equal to sum of effect of individual drug. • Levodopa + Carbidopa • Sulfamethoxazole + Trimethoprim • Acetylcholine + Physostigmine

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Drug Antagonism • One drug decrease or inhibit the effect of another drug by opposite action • Physical • Chemical • Physiological • Pharmacological Physical- • Activated charcoal in Alkaloid poisoning Chemical- Chelating agent BAL and Arsenic • HCl & H2CO3 Physiological Antagonism • Opposite effects of two drug on same function • Insulin and glucagon on blood sugar level • Hydrochlorothiazide and amiloride on urinary K+ execration • Histamine and adrenaline on BP or bronchial muscles

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Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206 Drug Cumulation • Repeated drug administration • Rate of administration > rate of elimination Cumulative toxicity – • Digoxin • Digitoxin • Chloroquine • Arsenic

PowerPoint Presentation: 

Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206

PowerPoint Presentation: 

Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206

PowerPoint Presentation: 

Copy right: Md. Habibur Rahman, M. Pharm., Asst. Professor, Dept. of Pharmacology, Anurag Pharmacy College, A.P-508206