INTRODUCTORY LECTURE IN PHARMACOLOGY Learning Resources 1 Textbooks

INTRODUCTORY LECTURE IN PHARMACOLOGY

Learning Resources 1. Textbooks: 1. Basic and Clinical Pharmacology by Bertram G. Katzung, Mc Graw-Hill. 2. Lippincott’s Illustrated Reviews: Pharmacology, Mary J Mycek, Richard A Harvey, Pamela C Champe 3. Goodman and Gillman’s Pharmacological Basis of Therapeutics, Laurence Brunton, John Lazo, Keith Parker.

Cont’d e-Books Journals

Course Objectives To establish a good grasp of concepts important to the discipline of pharmacology. To have a thorough understanding of pharmacodynamics and pharmacokinetics.

What is Pharmacology? Pharmacology: derived from 2 Greek words - Pharmakon = drug - Logos = word/discourse i. e. the study of substances (drugs or chemicals) that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes.

Cont’d Among chemical agents are: Hormones Neurotransmitters Growth factors Drugs Toxic agents in the environment

Cont’d The medicinal/organic chemist may discover a new chemical compound, but it is the pharmacologist who is responsible for testing it for pharmacological activity.

Cont’d A drug is a single chemical entity present in a medicine, that is used for diagnosis, prevention and treatment of diseases. It brings about a change in the normal body physiology through chemical interaction and does not produce a new effect.

Cont’d WHO (1966): “Drug is any substance or product which is used to modify or explore physiological system or pathological states for the benefit of the recipient”.

Cont’d A drug can be defined as a natural product, chemical substance, or pharmaceutical preparation intended for administration to a human or animal to diagnose or treat a disease.

Cont’d The word drug is derived from the French drogue , which originally meant dried herbs and was applied to herbs in the marketplace used for cooking rather than for any medicinal reason.

Cont’’d Medication, and less frequently, medicament are terms that are synonymous with the word drug.

Cont’d Pharmacology studies drug’s: - Origin - History - Dosage - Pharmacokinetics - Pharmacodynamics (action) - Effect - Side effects - Adverse effects

Cont’d - Toxicity Clinical uses Contraindications

Cont’d Pharmacology is a unique combination of the biomedical and clinical sciences, and it serves as a link between the two broad areas.

Cont’d There are two main branches of Pharmacology: Pharmacokinetics-what the body does to the drugs. It studies the fate of drugs once ingested and the variability of drug response in varying patient population. It includes: drug absorption drug distribution drug metabolism drug excretion

Cont’d Pharmacodynamics-what drugs do to the body. It studies the mechanism by which drugs act. Also studies endogenous agents.

Cont’d Pharmaceutical: Administration; Drug Dose Disintegration of Drug. * Pharmacokinetics: Absorption/Distribution Metabolism/Excretion. * Pharmacodynamics: Drug Receptor Interaction. * Pharmacotherapeutics: Drug Effect or Response.

Subdivisions of Pharmacology Pharmacotherapeutics: Use of drugs for prevention and cure of diseases. Pharmacy: is the science and profession concerned with the preparation, storage, dispensing, and proper use of drug products. Related sciences include pharmacognosy, medicinal chemistry, and pharmaceutical chemistry. Pharmacognosy is the study of drugs isolated from natural sources, including plants, microbes, -

Cont’d minerals. Medicinal chemistry is a branch of organic chemistry that specializes in the design and chemical synthesis of drugs. Pharmaceutical chemistry , or pharmaceutics , is concerned with the chemical properties and formulation of pharmaceutical products, such as

Relationship between P’kinetics & P’dynamics,

Cont’d Chemotherapy: the branch of therapeutics, which is concerned with the effects of drugs on microorganisms and parasites as well as on malignancies.

Cont’d Toxicology: the science of poisons, which includes detection and measurement of poisons as well as treatment of poisoning.

Cont’d - - - Neuropharmacology: study of the effect of drug components on the nervous system Molecular Pharmacology: study of the biochemical and biophysical characters of drug molecules Clinical Pharmacology: study of drugs in the humans

Cont’d - Posology: how medicines are dosed or calculation of dose - Pharmacogenomics: It describes the use of genetic information to guide the choice of drug therapy on an individual basis. It’s in essence a branch of pharmacogenetics.

Cont’d Pharmacogenetics: Study of drugs and their interaction with genetic molecule. Pharmacoepidemiology: The study of drug effects at the population level. It is concerned with the variability of drug effects between individuals in a population and between populations.

Cont’d - - Pharmacoeconomics: Quantifies in economic terms the cost and benefit of drugs used therapeutically. Immunopharmacology: The area of Pharmacology that relates the response of the immune systems of the body to drugs.

Cont’d - Systemic Pharmacology: How drugs affect the various body systems e. g. CVS, Renal, Respiratory, GIT.

Sources of Drugs are obtained mainly from plants, animals, microbes and mineral sources, but a majority of them that are used therapeutically are from synthetic or semi-synthetic products.

From Plants The pharmacologically active components in vegetable drugs are: Alkaloids: are basic substances containing cyclic nitrogen. The important alkaloids are obtained from: • Opium (Papaver somniferum): Morphine group. • Cinchona (Cinchona officinalis): Quinine etc.

Cont’d Belladonna (Atropa belladonna): Atropine group. • Pilocarpus sp. : Pilocarpine. • Vinca (Vinca rosea): Vincristine, vinblastine. • Rauwolfia serpentina (root): Reserpine. • Coca (Erythroxylum coca): Cocaine.

Cont’d Glycosides are ether like organic structure combined with sugars, the non-sugar component called aglycone or genin. The important glycosides are: • Digitalis (Digitalis purpurea, Digitalis lanata): Digoxin etc. • Stropanthus (Stropanthus kombe): Stropanthin etc. • Senna (Cassia acutifolia): Sennoside etc.

Cont’d Oils a. Fixed oils are glycerides of oleic, palmitic and stearic acids. Mostly fixed oils are edible and used for cooking. The fixed oils used as drug are: • Castor (Ricinus communis): Castor oil. • Olive (Olea europaea): Olive oil. • Cocoa butter (Theobroma cacao):

Cont’d Theobroma oil used as emollient in skin cream and making suppositories. • Cod liver oil and shark liver oil: Rich source of vitamins A and D. b. Volatile oil or essential oil contains the hydrocarbon terpene. The important volatile oils are:

Cont’d • Turpentine oil, from species of pines, used as a counterirritant. • Lemon oil (from Citrus limon), used as flavouring agent. • Peppermint, cardamom and fennel used as carminative and flavouring agent. Oil of clove is mainly useful in relieving pain in toothache.

Cont’d Resins are produced by oxidation and polymerization of volatile oils. The different types of resins are: • Oleoresins: Male fern extract used for tapeworm infestation. • Gum resins: Asafoetida, used as carminative and antispasmodic. • Oleo gum resin: Myrrh, it has a local stimulant and antiseptic properties and generally used in mouthwash.

Cont’d Balsams: Benzoin, used internally as expectorant and externally as astringent. • Balsam Tolu, used as stimulating expectorant.

Cont’d Gums are the secretory products of plants. On hydrolysis they yield simple sugar like polysaccharides. They are pharmacologically inert substances and mainly employed as suspending and emulsifying agent in various pharmaceutical products. The widely used preparations are gum acacia and tragacanth.

Cont’d Tannins are nonnitrogenous constituents of plant. Chemically they are phenolic derivatives and are characterized by their astringent action. Tannins are generally employed in the treatment of diarrhoea and burns. The important plants which contains tannins are: Amla, Behera, Hirda (in combination form ‘Triphala’), Black catechu and Ashoka bark.

Animal Sources Drug Category Insulin Hormone Thyroid extract Hormone Shark liver oil Vitamin A Animal source Pancreas of beef or pig Thyroid gland Livers of shark and allied species Cod liver oil Vitamin A and D Livers of Gadus species Antisnake venom Immune serum Blood of horse Hyaluronidase Enzyme Testis of bull Pepsin Enzyme Stomach of beef and pig

Cont’d Humans: There are certain products which are obtained from human being e. g. • Immunoglobulins: From blood. • Placental extract: From placenta. • Chorionic gonadotropin: From urine of pregnant women. • Growth hormone: From pituitary gland.

Cont’d From Microorganisms: The different classes of drugs obtained/ isolated from microbes are: • Penicillin: Penicillium chrysogenum and notatum (Fungus). • Streptomycin: Streptomyces griseus (Actinomycetes). • Erythromycin: Streptomyces erythreus (Actinomycetes).

Cont’d • Chloramphenicol: Streptomyces venezuelae (Actinomycetes). • Tetracyclines: Streptomyces aureofaciens and rimosus (Actinomycetes). • Polymyxin B: Bacillus polymyxa. • Bacitracin: Bacillus subtilis. • Nystatin: Streptomyces nouresi.

Cont’d • Griseofulvin: Penicillium griseofulvum. Apart from various other antibiotics obtained from microorganisms, there are other products that are also produced by microorganisms.

Cont’d They are: • Streptokinase, an enzyme from gram positive cocci (Streptococcus pyogenes). • Vitamin B 12 (cyanocobalamin): Streptomyces griseus.

Cont’d E. Synthetic Paracetamol F. Semi-synthetic Ampicillin G. Minerals Magnesium Sulphate Sodium Chloride Magnesium trisillicate.

Cont’d Synthetic Drugs: Modern chemistry in the 19 th century enabled scientists to synthesize new compounds and to modify naturally occurring drugs. Aspirin, barbiturates, and local anesthetics (e. g. , procaine) were among the first drugs to be synthesized in the laboratory.

Cont’d Semisynthetic derivatives of naturally occurring compounds have led to new drugs with different properties, such as the morphine derivative oxycodone.

Cont’d Genetic Engineering: human insulin, growth hormone genes. Hybridoma techniques: monoclonal antibodies.

Drug Preparations Drug preparations include crude drug preparations obtained from natural sources, pure drug compounds isolated from natural sources or synthesized in the laboratory, and pharmaceutical preparations of drugs intended for administration to patients.

Csrude Drug Preparation Crude Drug Preparations Some crude drug preparations are made by drying or pulverizing a plant or animal tissue. Others are made by extracting substances from a natural product with the aid of hot water or a solvent such as alcohol.

Cont’d Familiar examples of crude drug preparations are coffee and tea, made from distillates of the beans and leaves of Coffea arabica and Camellia sinensis plants, and opium, which is the dried juice of the unripe poppy capsule of the plant, Papaver somniferum.

Cont’d

Pure Drug Compounds It is difficult to identify and quantify the pharmacologic effects of crude drug preparations because these products contain multiple ingredients, the amounts of which may vary from batch to batch. Hence, the development of methods to isolate pure drug compounds from natural sources was an important step in the growth of pharmacology and rational therapeutics.

Cont’d Frederick Sertürner, a German apothecary, isolated the first pure drug from a natural source, when he extracted a potent analgesic agent from opium in 1804 and named it morphine , from Morpheus, the Greek god of dreams. The subsequent isolation of many other drugs from natural sources provided pharmacologists with a number of pure compounds for study and characterization.

Cont’d One of the greatest medical achievements of the early 20 th century was the isolation of insulin from the pancreas. This achievement by Frederick Banting and Charles Best led to the development of insulin preparations for treating diabetes mellitus.

Pharmaceutical Preparations Pharmaceutical preparations or dosage forms are drug products suitable for administration of a specific dose of a drug to a patient by a particular route of administration. Most of these preparations are made from pure drug compounds, but a few are made from crude drug preparations and sold as herbal remedies.

Cont’d TABLETS AND CAPSULES. Tablets and capsules are the most common preparations for oral administration because they are suitable for mass production, are stable and convenient to use, and can be formulated to release the drug immediately after ingestion or to release it over a period of hours.

Cont’d A tablet must disintegrate after it is ingested, and then the drug must dissolve in gastrointestinal fluids before it can be absorbed into the circulation. Variations in the rate and extent of tablet disintegration and drug dissolution can give rise to differences in the oral bioavailability of drugs from different tablet formulations.

Cont’d Tablets may have various types of coatings. Enteric coatings consist of polymers that will not disintegrate in gastric acid but will break down in the more basic p. H of the intestines. Enteric coatings are used to protect drugs that would otherwise be destroyed by gastric acid and are also to slow the release and absorption of a drug when a large dose is given at one time, for example, in the formulation of the antidepressant, fluoxetine.

Cont’d Sustained-release products , or extendedrelease products, release the drug from the preparation over many hours.

Cont’d Capsules are hard or soft gelatin shells enclosing a powdered or liquid medication. Hard capsules are used to enclose powdered drugs, whereas soft capsules enclose a drug in solution. The gelatin shell quickly dissolves in gastrointestinal fluids to release the drug for absorption into the circulation.

Cont’d SOLUTIONS AND SUSPENSIONS. Drug solutions and particle suspensions, the most common liquid pharmaceutical preparations, can be formulated for oral, parenteral, or other routes of administration. Solutions and suspensions provide a convenient method for administering drugs to pediatric and other patients who cannot easily swallow pills or tablets.

Cont’d They are less convenient than solid dosage forms, however, because the liquid must be measured each time a dose is given. Solutions and suspensions for oral administration are often sweetened and flavored to increase palatability.

Cont’d Sweetened aqueous solutions are called syrups , whereas sweetened aqueous – alcoholic solutions are known as elixirs. Alcohol is included in elixirs as a solvent for drugs that are not sufficiently soluble in water alone.

Cont’d SKIN PATCHES. Transdermal skin patches are drug preparations in which the drug is slowly released from the patch for absorption through the skin into the circulation. Most skin patches use a rate-controlling membrane to regulate the diffusion of the drug from the patch. Such devices are most suitable for potent drugs, which are therefore effective at relatively low dosages, and have sufficient lipid solubility to enable skin penetration.

Cont’d AEROSOLS. Aerosols are a type of drug preparation administered by inhalation through the nose or mouth. They are particularly useful for treating respiratory disorders because they deliver the drug directly to the site of action and may thereby minimize the risk of systemic side effects. Some aerosol devices contain the drug dispersed in a pressurized gas and are designed to deliver a precise dosage each time they are activated by the patient.

Cont’d OINTMENTS, CREAMS, LOTIONS, AND SUPPOSITORIES. Ointments and creams are semisolid preparations intended for topical application of a drug to the skin or mucous membranes. These products contain an active drug that is incorporated into a vehicle (e. g. , polyethylene glycol or petrolatum), which enables the drug to adhere to the tissue for a sufficient length of time to exert its effect. Lotions are liquid preparations often formulated as oil-inwater emulsions and are used to treat dermatologic conditions.

Cont’d Suppositories are products in which the drug is incorporated into a solid base that melts or dissolves at body temperature. Suppositories are used for rectal , vaginal , or urethral administration and may provide either localized or systemic drug therapy.

Drug Nomenclature 1. 2. 3. 4. Chemical Name: describes the chemical composition and molecular structure e. g. Paraaminobenzenesulfonamide (sulfanilamide) Code Name e. g. WR 180409 (empiroline), WR 142490 (mefloquine). The code name is retained before an approved name is coined. Non-proprietary name: as listed in the Pharmacopeia e. g. Sulfanilamide, phenothiazines, aminoglycosides, paracetamol. Proprietary or Trade name: coined by the manufacturer e. g. panadol, septrin,

Sources of Drug Information United States Pharmacopeia (USP) Physician’s desk reference (PDR) British Pharmacopoeia Internationalis British Pharmaceutical Codex Canadian Formulary