General Pharmacology

1. General Pharmacology Dr NasimUllahSiddiqui

2. What is Pharmacology? • Pharmacology: • Pharmacon (drugs) + Logos (studies) • The study of drugs

3. Drugs & Medicines • Drugs: • Any substance that, when absorbed into the body of a living organism, alters (changes) normal body function • Examples: • aspirin, • Antibiotics, • Nicotine, • alcohol, • Marijuana….

4. Drugs & Medicines • Medicines: • In pharmacology, a drug is a chemical substance used in the: • treatment, cure, prevention, or diagnosis of disease • Or used to enhance physical or mental well-being

5. Drugs & Medicines • Drug is called medicine when used in proper dosage form for safe administration • All medicines are drugs but all drugs are not medicines

6. Clinical / Experimental • Clinical Pharmacology • deals with the study of drug effects in humans beings, i.e. healthy volunteers and patients • Experimental Pharmacology • deals with the study of drug effects in laboratory animals • In vitro – Isolated tissue • In vivo – Intact organism

7. Definitions • Toxicology: • deals with adverse (undesired) reactions of drugs & their treatment • Pharmacogenetics: • How genetics influence the mode of drug actions (e.g.. Metabolism) and biological variations of drug responses

8. Definitions • Pharmacogeneticsis generally regarded as the study or clinical testing of genetic variation that gives rise to differing response to drugs. • Pharmacogeneticsrefers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.

9. Definitions • Pharmacokinetics: • How the body handles the drug • Includes absorption, distribution , biotransformation, and elimination • Pharmacodynamics: • How drug handles the body • Deals with the biochemical and physiological effects of drugs on man

10. Definitions Receptors • Biochemical receptors are large protein molecules that can be activated by the binding of a ligand (such as a hormone or drug). • Receptors can be membrane-bound, occurring on the cell membrane of cells, or intracellular, such as on the nucleus or mitochondrion. Binding occurs as a result of noncovalent /covalentinteraction between the receptor and its ligand, at locations called the binding site on the receptor.

11. Definitions • Potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. • A highly potent drug (e.g., morphine) evokes a larger response at low concentrations. • while a drug of lower potency (acetylsalicylic acid) evokes a small response at low concentrations • It is proportional to affinity and efficacy

13. Definitions • Affinity is the ability of the drug to bind to a receptor. • Efficacyis the relationship between receptor occupancy and the ability to initiate a response at the molecular, cellular, tissue or system level. • The response is equal to the effect(E), and depends on both the drug binding and the drug-bound receptor then producing a response; thus, potency depends on both affinity and efficacy.

14. Definitions • The agonist (ligand, drug or hormone) that binds to the receptor and initiates the response. • The less the concentration of a drug is required to produce 50% of maximum effect and the higher the potency.

15. Definitions • A receptor antagonist is a type of receptorligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses. • The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally-defined binding sites on receptors. • Antagonistshave affinity but no efficacy for their receptors, and binding will disrupt the interaction and inhibit the function of an agonistat receptors.

16. Antagonist • Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist receptor binding. • Physiological antagonists, substances that have opposing physiological actions, but act at different receptors. For example, histamine lowers arterial pressure through vasodilation at the histamine H1 receptor, while adrenaline raises arterial pressure through vasoconstriction mediated by β-adrenergic receptor activation.

17. Definitions • Tachyphylaxis : Rapidly developed tolerance is tachyphylaxis, is a medical term describing a decrease in the response to a drug due to previous exposure to that drug. • Caused by depletion or marked reduction of the amount of neurotransmitter responsible for creating the drug's effect, or by the depletion of receptors available for the drug or neurotransmitter to bind to. Examples: Amphetamine, ephedrine(indirectly acting drugs) • Tachyphylaxis is characterized by the rate sensitivity i.e, a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished response also known as desensitization.

18. Definitions • Physiological tolerance or drug tolerance is a subject's reaction to a drug (such as an opiates painkiller, benzodiazepine drug) is reduced at a later time even though the dose or concentration at the effect site is the same. • This means that larger doses are required to achieve the same effect. • Drug tolerance can involve both psychological & physiological drug tolerance factors. • Itis reversible • Physiological tolerance occurs after repeated exposure .

19. Definitions • Idiosyncrasy (idiosyncratic drug reaction) denotes a non-immunological hypersensitivity to a substance, without connection to pharmacological toxicity. • Is an individual based on a specific condition of the one who suffers it. Most commonly, this is caused by an enzymopathy, congenital or acquired.

20. Drugs actions • Drug actions are mediated by 3 ways: • Acting on somatic or psychic processes or functions • Correction of deficiencies • Toxic action on pathogenic microorganism

21. Ideal drug effects • Drug effects should be: • Selective • Temporary • Dose-related (controllable) • Show close relationship with bioavailability

22. Drug Responses • How are drug responses produced? • By interaction with active binding sites called RECEPTORS • Drug may be agonist or antagonist for the receptors

23. Nature of drugs • Physical: • Solid (aspirin) • Liquid (nicotine, ethanol) • Gas (nitrous oxide) • Chemical structure: • Protein, lipid, carbohydrate • To be weak acid or weak base • Amine (primary, secondary, tertiary, ..)

24. Sources of drugs • Natural from: • Plants • Animals / Humans • Micro-organisms • Minerals • Inorganic metals • Semi-synthetic • Synthetic • Bio-synthetic

25. Sources of drugs Natural from Plants: • Active principles are found in roots, leaves and seeds in 2 forms: • Glycoside, e.g • Cardiac glycoside Digoxin ( from the Foxglove plant) • Alkaloid, e.g • Morphine (from Poppy capsules), • Atropine (from Belladonna leaves) • Quinine (from bark of Cinchona tree) • Castor oil (from castor seed)

26. Sources of drugs Natural from animals / humans: • Hormones: • Heparin from Pig or Ox liver, • Insulin from Pig or Ox pancreas • Gonadotrophins from urine of pregnant women • Plasma or serum from blood • Thyroxin from Pig or Ox thyroid gland • Cod Liver Oil from Cod fish Liver

27. Sources of drugs Natural from micro-organisms: • Antibiotics: • Penicillin from Penicilliumnotatum, • Streptomycin from Streptomycesgriseus, • Bacitracin from Bacillus

28. Sources of drugs Minerals: • Calcium, Magnesium, Aluminium, Sodium, Potassium & Iron salts, • Liquid paraffin from petroleum. Inorganic metals: • Iodine, • Lithium, • Radioactive elements: I131

29. Sources of drugs Semi synthetic drugs: • Prepared by chemical modification of natural drugs in labs. • Ampicillin from Penicillin-G, • Semisynthetic cephalosporin's from 7-amino cephalosporinic acid

30. Sources of drugs Synthetic Drugs: • Prepared by chemical synthesis in pharmaceutical laboratories • Sulphonamides • Salicylates • Barbiturates • Benzodiazepines

31. Sources of drugs Bio-Synthetic Drugs: • Prepared by cloning of human DNA into bacteria like E.Coli.

32. Sources of drugs Bio-Synthetic Drugs: • Technique is called Recombinant DNA technology or Genetic Engineering • Cells from animals or human that produce active substance • Isolation of DNA • Transfer to bacteria (E-coli) by plasmids (Gene cloning) • A new E-coli synthesizes the new substance • Cloning of ‘new’ E-Coli means production of identical subjects like parent

33. Sources of drugs Bio-Synthetic Drugs: • Examples: Human Insulin's, Human Growth Hormones, Human BCG vaccine , Human Hepatitis B Vaccine

34. Criteria for drug classification • Chemical structure: • Cholinesters, • Organophosphates, • Catecholamine's • Location of action: • Cardiac glycosides, • Autonomic drugs

35. Criteria for drug classification • Purpose of medication: • Antihypertensive • Diuretic • Antiemetic • Analgesic • Name of plant: • Opium alkaloids • Cardiac glycosides • Belladonna alkaloids

36. Prescription / Over the counter • Drugs fall into two distinct categories: 1)Those that require a physician’s prescription to obtain (Rx) 2)Those that can be purchased over-the counter (OTC) • both are regulated by the regulatory authorities

37. Pharmacotherapy • Employment of drugs for the prevention and treatment of diseases • Its scope: • Indications • Contraindications • Drug interactions • Therapy: • Radical (full healing) • Symptomatic (treatment of symptoms only) • Prophylactic (e.g. contraception, vaccine)

38. Therapeutic Index • Therapeutic Index (TI): • Toxic dose / Effective dose • Indicates the relative safety of a drug • Examples: • Acetominophen : 27 • Valium: 3 • Methotrexate, vincristine: 1 • Narrow TI indicates the need for frequent blood tests to monitor drug levels

39. Mechanism of Action • Agonist: • drug mimics an endogenous substance that would normally stimulate a receptor • Antagonist: • drug which binds a receptor site, doesn't stimulate it, but blocks other substances from stimulating it

40. Drug Nomenclature Most drugs have at least three names: • Chemical name • Generic name (Official, Approved) • Proprietary name (Trade name, Company name)

41. Drug Nomenclature • Chemical name • The chemical composition and structure

42. Drug Nomenclature • Generic name (Official, Approved) • is usually the abbreviated form of the chemical name • this name is used and chosen by official bodies

43. Drug Nomenclature • Proprietary name (Trade name, Company name) • the name given by the company which markets the drug • It is the commercial property of a pharmaceutical company • It indicates a particularly formulation of a particular substance by a particularly manufacturer

44. Drug Nomenclature • Since several companies market the same drug under different proprietary names, unnecessary confusion may arise • Whenever possible drugs should be prescribed by their approved names • Chemical name: • Acetyl-p-aminophenol • Official name: • Paracetamol • Proprietary name: • Panadol, Calpol, Adol, Fevadol

45. Routes of Drug Administration

46. Routes of Drug Administration • Factors Deciding Choice of Route • Type of described effect, systemic or local • Physiochemical properties, solid or insoluble • Rapidity of effect, oral, intramuscular (IM), intravascular (IV) • Condition of patient, conscious or unconscious, vomiting

47. Topical Application - Mucous Membrane • Conjunctiva, nasopharynx , oropharynx, vagina, urethra, urinary bladder, ear, nose, anal canal for local / systemic effects • Absorption rapid • Local anesthetic for local effects rapidly absorbed, produce systemic toxicity • Types: • ointment, cream, drops, jelly, powder, tablet, suppository, pessary

48. Topical Application - Skin • Absorption- depends on • surface area, lipid solubility • Few drugs readily penetrate skin • Burned, denuded, abraded, inflamed skin increase systemic absorption • Toxicity by highly lipid soluble insecticides • Controlled- release by topical patches

49. Topical Application - Injection • Intra articular (in joint) • hydrocortisone • Intra thecal into subarachnoid space of L2-3 or L3-4, • Local anaesthetics • Subcutaneous (under skin) • Local anaesthetics • Intra arterial • anticancer drugs in limbs cancer

50. Systemic Routes • Enteral through GIT • Orally • Buccal or sublingual • Rectal • Parental • Intravenous (IV) • Intramuscular (IM) • Subcutaneous (SC) • Transdermal Therapeutic system (TTS) • Inhalation