1. Different categories of medicines and their actions Iain G. Jack 4 th February 2011

2. Content of today’s lecture How can we categorise drugs? How do drugs cause their effects? Specific receptors: lock & key Non-specific effects Pharmacokinetics

3. Introduction What is a drug? Any biologically active chemical that does not occur naturally in the human body that can affect living processes

4. A little light history 16th century Egypt Ebers papyrus Ebers papyrus Poppy Poppy juniper berries juniper berries beer beer lead lead swine teeth swine teeth goose grease goose grease lizard's blood lizard's blood donkey hooves donkey hooves crushed precious stones crushed precious stones excreta from various animals excreta from various animals

5. Where do drugs come from now? Plants: Plants: Digoxin (foxglove) Belladonna (deadly nightshade) Diamorphine (opium poppy) Animal tissue: Animal tissue: Insulin, growth hormone Synthetic manufacture: Synthetic manufacture: Most modern medicines

6. Names of drugs Chemical name: describes the chemical structure:acetyl-p-amino-phenol Generic name: a name that can be used by anyone:paracetamol Trade name: owned by the manufacturer:Calpol

7. Other ways to categorise drugs What kind of molecule is it? What organ system (or what disease) is it for? e.g., cardiac, psychotropic What parts of cells are affected?

8. What is the drug used for? To cure e.g., infections, cancer To suppress diseases or symptoms without attaining a cure e.g., hypertension, diabetes, pain control To prevent disease (prophylactic) e.g., immunisation

9. How does the drug act? Replace a deficiency, e.g., vitamins, minerals, hormones Interfere with cell function, e.g., block enzyme action Kill / prevent growth of viruses, bacteria, fungi, protozoa, cancer

10. Categories of drug Anti-inflammatory Analgesic Antipyretic Vaccine Antihypertensive Vitamin supplement Antitussive Antiviral Antifungal Antibiotic Anaesthetic Surfactant Laxative

11. Content of today’s lecture How can we categorise drugs? How do drugs cause their effects? Specific receptors: lock & key Non-specific effects Pharmacokinetics

12. How do drugs work? Pharmacodynamics: study of how chemicals exert their effects The practical importance of this is enabling the design of new and better drugs

13. receptor signal Receptors Receptors are proteins on the cell surface or inside the cell. They bind the body’s own chemical messenger chemicals Convert the binding event to a signal that the cell can recognize and respond to

14. “Lock & Key” Interaction between a receptor and its signal molecule (ligand) is like “lock & key”. Perfect fit depends on exact 3D shape and size of both molecules.

15. Receptors Drugs also bring information to cells by fitting into the same receptor molecules. The drug picks the lock and triggers a response by the cell. receptor receptor drug

16. Cannabinoid receptor Where? Surface of brain cells and cells of digestive system and immune system What for? Normal brain function and healthy appetite So what? THC picks the lock.

17. Agonists and Antagonists Agonist: a drug that fits into a receptor and activates a response e.g., morphine, nicotine Antagonist: a drug that fits into a receptor but blocks the receptor and does not activate a response. ??? new anti-obesity drug: antagonist to cannabinoid receptor

18. Content of today’s lecture How can we categorise drugs? How do drugs cause their effects? Specific receptors: lock & key Non-specific effects Pharmacokinetics

19. Non-specific effects Acidic or alkaline properties Surfactant properties (amphotericin) Osmotic properties (laxatives, diuretics) Interactions with membrane lipids (anaesthetics)

20. Side-effects and other effects Not the “wanted” effect e.g. aspirin causes gastric ulcer Diphenhydramine has a useful side- effect

21. Side-effects and other effects Hypersensitivity / allergy: exaggerated adverse reaction to drug Toxic effects e.g., Thalidomide: teratogenic Tolerance: increasing amounts are needed to produce the same effect

22. Content of today’s lecture How can we categorise drugs? How do drugs cause their effects? Specific receptors: lock & key Non-specific effects Pharmacokinetics

23. How the body deals with the drug We need to consider: Dose Route of Administration Absorption and distribution Metabolism and excretion

24. Dose: amount of drug taken at any one time Aim is to give the patient a dose of drug that achieves the desired effect without causing harmful side effects Therapeutic Index (TI) is the ratio of the therapeutic dose to the toxic dose E.g.’s of drugs with low TI include digoxin, lithium and methotrexate

25. Administration Route of administration depends on: How easy it is to use for patient The chemical make-up of the drug How quickly a drug needs to reach site of action Where it has to work in the body

26. Intravenous Inhaled Oral Transdermal Rectal Topical Subcutaneous or intramuscular or intramuscularinjection Routes of Administration

27. Oral Route Medications taken by mouth Formulated in either a solid or liquid form Absorbed from the GI tract mainly in the small intestine which is specialised for absorption (large surface area due to villi and microvilli).

28. Disadvantages Onset of action is relatively slow Absorption may be irregular Some drugs destroyed by enzymes or other secretions found in GI tract Because blood from GI tract passes through liver it is subject to hepatic metabolism before reaching systemic circulation

29. Buccal Route Drug is formulated as a tablet or a spray and is absorbed from the buccal cavity Sublingual absorption very fast onset of action but duration is short Buccal absorption quick onset of action that is of longer duration than sublingual route

30. Rectal Route Drugs formulated as liquids,solid dosages and semi solids. The chosen preparation is inserted into the rectum where it is released to give local effect or absorbed to give a systemic effect

31. Rectal & Vaginal Route Advantages Can be used when oral route unsuitable Useful when drug causes GI irritation Can be used for local action Disadvantages Absorption irregular and unpredictable Less convenient than oral route Low patient acceptability

32. Inhalation Route Used predominately in the treatment of asthma Drugs delivered directly to their site of action ie lungs Advantages Drugs inhaled through the nose or mouth to produce local or systemic effects Drug dose required to produce desired effect is much smaller than oral route therefore reduction in side effects

33. Topical Route Skin used as site of administration Lotions,creams,ointments, powders Skin has natural barrier function but specialised dosage forms have been developed that when applied they allow the drug to pass through and produce systemic effect

34. Parenteral Route (drugs that are given by injection) IV route -drugs injected directly into the systemic circulation (fast onset of action) Subcutaneous route -drugs injected into the s/c layer of the skin (easiest and least painful) Intramuscular route –drugs injected into muscle layers

35. Examples in each category RouteLocal ActionSystemic Action InhaledVicks VaporubCigarette OralGaviscon liquidNurofen Tabs TransdermalZovirax sore cream Nicotene patch RectalLaxative Sippository Paracetamol Suppository I.V.NovocaineContraceptive S.C / I.MLocal thrombolytic therapy Adrenaline

36. ADME Absorption: the mechanism by which a drug enters the body Distribution: the drug is transported throughout the body Metabolism: the drug interacts with, and is processed by, the body Elimination: the drug is removed from the body

37. Absorption Disintegration Dissolution Direct absorption at site of action, e.g., in the gut

38. Steps in distribution Drug must spread throughout blood volume Drug must get out of the bloodstream between or through endothelial cells Drug must cross the cell membrane into cells

39. Factors affecting distribution Binding to plasma proteins: if a drug is bound to large plasma proteins, it will be unable to get out as the proteins are too large. Arggh! I can’t fit through!

40. Factors affecting distribution Extent of blood supply. If a tissue is well perfused with blood, drugs will get there faster. Adipose tissue has low blood perfusion so drugs reach it slowly.

41. Factors affecting distribution pH. A drug will pass through membranes better if it is not ionised Binding of drugs to other tissue components

42. Metabolism: what happens to a drug Time Drug Concentration TherapeuticRange Sub-Therapeutic LethalDose Injected Dose Oral Dose

43. First pass effect All nutrients and drugs absorbed from the gut travel in the blood directly to the liver. The liver breaks down many drugs so they are inactivated before they ever enter the systemic circulation! This can decrease drug delivery to target tissues But some drugs are activated by the first pass effect

44. Elimination Mainly in the kidney. Also bile, gut, lung, breast milk. Elimination of a drug is usually linked to renal function.

45. Individual variation Each person is unique how they respond to a drug Age and sex (hormonal differences) Weight: some drugs are stored in fat so less effective and longer lasting in obese people Allergy Kidney & liver function: how will they affect elimination?