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An Introduction to Pharmacology Prof. Dave Kendall School of Biomedical Sciences Drugs in the news Glaxo develops Vioxx rival to treat arthritis Heather Tomlinson Wednesday November 24, 2004 The Guardian Psychedelic drugs could cure thousands. Andrew Feldmar. August 18th 2008 Antidepressants boost GI bleeding time. Fri Oct 12th 2007 Reuters The Guardian Drugs acting on the brain could transform battlefield of the future Ian Sample, The Guardian, August 14th 2008 New class of antibiotic could be effective against superbugs Thursday May 18, 2006 Phytopharm flies on Parkinson's disease promise. Nick Fletcher The Guardian August 14th 2008, October 14th The Guardian, 2009. Q: David, did you take drugs at Oxford? A: I don't think I should talk about it now that I am a politician Sunday October 16, 2005 The Observer 'No faults in calamitous drug trial' Wednesday April 5, 2006 The Guardian Pharmacology; study of the effects of drugs on living systems. Drug; chemical that has some effect on living things. Vary enormously in structure, size and chemical properties; lithium → insulin Medicine; preparation of drug used to treat disease. Systems of medicine Pharmacology only recognised as a separate discipline in 19th century. Before that, medicines used empirically; not understood enough to enable rational therapy. James Gregory (1735-1821) formulated principles of Allopathy; "the treatment of disease by conventional means, i.e. with drugs having effects opposite to the symptoms”. Used blood letting, emetics, purgatives (often fatal!) Samuel Hahneman promoted Homeopathy, in reaction to horrors of allopathy? (1755-1830); Principle is “like cures like”. Drugs used in enormous dilutions (1060). No rational basis for efficacy but popular due to lack of side effects. Royal London Homeopathic Hospital newly refurbished and re-opened. Never forget the placebo effect! Paul Ehrlich (1855-1915) Won Nobel prize in 1908. Established that drugs must bind to biological targets to have an effect. Most drugs produce their effects by binding to specific macromolecules, usually complex proteins, on or within cells. DNA is another target (cancer chemotherapy) and some drugs have direct chemical effects (e.g. antacids). Four major protein targets for drugs: •Enzymes •Trans-membrane carriers •Ion channels •Receptors Receptors are proteins that recognise chemical signals and convert them into biological responses e.g. β-adrenoceptors in the heart, bind adrenaline and turn on an enzyme that causes heart rate to increase. Receptor Receptor Agonists & Antagonists: Agonists have the right shape both to occupy and activate receptors. Antagonists can only occupy. They have affinity but no efficacy. Any drug with some affinity for a receptor is called a ligand. Dose/response curve Comparison of dose-response curves for drugs X, Y, and Z. Drug X, having greater biologic activity per dosing equivalent, is more potent than drug Y or Z. Drugs X and Z have equal efficacy, indicated by their maximum attainable response (ceiling effect). Drug Y is more potent than drug Z, but its maximum efficacy is lower. Competitive antagonism Log Irreversible antagonism response Sir James Black; Nobel prize for medicine 1988. Discovered beta-blockers and histamine H2 receptor antagonists. Revolutionized treatment of hypertension and gastric ulcers. Arguably, the first rationally designed therapeutics. Drug selectivity: To be useful, drugs must act selectively on defined targets in particular cells. By chance, drugs are likely to bind to more than one target. Drugs can be selective but are never completely specific. Therefore, all drugs have the potential to have unwanted side-effects. These are usually dose-related. Side effects of diclofenac (common antiinflammatory drug) Diclofenac may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: stomach pain diarrhea heartburn upset stomach constipation gas or bloating headache dizziness Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor immediately: black and tarry stools red blood in stools bloody vomit vomiting material that looks like coffee grounds ringing in the ears swelling of the hands, feet, ankles, or lower legs unexplained weight gain excessive tiredness lack of energy itching pain in the upper right part of the stomach yellowing of the skin or eyes flu-like symptoms rash hives difficulty breathing or swallowing pale skin fever confusion blurred vision changes in color vision Diclofenac may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. Drug Interactions Interaction said to occur when the effects of one drug are changed by another drug, food, drink or some chemical in the environment. Interactions might be pharmacokinetic e.g. the result of competing for absorption mechanism, metabolic route, chemical reaction between the drugs or pharmacodynamic; similar or opposing mechanisms at site of action lead to increased or decreased effects. Adverse reactions increase with numbers of drugs taken; 7% incidence in patients taking 6-10 drugs, 40% if taking 16-20 drugs. BNF British National Formulary • THE guide to drug usage • Contains information on all prescribed and OTC medicines – Indications – Contra-indications – Adverse Effects – Dosages – Interactions – Prescribing in renal and hepatic impairment – Prescribing in pregnancy and lactation Local Formulary • Formulary: list of commonly prescribed drugs. •Placed on the NLE •Drugs which you should become familiar over the next 4/5 years. •Drug names: not expected to learn all names but it helps to know commonly used agents In exams: “A beta-adrenoceptor antagonist (such as atenolol).” Drug Names Official, generic, non-proprietary names e.g. fluoxetine (common nouns so no capitalisation). Proprietary, trade, brand names e.g. Prozac (Dista) are proper nouns, so capitalised. Always use the official name unless relating to a particular preparation. N.B. Different brands of the same drug might have different properties. Best textbook? Pharmacology Teaching • Taught as an integrated part of the course alongside physiology, pathology and therapeutics. • Take systems approach; CNS, CVS, RS, GI etc. • Later in course, case study-based; Clinical Pharmacology and Management of common conditions (BMedSci) and Disease and Goals of Treatment (MPharm).