Draft Core Curricula in Pharmacology

Draft Core Curricula in Pharmacology The British Pharmacological Society has formulated core curricula for pharmacology teaching within Science and various professional courses and suggests that these can be used:      as a source of ideas for course developers as to what to include in their courses as a benchmark from the Society where course developers feel under pressure to reduce the content of their course to identify the changing nature of the subject as a a guide to the minimum pharmacological knowledge and skills a student should possess for University management, quality assurance and professional bodies to see what the Society considers to be core curricula At the ASCEPT meeting in Newcastle, there was general agreement at the education workshop that:    the development of core curricula for various pharmacology courses should proceed these should be advisory rather than prescriptive and should allow and encourage local flavour to be introduced we should develop our own curricula to reflect the ideas of local teachers, accepting that there would be similarities between the ASCEPT and the BPS documents. Drafts of core curricula for pharmacology courses in Science, Medicine and Pharmacy follow. These have been prepared by three separate groups, coordinated by Michael Lew (Science), Paul White (Pharmacy) and Vimal Kapoor (Medicine). After a brief general introduction, the workshop at the AHMR Congress will break into three groups (chaired by Michael, Paul and Vimal), one to work on each of the drafts. It is anticipated that the outcome of the workshop will be a final draft for each of the curricula, which can then be presented to the ASCEPT membership with the proposal that they be adopted by the Society. ASCEPT Core Curriculum for pharmacology in Science Introduction The desirable set of attributes, skills and areas of knowledge for science pharmacology graduates is likely to appear rather nebulous and variable compared to those for graduates of professional courses, like medicine and pharmacy, where a definable set of skills and areas of knowledge are desirable for accreditation and safe practice. The following outline of core areas for science pharmacology is intended to circumvent that problem through being based on a reasonable answer to the question “What might an employer of our graduates expect them to understand?” Four broad areas of understanding are specified: dose-response relationships; sites of drug action; drug selectivity; drug discovery and development. Specific topics are arranged under those headings, but no attempt has been made to arrange them in order of importance or size. The outline is not intended to be directly the basis of course design. One feature that is notably absent from the listing of core areas is any specification of particular drugs and receptors. The vexing issue of a drug list was raised, and no doubt will be raised in the future. However, it is likely that list of important drugs would be subject to disputation, need continual updating, and would inevitably inappropriately imply low importance of drugs omitted. It is expected that different courses in pharmacology will have different emphases and strengths and it is also likely that students might not cover all of the listed areas in any particular pharmacology course. These differences are in accord with the federal government‟s preference for diversity in the university sector. I. A. An understanding of dose-response relationships Pharmacokinetics 1. Absorption and distribution - influence of physicochemical properties of drugs 2. Elimination - metabolism - excretion 3. Bioavailability B. Concentration-response relationships 1. Affinity - Molecular determinants of affinity - Binding assays 2. Antagonism + Competitive - Analytical approaches: Schild et al. + Noncompetitive - Allosteric inhibitors (and enhancers) - ‘Mechanistic’ antagonism by inhibitors of signalling pathways - Functional/physiological antagonism 3. Efficacy + Agonist fullness and partiality - Tissue (assay) stimulus-response sensitivity, receptor reserve + Conceptual and theoretical models of efficacy - Stephenson/Furchgott, multi-state models, Operational model II. An understanding of the sites of drug action A. Receptors 1. Classes 2. Molecular regulation of receptors + Desensitization and resensitization - Modulation of expression levels - Receptor modification and internalization + Signalling pathways - Generic signalling for each class of receptor - Signalling pathways for specific receptors - GPCRs as monomers and polymers B. Enzymes and transporters 1. Similarities and differences from receptors 2. Modes of inhibition III. An understanding of drug selectivity A. Selectivity 1. Selective affinity 2. Selective delivery + Concentrations: sources and sinks - Drug removal (e.g. neuronal uptake) - Restricted diffusion (e.g. blood-brain barrier) - Prodrug conversion (e.g. AngI in tissues) 3. Functional selectivity - Efficacy - Combination of effects B. Whole organism influences on drug selectivity 1. Simplicity of assay vs relevance 2. Reflexes and other feedback processes 3. Functional redundancies 4. Side-effects - From primary drug action or from other actions IV. Drug discovery and development A. Drug categories 1. small molecules 2. proteins - antibodies 3. gene therapies B. Screening candidates 1. Screening approaches 2. Natural sources of drugs - Toxins, hormones etc. - „herbal‟ vs „drug‟ C. Rational drug design strategies 1. Structure-activity series 2. Starting from a candidate (e.g. a natural product) 3. Starting from target structural information (e.g. relenza) D. Biotechnological drug discovery 1. Bioinformatics 2. Transgenic approaches E. In vivo assays 1. Complications of integrated systems 2. Clinical trials - Placebo F. Drug regulation and legal/ethical issues ASCEPT Core Curriculum for pharmacology in Pharmacy Introduction Pharmacology is taught in a variety of ways in Australian Pharmacy courses. The following curriculum is intended to reflect the areas that should be covered in an undergraduate Pharmacy degree, whether under a pharmacology banner or taught in another subject. As an integral part of the professional preparation of a pharmacist, the pharmacology curriculum must be actively and closely integrated with the rest of the course. A thorough understanding of Pharmacology requires knowledge of a range of related disciplines. These are generally taught across a range of subjects within a Pharmacy program, including physiology, pharmacokinetics, medical chemistry, biochemistry, physical pharmaceutics, formulation and pharmaceutical microbiology – each of which is recognised as a stand alone sub-discipline. A brief summary of the areas that form the wider context upon which pharmacology is based is included. Aspects of mechanism covered in counselling document. the clinical practice of Pharmacy that do not relate to the of action or adverse effects of therapeutic agents are generally subjects such as Clinical Pharmacy. These areas, including issues, drug choices within a class etc, are not included in this “Pharmacology” has been defined here as “pertaining to the study of the mechanism of action and clinical use of drugs for the treatment of human disease states. Finally, “emerging drugs” have not been included in this document; as these drugs become clinically relevant they will be included in the appropriate clinical section. Core Curriculum The curriculum for Pharmacology has been divided into three overlapping sections; a) Physiology and Pharmaceutical Biology underlying the actions of drugs in human systems Basic Pharmacology Clinical Pharmacology b) c) A. Physiology and Pharmaceutical Biology underlying the actions of drugs in human systems Detailed knowledge of the actions of drugs within living systems, the therapeutic uses of drugs and medicines in man, the aetiology and epidemiology of major diseases and the principles of their drug treatment and the clinical evaluation of new drugs and medicines must be set in the wider context of an understanding of:  Systems physiology and basic anatomy    Pathophysiology and physiological adaptations to disease states Awareness of primary and secondary disease states, idiopathic and well-described pathophysiology Mechanisms of drug absorption and the passage of drugs across cell membranes; routes of administration, bioavailability and dosage forms The distribution of drugs. Drug biotransformation; sites of metabolism and the activation/inactivation of drugs. Drug excretion  and the entero-hepatic circulation. Factors affecting the absorption, distribution, metabolism and excretion of drugs.      Alterations in drug absorption, distribution, metabolism and excretion upon ageing, disease and other changes; Clinical toxicology associated with drug over-dosage, drug or substance misuse or accidental exposure; Properties of materials used in formulations and devices for the delivery of biologically-active molecules; Functionality of pharmaceutical excipients; Pharmacopoeial and regulatory requirements; degradation of medicines: evaluation and control of biological, chemical and physical degradation. Systems physiology Pharmacokinetics and concepts of therapeutic range; half-life, clearance, first order and zero order kinetics, loading dose and maintenance dosing. Factors affecting pharmacokinetics such as disease, physiological conditions (eg age, pregnancy, obesity etc), drug interactions and pharmacogenetics. Compliance/adherence to medication regimes   B. Basic Pharmacology Molecular targets of drug action    Protein targets vs others (e.g., nucleic acids) Proteins = receptors, enzymes, ion channels, other proteins (see below); structure, function, classification Principles of drug-receptor interactions: Concepts of affinity, intrinsic activity and efficacy; Occupancy theory. Dose response relationship. Rate and receptor inactivation theories. Multi-state theory. Classification of drugs: Agonists, antagonists/inhibitors, inverse agonists, allosteric modulators Signal transduction. G proteins and accessory cellular proteins.   Neurotransmitter pharmacology  Adrenergics. The pharmacological actions of noradrenaline; comparison with adrenaline and isoprenaline/dopamine. Actions and uses of - and - adrenoreceptor agonists and antagonists; adrenergic neurone blocking drugs. Drugs that interfere with synthesis, storage and metabolism of noradrenaline. The pharmacological actions of acetylcholine. Drugs affecting cholinergic transmission. Anticholinesterases. Actions and uses of selective agonists and antagonists for muscarinic and nicotinic receptors. Non-adrenergic, non cholinergic transmission. Nitric oxide, adenosine and other NANC transmitters. Central neurotransmission. Location and function of neurones that release dopamine, GABA, glutamine, 5-HT and acetylcholine. Lipid mediators - endocannabinoids     Autacoid Pharmacology   Histamine receptor sub-types; clinical uses of histamine receptor antagonists. 5-hydroxytryptamine (5-HT) – synthesis, storage, release, catabolism and pharmacological effects. 5-HT receptor sub-types, clinical uses of receptor selective antagonists. Drugs that inhibit formation or actions of bradykinin. Prostaglandins and their pathophysiological roles in inflammation, fever and pain. Drugs that block prostaglandin production; COX-1 and COX-2 inhibition; leukotrienes – synthesis, actions, pathological roles. 5lipoxygenase and FLAP inhibitors, LT receptor antagonists. C. Clinical Pharmacology Analgesics  Opioid and non-opioid analgesics. Sites of analgesic activity; local and central analgesia. Anaesthetics  Local anaesthetics. General anaesthetics. Inhalational and intravenous anaesthetics. Anti-infectives  Antibiotic treatment, modes of action and resistance including penicillins, cephalosporins, carbapenems, monobactams, blactamase inhibitors, tetracyclines, aminoglycosides, erythromycin, 4-quinolones, vancomycin and fusidic acid and anti-tuberculosis agents. Antimicrobial synergy, antagonism and resistance. Viral infections and their treatment including Herpes, Varicella and HIV. Fungal infections including dermatophytes and Candida albicans and treatment with amphotericin and azole agents. Treatment of protozoal infections, including malaria. Helminths and arthropods, especially tropical issues such as schistosomiasis, filariasis. Tropical diseases: malaria, tuberculosis, leprosy, trypanosomiasis; also public health issues.   Cancer Drugs  Introduction and principles of chemotherapy. The mechanisms of action, uses and limitations of the major groups of chemotherapeutic agents, e.g. alkylating and cross linking agents, antimetabolites, topoisomerase inhibitors, spindle inhibitors and biologicals. New and future therapies. Immunomodulation, monoclonal antibodies and conjugates, prodrugs, vaccines, gene and RNA targeting, aptomers, gene therapy, DNA repair and resistance inhibition. Novel delivery systems. Inhibition of angiogenesis and the metastatic cascade. Radiation and chemotherapy sensitisers and protectors.  Cardiovascular Drugs  Hypertension and antihypertensive drugs. Diuretics, vasodilators, ACE inhibitors etc.A for ACE inhibitors, AT1 antagonists, alphaadrenoceptor blockers; B for beta-adrenoceptor antagonists; C for calcium entry blockers and CNS active drugs; D for diuretics; E for endothelin antagonists, endopeptidase inhibitors Ischaemic heart disease and its treatment; nitrates, badrenoreceptor blockers and calcium channel blockers.    Lipid lowering drugs including the statins, cholestyramine, nicotinic acid and ACAT inhibitors. Arrhythmias and antiarrhythmic drugs. Class I-IV anti-arrhythmic drugs Sodium channel blockers such as quinidine and lignocaine, Potassium channel blockers such as amiodarone and sotalol; calcium entry blockers, digoxin, adenosine, beta-adrenoceptor antagonists. Heart failure: ACE inhibitors, b-blockersadrenoceptor antagonists, inotropic agents and vasodilator drugs in the treatment of heart failure.such as digoxin and dopamine Anticoagulant therapy - warfarin, heparin, ximelagatran. Fibrinolytic mechanisms. Pharmacology and therapeutic role of streptokinase and tissue plasminogen activator (tPA) . Anti-platelet drugs and their use in vascular embolic disease. Treatment of anaemia    Dermatological Drugs   Acne, pathogenesis and treatment; keratolytics, comedolytics, antibiotics, retinoids. Psoriasis – inflammatory and hyperproliferative nature of the disease. Use of topical vitamin D analogues, corticosteroids, dithranol; use of intravenous therapy in resistant cases. Alopecia – involvement of androgens. Use of minoxidil, antiandrogens.  Ear Nose and Throat Drugs  Drugs for rhinitis and sinusitis - Oral and topical sympathomimetics, nasal corticosteroids, antibiotics. Endocrine and Reproductive Drugs  Drug treatment of diabetes mellitus. Insulin and oral hypoglycaemics. (sulphonylureas, metformin, thiazolidinediones).Hormones of the pituitary and hypothalamus. Drugs suppressing prolactin release. Vasopressin and analogues. Drugs used in diseases of the thyroid. Corticotrophin and adrenal steroids. Drugs affecting calcium homeostasis. Osteoporosis and Paget‟s disease. Use of calcitonins, bisphosphonates, oestrogen receptor modulators, vitamin D analogues, calcium Hormone replacement therapy. Drugs used for contraception; oestrogens and progestagens. Mechanism of contraceptive action. Drugs affecting the uterus – uterine relaxants (b-agonists) and stimulants (prostanoids, oxytocin). Anabolic/androgenic steroids - use and abuse Treatment of impotence       Eye Drugs  Glaucoma – open and closed angle glaucoma. Pharmacotherapy – b-blockers, a2 agonists, cholinergic drugs. Drugs for allergic and inflammatory eye conditions – decongestants and antihistamines. Gastrointestinal Drugs  Drugs for peptic ulcer disease – antacids, cytoprotective agents, H2 antagonists and proton pump inhibitors. Antibiotic treatment to eliminate H. pylori. Drugs for motility disorders – stimulants and anti-spansmodics. Drugs for nausea and vomiting – dopamine antagonists, antihistamines, anticholinergics and 5HT3 antagonists. Laxatives – bulking agents, stool softeners, stimulant and osmotic laxatives    Genitourinary Drugs  Drugs for urinary incontinence – anticholinergics, antidiuretic hormone analogues Drugs for benign prostatic hypertrophy – a blockers and 5-alpha reductase inhibitors. Antiandrogens and prostate cancer. Drugs for erectile dysfunction – phosphodiesterase inhibitors.   Anti-inflammatory / Musculoskeletal Drugs  Anti-inflammatory drugs – first-line, second-line, third-line. Nonsteroidal anti-inflammatory drugs (NSAID). Glucocorticoids as antiinflammatory agents. Second-line antirheumatic drugs. Pharmacology of immuno-modulatory drugs used to treat autoimmune diseases, including cytotoxic and immunosuppressive agents. Drugs for Neurological diseases and Psychotropics  First line and second line anti-epileptic drugs. Side effects and mechanisms of action.  Alzheimer‟s disease. Drug treatment of memory disorders. Anticholinesterases, muscarinic agonists, nicotine, nootropics and cognitive enhancers. Drug dependence. Definitions of dependence, misuse and abuse of drugs. Classification of drugs of dependence. Mechanisms of dependence. Parkinson‟s disease and its treatment. L-dopa, decarboxylase inhibitors, MAO inhibitors, Muscarinic antagonists, dopamine receptor agonists. Other neurodegenerative disorders. Huntington‟s chorea; Amyotrophic lateral sclerosis; drugs used to treat spasticity. Treatment of depression – Electroconvulsive therapy (ECT). Monoamine oxidase inhibitors (MAOI). Reversible inhibitors of monoamine oxidase A (RIMA). Tricyclic antidepressant drugs and Selective Serotonin Reuptake Inhibitors (SSRI). „Atypical‟ antidepressants. Mania and its treatment. Prophylactic and therapeutic uses of lithium. Antipsychotics, antidepressants and anticonvulsants in the treatment of mania. Antipsychotics for the treatment of schizophrenia. Typical vs atypical agents.       CNS stimulants. Caffeine, amphetamines, cocaine, hallucinogens (this will overlap to some extent with drugs of abuse?). Treatment of attention deficit hyperactivity disorders. Hypnotics and sedatives: the barbiturates, benzodiazepines, nonbenzodiazepine anxiolytics and sedatives.  Respiratory Drugs  Pathophysiology of asthma – constrictive and inflammatory components. Role of eosinophils. Pharmacotherapy of asthma – bronchodilators; b-agonists, xanthines, anticholinergics, leukotriene receptor antagonists. Anti-inflammatory drugs – corticosteroids, chromoglycate, etc. Use of longer acting b-agonists. Chronic obstructive pulmonary disease. – chronic bronchitis, emphysema and smoking. Pharmacotherapy  ASCEPT Core Curriculum for pharmacology in Medicine Introduction Medical courses around Australia have undergone dramatic changes in the last few years, which on the whole, have been very positive for medical graduates and teaching outcomes. As has been the British experience, there is a feeling that the dramatic shifts in teaching methods may result in some „knowledge gaps‟. In this respect, ASCEPT has taken the initiative to develop a (non-prescriptive) core curriculum for „pharmacology for medical students‟. The aims of exercise are to outline the basic pharmacology knowledge that all medical graduates should have and to define learning objectives for pharmacology learning – irrespective of the teaching modality. In medical curricula, there should be an attempt to move from „teaching about drugs‟ to a more student-centred approach of „learning about rational therapeutic intervention in individual patients‟. The Aim of the core curriculum is to define the knowledge required to: 1. integrate the mechanism of drug action with clinical effects and side effects in individual patients. relate drug metabolism and disposition clinical status of the individual patient (life stage, co-morbidity, poly-pharmacy, etc). allow for „rational prescription‟ and evaluate the „evidence base‟ of existing and new therapeutic agents. enable effective communication of drug effects and to enable critical evaluation of therapeutic decisions. 2. 3. 4. It is not intended that the core curriculum should provide a list of drugs that need to be learned. Furthermore it should be assumed that this recommended „basic course definition‟, provides more of a check list of medical pharmacology learning-objectives, which will necessarily be modified (in order and detail) at local institutions to suit teaching programs (and expertise). Student assessment should be aligned to the learning-objectives, and as far as possible should be authentic to the „graduate attributes‟ of the institution. This draft has been developed with reference to the American and British (BPS) models, with the assistance of O. Woodman, P. Seale, A. Tonkin, J. Vial, T. Campbell, T. Smith and R. Einstein and with valuable advice and insight from D Walker and S Maxwell, Univ. Edinburgh. Particular drugs or drug classes may be used to highlight the following learning-objectives. Students, by the end of the course should be able to:  Outline general issues relating to sources of drugs, their uses and place in the treatment of disease, and in society. Describe the drug development process in general (including regulatory affairs), describe basic clinical trial design and interpret clinical trial data. Identify the targets and potential targets/sites of drug action. Describe the nature of the drug interaction with the target. Identify and evaluate other sites of action of drugs as the possible basis/cause for unintended actions or side effects. Analyse and evaluate sources of information about drug action, treatment and side effects and appraise the value of the treatment against its side effect profile. Recognise the importance of the drug monitoring and the reporting of adverse drug reactions. Relate the formulation, sites of absorption, distribution and metabolism of a drug to how these may alter the effectiveness of the drug and impinge on its side effect profile. Analyse how the actions or disposition of a drug may be affected by the status of the patient – pre-existing diseases (liver, kidney function), age, sex, ethnicity, pregnancy (mother and fetus), life style, etc. and recommend how these may be managed. (Pharmacogenetics, polypharmacy, etc). Recognise and manage drug interactions. Evaluate alternatives for treatment (choice of drug for the patient to alternatives to pharmacotherapy and complementary medicines), the „evidence-base‟ for treatment and issues relating to rational prescription. Recognise issues (pharmacodynamic/kinetic to social) which may impinge on patient compliance with therapy, evaluate them and discuss their management. Clearly communicate issues relating to drugs (action, prescription, interaction, etc) to patient management teams and to patients.        The following list of topics could be used to highlight particular issues from the learning-objectives above. If required, the following may make the basis (essential not exhaustive) for a list of topics students should have studied: Basics of drug chemistry. Receptor theory, agonists and antagonists, dose response relationships, etc. Basics of signal transduction mechanisms and drug targets (eg. using gleevec as an example). Drug development. Clinical trials. Pharmacokinetic theory (also pharmacogenomics). Autonomic Nervous System drugs. Parasympathetic, muscarinic agonists and antagonists, neuromuscular blockers and anticholinersterases. Sympathetic, alpha, beta ant/agonists (basics). Basics of other transmitter systems (Histamine, serotonin, NO, dopamine, others). Drugs which release transmitters, interfere with synthesis or metabolism. Gastrointestinal drugs (autonomic system and H+ pump inhibitors, prostaglandin analogues, etc). Respiratory system drugs (xanthines, adrenergics and leukotriene antagonists, PAF, etc) Antiinflammatory drugs including drugs specifically affecting rheumatoid Arthritis and gout (incl. Steroids, NSAIDs, disease modifying, cytokines – anti-TNF, etc). Immunosuppressants. Antineoplastics (including monoclonal antibodies and conjugates, susceptibility genes, introductory gene therapy – or with respiratory system, cystic fibrosis). Local and general anaesthetics. Drugs used in the management of pain (acutely and long-term). Opiates, NSAIDs, etc. (eg. pain management of osteoarthritis, side effects of selective and non-selective COX-inhibitors, „natural product‟ remedies, evidence base for glucosamine, etc) Antiarrythmics. Antianginals and glycosides. Anticoagulants. Thrombolytics and antiaggregatory drugs. Diuretics (thiazides, loop diuretics and potassium sparing diuretics, etc). Antihypertensives (diuretics, b-blockers, ACE inhibitors, AT1 antagonists, etc). Lipid lowering drugs (statins, fibrates, resins, nicotinic acid, etc) Alcohol and drug abuse/ drug dependence. CNS drugs - - - - - - - - anti-depressants (Tricyclics, MAOI, SSRI, Atypical) anti-psychotics / neuroleptics (Classical and atypical) anti-epileptics (use-dependent Na+-channel blockers, valproate, GABA enhancers, etc) hypnosedatives / anxiolytics. - Parkinson‟s disease (L-dopa, anti-muscarinics, dopamine agonists, etc) Alzheimer‟s disease (anticholinesterases, nicotine, cognitive enhancers, etc – neurodegenerative diseases could be used to highlight genes and susceptibility to disease) Steroids thyroid (other hormones) hypoglycaemics. (insulin and oral hypoglycaemics to diet management, exercise, etc) Sex hormone based drugs (HRT, contraceptives, etc) - -