I. GENERAL OBJECTIVES:
1. To integrate essential principles of the basic medical sciences
with an understanding of the actions of drugs in the whole body and their
therapeutic applications.
2. To permit the medical graduate to use drugs optimally in the
prevention, diagnosis and treatment of disease.
3. To enable the medical graduate to appraise the benefits and risks
of therapeutic innovations.
4. To enable the medical graduate to review critically his or her own
therapeutic decisions in patient management.
Some aspects of the core curriculum (identified in IVpartA below) will not fit readily into the proposed "Systems and Topics" courses and will therefore need to be taught separately. Other aspects (see IVpartB below) will complement and should be taught alongside the appropriate "Systems/Topics" courses, identified as "Principles of Drug Therapy". An important focus of the course as a whole will be the understanding of drug action in the body as a whole rather than in isolated systems. Teaching will necessarily draw upon and therefore reinforce material (particularly physiology and biochemistry) taught in other courses. This integrated approach is fundamental to the understanding of drug action and hence to the effective and safe use of drugs in clinical medicine. A coherent thread of pharmacology and therapeutics will provide a substantial strength to the course as a whole, crossing the boundaries between "Systems and Topics".
II. BASIC KNOWLEDGE TO BE ACQUIRED BEFORE UNDERGRADUATE TRAINING IN "PRINCIPLES OF DRUG THERAPY" CAN COMMENCE:
The starting point requires a working knowledge of the basic physiology,
biochemistry and structure of the major systems of the body, as will be
taught within the systems approach. "Principles of Drug Therapy" will then
give a focus to the way in which the major systems interact with one
another. For example: for the pharmacological treatment of hypertension the understanding of
antihypertensive drug action requires in addition to a knowledge of the
CVS, a knowledge of:
(i) the autonomic nervous system (ANS) and the systems/tissues it
innervates - antihypertensive drugs which interfere with autonomic
transmission (e.g. beta-adrenoceptor blocking drugs) predictably produce
wide-spread actions on other systems innervated by the ANS.
(ii) the central nervous system - some antihypertensive drugs have
central actions; in addition a number of drugs interfere with the reflexes
controlling blood pressure leading, for example, to troublesome postural
hypotension
(iii) the regulation of salt and water balance - i.e. the kidney and the
renin angiotensin system
(iv) autacoids and the local regulation of blood flow
(v) the physiology/biochemistry of the principle organs concerned with
pharmacokinetics
Much of the material scheduled in "Molecules, Cells and Tissues" will be
essential prior knowledge. For example:
(i) structure of cells, and membranes - essential for the understanding
of the entry of drugs to the body, their distribution and subsequent
excretion,
(ii) mechanisms of cell-cell communication, receptors and signal
transduction cascades - fundamental to the understanding of drug action
(iii) enzyme activity/kinetics - highly relevant to drug metabolism,
aspects of drug-drug interactions and to the biological actions of some
drugs
(iv) acid-base balance - critical to the understanding of the
pharmacokinetics and pharmacodynamics and hence the use and administration
of drugs
(v) the cell cycle - needed to understand the mechanisms of action of
some chemotherapeutic agents
(vi) the role of nucleic acids and the principles of protein synthesis -
essential to the understanding of drugs such as steroids and to
comprehension of much of the basis of antimicrobial drugs and cancer
chemotherapy
The "Molecules, Cells and Tissues" course will provide an excellent foundation on which to base the teaching of the molecular basis of drug action. It will also be essential to the understanding of aspects of "Principles of Drug Therapy" taught later in the course and will therefore be subsequently reinforced and extended in both clinical and basic medical science contexts.
III. ASSESSMENT
The material taught in "Principles of Drug Therapy" should be examined at intervals within the course. Assessment should take several forms including formal examinations, project work including data analysis, essays and self-appraisal.
IV.CONTENT
Teaching of the following will be identified as "Principles of Drug therapy". Where repetition occurs it is generally in a new integrative context and is deemed advantageous.
Part A: Core material to be scheduled alone as "Principles of Drug Therapy":
(i) Principles of drug administration, drug action and pharmacokinetics
..... Routes of administration
..... Mechanisms of absorption, distribution, metabolism and excretion of
drugs
..... Desired and undesired actions of drugs
..... Principles of drug interactions and adverse drug reactions;
emphasis on the global actions of the major drug groups in the whole body -
multiple actions of single agents
..... Drug allergy - mechanisms and common examples of four types of
allergic response; common clinical presentations and their management
..... Monitoring of plasma/tissue concentrations of drugs - when are
these necessary; limitations
..... Practical demonstration: Bioavailability of aspirin.
(ii) Variability in human response to drugs and influence of disease
processes
..... Drug handling and prescribing in the elderly, infants and children: altered
pharmacokinetics and pharmacodynamics; altered pathophysiology special problems with
polypharmacy
..... Drug usage in pregnancy and in breast-feeding women: special concerns for drug
toxicity, drugs of choice in common diseases
..... Prescribing for patients with renal or hepatic disease: altered pharmacokinetics and
dynamics;drugs to be avoided; drug induced nephrotoxicity and hepatotoxicity
..... Influence of other concurrent diseases - e.g. asthma, gout,
diabetes, hypertension, porphyria, hypercholesterolaemia, heart failure -
on prescribing; and precipitation of the conditions by drugs
..... Pharmacogenetics: implications for altered or unusual drug
handling, drug efficacy or toxicity, common and dangerous clinical
examples, gene therapy
..... Practical demonstration: Sources of variation in response to drugs
- group estimate of sulphadimidine acetylation
(iii) Knowledge of adverse drug reactions and interactions
..... Epidemiology; mechanisms; pharmacologic and non-pharmacologic
..... How to recognise, how to avoid
..... Voluntary reporting systems, post-marketing surveillance
..... Role of SMC in UK, FDA in USA
(vi) Elements of drug abuse, toxicology and poisoning
..... Overdose and addiction problems; epidemiology; recognition
..... Clinical toxicology, nature of the toxic response
..... Food toxicology, additives, contaminants and components
..... Forensic aspects of poisoning
..... Management of commonly abused substances (e.g. alcohol, nicotine,
cocaine, opioids)
..... General approach to treatment of the poisoned patient:
..... Stabilisation, assessment, decontamination, antidotes, general
treatment procedures to increase drug clearance
..... Recognition of common presenting syndromes
..... Management of common poisons (e.g. salicylate, paracetamol...)
(v) Evaluation of drug actions in man
..... Emergence of new drugs, drug design and discovery
..... Preclinical development and testing, phased clinical volunteer studies
..... Essential elements of a valid clinical trial
..... Legislatory control of new drugs
..... Ability to assess critically commercial claims for established and
new drugs
..... Understanding of the pharmaceutical industry's achievements and
educational role
Part B: Core material, identified as "Principles of Drug Therapy" to be scheduled in relation to relevant systems and topics:
Sections (i) and (ii) cover general topics. Sections (iii) - (xiii) describe the "Principles of Drug Therapy" core by reference to classes of drugs used within systems rather than as drugs used for specific diseases. This is because the various actions of a group of drugs within the body as a whole often depends on a common mechanism of action; it is these underlying principles which must be understood for drugs to be used effectively and safely.
(i) Principles of drug actions; molecular mechanisms of drug action
including:
..... receptor theory and targets of drug action
..... agonists and types of antagonism
..... cellular basis of quantitative pharmacology
..... principles of structure-activity and dose-response relationships
..... mechanism by which drugs modulate signal transduction pathways
..... interactions between drugs and ion channels
..... modulation of gene expression by drugs
..... receptor-independent mechanisms of drug action e.g. inactivation of
enzymes, interactions with structural components of the cell
..... active and passive mechanisms by which drugs cross cell membranes
..... molecular basis of inadequate or excessive drug actions including
drug interactions
..... mechanisms of termination of drug actions (e.g. uptake into cells;
degradation)
..... Practical demonstration illustrating mechanisms of drug action:
Bioassay and competitive antagonism - actions of acetylcholine +/- atropine
on guinea pig ileum
Timing/location: The "Molecules, Cells and Tissues" course will provide an
essential foundation for teaching the molecular basis of drug action.
(ii) Using drugs effectively
..... choice of therapy
..... when not to prescribe
..... identification of therapeutic problem lists
..... preparation of planned therapeutic regimes
..... drug use in multiple illnesses
..... combination therapies, tailored therapy
..... reading and understanding prescriptions
..... instruction in prescribing techniques
..... awareness of iatrogenic disease
..... principles of using approved names vs. brand names
..... non-Textbook information sources needed for effective use of drugs
e.g. BNF, District Drugs Guide, Drug And Therapeutics Bulletin,
Prescribers' Journal
..... communication with patients about their medication
..... assessment of compliance problems and methods of enhancing compliance
..... relationship between compliance and understanding
Timing/location: within "Dr-Patient Clinical & Communication Skills"
(iii) Drugs and the autonomic nervous system
..... directly and indirectly acting cholinomimetics
..... muscarinic and nicotinic receptor blockers
..... a/b-adrenoceptor agonists/antagonists
..... indirectly acting sympathomimetics
..... practical demonstrations:
..... investigation of drug response in man - the action of beta-blockade
in volunteers
..... the actions of nitrates and nicotine in man
..... drugs acting on the human eye - anticholinergic, cholinergic,
sympathomimetic
Timing/location: "Nervous and autonomic nervous system". Knowledge of the
autonomic nervous system is critical to the understanding of pharmacology
and it should therefore be taught early on in "Principles of Drug Therapy".
It is essential that adequate time is devoted to this important, complex
topic.
(iv) Drugs acting primarily on the central nervous system
..... antidepressants
..... anti-Parkinsonian agents
..... anxiolytics
..... sedatives/hypnotics
..... anti-convulsants
..... anti-spastics
..... CNS stimulants
..... appetite suppressants
..... drugs of dependence, alcohol
..... analgesics and pain control
..... drugs for migraine
..... neuroleptics
..... drugs in affective disorders
..... practical demonstration:
Timing/location: at appropriate points within "Nervous system & autonomic
nervous system"
(v) Drugs and the cardiovascular system:
..... anti-hypertensives
..... anti-anginals
..... drugs used in heart failure and shock
..... anti-dysrhythmics
..... diuretics
..... anti-coagulants*
..... drugs affecting platelets*
..... fibrinolysins*
..... anti-anaemic drugs*
..... lipid lowering drugs
..... practical demonstrations:
..... Drugs and cardiac tissue - computer simulation with monitored
animal preparation.
..... Practical demonstrations: Autonomic pharmacology and cardiovascular
function, video and clinical demonstration; vasodilators and
vasoconstrictors - isolated rat preparation
Timing/location: Much of this would fit well alongside "Cardiovascular".
However groups asterisked* are also highly relevant to "Blood and
Lymphatics". It will also be appropriate to teach diuretics within the
Renal system.
(vi) Drugs acting on the kidney:
..... diuretics
..... anti-diuretics
..... drugs affecting urine pH
..... uricosuric
Timing/location: within kidney and urinary tract, and also -
Diuretics - CVS system; anti-diuretics - endocrine with diabetes insipidus;
drugs affecting urine pH - poisoning; uricosuric - musculoskeletal system.
(vii) Drugs acting on the respiratory system:
..... bronchodilators
..... inhibitors of mast cell mediator release
..... anti-inflammatory steroids
Timing/location: Respiratory system but as most will have been covered in
other aspects of the course this will be essential contextual reinforcement.
(viii) Drugs for infection
..... antibacterial
..... antiviral - including principles of vaccination
..... antimalarial
..... antifungal
..... antiprotazoal and antihelminthic
Timing/location: within "Infection, Immunity and Neoplasia".
(ix) Cancer chemotherapy and immunosuppressive drugs
..... neoplastic cell burden and principles of therapy
..... cell cycle specific and non-specific agents
..... alkylating agents, antimetabolites, plant alkaloids, antibiotics,
cisplatin, nitrosoureas, hormonal agents
Timing/location: "Infection, immunity & neoplasia"
(x) Drugs affecting the GI tract
..... autacoids
..... ulcer healing drugs
..... anti-spasmodics
..... anti-diarrhoeal drugs
..... laxatives
..... motility stimulants
..... anti-inflammatory
..... anti-emetic
Timing/location: Most could be taught alongside the "Gastrointestinal
system"' although aspects of these drugs will also be taught elsewhere -
e.g. codeine will be taught not only as an anti-diarrhoeal but also as an
analgesic and anti-tussive agent. The principles of anti-inflammatory
drugs will be taught elsewhere. Anti-emetics will recur in the CNS and may
therefore be considered separately.
(xi) Drugs and the blood
..... drugs for anaemias
..... anti-platelet agents
..... anticoagulants and fibrinolytic agents
Timing/location: "Blood and lymphatics"
(xii) Drugs and endocrine systems (diabetes, thyroid disease, adrenal
disorders, hypothalamic and pituitary disorders, bone metabolism)
..... adrenocortical steroids, their analogues and drugs affecting their
release
..... thyroid and anti-thyroid drugs
..... growth hormone and drugs affecting its release
..... drugs affecting blood sugar
..... drugs affecting Ca++ homeostasis
..... vasopressin and its analogues
Timing/location: Mainly in the endocrine system but:
..... anti-inflammatory steroids will be taught with inflammation and
within Infection, Immunity & Neoplasia
..... aldosterone antagonists with diuretics
..... drugs affecting Ca++ homeostasis are also relevant to musculoskeletal.
(xiii) Drugs and reproduction
..... gonadal steroids, their analogues and drugs affecting their release
..... fertility drugs
..... contraceptive drugs
..... oxytoxics and tocalytics
..... drugs suppressing lactation
Timing/location: Within "Reproductive system"
Part C: Special subject areas Some groups of drugs are used to treat a wide variety of conditions and in other circumstances many drugs are used to a common end. Integration of these complex areas is required and a range of specialists should contribute to the relevant teaching in relation to the "Drugs and Therapy" aspect.
(i) Autacoids and anti-inflammatory drugs
..... aspirin, cyclo-oxygenase inhibitors, non-steroidal anti-inflammatories
..... eicosanoids: prostaglandins, thromboxane, leukotrienes and antagonists
..... corticosteroids
..... cytokines and anti-cytokines
..... histamine serotonin, kinins, platelet activating factor and antagonists
(ii) Management of pain
..... principles of pain relief
..... analgesics - opioid and non-opioid
..... techniques of analgesic administration
(iii) Drugs used in surgery
..... pre-anaesthetic medication
..... general anaesthetics; local anaesthetics
..... skeletal muscle relaxants
..... preparation for surgery in special cases - e.g. diabetes,
hypertension, phaeochromocytoma, steroid dependence
Further suggestions, either of special subject areas of how to deal with them, are welcome.
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By the end of the undergraduate course students should be familiar with:
(a) The mechanisms of action of the major groups of drugs at the cellular level and their effects within the whole body
(b) Clinical pharmacokinetics. Students should be able to solve the most common pharmacokinetic problems presented by usual and complicated patients: be familiar with computing loading doses and maintenance doses for patients with normal and abnormal kinetic parameters; be able to apply their knowledge of half-life to prescribing drugs with optimal dosing intervals; be able to use recent reference sources to locate accurate pharmacokinetic data for commonly used drugs.
(c) Therapeutic drug monitoring. Students should become skilled at ordering drug levels at optimal times and for appropriate indications; become skilled at recognising possibly misleading data; and become skilled at incorporating valid results into revised therapeutic regimens.
(d) Adverse drug reactions. Students should develop reasonable skills at analysing complicated cases in which patients have several diseases, several complaints and are receiving several drugs; practice and sharpen their skills at distinguishing symptoms and signs caused by disease from those caused by drugs themselves.
(e) Drug allergy. Students should become skilled at recognising and treating the most common presentations of allergic responses to drugs; know the correct approach to managing a patient with an acute anaphylactic reaction; improve their skills in taking a history of drug use, including history of medication allergy or intolerance.
(f) Drug interactions. Students should become skilled in recognising common drug interactions. Equally important, they should be skilled in using common reference materials to ascertain potential drug interactions with the drugs they will be prescribing to avoid unintended and unexpected drug interactions; when interacting drugs must be prescribed, students should be familiar with approaches to rational prescribing to minimise toxic interactions.
(g) Pharmacogenetics. Students should develop the ability to use reference sources to find the most commonly described clinically important pharmacogenetic syndromes that produce atypical patient responses to medications.
(h) Prescribing for elderly patients. Students should be able to recognise and avoid drugs that pose special problems and risks for elderly patients and should understand characteristics of drugs that indicate a need for dosage modification in elderly patients.
(i) Prescribing for paediatric patients. Students should be able to apply dosing strategies on the basis of weight and surface area calculations.
(j) Prescribing for pregnant and nursing women. Students should be able to use current reference sources to ascertain drug risk in these populations; be able to prescribe drugs of proven safety and efficacy for commonly encountered illnesses such as urinary tract infections and hypertension.
(k) Prescribing for patients with renal disease. Students should be able to calculate an estimated value for creatinine clearance and use this figure to calculate drug clearance and maintenance doses for drugs with predominant renal clearance.
(l) Writing prescriptions. Students should be skilled in writing complete, accurate and unambiguous prescriptions for use in both inpatients and outpatients, including drugs with special restrictions.
(m) Substance abuse. Students should begin to develop their skills in obtaining a history of drug or substance abuse and in recognising which patients may have such problems.
(n) Poisoning and drug overdose. Students should be familiar with sources of accurate information about the diagnosis and treatment of toxic emergencies.
(o) Learning about new drugs. Students should be familiar with sources of accurate information concerning indications, pharmacokinetics, and appropriate use of new drugs. Students should begin to develop skill in reading and assessing scientific papers describing clinical trials, and develop their skills in distinguishing valid studies from those with serious methodologic flaws or bias. All students should know how to use available reference texts, library resources, computer data bases (e.g. Medline) to carry out their own programmes of continuing education.
(p) Communication skills. Students should become skilled in talking with their patients to assess and encourage drug compliance; ascertain previous adverse drug reactions and drug allergies; elicit a complete drug history, including prescription drugs, nonprescription drugs, and topical preparations. They should have an understanding of the nature of informed consent and how it applies to drug use.
(q) Recognition of pressures to prescribe irrationally. Students should develop the ability to recognise in themselves tendencies to irrational prescribing and should recognise the forces encouraging such habits. They should understand the potential for their accepting misleading, incomplete, or biased information when they learn about medications from a variety of sources, including reports of flawed clinical trials, personal experience, advertisements, pharmaceutical representatives, colleagues (word of mouth), patients, or sponsored symposia. They should also begin to appreciate how potential conflicts of interest might affect their ability to prescribe objectively and rationally.
For further information contact: Professor J.C. Buckingham, Dept. of Neuroendocrinology, Imperial College School of Medicine, Charing Cross Campus, Fulham Palace Road, London W6 8RF: Tel: +44-(0)-181 846 7279; Fax: +44-(0)-181 846 7253; j.buckingham@ic.ac.uk