CCT in Anaesthetics - Core Level Training

Published: 15/08/2019

Pharmacology

Demonstrates knowledge of:

Competence

Description

 

GMP

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Organic chemistry: drugs as organic molecules: types of intermolecular bonds; interactions between molecules; organic compared with inorganic compounds; bond strength; important atomic constituents: C, N, O, P, S and halides

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Organic chemistry: ionization of molecules: type of groups that ionize: amides, hydroxyl, carboxyl. Oxidation and reduction.

Permanently charged [quaternary ammonium] drugs. 

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Drug chemistry: solubility, partition coefficients and movement of drugs through membranes: Lipid solubility; influence of pKa and pH; partition coefficients. Passive and active transport mechanisms

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Isomers: structural and stereoisomers: classification systems; clinical relevance

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Mechanisms of drug action: physicochemical; pharmacodynamic; pharmacokinetic: drug-receptor interactions; doseresponse and log[dose]-response curves; agonists, partial agonists, antagonists. Reversible and irreversible antagonism. Potency and efficacy

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Non-specific drug actions: Physicochemical mechanisms:  e.g. adsorption; chelation; neutralization

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Voltage-gated ion channels; membrane-bound transport pumps. Sodium, potassium and calcium channels as targets for drug action

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Receptors as proteins; ion channels; transmembrane transduction and intermediate messenger systems; intracellular/nuclear receptors. Receptor regulation and tachyphylaxis

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Transduction systems as receptors: G-protein coupled receptors [GPCRs] and non-GPCR systems. 

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Nuclear receptors: Intracellular hormone receptors. e.g. cytoplasmic receptors for steroids; corticosteroids vs.

mineralocorticoid receptors

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Enzymes as drug targets: Michaelis-Menten kinetics. Direct and allosteric mechanisms. e.g. acetylcholinesterase; cyclooxygenase; phosphodiesterase

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Anticholinesterases: Classification of drugs that inhibit acetylcholinesterase and plasma cholinesterase including organophosphates

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Predictable side effects of drugs: non-selective actions of drugs; action at multiple receptors; multiple anatomical locations; predictable enzyme induction-inhibition

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Idiosyncratic side effects of drugs: e.g. blood and bone-marrow dyscrasias; pulmonary fibrosis; anti-platelet effects.

Anaphylactic and anaphylactoid reactions: comparison; treatment; identification of responsible drug; risks with polypharmacy

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Tachyphylaxis and tolerance: Examples of drugs demonstrating tachyphylaxis; proposed mechanisms. Opioid dependence and tolerance

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Drug interactions: Types of interaction: synergism, additivity, antagonism; isobolograms. Classification of mechanisms of drug

interaction

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Pharmacokinetics: general principles: absorption, distribution and redistribution; elimination, excretion. Chemical properties of drugs and their pharmacokinetics: blood-brain-barrier and placental barrier. Protein binding: plasma and tissue. Body compartments; adipose and vessel-poor tissue. Bioavailability; clearance

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Administration and absorption: routes of administration; first-pass metabolism and bioavailability. Selection of appropriate route. Drug delivery systems: e.g. sustained release, enteric coated, transdermal patch and iontophoretic systems

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Oral administration: Time-course for systemic appearance; factors e.g. pKa, lipid solubility, active transport. Bioavailability of drugs given orally and its measurement

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Drug elimination from plasma. Mechanisms: distribution; metabolism; excretion: exhalation; renal; biliary; sweat; breast milk. Factors affecting e.g.: pathological state: renal and hepatic failure; age, including extremes of age; gender; drug interactions.

Active and inactive metabolites; pro-drugs. Enzyme induction and inhibition

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Non-enzymatic drug elimination: Hofmann degradation

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Pharmacokinetic modelling: types of models available: one, two and three-compartment models; non-compartmental; physiological. Pharmacokinetic parameters: volume of distribution, half-life and time constant, clearance 

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Context-sensitive half-time: comparison of drugs e.g. propofol, fentanyl and remifentanil. Target-controlled infusions [TCI]

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TCI in practice: accuracy, applicability, cost. Variations due to patient differences: predictable and unpredictable

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Differences in patient response to therapy: gender; pathology; polypharmacy; in particular, changes occurring with increasing age

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Pharmacogenetics: pharmacokinetic variation e.g. pseudocholinesterase; acetylation; CYP450 variants. Poor and fast metabolizers; racial and geographic distribution of common abnormal genes

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PR_BK_27

Volatile and gaseous anaesthetic agents: Structure of available agents. MAC. Clinical effects: CNS [including ICP], CVS, RS. Unwanted effects of individual agents. MH susceptibility; hepatitis risks. Factors affecting onset and offset time. Oil/gas partition coefficient

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Intravenous anaesthetic agents: Chemical classes. Properties of an ideal induction agent. Adverse effects on CNS [including effects on ICP], CVS, RS; pharmacokinetics including metabolism

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Mechanisms of general anaesthetic action

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Benzodiazepines: classification of action. Clinical actions. Synergism with anaesthetic agents. Antidote in overdose 

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Local anaesthetic agents. Additional effects, including anti-arrhythmic effects. Mechanism of action. Clinical factors influencing choice: operative site, patient, available agents. Toxicity syndrome; safe clinical and maximum clinical doses; treatment of overdose

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Analgesics. Simple analgesics, NSAIDs and opioids. Available routes of administration; peri-operative prescribing; chronic compared with acute pain prescribing

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Aspirin and paracetamol. Comparison of structures; indications and contraindications; mechanisms of action. Bioavailability; metabolism; toxicity

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Non-steroidal anti-inflammatory analgesics: Classification. Mechanism of action. Clinical effects and uses; unwanted effects, contraindications

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Opioid analgesics: Receptor classification. Mechanism of action. Inhibitory effects, sites of action on pain pathways.

Unwanted effects. Full and partial agonists and partial agonists. Routes of administration

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Muscle relaxants.  Classification. Sites of action. Properties of an ideal muscle relaxant. Dantrolene and management of MH

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Depolarizing muscle relaxants: Structure, mechanism of action. Organophosphate poisoning. Adverse effects and contraindications

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Non-depolarizing muscle relaxants: Structural classification; sub-classification according to onset-time and duration of action. General comparison of aminosteroids and bisbenzyisoquinoliniums. Comparison of individual agents; metabolism and active metabolites. Unwanted effects.

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Reversal of neuromuscular blockade: Indications for use; mechanisms of action; clinically unwanted effects of reversal of neuromuscular blockade

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Drugs and the autonomic nervous system: anatomy; myelinated and unmyelinated nerves; ganglia and rami communicantes.

Neurotransmitters. Sites at which drugs can interfere with autonomic transmission

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Drugs and the sympathetic nervous system: adrenergic receptors and molecular mechanisms of action: Indications for pharmacological use of naturally occurring catecholamines and synthetic analogues. Other classes of drugs active in the sympathetic system: e.g. MAOIs:

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Drugs and the parasympathetic nervous system: nicotinic and muscarinic receptors with subgroups. Mechanism of action.

Agonists, antagonists. Comparison of available drugs. Hyoscine and antiemesis

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Cardiovascular system: general: drug effects on the heart [inotropy and chronotropy] and on the circulation: arterial and venous effects; systemic and pulmonary effects

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Inotropes and pressors: Classification; site of action. Synthetic inotropes compared with adrenaline

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Drugs used in ischaemic heart disease: Classification of drugs used. Mechanisms of drug action. Unstable angina

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Antiarrhythmics: Classification. Indications for use, including use in resuscitation

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Hypotensive agents: Classes of drugs to produce acute hypotension in theatre. Therapeutic antihypertensive agents:

classification according to mechanism of action. Adverse effects of drugs in each class

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Anticoagulants: oral and parenteral.  Sites of action; indications use; monitoring effect. Comparison of heparins:

unfractionated and fractionated. Newer anticoagulants

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Antiplatelet agents. Perioperative management of antiplatelet medication

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Pro-coagulants: Drugs. Individual factor concentrates; multi-factor preparations including FFP; vitamin K

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Colloids, including blood and blood products: Composition of preparations; safe use and avoidance of errors

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Crystalloid fluids: Composition; suitable fluids for maintenance and replacement of losses. Comparison with colloids; unwanted effects 

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Respiratory system: general: Classes of drugs acting on the respiratory tract including bronchodilators; oxygen; surfactant; mucolytics; pulmonary vasodilators. Methods of administration; indications for use; mechanisms of action; adverse effects

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Respiratory system: drugs used in acute severe asthma and chronic asthma; volatile agents. Mechanisms of action

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Gastrointestinal system: general: antisialogogues; drugs reducing gastric acidity; drug effects on the GI tract including gastric and bowel motility

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Antiemetics: Anatomical sites for antiemetic action; central and peripheral inputs to vomiting centre; use of dexamethasone 

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Renal system: diuretics: Classification of diuretics. Unwanted effects; indications for use

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CNS: antiepileptic agents: Mechanisms of action; unwanted side effects

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CNS: antidepressants: Classes of drug: anaesthetic relevance

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Therapy for diabetes mellitus: Drugs used in type 1 and type 2 diabetes: Insulins: classification of types available; routes of administration; perioperative management. Unwanted effects and risks and therapy of hypo- or hyperglyaemia

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Hormones: corticosteroids: Indications for use; clinical effects; long-term complications of glucocorticoid use

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Hormones: treatment of thyroid disorders: Synthesis and release of thyroid hormones. Preparations used in hyper- and hypothyroidism 

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CNS stimulants; classes, mechanisms of action, uses in anaesthesia

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RS stimulants including theophyllines, doxapram

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Antimicrobial agents: general classification: Types of antimicrobial agents: antiviral; antibacterial; antifungal; bacteriostatic and bacteriocidal. Mechanism of action. Indications for use of different classes of antibiotics. Bacterial resistance

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Effects of drugs on the eye and vision; includes intra-ocular pressure

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Social drugs including tobacco, alcohol and non-legal drugs: anaesthetic relevance

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