Basic Pharmacology What is an emulsion? Additives to parenteral preparations Effects of additives to drugs Storage of drugs and potency Drug interaction Discuss the principles of drug interactions using opioids and MAOIs as examples Define potency Potency, dose response curves and use of log dose Dose response curves Draw a log dose/effect curve Hill equation ED 90 ED95 How do you express drug safety? What is meant by the Therapeutic Index? Mechanisms of drug effect What is a receptor? Receptor theory Spare receptors Evidence for the existence of receptors Functional properties of receptors GABA receptors G-protein-linked receptors Interactions of drugs and receptors Tell me about pharmacogenetic disorders. Pharmacogenetics - examples related to anaesthesia. Tolerance - tachyphylaxis Transdermal preparations What is an isomer Stereoisomerism Pharmacology in neonates Pharmacology in pregnancy Pharmacotherapy Cerebral blood flow and anaesthetic agents Classify the drugs used in the treatment of asthma Classify drugs used in cardiac failure Define dissociative anaesthesia Define the term "an Hypnotic drug". Drug induced histamine release and anaphylaxis Drugs acting on sodium channels Drugs influencing ligand-gated vs voltage-gated ion channels Effects of anaesthetic agents on CNS Effects of isoflurane, propofol, fentanyl on blood pressure, in healthy adults Factors predisposing to thrombogenicity of drugs Influence of salbutamol, frusemide, captopril or ranitidine therapy on anaesthetic agents. Interaction of chemotherapeutic agents and anaesthesia Mechanisms of anaesthesia Mechanisms of drug-induced histamine release Methods to reduce stress response in anaesthesia Obtundation of the pressor response to intubation Precautions with "prophylactic" antibiotics Pro-convulsant anaesthetic agents Treatment of anaphylaxis Treatment of hyperkalaemia Pharmacokinetics pH & pKa, Henderson Hasselbach equation. Define bioavailability Determination of, and factors influencing, oral bioavailability First-pass metabolism Difference between plasma and biophase concentrations Effect site concentrations of drugs What is protein binding? What is meant by the term “volume of distribution”? How do you calculate volume of distribution Definition and clinical significance of volume of distribution Volume of distribution, clearance and half-life Redistribution Steady state Definition of clearance and estimation of clearance What is clearance? Explain clearance Intrinsic clearance Halflife and time-constant What is meant by "loading dose"? Enzyme substrate interactions Esterases Elimination half life First order and second order kinetics What is the difference between zero and first order kinetics? Why infuse a drug? Infusion kinetics Infusion regimens to achieve target concentrations Pharmacokinetics of propofol infusions What do you understand by the term “context sensitive half-life”? Kinetics of drugs in the epidural space Kinetics of inhalational agents Outline pharmacokinetic drug interactions Drug delivery systems Modelling Drug handling by the liver Cytochrome P450 Renal failure and drug metabolism Pharmacokinetics in heart failure How does liver disease affect the way the body handles drugs. Influence of pregnancy and liver disease on pharmacokinetics Inhalation Anaesthetic Agents Define saturated vapour pressure and boiling point Can you explain the concentrating and second gas effects? Please explain the second gas effect. Describe the uptake of volatile agents Draw a set of wash in curves versus time for commonly used volatile anaesthetic agents. Draw and explain the FA F1 curve. Does the curve reach unity at infinity ? What determines uptake of volatile anaesthetic agents from the alveolus? What factors influence the onset of action of volatile agent ? Wash-in curves of volatile anaesthetics Uptake and wash-out curves Induction and recovery with inhalational agents Definition and clinical utility of MAC, MACawake, MACBAR MAC – Definition. Tell me about factors effecting MAC. MAC uses and shortcomings What is MAC 95? Determination of MAC Quantitation of agent potency Draw or describe the concentration/response curve for an inhalational agent Ideal volatile anaesthetic agent Why is N2O used ? N2O properties and contra indications Nitrous oxide - indications Adverse effects of nitrous oxide; diffusion hypoxia How is nitrous oxide manufactured? Contraindications to the use of nitrous oxide Side effects of N2O. Entonox Uptake of nitrous-oxide What are the side effectsof nitrous oxide? Structure of an ether Tell me about the structure-activity relationships of volatile anaesthetic agents. Metabolism of inhaled anaesthetics Discuss the metabolism of sevoflurane/halothane Metabolism of halothane Metabolism of sevoflurane Chemical and biochemical breakdown of agents Systemic effects of different agents Respiratory effects of volatile anaesthetic agents Inhalation agents and hypoxic drive to ventilation Cardiovascular effects of inhaled anaesthetics Effects of agents on blood flow in specific tissues Endocrine and Metabolic effects Changes of induction dose in different patient groups Use in neonates Use in pregnant patients Toxicity of volatile anaesthetics Renal/hepatic toxicity Occupational hazards What volatile agent are you most familiar with and can you tell me about that agent? Advantages and disadvantages of enflurane Draw the structure of sevoflurane/isoflurane/halothane Isoflurane, Sevoflurane, Halothane Comparison of enflurane and isoflurane Isomerisation of isoflurane. What are the cardiovascular effects of isoflurane? Central nervous system effects of isoflurane Can you describe the effects of Isoflurane on respiration? Isoflurane and brain. Discuss factors affecting awakening from isoflurane Isoflurane vs sevoflurane Sevoflurane - its advantages over other volatile agents Structure/activity of sevoflurane. Adverse effects of sevoflurane Desflurane Intravenous Hypnotic Agents Classification of agents Classification of hypnotics Characteristics of intravenous induction agents What factors determine variation in doses of induction agents, for example with age and shock? Determinants of an induction dose Influence of age, anxiety, hypovolaemia on induction of anaesthesia Metabolism of different agents What is the structure activity relationship of barbiturates? Draw barbituric acid nucleus. What are the keto and enol forms ? Comparision of Thiopentone and Methohexitone. What are the contents of an ampoule of Sodium Thiopentone? Role of each adjuvent. Pharmacokinetics and biotransformation of thiopentone Time course of plasma concentrations of thiopentone Metabolism of thiopentone Cardiovascular effects of thiopentone Compare thiopentone and propofol Comparison of thiopentone and propofol induction Compare propofol and midazolam as induction agents Tell me about the formulation of Propofol. What are the contents of a propofol ampoule? Factors determining the effect of propofol What is the induction dose of propofol and what is its disposition in elderly patients? Propofol uptake and distribution Draw a concentration/time curve after an IV bolus of propofol Pharmacokinetics of propofol infusions Calculation of propofol dosage for TIVA Draw the plasma concentration time curve of propofol and the effect site (brain) concentration time curve. Effects of propofol on cardiovascular system Non anaesthetic effects of propofol Offset of action of propofol Ketamine Ketamine - advantages Ketamine, mechanism of action Ketamine, Propofol, Thiopentone Analgesic actions of ketamine Cardiovascular effects of ketamine Discuss the properties of benzodiazepines Benzodiazepene kinetics Benzodiazepine receptors Gaba receptor How do benzodiazepines exert their effects in the body? Mechanism of action of benzodiazepines Diazepam metabolism. Differences between midazolam & diazepam. Metabolism of midazolam vs diazepam Formulation and pharmacology of midazolam Structure of midazolam Flumazenil Alpha-2 agonists in anaesthesia Neuromuscular Blocking Drugs What is muscle relaxation and how can it be achieved. Nicotinic cholinergic receptors Please describe the site of action of neuromuscular blocking agents. Margin of safety of neuromuscular function. Describe events during onset of depolarising / non-depolarising neuromuscular block Characteristics of depolarising and non depolarising block Comparison of depolarising and non-depolarising neuromuscular blockers Structural features of non-depolarising muscle relaxants Structure activity relationships Classify muscle relaxants. Absorption and elimination of quarternary ammonium compounds Advantages of newer NMBs Factors affecting onset of muscle relaxants Factors determining onset time Can you explain the offset of non-depolarising muscle relaxants? Dose-response curves of neuromuscular blocking agents. Dose-response curve of different muscle group Definitions of ED95 Cardiovascular effects Drug effects on skeletal muscle tone Intraocular pressure Elimination of NMBs Breakdown of agents Effects of antibiotics on neuromuscular blockade Renal failure and use of muscle relaxants Prolonged blockade Sevoflurane Cisatracurium Suxamethonium Types of block with suxamethonium Can you classify and list the side effects of Suxamethonium administration? Contraindications and side-effects of suxamethonium, Suxamethonium apnoea. Dibucaine number. Site of action of atracurium Rocuronium Contents of an ampoule of Vecuronium Vecuronium infusion Compare/contrast pancuronium and vecuronium Account for a case of delayed recovery from vecuronium Vecuronium vs atracurium kinetics Vecuronium, Pancuronium, Suxamethonium Formulation of atracurium Metabolism and chemical breakdown of atracurium Cardiovascular effects of atracurium Cis-atracurium vs atracurium Cisatracurium Mivacurium Laudanosine Explain the techniques used to monitor neuromuscular block. Measurement of muscle relaxant effect Use of peripheral nerve stimulator Train of four ratio Assessment of neuromuscular block. How do you assess reversal of muscle relaxants? Monitoring of adequacy of reversal of block Tell me about neuroleptic malignant syndrome. Dantrolene Reversal Agents Antagonism of residual neuromuscular block Cholinesterase and anticholinesterases Types of anti-cholinesterase drugs. Explain the mechanism of action of anticholinesterases. Atropine, Glycopyrrolate, Neostigmine How does neostigmine act on acetylcholinesterase? Neostigmine Compare neostigmine and edrophonium Neostigmine like drugs Organophosphate toxicology Anticholinergics Atropine toxicity Comparison of atropine and glycopyrrolate Discuss the pharmacodynamics of atropine. Pharmacology of atropine and scopolamine Synthesis and release of acetylcholine Opioids Mechanism of action of opioids Opiate receptors Structure activity relationships of opioids Epidural/intrathecal opioids Conversion to oral opioids Log dose-response curves for opioids Opioid metabolism Duration of action Discuss the clinical uses of long acting opioids. What are the side effects of opioids ? Describe tolerance to opioids What drug factors influence the side effects of opioids ? Cardiovascular effects of opioids Codeine bioavailability and metabolism Codeine, Morphine, Fentanyl, Alfentanil, Remifentanil, Tramadol Pentazocine Remifentanil, kinetics and cardiovascular effects Onset of action of Fentanyl. Tell me about the effects of Fentanyl on the cardiovascular system. Compare fentanyl, alfentanil and remifentanil Pharmacokinetics of pethidine and fentanyl Morphine vs fentanyl vs alfentanil Comparison of fentanyl and morphine Fate of I.V. bolus of morphine. Describe the metabolism of morphine Plasma concentration time graph of morphine. Change of etCO2 with time after an IV bolus of morphine. Side effects of morphine Morphine structure and substitutions Tell me about the effects of Morphine on the cardiovascular system. Comparison of morphine and pethidine Pharmacology of naloxone Naloxone pharmacokinetics Analgesics NMDA receptors Codeine Tramadol Compare and contrast Paracetamol and Acetylsalicylic acid. Give a classification of non-opioid analgesic drugs. How do N.S.A.I.D.S. work? (mechanisms of action) Side effects nonsteroidal anti-inflammatory drugs. Aspirin Toxicity of aspirin and paracetamol Paracetamol What is your recommended dose of paracetamol? What is the toxic dose of paracetamol? Tramadol, kinetics and effects Pharmacodynamics of tramadol. Local Anaesthetics Classification of local anaesthetics Draw the structure of an ester local anaesthetic Structure - Activity - Relationships of local anaesthetics Describe the structure/function relationships of local anaesthetics Isomers of local anaesthetics Significance of isomers Mechanism of action of local anaesthetics Describe the site of action of local anaesthetics Topical use of local anaesthetics Contents in an ampoule Additives to local anaesthetics Effect of adrenaline and pH Kinetics after epidural injection Spread of agents administered into the epidural space Significance of protein binding Significance of pKA Correlate the pKa of local anaesthetics and their activity Metabolism of local anaesthetics Local anaesthetic toxicity, toxic dose, blood levels Systemic toxicity Foetal LA toxicity Toxicity lignocaine vs bupivacaine (R + S). Toxicity of amide local anaesthetics (lignocaine, prilocaine and bupivacaine) Treatment of amide local anaesthetic CVS/CNS toxicity Cardiotoxicity of local anaesthetic Comparative toxicity of bupivacaine vs ropivacaine Ropivacaine Ropivacaine, Lignocaine, Bupivacaine, Prilocaine, Cocaine Comparison of bupivacaine with lignocaine Epidural administration of bupivacane Discuss the brain concentration of bupivacaine after an epidural dose Recognition of structure of lignocaine. Pharmacokinetcs of lignocaine Metabolism and protein binding of lignocaine. Effects of lignocaine on nerve conduction EMLA Cocaine What are the effects of cocaine on the heart ? Cardiovascular Pharmacology Drugs acting on calcium channels What drugs are used in cardiac arrest? Management of myocardial ischaemia Classify drugs used in cardiac failure What is the structure-activity relationship of vasopressors? Types of vasoconstrictors Choice of drugs to treat hypotension after spinal anaesthesia Catecholamines: structure-activity, receptors Metabolism of catecholamines, MAO inhibitors Direct and indirect adrenergic agents Structure activity relationships in adrenergic agonists Pharmacology of beta adrenergic agents What is the structure-activity relationship in β agonists What is the effect of B2 agonist drugs, how do they work ? Adrenaline Describe the production of adrenaline in the body. Termination of effect of noradrenaline Dopamine Dopamine receptors Pharmacology of ephedrine Choosing between ephedrine and metaraminol Comparison of ephedrine and metaraminol Classify positive inotropic drugs Classify inotropes What is phosphodiesterase. What drugs affect it ? Classification and clinical indications of phosphodiesterase inhibitors PDE inhibitors: theophylline, milrinone Antiarrhythmics: classification and electrophysiology Pharmacological treatment of ventricular fibrillation Adenosine, Amiodarone Actions of adenosine. Tell me about the cardiac effects of Adenosine. Discuss digoxin What are the side effects of digoxin? Beta blockers What are the side effects of sotalol? What can you tell me about Esmolol? Alpha blockers 2 agonists a2 agonists pharmcodynamics. The pharmacology of clonidine Effects of IV clonidine Classify the anti-hypertensive drugs Tell me about agents that are used to lower blood pressure. Antihypertensives in pregnancy Discuss one parenteral antihypertensive. Renin-Angiotensin system Classification of vasodilators. Glyceryl trinitrate and sodium nitroprusside How does GTN work ? Pharmacology, metabolism and toxicology of sodium nitroprusside Sodium nitroprusside mechanisms of action and metabolic toxicity. Pulmonary vasodilators Nitric oxide Diuretics Classify diuretics by their site of action Actions of diuretics, Dose response curve for diuretics Comparision of thiazide & loop diuretics Specific Agents Gastrointestinal Pharmacology Antiemetics Classification of anti-emetics Pharmacology of anti-emetics Classify drugs that affect the gastric acidity. What agents can be used to decrease gastric acidity ? Mechanisms of altering intraluminal gastric pH Drugs that increase gastric emptying Obstetric Pharmacology What drugs affect uterine motility? Can you tell me about Ergometrine? Clinical toxicity of Mg Drugs that affect the uterus Oxytocics Oxytocin Uterine relaxants Endocrine Drugs that affect blood sugar Classify insulins Insulin preparations Classify oral hypoglycaemics Hypoglycaemic agents Coagulation Drugs affecting haemostasis Drugs and haemostasis Anticoagulants and the reversal of their effect Action of warfarin What are the kinetics of heparin? Explain how Heparin exerts its anticoagulant effect. Heparin vs LMW heparin Heparin-effects, metabolism Describe the anti-platelet agents Heparin, Protamine, Antiplatelet agents Side effects of Protamine DDAVP, mechanism of action Fluids Dextrose vs dextran Haemmaccel Side effects of sodium bicarbonate Mechanism of action of mannitol Colloids; mannitol Acetylcholine Bradykinins Histamine and antagonists Histamine and histamine receptors Describe the distribution of histamine receptors Prostaglandins, synthesis and inhibition Drugs used to treat asthma Methylxanthines Theophylline Recognise 5-hydroxy typamine. What drugs interact with 5HT ? Serotinergic receptors Serotonin agonists and antagonists Tricyclic antidepressants Monoamine oxidase inhibitors Describe the mechanism of action of anti-convulsants Mechanism of action of antiepiliptic drugs Can you tell me about Phenytoin? Kinetics and side effects of phenytion Antibiotics mechanisms of action Differences within the penicillin class of drugs DNA and RNA, and recombinant drugs Statistics: Types of data Define nonparametric data ? Parametric and non parametric data What are ordinal data? What are descriptive and inferential data? Appropriate statistical test for various types of data Selection of statistical tests Type I and II errors What is a type II error? Power of statistical tests Null hypothesis Outline a chi-squared test Normal distribution, Measures of central tendency What is a standardised normal distribution? Standard error of the mean Role of SD versus SEM What is a t distribution? Can you define standard deviation and explain confidence levels? Information from confidence intervals versus P-value Confidence intervals How does one determine sample size in statistics? Methods of determination of statistical significance Tests of significance Meaning of P values (<0.5) and confidence limits Modelling What is meant by meta-analysis? Odds ratio Risk ratio Specificity / sensitivity / predictive value Correlation What is bias? What are some sources of bias Bias in clinical research Basics of study design and clinical trials Early phase (I-II) drug testing Statistical classification of data relating to trial of antiemetic drug and test that may be used to analyse the data. Statistical classification of data relating to trial to assess potency of inhalational agent and appropriate statistical test. Statistical determination of analgesic efficacy