12 a) True Dobutamine is a synthetic catecholamine with a similar structure to isoprenaline. b True Dobutamine is an agonist at catecholamine receptors. Activation of these receptors results in an increase in the activity of adenyl cyclase, which catalyses the conversion of ATP to cAMP. This increases the cell membrane permeability to calcium resulting in inotropy. c) False Dobutamine is predominantly a ß1 adrenergic agonist which increases contractility, heart rate and myocardial oxygen requirements. It is a weak agonist at ß2 and a adrenoceptors. d) True The plasma half life of dobutamine is 2 minutes and it is infused at 2.5-10 µg/kg/min. it is metabolised by COMT to in active metabolites that are conjugated and excreted in the urine e)False Dobutamine causes a decrease in left ventricular end-diastolic pressure. 3 4 . cerebral and coronary arteries (D1 effect) and stimulation of sympathetic prejunctional receptors decreasing noradrenaline release (mild D2 effect). tremor. mild tachycardia. angina. 5 . c) TrueDopexamine is a positive inotrope and therefore increases cardiac output. Dopexamine also has strong beta-2 agonist action and inhibits uptake-1 of noradrenaline. mesenteric.a) False Dopexamine causes arterial vasodilatation causing a small decrease in diastolic blood pressure and decreased afterload. d) True Increased cardiac output and decreased renal vascular resistance causes an increase in renal blood flow. flushing nausea and vomiting and headache. e) True Side-effects of dopexamine include arrhythmias. b) True This leads to relaxation of vascular smooth muscle in renal. 6 . 7 . It usually refers to removal by the kidney and is calculated from: Amount of substance excreted in urine per unit time / plasma concentration of substance c) False If clearance is greater than glomerular filtration rate.Total volume of drug cleared from a compartment per min is is the product of the rate constant for elimination and the volume of distribution. d) True e) False Creatinine clearance is the clearance of creatinine and is used as an estimate of glomerular filtration rate (GFR). clearance will be different to GFR and hence different to creatinine clearance. a) False Clearance usually refers to elimination by the kidney but may be by the liver or the lungs. the drug is secreted by the tubular cells of the kidney into the urine. If the drug is secreted by the renal tubular cells or incompletely removed by the kidney. b) True Clearance is a calculated number which is used to indicate how much of a drug is removed from the plasma in a given period of time. 8 . c) True Esmolol competitively blocks beta-adrenergic receptors and causes a dosedependent decrease in heart rate.a) True The cardiac output is decreased by about 20%.6 to 8.3 minutes. [However. e)True Most texts quote that it has been shown to increase the time to recovery from suxamethonium from 5. b) True Esmolol has little or no sympathomimetic activity. Peck & Williams state that it does not prolong the actions of suxamethonium!] 9 . d)True Esmolol may precipitate bronchospasm in susceptible individuals. 10 . a) FalseDiethyl ether is also known simply as ether. middle age and female sex are risk factors for the more serious halothane hepatitis. obesity. d) TrueHepatic damage can occur with enflurane. which has a mortality rate of 50-75%. 11 . Multiple exposures. b)TrueChloroform is no longer used due to hepatic and cardiac toxicity. e) TrueHalothane can cause a reversible hepatitis with high transaminases. c) FalseCyclopropane was explosive and caused cardiac irritability and emergence delirium and is no longer produced. It causes a decrease in hepatic function and biliary secretion which is transient only. 12 . d)True Pethidine may be safely used. including co-trimoxazole and sulfasalazine. b) False The BNF states that ketamine is unsafe to use in acute porphyrias. C)True Midazolam is probably safe. 13 .a False Etomidate is unsafe to use in acute intermittent porphyria. should not be used. e) False Sulphonamides. use with caution. 14 . 15 . 16 . tachycardia and arrhythmias. d) True L-dopa may cause involuntary movements and psychiatric symptoms.a) True L-dopa crosses the blood-brain barrier. c) True Nausea and vomiting are side effects that are decreased by giving an extracerebral dopa-decarboxylase inhibitor. e) False It is given orally. dopamine does not. b) True L-dopa may produce hypotension. 17 . 18 . 3 minutes. renal and cardiac failure. cancer and with certain drugs. muscular dystrophy.a) False Blood group is independent of plasma cholinesterase activity. A-Z and Peck & Williams say that esmolol is not affected by plasma cholinesterase but Sasada & smith say that it prolongs the duration of action of suxamethonium from 5. e) True Plasma cholinesterase can have decreased activity in malnutrition. b) False c) True The organophosphorus anticholinesterases also inhibit plasma cholinesterase. 19 .6 to 8. thyrotoxicosis. pregnancy. d) True Controversy. burns patients. liver disease. hypoproteinaemia. 20 . a) True Histamine release may cause pruritus. d) True The glucuronide conjugates are excreted by the kidney. The latter has analgesic activity. e) True Pentazocine is a partial agonist with agonist activity at ? receptors and antagonist activity at µ receptors. it may therefore antagonise the agonist activity of morphine at µ receptors 21 . b) False Morphine is metabolised to normorphine. morphine-3-glucuronide and morphine-6-glucuronide. c)True Oral bioavailability is 15-50% due to this. 22 . a)False It is excreted mostly unchanged by the kidney. with an elimination half-life of 50-90 minutes. b) False Neostigmine has a low volume of distribution and does not cross the bloodbrain barrier or placenta because it is ionised. d) True Neostigmine is a quaternary amine cholinesterase inhibitor/anticholinesterase 23 . miosis and bladder contractility. c) True It also causes the muscarinic side effects of sweating. 24 . Cardiac output is thus increased. 25 .a) True The blood pressure is reduced causing reflex increases in heart rate and contractility. It therefore causes myocardial and peripheral arterial dilatation. c) False Nifedipine does not cause hypoglycaemia. e) True It blocks calcium channels. b) True Nifedipine may cause a tremor. d)True Sublinugal administration has a faster onset than if given orally. reducing the entry of calcium into the cells and thus causing inhibition of contraction of smooth muscle. 26 . D) True Hypermagnesaemia prolongs the action of neuromuscular blocking drugs.a) True Lithium prolongs blockade by blocking sodium channels. b) False Diazepam does not affect the action of neuromuscular blocking agents. c) True Trimetaphan prolongs the action of both depolarising and non-depolarising neuromuscular blockers. e)True Suxamethonium prolongs the duration of non-depolarising neuromuscular blockade 27 . 28 . seizures or nicotinic effects.a) True Organosphorous anticholinesterases irreversibly phosphorylate the esteratic site of acetylcholinesterase inhibiting it. 29 . d) True They are very lipid soluble and so are quickly absorbed through the skin. c) True Atropine can be used to reverse the muscarinic effects but will not prevent the central effects. Inhibition lasts for weeks until new enzyme is produced. Inhibition lasts for weeks until new enzyme is produced. b) True Organosphorous anticholinesterases irreversibly phosphorylate the esteratic site of acetylcholinesterase inhibiting it. 30 . but not vitamin B2 deficiency. d)False Idiosyncratic side-effects include rash. It shows zero-order elimination just above the therapeutic range. 31 . pethidine. as a result of saturation of liver enzymes. but is prolonged when the zero-order kinetics range is reached. systemic lupus erythematosus. hepatotoxicity and allergy. so that toxicity can occur with a small increase in dose. b)True Phenytoin induces hepatic enzymes reducing the effectiveness of benzodiazepines. heart block. e) False The elimination half-life is 9-22 hours in the first-order kinetics range. ventricular fibrillation or asystole.a) True Phenytoin shows first-order elimination kinetics in the therapeutic range. blood dyscrasias. gum hyperplasia. acne. the oral contraceptive pill and warfarin. c) True Rapid intravenous infusion may cause hypotension. 32 . d) True Side-effects include systemic lupus erythematosus.a) True It causes a reflex tachycardia and increased cardiac output. particularly in slow acetylators and women. c) False This is not a side-effect. b) False This is not a side-effect. e)False This is not a side-effect. 33 . 34 . 35 .d) FalseSodium valproate can be given to children. Liver function tests should be monitored during chronic treatment.b)Truec)FalseIt can cause hepatic dysfunction and should not be used in patients with liver disease.a)TrueSodium valproate is used for petit-mal and grand-mal epilepsy and chronic pain especially trigeminal neuralgia.e)TrueThe mode of action of valproate is thought to be by increasing brain concentrations of the inhibitory neurotransmitter GABA. 36 . d) True The p value is used to indicate the probability that a result could occur by chance alone. 37 . They must be interpreted to determine whether they are clinically significant.a) False Observer bias is eliminated by blinding the observer to the treatment. c) False They are used to compare data and calculate the probability that the observed differences are due to chance alone. e) False Tests can show whether results are statistically significant. b) False The use of a control is to attempt to eliminate the placebo effect. 38 . c) False They may cause neonatal hypoglycaemia and are usually substituted with insulin during pregnancy.a) True Sulphonylureas are used in type II diabetes and increase insulin release from the pancreas. e) True The increased release of insulin may cause hypoglycaemia 39 . b) False Treatment with sulphonylureas is associated with weight gain. d) False Correction of ketoacidosis requires insulin. 40 . as is age under 12 years old. b) False 95% is excreted unchanged. as well as gastrointestinal and haematological disturbances. e)True Chelation with magnesium and calcium ions in the intestine decreases absorption.a) True Tetracycline may cause renal and hepatic impairment. c) True Breastfeeding and pregnancy are contraindications. d) True Tetracycline does increase the actioin of non-depolarising muscle relaxants. 41 . 42 . a) False Warfarin acts by inhibiting the conversion of oxidised to reduced vitamin K in the liver. b)True Warfarin acts by inhibiting the conversion of oxidised to reduced vitamin K in the liver. its effect can be reversed. It therefore takes days to establish its effect. VII. d) True Increased effects can occur with drugs that are highly protein bound such as sulphonamides and NSAIDS such as phenylbutazone. IX and X. More rapid reversal of anticoagulation can be achieved with coagulation factors or fresh frozen plasma. 43 . which is necessary for production of coagulation factors II. IX and X. VII. which is necessary for production of coagulation factors II. It therefore takes days to establish its effect. e) False Its effect can be reduced by drugs that induce hepatic enzymes. such as barbiturates. c) True By giving vitamin K and waiting for the production of new coagulation factors. rifampicin and carbamazepine. 44 . The Chi-squared test is used for non-parametric nominal data. requires the standard error of the mean to be calculated False Standard error of the mean is used to compare how well the mean of a sample represents the true mean of the population. True If any expected frequency is less than 5. does not involve the null hypothesis False The null hypothesis is that there is no difference between the two groups. 45 . and Fisher’s exact test should be used. It is equal to the standard deviation divided by the square root of the number of values.True The Chi-squared test is used to compare the observed versus the expected frequencies of an occurrence. then results are not reliable with the Chi-squared test. It is therefore used for normally distributed continuous data (parametric). does not require a knowledge of the number of degrees of freedom False The degrees of freedom is equal to the [number of columns minus one] multiplied by the [number of rows minus one] and is needed to read off the Chi-squared value from a set of tables. 46 . 47 . which is exchanged for sodium) and decreasing the concentration of potassium.a) True Trimetaphan is a ganglion-blocking drug that blocks nicotinic acetylcholine receptors at autonomic ganglia. d) True Benzhexol is a muscarinic antagonist which crosses the blood-brain barrier and is used to treat Parkinsons disease. c) False Ouabain is a cardiac glycoside drug which acts by inhibition of the sodium/potassium pump. b) True Hexamethonium is also a ganglion-blocking drug. which therefore crosses the blood-brain barrier. It is used as an infusion to produce hypotensive anaesthesia. e) False Physostigmine is an anticholinesterase with a tertiary amine structure. increasing the intracellular concentration of sodium (and also calcium. 48 a) False The mean is the sum of all the values divided by the number of values, commonly known as the average. It is a measure of the central tendency of the values rather than scatter. b) True This is equal to the standard deviation divided by the square root of the number of values. It is a measure of how well the mean of a sample represents the mean of the population. c)True This is a measure of scatter and is equal to the square root of the variance. Two standard deviations on either side of the mean contain about 95% of the values. d) True Range is defined as the upper and a lower limit of the values. e) False The p value indicates the likelihood of the observed event occurring by chance alone. 49 50 e) False Dopamine is metabolised by dopamine ß-hydroylase.a) False Isoflurane is mainly eliminated unchanged through the lungs. d)False Suxamethonium is eliminated by plasma cholinesterase to succinic acid and choline. b) True Morphine is metabolised by the liver to morphine-3-glucuronide and morphine6-glucuronide. 51 .2% is metabolised by the liver and excreted by the kidneys. kidneys and plasma. only 0. catechol-Omethyltransferase and monoamine oxidase in the liver. A small amount of metabolism is by non-specific plasma esterases to a quaternary alcohol and quaternary acid. c) False Atracurium is metabolised by Hoffman degradation to laudanosine and a quaternary monoarylate. 52 . d) False Neostigmine has a low volume of distribution and does not cross the bloodbrain barrier or placenta because it is highly ionised. c) False Bupivacaine is less able to cross the placenta than lidocaine as its pKa makes it more ionised at maternal plasma pH. It also has high lipid solubility and for these reasons readily crosses the placenta. 53 . e) True Propranolol is a lipophilic ß-blocker which causes neonatal growth retardation.a) False Non-depolarising neuromuscular blocking agents are large polar molecules which do not cross the placenta. bradycardia and hypoglycaemia. b) True Lidocaine has low plasma protein binding and relatively low ionisation at physiological pH. respiratory depression. 54 . the quicker it will diffuse across a membrane. c) False The smaller the molecule.a) True Increasing lipid solubility increases the rate of passage of a drug across the cell membrane. b) False A high concentration gradient encourages drug passage across the cell membrane. Fick’s Law states that the rate of transfer across a membrane is proportional to the concentration gradient across the membrane. d) False This will not encourage passage across the cell membrane e) False Only unionised drug can pass through the cell membrane. 55 . Graham’s Law states that the rate of diffusion is inversely proportional to the square root of molecular size. 56 . c) True Methadone has a long half-life.a) True Diazepam is metabolised in the liver by oxidation to active metabolites. b)False Excretion is by the kidney with an elimination half-life of 1. e) true Only 40% of hydroxyethyl starch is excreted within 24 hours 57 . which makes it suitable for oral administration in the weaning of patients addicted to intravenous opioids. including oxazepam and temazepam.5-3. The glucuronide derivatives are excreted by the kidney with an elimination half-life of 20-70 hours.5 hours. d) False Gelofusine has a plasma half-life of 2-4 hours and the bulk of its excretion by the kidney occurs within 24 hours. A. Lignocaine and Phenytoin are the more commonly used agent if the manifestation is arrthythmia D. it is contraindicated if the manifestation is AV block B. And C. Propranolol can be used digoxin toxicity if the manifestation is tachycardia or ventricular extrasystole. However. Potassium is used to treat hypokalemia which precipitates digoxin toxicity 58 . Calcium exacerbates digoxin toxicity. 59 . 60 . c) False d) True Convulsions occur in approximately 1 in 10. although heart rate and cardiac output may be decreased. endothelial cell damage and pulmonary oedema. b) True Oxygen toxicity mainly affects the lung.a) False Joint pains are due to decompression sickness (the bends) caused by the release of bubbles of inert gases in divers returning to the surface. They may be experienced by the tender in a compression chamber who is breathing air. the central nervous system and the eye. It may cause atelectasis.000 exposures. 61 . but not the patient who is breathing oxygen. e)False Bradycardia is not seen with oxygen toxicity. 62 . b) True Halothane decreases uterine tone.a) True Ketamine increases uterine tone. [Although Sasada & Smith says that propranolol decreases utrerine tone] d) True e) True Uterine activity is decreased by the drug. c) True Stimulation of beta-2 receptors causes decreased uterine tone. 63 .