Pharmacology (reverse)

Question 1

A discontinued NSAID. Has a half-life of approximately 20 hours and is not extensively metabolised

Answer 1

Azapropazone

Question 2

An ester of paracetamol and aspirin

Answer 2

Benorylate

Question 3

A prostaglandin F2-alpha analogue used to promote uterine contraction. May cause hypotension, tachycardia and bronchospasm. Otherwise known as haemabate. Avoid in asthma.

Answer 3

Carbaprost

Question 4

A partial agonist at both ALPHA-1 and 2 receptors (200:1 affinity for alpha 2:1). Reduces MAC up to 50%. Inhibits the release of ADH

Answer 4

Clonidine

Question 5

An atypical antipsychotic working as a partial agonist at D2 receptors, amongst myriad other receptors. Known to cause agranulocytosis so regular blood monitoring is mandatory

Answer 5

Clozapine

Question 6

A VASODILATOR chemically related to thiazide diuretics. Used in hypertensive emergencies associated with renal disease, intractable hypoglycaemia and malignant islet cell tumours. Hypotension is mediated by reducing cAMP. Increased glucose due to inhibition of insulin secretion. Also increases catecolamine release. Hyperglycaemia lasts longer than the hypotensive effects. Classically causes arteriolar vasodilatation with minimal affect on the capacitance vessels (postural hypotention is NOT a problem). Increases levels of glycose, catecholamines, renin and aldosterone. May cause fluid retention (despite its relation to a thiazide)

Answer 6

Diazoxide

Question 7

A Class 1A anti arrhythmic (Na channel blocker causing PROLONGATION of the AP). Causes a centrally mediated hypotention. No peripheral activity. Suppresses ventricular extrasystoles. CAN cause some ventricular tachycardia, VF or Torsades.

Answer 7

Disopyramide

Question 8

A direct acting synthetic catecholamine derivative of isoprenaline. Predominately Beta 1, with some Beta 2 (and Alpha 1 to an even smaller degree). Reduces LVEDP via its action on beta 2 receptors. Used in myocardial stress testing.

Answer 8

Dobutamine

Question 9

An endogenous catecolamine. Acts via D1, D2 and Beta receptors. At low doses beta effects predominate, Alpha effects occur at high doses. Does not cross the BBB, although causes nausea and vomitting via action on D1 receptors in the CTZ. Inhibits prolactin secretion. Causes vasodilitation of the mesenteric and renal vascular beds. Increases AV conduction. It has a short half life of 3 minutes, and is metabolised via MAO and COMT to 3,4-dihydroxyphenylacetic acid and homovanillic acid.

Answer 9

Dopamine

Question 10

Synthetic analogue of dopamine. It acts mainly at Beta-2 and D-2 receptors, it has minimal activity at Beta-1 and D-1. It has no alpha activity whatsoever. Inhibits uptake-1, promoting NA. Rapidly cleared with a half life of 7 minutes

Answer 10

Dopexamine

Question 11

Imidazole derivative; a selective phosphodiesterase III inhibitor. An “inodilator”. Similar effect to milrinone. Stored 5-8 degrees, and presented in a plastic syringe (glass causes crystal formation). Takes 30 minutes for effect to occur. Typically used in CCF/low CO associated with cardiac surgery. CO rises 30%, LVEDP falls 30%. Oxygen extraction unchanged (lower LV wall tension versus improved coronary blood flow). Shortens refractory time. May trigger further ischaemia in IHD. Well absorbed, but extensive 1st pass metabolism. T-half 7.5 hours, 70% protein bound.

Answer 11

Enoximone

Question 12

Mixed direct/indirect acting alpha/beta sympathomimetic (also found naturally in some plants). Causes some inhibition of MAO, potentiating NA. Causes unacceptably poor cord pH in obstetric population. Can treat hypotension, bronchospasm, nocturnal enuresis and narcolepsy. 4 sterio-isomers, only the L-isomer is active. Often presented as a racemix. Well absorbed orally. T-half 4 hours (as not metabolised by MAO or COMT). 65% excreted unchanged in urine. Subject to tachyphylaxis.

Answer 12

Ephedrine

Question 13

Agonist at alpha-1 adrenoceptors, 5HT and dopaminergic recptors. Used to aid delivery of the placenta or help gain control of PPH with an atonic uterus. Causes hypertension and vomiting and should not be used in pre-eclampsia.

Answer 13

Ergometrine

Question 14

A non-selective beta blocker (although beta-1 predominates, beta-2 is only seen at high dose) used in the treatment of hypertension/tachycardia under anaesthesia. Has an extremely short half life of only 10 minutes due to rapid hydrolysis by red cell esterases to inactive acid metabolite and methyl alcohol. Does NOT potentiate suxamethonium. No intrinsic sympathomimetic activity. Vd 3.5 l/kg. 60% protein bound.

Answer 14

Esmolol

Question 15

Prostaglandin F2-alpha used to stimulate uterine contraction, by potentiating the uterotonic effect of oxytocin. Causes bronchoconstriction, hypotension and tachycardia. Used to treat postpartum haemorrhage due to uterine atony in patients unresponsive to ergometrine and oxytocin. Dose: 250mcg by deep i.m. injection. Direct intramyometrial injection of Carboprost has a faster onset of action. This dose may be repeated but after at least 15 minutes in severe cases. The total dose should not exceed 2 mg (8 doses). Cautions: History of glaucoma or raised intra-ocular pressure, uterine scars; excessive dosage may cause uterine rupture

Answer 15

Carboprost (Haemabate)

Question 16

Acts to promote ARTERIOLAR smooth mucle cGMP and hence decrease Ca causing arteriole vasodilitation. Undergoes acetylation in the liver, which shows significant pharmacogenetic variation. Crosses the placenta and can cause a foetal tachycardia. Can cause lupus like syndrome (blood dyscrasias and peripheral neuropathies)

Answer 16

Hydralazine

Question 17

A potant anti-sialogue with some anti-emetic properties (hence it crosses the BBB). Additionally used as sedative and amnesic. Presented as racemix, only L-hyoscine is active. Extensively metabolised by liver esterases (only 1% is excreted unchanged), oral bioavailability highly variable but poor (10-50%). Can be used as a patch behind the ear for motion sickness, although takes >12 hours for effect to occur

Answer 17

Hyoscine

Question 18

A POTENT synthetic catecholamine that acts at BETA-1 and BETA-2 receptors. May cause a fall in MAP secondary to its beta-2 effects causing vasodilitation. Despite this, it increases myocardial oxygen requirements owing to its Beta 1 effect.

Answer 18

Isoprenaline

Question 19

A mixed alpha/beta blocker with greater affinity for beta receptors (1:3 following oral administration and 1:7 following IV administration!). Has significant sympathomimetic activity. Can cause retrograde ejaculation secondary to its alpha effects

Answer 19

Labetalol

Question 20

An “inodilator”. Works by increasing sensitivity of troponin C to calcium, causing increased inotropy. Causes peripheral vasodilitation that reduces pre and after load

Answer 20

Levosimendan

Question 21

Bipridine derivative selective phosphodieserase III inhibitor. Used in the treatment of heart failure. Cause peripheral vasodilitation. 70% protein bound and long half life of 2 hours. Excreted up to 80% unchanged in the kidney so dose adjustment is necessary in renal impairment. Incompatible with frusemide when given via the same cannula. Increased mortality when used in patients with severe heart failure.

Answer 21

Milrinone

Question 22

Opioid receptor antagonist

Answer 22

Naltrexone

Question 23

Stimulates insulin release

Answer 23

Nateglinide

Question 24

A Non-opiod, non-NSAID analgesic of the benzoxazocine class. Useful in postoperative shivering and as an opioid sparring agent. Can cause anticholinergic side effects.

Answer 24

Nefopam

Question 25

A dihydropyridine calcium channal antagonist. Available as oral (60% bioavailability) or sublingual preparation. Used in angina prophylaxis, hypertension and raynaud’s. Does not affect rate of recovery of L-Ca channel in SAN and does not delay conduction through the AVN So OK to use with a beta blocker. 90% protein bound. Half life 5 hours. Inactive metabolites are excreted in the urine

Answer 25

Nifedipine

Question 26

A first generation (typical) antipsychotic of the butyrophenone class. Acts as an antagonist at multiple receptors, particularly D2 (in the CTZ to promote anti-emesis), Alpha adrenergic and mAch. Side effects include increased prolactin production, hypothermia, hypotension, anticholinergic side effects (although generally limited) and extra-pyramidal side effects, which includes parkinsonian like syndromes, and the neuroleptic malignant syndrome.

Answer 26

Haloperidol

Question 27

A benzamide anti-emetic active at D2 and 5HT receptors (the latter, particularly in high doses). A pro-kinetic effect is mediated by a cholinergic final pathway, and hence this aspect is antagonised by atropine.

Answer 27

Metoclopramide

Question 28

An organophosphate used topically for the treatment of glaucoma. Also causes myosis. Unique to the organophosphates in containing a quaternary nitrogen that also binds to the anionic site of acetylcholinesterase.

Answer 28

Ecothiopate

Question 29

A non-selective muscarinic receptor agonist (parasympathomimetic alkaloid) used in the treatment of dry mouth and glaucoma.

Answer 29

Prilocarpine

Question 30

A tricyclic antidepressant causing a greater degree of postural hypotension than other drugs in its class. Metabolised in the liver to form nortriptyline and desipramine. It is contraindicated in glaucoma. TCA note: Main mechanism of action via competitive blockade of uptake 1 for NA and 5HT causes. Blockade of muscarinic, histaminergic and alpha-adrenoreceptors leads to their non-specific and broad side effects. Typically they are well absorbed, highly lipid soluble, highly protein bound. Metabolism is typically hepatic, but shows significant variability between patients.

Answer 30

Imipramine

Question 31

An antihistamine anti-emetic with significant sedative side effects, so often used as a premedicant. Well absorbed orally, but subject to a high first pass metabolism in the liver, rendering its oral bioavailibility at 25% (similar to morphine). Duration of action is around 3-6 hours, with metabolites entirely eliminated in the urine.

Answer 31

Promethazine

Question 32

An analogue of L-DOPA acting as a false substrate for dopa-decarboxylase, thus resulting in the formation of a false neurotransmitter.

Answer 32

Methyldopa

Question 33

A 5-HT2 Receptor antagonist, with particularly high affinity for the 5-HT2-alpha subgroup.

Answer 33

Ketanserin

Question 34

A xanthine oxidase inhibitor.

Answer 34

Allopurinol

Question 35

A cardiac glycoside with positive inotropic effects secondary to an increase in intracellular calcium levels. Inhibits Na/K-ATPase. Slows AV nodal conduction resulting in ventricular rate control in AF. Less than 10% undergoes metabolism in the liver. Primarily excreted unchanged via the kidney by glomerular filtration and tubular secretion, hence the necessity for dose adjustment in renal impairment. Has a long elimination half-life of 35 hours, which is increased by renal impairment.

Answer 35

Digoxin

Question 36

A class 1b antiarrhythmic drug which enhances AV nodal conduction. Metabolised by hydroxylation in the liver, a pathway that is easily saturable just above therapeutic levels. Even mild increases in dose result in zero order kinetics. Has a narrow therapeutic index and it is important to check plasma levels in order to avoid toxicity. Plasma protein binding is about 90%. Crosses the placenta and causes fetal hydantoin syndrome, with craniofacial abnormalities, growth retardation, cardiac defects and mental retardation. Induces mixed function oxidases and increases metabolism of benzodiazepines and warfarin.

Answer 36

Phenytoin

Question 37

A preparation of theophylline and ethylenediamine.

Answer 37

Aminophylline

Question 38

An anti diabetic drug of the biguanide class. Works to increase peripheral glucose utilisation. Does not cause hypoglycaemia.

Answer 38

Metformin

Question 39

An oligopeptide structurally similar to ADH and possesses ADH-like activity. Used to promote uterine contraction in failure to progress and following delivery at c-section. Water intoxication may occur, especially when administered with large volumes of intravenous 5% glucose. Decrease in blood pressure occurs within 30 seconds of administration, particularly if given rapidly. Arrhythmias may ensue, most commonly sinus tachycardia, sometimes with ST changes on the ECG. Care is required in parturients with heart disease. Should be administered after delivery by slow bolus of 5 units, then by infusion if required.

Answer 39

Oxytocin

Question 40

An endogenous catecolamine. Beta effects predominate at low doses, Alpha effects occur at high doses. L-isomers are 15x more potent. Diastolic blood pressure can fall secondary to beta-2 associated vasodilatation.

Answer 40

Adrenaline

Question 41

A TCA. Inhibits catecholeamine re-uptake.

Answer 41

Amitriptyline

Question 42

An irriversible inhibitor of COX-1. Inhibits renal tubular secretion of URATE.

Answer 42

Aspirin

Question 43

Non selective beta blocker with increased water solubility, so metabolised by the kidney.

Answer 43

Atenolol

Question 44

A potent vasodilator. Synthesised from L-arginine. The haemoglobin molecule has an affinity 1500 times higher to this substance than to carbon monoxide. Nitrosyl haemoglobin is produced, which in the presence of oxygen, is oxidised to methaemoglobin.

Answer 44

Nitric Oxide

Question 45

Opiod agonist, with mixed agonist/antagonist properties

Answer 45

Phenazosin

Question 46

A hydrazine non-selective irreversible MAO-I (starting with P). Inhibit hepatic enzymes and may cause hepatotoxicity. Interacts with Pethidine to cause cerebral irritability, hyperpyrexia and CVS instability.

Answer 46

Phenelzine

Question 47

A hydrazine non-selective irreversible MAO-I (starting with I). Inhibit hepatic enzymes and may cause hepatotoxicity. Interacts with Pethidine to cause cerebral irritability, hyperpyrexia and CVS instability.

Answer 47

Isocarboxazid

Question 48

A non-hydrazine non-selective irreversible MAO-I, probably the most dangerous as also posses significant stimulant activity. Inhibit hepatic enzymes and may cause hepatotoxicity. Interacts with Pethidine to cause cerebral irritability, hyperpyrexia and CVS instability.

Answer 48

Tranylcypromine

Question 49

A non-selective alpha blocker used in the treatment of phaochromocytoma

Answer 49

Phenoxybenzamine

Question 50

A NON-SELECTIVE Beta-blocker with partial beta-agonist activity. It also has partial agonist / antagonist activity at the 5-HT1A receptor.

Answer 50

Pindolol

Question 51

A thiazolidinedione; activates peroxisome proliferator-activated receptor gamma (PPAR-gamma) within the cell nucleus to regulate the genes responsible for glucose and lipid metabolism. As a result, increases sensitivity of peripheral tissues to insulin. May cause fluid retention (avoid in heart failure). Extensively metabolised by the CYP450 system in the liver. Produces some active metabolites, secreted in the faeces and urine. Troglitazone was withdrawn due to hepatitis, so patients on this medication must have regular liver function.

Answer 51

Pioglitazone

Question 52

A thiazolidinedione; activates peroxisome proliferator-activated receptor gamma (PPAR-gamma) within the cell nucleus to regulate the genes responsible for glucose and lipid metabolism. As a result, increases sensitivity of peripheral tissues to insulin. May cause fluid retention (avoid in heart failure). Extensively metabolised by the CYP450 system in the liver. Produces inactive metabolites, secreted in the urine. Troglitazone was withdrawn due to hepatitis, so patients on this medication must have regular liver function.

Answer 52

Rosiglitazone

Question 53

Anti-pseudomonal penicillin only available IV

Answer 53

Piperacillin

Question 54

An antifibrinolytic drug. A synthetic analogue of the amino acid lysine. It binds to plasminogen on its lysine binding sites, preventing plasmin formation, and also displaces plasminogen from thrombin. Additionally, it may improve platelet function and have anti-inflammatory effects (inhibits complement activation, monocytes, and neutrophils). In the CRASH-2 trial there was a significant reduction in mortality (1.5%) if given within 8 hours. In elective surgery patients at risk of thromboembolism may increase this risk. The evidence for this is patchy and therefore a risk assessment of all patients should be undertaken before administration. The dose is 1-1.5 g given by slow intravenous injection. If injected too quickly, it causes significant hypotension.

Answer 54

Tranexamic Acid

Question 55

Phenylalkylamine calcium channel antagonist. A derivative of papaverine. DOES affect rate of recovery of L-ca channel in SAN and delays conduction through AVN (better for treating SVTs than nifedipine). Should NOT use with a beta blocker as greater risk of complete heart block. Although well absorbed, undergoes extensive first pass metabolism to yield an oral bioavailibility of only 10%. 70% protein bound and largely excreted by the kidney.

Answer 55

Verapamil

Question 56

A quaternary ammonium ganglion blocker used to produce hypotensive anaesthesia. It is a competitive antagonist at all nicotinic ganglion receptors, including those of the adrenal cortex. Side effects are myriad and result mainly from blockade of parasympathetic system. Short half life of only 2 minutes. Direct vasodilating effect on peripheral vessels. Histamine release, significant enough to cause bronchospasm, but probably not responsible for its hypotention. CBF is maintained provided pre-load is kept up and MAP maintained >50. DOES NOT cross the BBB. Implicated in meconium ileus of the newborn and therefore DOES cross the placenta. Is inactivated by plasma cholinesterase and therefore inhibits the metabolism of suxamethonium (by acting as a competitive substrate).

Answer 56

Trimetaphan

Question 57

Works in the distal tubule to inhibit sodium resorption in exchange for potassium and hydrogen ions (i.e. a potassium sparring diuretic similar to spironolactone)

Answer 57

Tiamterine

Question 58

5-HT1 AGONIST used in the treatment of acute migrane and cluster headache

Answer 58

Sumatriptan

Question 59

A non-selective beta blocker with additional class I and III antiarrythmic properties. A racemic mixture, with the D-isomer conferring its class III activity, whilst L-isomer has beta blocking and class III activity. Prolongs the AP and refractory period, and is more effective in maintaining sinus rhythm following DC cardioversion than other beta blockers. 2% of those being treated for sustained VF/VT will go into torsades. 90% oral bioavailibility and not metabolised, water soluble so excreted unchanged by the kidney. Dose adjustment is needed in renal impairment

Answer 59

Sotalol

Question 60

A moderately selective beta 2 agonists used to arrest premature labour. Crosses the placenta and can cause foetal tachy. Other associations include: FATAL maternal pulmonary oedema, hypokalaemia, hyperglycaemia, vommitting and seizures.

Answer 60

Ritodrine

Question 61

Centrally and peripherally acting by preventing storage vesicles incorporating noradrenaline from cytoplasm. As a result, NA is rapidly broken down by cytoplasmic MAO and hence stores are depleted. This leads to hypotension from reduced SVR and CO. Side effects include sexual dysfunction, hyperprolactinaemia, gynacomastia, galactorrhoea.

Answer 61

Reserpine

Question 62

H2 receptor antagonist. Reduces gastric secretion of H ions. Has NO effect on gastric motility.

Answer 62

Ranitidine

Question 63

A dopamine antagonist anti-emetic of the butyrophenones class. Avoid in parkinsons disease.

Answer 63

Droperidol