CNS Flashcards
Which of the following agents has a pure beta agonist effect in the circulation?
A Adrenaline
B Dopamine
C Noradrenaline
D Isoprenaline
D
Explanation
Adrenaline is a very potent vascular bed vasoconstrictor (alpha R) and a cardiac stimulant (B R).
NA is a very potent vascular bed vasoconstrictor (Alpha R) and has B1 effects on the heart.
Isoprenaline activates B receptors almost exclusively and is a potent vasidilator.
Dopamine effects several D1 R vascular bed (Vasodilatation) and at a higher doses B and A receptors
Extra: Agonists
Phenylephrine a1>a2»»b
Clonidine a2>a1»»b
Dobutamine b1>b2»»a Isoproterenol (Isoprenaline) b1=b2»»a
Terbutaline, Albuterol, Metaproterenol b2»b1»»a1
Dopamine D1=D2»b»a Fenoldopam D1»D2
Noradrenaline: b1»b2, a1=a2
Adrenalne: b1=b2, a1=a2
Which of the following statements regarding carbamazepine is correct?
A Sodium valproate increases carbamazepine clearance
B Overdose causes seizures
C It metabolises to non-active metabolites.
D It is an enzyme inhibitor
B
Explanation
Overdose can cause seizures but the most common side effects are diplopia and ataxia. Foetal aplastic anaemia and agranulocytosis can also occur. Carbamazepine in an enzyme inducer and has active metabolites. Sodium valporate inhibits carbamazapine clearance whereas phenytoin and phenobarbitone increase clearance
Regarding L-dopa, which of the following statements is correct?
A It causes a negative Coombs test.
B It has a half life of 5 hours
C 25% of the oral dose reaches the brain
D It is a precursor to dopamine
D
Explanation
L-dpoa is an immediate precursor of dopamine. 1-3% enters the brain unaltered, but this number will be higher if given with dopa decarboxylase inhibitor. Concomitant administration of a peripheral dopa decarboxylase inhibitor (carbidopa) may reduce the daily requirement of levodopa by approximately 75%. L-dopa causes a positive Coombs test. L-dopa has a half life of between 1-3 hours.
Regarding ergotamine, which of the following statements is incorrect?
A It works well in the early treatment of acute migraine
B It can be given parenterally
C It causes GI haemmorhage
D It causes vasoconstriction
C
Explanation
Ergotamine can be administered orally, via rectum, via aerosol inhaler and intramuscular injection. Ergot derivatives are highly specific for migraine pain. They are not analgesic for any other condition. The vasoconstriction (partial agonist effects at alpha adrenoreceptors and some as a result of effects at 5-HT receptors) produced by ergotamine is long lasting and cumulative. The direct receptor stimulation thus prevents vasodilatation and stretching of the pain endings. The most toxic effects of the ergot derivatives are GIT disturbances, including diarrhoea, nausea and vomiting. GIT haemorrhage does not occur. There have been reports of bowel infarction/ischaemia due to blood vessel vasoconstriction
–ChatGPT–
Ergotamine is an ergot alkaloid derived from the fungus Claviceps purpurea. It primarily acts as a vasoconstrictor and is used in the treatment of certain types of headaches, such as migraine and cluster headaches.
Mechanism of Action:
1. Partial Agonist/Antagonist at Serotonin Receptors:
- Acts on 5-HT1 and 5-HT2 receptors in cranial blood vessels, causing vasoconstriction. This reduces the vasodilation thought to contribute to migraines.
2. Agonist/Antagonist at Dopaminergic Receptors:
- Can affect dopaminergic pathways, contributing to its diverse effects.
3. Alpha-Adrenergic Effects:
- Acts as a partial agonist on α-adrenergic receptors, enhancing vasoconstriction.
Inhibition of Neurogenic Inflammation:
Reduces the release of inflammatory neuropeptides involved in migraine pathophysiology.
Uses:
- Migraine Treatment: Particularly effective in stopping migraines during the prodrome or early stages.
- Cluster Headaches: Sometimes used for acute attacks.
Side Effects:
1. Vasoconstrictive Effects:
- Can cause peripheral ischemia (e.g., cold, pale extremities, cyanosis).
- Severe vasospasm may lead to gangrene in rare cases.
- Gastrointestinal Symptoms:
- Nausea, vomiting, and abdominal pain are common due to stimulation of the chemoreceptor trigger zone. - Central Nervous System Effects:
Dizziness, confusion, or drowsiness.
Ergotism (Toxicity):
Symptoms include intense vasoconstriction, ischemia, muscle pain, and, in severe cases, hallucinations or seizures.
Dependency:
Chronic use may lead to rebound headaches or medication-overuse headaches.
Contraindications:
1. Cardiovascular Disease:
Avoid in patients with coronary artery disease, peripheral vascular disease, or hypertension due to the risk of severe vasoconstriction.
- Pregnancy:
Category X: Can cause uterine contractions and miscarriage. - Liver or Kidney Impairment:
Metabolized by the liver and excreted by the kidneys, requiring caution in dysfunction.
Concurrent Use with CYP3A4 Inhibitors:
Co-administration (e.g., with certain antifungals or macrolides) increases the risk of ergot toxicity.
Important Notes:
Ergotamine is often combined with caffeine (e.g., in formulations like Cafergot) to enhance its absorption and effectiveness.
Modern migraine treatments (e.g., triptans and CGRP inhibitors) have largely replaced ergotamine due to its side-effect profile.
Summary:
Ergotamine is a potent vasoconstrictor used for migraine and cluster headache treatment but carries significant risks, including vasospasm and ergotism. It requires careful monitoring and is typically reserved for cases where other treatments are ineffective.
Regarding drugs that are used to treat glaucoma, which is the correct pairing of drug-mechanism of action?
A Latanoprost - increased aqueous production.
B Pilocarpine - ciliary muscle contraction
C Acetazolamide - increased aqueous production
D Timolol - ciliary muscle contraction
B
Explanation
Pilocarpine: acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle, causing the muscle to contract -resulting in pupil constriction (miosis). Pilocarpine also acts on the ciliary muscle and causes it to contract. When the ciliary muscle contracts, it opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure.
Timolol - decreases aqueous secretion.
Acetazolamide - decreases aqueous secretion due to a lack of HCO3.
Latanoprost - increased outflow of aqueous.
PG - increased outflow.
Beta blockers - decreased aqueous secretion
Which of the following statements regarding neuromuscular junction blockers is incorrect?
A Pancuronium and vecuronium are both steroid neuromuscular blocking drugs
B Vecuronium is predominantly renally excreted
C Pancuronium has a longer duration of action than vecuronium
D Atracurium is inactivated by Hofmann elimination
B
Explanation
Vecuronium is excreted by the liver- 85% and renal- 15%.
Pancuromium’s duration of action is >35m and vecuronium’s 20-35min.
Vecuronium, pancuronium, pipecuronium and rocuronium are steroidal neuromuscular blocking drugs.
Tubocurarine, atracurium and doxacurium are isoquinoline neuromuscular blocking drugs.
Atracurium is inactivated by Hofmann elimination
Note: Atracurium is so extensively metabolised that its pharmacokinetics are independent of renal and hepatic function, and less than 10% is excreted unchanged by renal and biliary routes. Two separate processes are responsible for metabolism:
Ester hydrolysis- this action is catalysed by non-specific esterases, not by acetylcholinesterase or pseudocholinesterase.
Hofmann elimination- a spontaneous non-enzymatic chemical breakdown occurs at physiologic pH and temperature
A young male presents with a high blood pressure, mydriasis and a high temperature. Which drug has he most likely taken?
A Cocaine
B Atropine
C Naloxone
D Adrenaline
A
Explanation
Cocaine is a sympathomimetic stimulant which cause cardiovascular, CNS and peripheral sympathetic stimulation
Atropine: the net cardiovascular effects of atropine in patients with normal haemodynamics are not dramatic: tachycardia may occur, but there is little effect on blood pressure.
Anticholinegic syndrome: includes central and peripheral effects e.g. tachycardia, CNS effects and hyperthermia. It does not include hypertension however.
Not a great question
In reality, all these drugs can cause the above symptoms. However, atropine and adrenaline are not frequently ingested, nor abused. Naloxone won’t cause the symptom profile unless it put the patient into opioid withdrawal. In other words the most likely drug taken is cocaine-it is easily ingested and the most abused and causes these symptoms
Regarding sodium valproate, which of the following statements is correct?
A It is highly protein bound
B It’s VD is 0.6L/kg
C T1/2 is 40 hrs
D It has a high first pass metabolism
A
Explanation
Sodium valproate (SV) is readily absorbed form the GIT. Its bioavailability is greater than 80% so it has a low first pass metabolism rate. Half-life varies from 9-18hrs. Peak blood levels are observed within 2 hrs. pKa of 4.7. 90% bound to plasma proteins. SV has a VD of 0.15L/kg (it is essentially confined to extracellular water). It is fully ionized at a normal body pH. Clearance of SV is low and dose dependent. Approximately 20% of the drug is excreted as a direct conjugate of valproate
Which of the following statements regarding L-Dopa is correct?
A Ingesting L-dopa with food does not delay its absorption
B L-dopa’s half life is unaffected when given with carbidopa
C Drug holidays are recommended to improve the the responsiveness to levodopa
D Suddenly stopping it will cause tremor
D
Explanation
L-dopa is an immediate precursor of dopamine. L-dopa is rapidly absorbed from the small intestine, but its absorption depends on the rate of gastric emptying and the pH of the gastric contents. Food will delay the appearance of L-dopa in the plasma. Ingested food can compete with the drug for absorption from the gut and for transport from the blood to the brain.
Note: When levodopa is given without a peripheral decarboxylase inhibitor, anorexia, nausea & vomiting occur in about 80% of patients. These adverse effects can be minimised by taking the drug in divided doses, with or immediately after meals or by increasing the total daily dose slowly. It is better to add carbidopa, as the prevalence of adverse effect occur in less than 20% of patients.
1-3% enters the brain unaltered, but this number will be higher if given with dopa decarboxylase inhibitor. Concomitant administration of a peripheral dopa decarboxylase inhibitor (carbidopa) may reduce the daily requirement of levodopa by approximately 75%. L-dopa causes a positive Coombs test. L-dopa has a half-life of between 1-3 hours but when administered with carbidopa, the plasma half-life is longer. Suddenly stopping L-dopa will cause tremor. This side effect part of the neuroleptic malignant syndrome that may occur on abrupt stopping of the drug. Because a drug holiday may only temporarily improve responsiveness to levodopa (but is of little benefit in preventing the on off phenomenon) and due to the risks of aspiration, PE, venous thromboembolism and depression (from the increasing immobility) during a drug holiday, they are not recommended.
What is the most common adverse effect of procainamide?
A Anaphylaxis
B Bradycardia
C Hypotension
D Fever
C
Explanation
Hypotension especially when administered IVI as it has ganglion-blocking properties
Procainamide is a Class Ia antiarrhythmic drug used to treat various cardiac arrhythmias. It works by altering the electrical activity of the heart to restore and maintain normal heart rhythm.
Mechanism of Action:
1. Sodium Channel Blockade:
Blocks fast sodium channels in the cardiac cells, reducing the rate of depolarization during Phase 0 of the action potential.
Slows conduction velocity, particularly in the atria, ventricles, and His-Purkinje system.
- Potassium Channel Effects:
Prolongs repolarization by inhibiting outward potassium currents, thereby increasing the action potential duration (APD) and effective refractory period (ERP).
- Overall Effects:
Slows conduction.
Prolongs the QRS complex and QT interval on an ECG.
Clinical Uses:
1. Atrial and Ventricular Arrhythmias:
- Treats supraventricular tachycardia (SVT) and atrial fibrillation (AF) associated with pre-excitation syndromes (e.g., Wolff-Parkinson-White syndrome).
2. Ventricular Tachycardia:
Used for hemodynamically stable monomorphic ventricular tachycardia (VT).
3. Conversion of Arrhythmias:
Effective for converting certain arrhythmias to sinus rhythm.
Pharmacokinetics:
- Administration: Can be given orally, intravenously, or intramuscularly.
- Metabolism: Metabolized in the liver to N-acetylprocainamide (NAPA), which has Class III antiarrhythmic properties (prolongs repolarization).
- Excretion: Renally excreted; dose adjustment is required in renal impairment.
Side Effects:
1. Cardiovascular:
- Hypotension (common with IV administration).
- Prolongation of QT interval, increasing the risk of torsades de pointes.
- Worsening of arrhythmias (proarrhythmic effects).
- Hematological:
- Agranulocytosis: A rare but severe side effect requiring regular monitoring of blood counts. - Systemic Lupus Erythematosus (SLE)-Like Syndrome:
- Long-term use may cause a reversible lupus-like syndrome (fever, arthralgia, rash, and positive antinuclear antibodies). - Gastrointestinal:
Nausea, vomiting, and diarrhea. - Others:
Fatigue, dizziness, and rash.
Contraindications:
1. Heart Block:
Avoid in patients with second- or third-degree heart block without a pacemaker.
- Torsades de Pointes:
Contraindicated in patients with a history of this arrhythmia or congenital long QT syndrome. - Severe Heart Failure:
Negative inotropic effects can worsen cardiac output.
Key Monitoring Parameters:
1. ECG Monitoring:
Watch for QRS widening and QT prolongation.
2. Blood Pressure:
Monitor for hypotension during IV administration.
3. Complete Blood Count (CBC):
Regular monitoring for agranulocytosis.
4. Renal Function:
Adjust dose in renal impairment.
Summary:
Procainamide is a versatile antiarrhythmic drug effective for treating a range of arrhythmias, particularly in acute settings. However, its use is limited by potential side effects such as lupus-like syndrome, QT prolongation, and proarrhythmia. Careful monitoring is essential to ensure safe and effective treatment.
A patient complains of muscle pain post-operatively. Which of the following drugs is most likely to cause this?
A Ketamine
B Propofol
C Atracurium
D Suxamethonium
D
Explanation
Muscle pain due to the depolarizing action of suxamethonium.
Which of the following muscle relaxants has the longest duration of action?
A Rocuronium
B Atracurium
C Vecuronium
D Pancuronium
D
Explanation
Mivacurium - 10-20m
Atracurium - 20-35m
Vecuronium - 20-35m
Rocuronium - 20-35m
Pancuronium - 35-45 min
Which of the following drugs has the greatest MAC?
A Methoxyflurane
B Nitrous oxide
C Isoflurane
D Halothane
B
Explanation
NO - 100%
Halothane - 0.75%
isoflurane - 1.4%
methoxyflurane - 0.16%
All the following drugs are anaesthetic agents except?
A Etomidate
B Midazolam
C Propofol
D Glycopyrolate
D
Explanation
Propofol is a hypnotic/amnesic used for induction and maintenance of general anaesthetic.
Midazolam is a benzodiazepine amnesiac used for sedation during GA.
Etomidate (GABA receptors) is used in ED for conscious sedation and RSI.
Glycopyrolate is a muscarinic antagonist that is used during sedation to dry up oral secretions.
At low dose, which of the following muscle relaxants is most commonly associated with tachycardia?
A Gallamine
B Suxamethonium
C Vecuronium
D Atracurium
A
Explanation
Vecuronium, pipecuronium, rocuronium have little or no CVS effects. Pancuronium causes a modest increase in HR (vagolytic or by blockade of norepinephrine from adrenergic ending)and a smaller increase in cardiac output, with little or no change in systemic vascular resistance. Atracurium has no effects on autonomic ganglia or on cardiac muscarinic receptors but may cause cardiovascular effects that are mediated by autonomic or histamine receptors.
Gallamine increases heart rate by both vagolytic action and sympathetic stimulation.
Succinylcholine causes various cardiac arrhythmias. The drug stimulates all autonomic cholinoreceptors. In low doses, negative inotrope and chronotrope occur, in higher doses positive inotropic and chronotropic effects may occur. Bradycardia is often observed when a second dose of the drug is given within 5minutes.
Extra:
An old question. Gallamine is not used in clinical practice. All questions are left in the bank as tools for learning.
Which of the following drugs is not an amide local anaesthetics?
A Prilocaine
B Lignocaine
C Benzocaine
D Bupivicaine
C
Explanation
Other amide local anaesthetics include mepivacaine, etidocaine and ropivocaine.
Extra:
Amide local anaesthetics have two “i”s in their names i.e lignocaine, prilocaine, bupivicaine.
Esters only have one “i” in their names i.e. Procaine, benzocaine
Which of the following is an ester local anaesthetic?
A Prilocaine
B Tetracaine
C Bupivicaine
D Lignocaine
B
Explanation
Ester local anaethetics: cocaine, procaine, tetracaine, benzocaine.
Note: A memory aid to memorize, which LA is an ester and which is amide. Amides have two “i’s” in the name (e.g. Lignocaine) Esters have only one “i” in the name (e.g. Benzocaine)
Regarding neuromuscular junction blockers, which of the following statements is correct?
A Gentamicin increases their efficacy
B Pancuronium causes histamine release
C Gallamine is eliminated by the liver
D Vecuronium is an isoquinolone derivative
D
Explanation
Pancuronium does not cause histamine release. Vecuronium is a steroid derivative. The kidney eliminates Gallamine only.
Gentamicin reduces acetylcholine release causing end-plate ion channel blockade. This action potentiates the action of non-depolarizing neuromuscular agents.
(Clearly an interesting medical concept without a clinical application)
Extra: of the non-depolarizing NM blockers, mivacurium causes the most histamine release. Atracurium also causes a slight increase in histamine release.
Which of the following drugs is a direct serotonin agonist?
A Sumatriptan
B Fluoxeteine
C Moclobemide
D Amitryptiline
A
Explanation
Fluoxetein = Selective Serotonine reuptake inhibitor SSRI
Amitryptiline = Tricyclic antidepressant : Blocks reuptake of noradrenaline and serotonin.
Moclobemide = Competitively and reversibly inhibits monoamine oxidase MAO A (selective). Note: from the evidence available, the reversible short acting MAO inhibitor moclobemide, appears to be relatively free of the hypertensive reaction due to tyramine.
Sumatriptan is a selective agonist for 5-HT1D and 5-HT 1B receptors.
Carbamazepine is closely related to which of the following drugs?
A Imipramine
B Quinidine
C Metoprolol
D Sodium valproate
A
Explanation
Carbamazapine resembles (in it’s chemical structure only) tricyclic antidepressants, of which Imipramine is one
Which of the following drugs acts by MAO inhibition?
A Clomipramine
B Paroxetine
C Moclobemide
D Sertraline
C
Explanation
Clomipramine is a tricyclic antidepressent that prevents reuptake of noradrenaline (NA), serotonin.
Paroxetine is a selective serotonin reuptake inhibitor, antidepressant, no effect on NA
Sertraline is a selective serotonin reuptake inhibitor, antidepressant, no effect on NA
Note: Paroxetine and sertraline have no antimuscarinic action (unlike chlomipramine)
Of the following drugs, which is the most dangerous in overdose?
A Paroxeteine
B Imipramine
C Sertraline
D Moclobenide
B
Explanation
Imipramine is a tricyclic antidepressant. In OD it causes VF arrest and coma. A dose of 10mg/kg of a TCA is lethal
A patient on phenytoin is found to have a low blood phenytoin level. Of the following drugs, which is LEAST likely to cause this?
Your answer was correct
A Hypoalbuminemia
B Carbemazepime
C Disulfiram
D Non-compliance
C
Explanation
Disulfiram retards the metabolism of phenytoin. Carbamazapine is an enzyme inducer and will increase phenytoins metabolism. Non-compliance obviously lowers blood levels. Because phenytoin is highly protein bound, low levels of albumin will decrease phenytoin blood levels
Extra: ‘Phenytoin Pharmacokinetics & Drug Interactions’: Low plasma albumin (such as in liver disease or nephrotic syndrome) can result in abnormally high free concentrations and toxicity.’
Extra: (from a subscriber)
Disulfiram only inhibits CYP2C9 Phenytoin is metabolised by CYP2C9 and 2C19. The textbook passage specifically mentions that hypoalbuminemia would cause HIGHER levels of FREE DRUG, but it seems to suggest that patient ‘may show toxicity even at normal/therapeutic drug levels’ - Perhaps the total ‘measured drug level’ is unchanged by hypoalbuminemia - because you are measuring the bound AND unbound part … but the higher amount of ‘free drug’ as a proportion of the whole gives toxicity earlier So hypoalbuminaemia causes a changed fraction of the drug to be bound/unbound but doesn’t affect the overall measured level? (I guess this would also depend on the type of assay)
Regarding SSRIs, which of the following statements is correct?
A They may be associated with seretonin syndrome with muscle weakness, hyperpyrexia and confusion.
B They are safe in overdose due to minimal drug interactions
C They may cause seizures in overdose
D They are readily removed by dialysis
C
Explanation
SSRis are dangerous in OD because they can cause serotonin syndrome that consists of muscle rigidity, hyperpyrexia, and confusion, which can lead to convulsions, coma and rhabdomiolysis. Dialysis is of no benefit as they have high volumes of distrubution
Which of the following opiates is associated with seizures when given in high dose to patients with renal failure?
A Morphine
B Fentanyl
C Pethidine
D Codeine
E Methadone
C
Explanation
Pethidine metabolite via liver cytochrome oxidases to Norpethidine and via liver carboxyesterases to Pethidinic acid and excreted by the kidneys Norpethidine is neurotoxic and thus build up of metabolites in the setting of repeated dosing and renal failure could lead to seizures
Note:
Morphine-3-glucuronide is a metabolite of morphoine produced by UGT2B7. It is not active as an opioid agonist but does have some action as a convulsant, which does not appear to be mediated through opioid receptors. It is mediated by GABA/glycinergic system. As a polar compound, it has a limited ability to cross the blood brain barrier, but renal failure may lead to its accumulation and result in seizures
Regarding neurotransmitters in the brain, which of the following statements is correct?
A Ondansetron antagonises serotonin receptors
B Strychnine stimulates glycine receptors
C Butyrophenones stimulate dopamine receptors
D Atropine antagonises GABA receptors
A
Explanation
Strychnine antagonizes glycine receptors. Atropine is an antagonist at the M2 (muscarinic receptor). Butyrophenones antagonize the dopamine receptor
Which of the following statements best describes buspirone’s mechanism of action?
A None of the above
B Direct GABA stimulation
C Direct noradrenaline receptor stimulation
D Indirect GABA stimulation
A
Explanation
Buspirone relieves anxiety without sedation; it is a non-benzodiazapine anxiolytic. It is a partial agonist at 5HT1 and a presynaptic antagonist at D2 (also D3 and D4). It is also a partial alpha one receptor agonist. There is no rebound anxiety on stopping drug. It takes a week to work, unsuitable in acute anxiety.
Of the following sedatives, which is the most potent?
A Chloral hydrate
B Diazepam
C Phenobarbitone
D Midazolam
D
Explanation
Potency is the dose required to produce 50% of THAT drugs effect. Phenobarbitone may have a stronger effect but it is required in much higher doses than midazolam and is therefore not as potent.
Of the following antipsychotics, which is most likely to cause extrapyramidal side effects?
A Clozapine
B Chlorpromazine
C Haloperidol
D Risperidone
C
Explanation
Chlorpromazine (a phenothiazine) causes medium EP side effects.
Risperidone (atypical antipsychotic) cause low EP side effects.
Haloperidol (a butyrophenone) causes very high side effects.
Clozapine (atypical antipsychotic) cause low EP side effect
Which of the following is not a pharamcological characteristic of propranolol?
A It has selective B receptor blocking properties
B Lipid soluble
C Half life of 3-6 hours
D Local anaesthetic action
A
Explanation
Propranolol is a non-selective beta receptor blocker. It has no sympathomimetic activity. It is highly lipid soluble and readily crosses the BBB. Because of its Na channel blocking activity, it causes widening of the QRS and therefore VF arrest in overdose. It also causes seizures in overdose as it crosses the BBB. Treatment is bicarbonate. Half-life 3.5-6hrs. Bioavailability 26%
A patient arrives in the ED staggering, agitated, hyperthermic with dilated pupils. Which of the following drugs in overdose is least likely to produce these effects?
A Tricyclic antidepressants
B Atropine
C Aspirin
D Amphetamine
C
Explanation
Aspirin overdose does present with hyperthermia and agitation but does not cause mydriasis
There is a spectrum of hypertensive disease it is important to understand. This case is most likely due to ANTICHOLINERGIC toxicity.
Anticholinergic: “Hot as hell (hyperthermia), dry as a chip (xerostomia, anhydrosis), blind as a bat (mydriasis), red as a beet (erythema), mad as a hatter (agitated delirium). Onset <12hrs after drug. Rx supportive, occasionally can give physostigmine (centrally acting ACh-esterase)
Serotonin syndrome: Sweaty, tachycardic, hot, very increased muscle tone, hyper-reflexia and clonus, dilated pupils, diarrhoea. Drugs implicated: SSRI/SNRI/TCA/tramadol/amphetamines/St John’s wort. Rx supportive, cooling and benzos.
Neuroleptic Malignant Syndrome: Slower onset. Pale, sweaty, tachycardia, pyrexial, lead-pipe rigidity, bradykinesia, bradyreflexia, normal or dilate pupils. Autonomic instability is key. Dopamine antagonists (antipsychotics) associated. Rx supportive, can consider dantrolene, bromocriptine occasionally.
Malignant Hyperthermia: Sweaty, mottled, tachycardia, pyrexial, pupils normal, tone rigid, bradyreflexic, agitated. Associated with inhalational anaesthetics. Rx dantrolene.
Salicylate toxicity: Not classically considered with the other 4 causes of fever and coma. Classically vomiting, tinnitus, hyperventilation with respiratory alkalosis and metabolic acidosis. Rx early diagnosis (can be hard) urinary alkalinisation and dialysis are effective.
A young man is injected with an iv drug. He shows a resultant tachycardia, midriasis, normal blood pressure and reduced sweating. Which of the following drugs is most likely to have caused this?
A Adrenergic agonist
B Nicotinic antagonist
C Cholinomimitic
D Muscarinic antagonist
D
Explanation
Reduced sweating is a sign of anticholinergic poisoning. Others include mydriasis-blindness, delirium, flushing.
Remember “Dry as a Bone, Mad as a Hatter, Hot as a Hare, Red as a Beet, Blind as a Bat”
- dry mouth
- hallucinations/ agitation/ delirium
- peripheral thermoregulatory inhibition
- hot flushed skin
- mydriasis / cycloplegia
A woman is taking an antihypertensive medication. Her blood workup reveals an elevated potassium.
Which of the following drugs is LEAST likely to cause this?
A Spironalactone
B Frusemide
C Methyldopa
D ACE inhibitor
B
Frusemide will decrease serum potassium levels
Spironolactone is a potassium sparing diuretic
ACE inhibitor can cause hyperkalaemia as a side effect
Methyldopa does not affect K levels
Which of the following is the major side effect of benztropine?
A Bronchorrhea
B Miosis
C Diarrohea
D Delirium
D
Explanation
Benztropine is a centrally acting antimuscarinic preparation. It is an antagonist at the M receptors in the basal ganglia. Benztropine reduces tremor and rigidity. It has little effect on bradykinesia. It greatest clinical application is in the treatment of Parkinson’s disease
The side effects are typical antimuscarinic side effects: mydriasis, delirium, flushing, decreased sweating (remember: blind as a bat, mad as a hatter, dry as a chip, red as a beet). The other options here represent cholinergic poisoning.
Regarding St Johns Wort, which of the following statements is correct?
A Has been trialed for use in viral diseases
B It is more effective than placebo in the management of depression
C Often causes hyperthermic or hypertensive reactions
D It has a side effect profile comparable to placebo
B
Explanation
St John’s wort is an enzyme inducer and has been trialed for depression. It has not trialed, and should therefore not be used for viral disease or cancers. Side effects: mania, photosensitization, autonomic arousal. It can lower the clinical concentration and efficacy of a number of drugs including benzodiazepines by induction of cytocrome p450 enzymes cyp3A4 and cyp2C19
St John’s wort is associated with a serotonin syndrome-like toxidrome, which may involve hyperthermia and hypertension if used in combination with other SSRIs. Alone it is unlikely to cause this toxidrome
What is the correct order of catecholamine synthesis?
A Tyrosine - dopamine - dopa - noradrenaline - adrenaline
B Tryptophan - dopa - dopamine - adrenaline - noradrenaline
C Tyrosine - dopa - dopamine - noradrenaline - adrenaline
D Tysosine - dopa- dopamine - adrenaline - noradrenaine
C
Regarding atracurium, which of the following statements is correct?
A It is eliminated by non renal or liver dependant mechanisms
B It has a longer duration of action than vecuronium
C It is a steroid derivative
D It is not associated with histamine release
A
Explanation
Atracurium’s duration of action 20-35m which is the same as vecuronium. Atracurium releases histamine slightly. It is an isoquinolone derivative. And is eliminated by Hofmann (non renal/liver) elimination
Please note: I am not going to change the stem or the answer of the question BUT, Katzung does say that atracurium is inactivated by the Hofmann elimination in addition to hepatic metabolism. The table of the non depolarising drugs reads that it is only Hofmann elimination. Lots of online sources do not refer to hepatic metabolism of this drug.
Also- the non-renal or liver dependant mechanisms- means Hoffman elimination (spotnaeous elimination) and or liver dependant mechanism. Poorly worded stem.
Regarding pancuronium, which statement is incorrect?
A It has a shorter duration of action than vecuronium
B It is a steroid
C It is renally excreted
D It does not release histamine
A
Explanation
Pancuronium’s (a steroid derivative) duration of action >35min. >80% kidney elimination. Vecuronium’s duration of action is 20-35m
Which drug-effect match is incorrect?
A Ethosuximide - hirsutism
B Phenytoin - gum hypertrophy
C Diazepam- ataxia
D Carbamazepine - blood dyscrasias
B
Explanation
Phenytoin causes gum hyperplasia (NOT HYPERTROPHY). In the prescribed texts, it is not clearly stated, but ethosuximide can cause hirsutism
Which local anaesthetic causes methaemoglobinaemia?
A Prilocaine
B Lignocaine
C Bupivacaine
D Tetracaine
A
Explanation
The side effect of methaemoglobinaemia is due to the accumulation of one of prilocaine’s metabolites o-toluidine, an oxidising agent.
Extra: Case reports exist of methaemoglobinaemia occurring due to lignocaine https://pubmed.ncbi.nlm.nih.gov/2563761. However, the textbook seems to only report on Prilocaine aas a cause.
A patient receiving multiple drugs for parkinsonism develops urinary retension, mydriasis and confusion. Which of the following drugs may be to blame?
A Pramipexole
B Tolcapone
C Levodopa
D Benztropine
D
Explanation
These benztropine side effects are typical antimuscarinic: mydriasis, delirium, flushing, lack of sweating (remember: blind as a bat, mad as a hatter, dry as a chip, red as a beet).
Levodopa (dopamine precursor): GIT upset, arrhythmias, dyskinesias, behavioral disturbance, on-off phenomena.
Tolcapone/Entacapone (catechol-O-methyltransferase (COMT) inhibitor used as adjunct therapy in the symptomatic management of idiopathic Parkinson’s disease): hepatotoxicity.
Pramipexole (dopamine agonist): nausea and vomiting, postural hypotension and dyskinesias
All of the following drugs prolong the refractory period in normal cells, except?
A Procainamide
B Amiodarone
C Quinine
D Lignocaine
D
Explanation
Lignocaine, Propanolol, Mexiletine and Moricizine shorten the RP in normal cells. Adenosine, Diltiazem, Esmolol, Flecanide,Tocainide and Verapamil have no effect on the RP of normal Cells
Which of the following cholinoceptor blocking drugs is the least absorbed by the brain?
A Benztropine
B Ipratropium
C Atropine
D Scopolamine
B
Explanation
Ipratropium is a quaternary amine-charged- and therefore poorly taken up by the brain and are relatively free-at low doses-of central nervous system effects. The other drugs are tertiary amines and are able to be taken up by the brain at lower doses.
Select the correct statement regarding L-Dopa.
A Carbidopa given with L-dopa worsens GIT side effects
B Dyskinesias occur in 80% of patients receiving L-dopa therapy for long periods
C Levodopa stops the progression of parkinsonism
D It is a precursor to tyrosine
B
Explanation
L-dopa is an immediate precursor of dopamine. L-dopa is rapidly absorbed from the small intestine, but its absorption depends on the rate of gastric emptying and the pH of the gastric contents. Food will delay the appearance of L-dopa in the plasma. Adding carbidopa will reduce GIT side effects. (only 20% will suffer as opposed to 80% without carbidopa). 1-3% enters the brain unaltered, but this number will be higher if given with dopa decarboxylase inhibitor. Concomitant administration of a peripheral dopa decarboxylase inhibitor (carbidopa) may reduce the daily requirement of levodopa by approximately 75%. L-dopa causes a positive Coombs test. L-dopa has a half life of between 1-3 hours but when administered with carbidopa, the plasma half lie is longer. Suddenly stopping L-dopa will cause tremor. This side effect part of the neuroleptic malignant syndrome which may occur on abrupt stopping of the drug. L-dopa does not stop the progression of parkinsonism but its early initiation will lower mortality.
Regarding stemetil, which of the following statements is correct?
A It has anti-emetic effect through serotonin antagonism
B It can cause neuroleptic malignant syndrome
C It can cause serotonin syndrome
D It can cause malignant hyperthermia
B
Explanation
Stemetil is prochlorperazine: gives dopamine (D2) receptor blockade, especially dopaminergic receptors in CTZ (chemoreceptor trigger zone) of the medulla. Also has anticholinergic, alpha blocker and NA channel blocking effects. Indications: anti emetic, migraines, not for psychotic episodes. Side effects: muscarinic (anticholinergic) blockade : dry mouth,/urinary retention, constipation, loss of accommodation, flushed (remember :red as a beet, mad as a hatter, blind as a bat, dry as a crisp). Alpha blockade: orthostatic hypotension. Another life threatening side effect is :Neuroleptic malignant syndrome (A high fever, stiff muscles, confusion, irregular pulse or blood pressure, tachycardia, sweating, arrhythmias.
Which of the following drugs is not used in the treatment of glaucoma?
A Cholino-mimetic agents
B Alpha blocker
C Carbonic anhydrase inhibitor
D Beta blocker
B
Explanation
Direct acting cholinomimetics (Pilocarpine) and Indirect acting cholinomimetics (Physostigmine): constricts ciliary and iris circular muscle = Decrease IOP
Prostaglandin analogues (Latanoprost): Relax ciliary muscle and modulate extracellular matrix = Increase uveoscleral outflow tract = Decrease IOP
Beta-adrenoreceptor antagonists (Timolol): Block B adrenoreceptors on ciliary muscle = Decrease aqueous secretion = Decrease IOP
Alpha-2 adrenoreceptor agonists (Brimonidine) decreases aqueous secretion and Non selective alpha agonist (adrenaline) increases uveoscleral outflow tract = Decrease IOP
Carbonic anhydrase inhibitors (Acetazolamide): Decrease HCO3 formation and aqueous secretion = Decrease IOP
Regarding pralidoxime, which of the following statements is correct?
A It regenerates succinylcholine
B It regenerates acetylcholine
C It regenerates acetylcholinesterase
D It regenerates acetylcholine receptors
C
Explanation
Pralidoxime is used to reactivate acetylcholinesterase inhibited by organophosphates. It is only effective if given before irreversible binding of the OP and the acetylcholinesterase has occurred. Re-establishment of enzymic function rapidly reverses the nicotinic and muscarinic effects of OP poisoning. It is used concurrently with Atropine. Atropine is usually administered prior to pralidoxime and the effects at muscarinic receptor are synergistic. Atropine is only effective at muscarinic receptors and not at nicotinic receptors
Regarding SSRI’s, which of the following statements is correct?
A They are effective in obsessive compulsive disorder
B They have more pronounced side effects than TCA’s
C They usually have short half-lives
D They are the treatment of choice in bipolar disease
A
Explanation
A. Lithium Carbonate is the drug treatment of choice in bipolar, especially the acute manic episodes and relapse prevention.
B. Due to their high plasma protein binding, they usually have long half-lives.
C. Side effects of SSRI are usually less and better tolerated than those of TCAs.
D. SSRIs are indicated in major depression, obsessive-compulsive disorder (OCD), Body dysmorphic disorder (BDD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder and social phobia (social anxiety disorder).
Regarding diazepam, which of the following statements is correct?
A It should not be used in convulsions of unknown origin
B It is an enzyme inducer
C It has a half life of 4 hours
D It is metabolised to oxazepam
D
Explanation
Diazepam has a half life of 20-40hrs. It is used for any seizure disorder. In contrast to barbiturates, benzodiazepines do not change hepatic drug metabolizing enzyme activity with continuous use.
Benzodiazepines are widely used as sedative hypnotics
They bind to the GABA-a receptor in the CNS. This receptor functions as a chloride ion channel is activated by the inhibitory neurotransmitter GABA. Benzodiazepines appear to increase the efficiency of GABAergic synaptic transmission. The benzodiazepines do not substitute for GABA but appear to enhance GABA’s effect allosterically without directly activating GABA-a receptors or opening the associated ion channel. There is an increase in the frequency of channel opening events
Benzodiazepines cross the placenta. If given during the predilvery period, they may contribute to the depression of neonatal functions. They are detectable in breast milk and may exert depressing effects in the nursing infant
Dantrolene is used in malignant hyperthermia. Which of the following statements best describes it’s mechanism of action?
A It has an antipyretic through prostaglandin inhibition
B It is a succinylcholine antagonist
C It causes hypothermia through muscle relaxation
D It decreases calcium release from sarcoplasmatic reticulum
D
Explanation
Dantrolene has a spasmolytic function outside the CNS. It reduces skeletal muscle strength by interfering with excitation–contraction coupling in the muscle fiber. Dantrolene interferes with the release of activator calcium via the sarcoplasmic reticulm calcium channel, possible by binding to the same receptor used by ryanodine. Malignant hyperthermia results in massive calcium release, massive muscle muscle contraction, hyperthermia and lactic acid production. Triggers are often general anaesthesia and neuromuscular blockers. Dantrolene is used to stem the calcium release
What is the earliest and most frequent neurological sing of an acute overdose of Lithium?
A Hyperreflexia
B Tremor
C Sedation
D Confusion
B
Explanation
In acute Lithium overdoses, neurological symptoms, if they develop, are delayed reflecting slow redistribution into the CNS. The earliest and most frequent neurological sign is tremor. Other CNS neurotoxic symptoms rarely progress beyond tremor provided adequate lithium excretion is maintained.
Source: Toxicology Handbook, Murray et al
With the MAOI tranylcypromine, which drug will be least problematic?
A Phenylephrine
B Propofol
C Ephedrine
D Pethidine
B
Explanation
Tranylcypromine is a MAOI, which will inhibit the catabolism of dietary amines-prevents breakdown of tyramine in the gut. When foods containing tyramine (cheese, tap beer, soy products and dried sausage) are ingested, the patient may develop a hypertensive crisis. The mechanism is poorly understood but is thought that tyramine displaces noradrenaline from the storage vesicles and enhance peripheral noradrenergic effects, including raising blood pressure dramatically. Similarly drugs with sympathommimetic properties may cause significant hypertension when combined with MAOIs. Over-the-counter preparations that contain pseudoephedrine and phenylpropanolamine are contraindicated in patients taking MAOIs. Pethidine is associated with serotonin syndrome when given with the MAOI drug group
Which is true regarding the group of antipsychotics
A Aripiprazole is an example of an atypical antipsychotic
B Haloperidol cause the most anticholinergic side effects
C Antagonism of all the dopamine receptors play a role in the action of antipsychotic drugs
D Chlorpromazine causes the most extrapyradimal (EP) toxicity
A
Explanation
The antipsychotics have antipsychotic properties as well as extrapyramidal (EP) toxicity, sedative action and hypotensive and anticholinergic effects. These side effects were traced to the blocking effects of alpha, 5-HT2, H1 receptors and muscarinic receptors
Aripiprazole is a second generation antipsychotic drug: These drugs have complex pharmacology, but they share a greater ability to alter 5-HT2A-receptor activity than to interfere with D2-receptor action. In most cases, they act as partial agonists at the 5-HT1A receptor, which produces synergistic effects with 5-HT2A receptor antagonism. Most are also either 5-HT6 or 5-HT7 receptor antagonists.
It seems that there is no demonstrable antipsychotic effect after blocking any other receptor than the D2 (dopamine). D1, D3, D4 receptors have been tested with no antipsychotic effects.
Haloperidol, a butyrophenone, is the most widely used antipsychotic. It has the highest EP toxicity relative to its antipsychotic effect.
Piperazine, a phenothiazine, has high EP as well.
Thioridazine, a phenothiazine, has the greatest anticholinergic side effects (anti muscarinic).
Atypical antipsychotics: clozapine, asenapine, olanzapine, quetiapine, paliperidone, risperidone, sertindole, ziprasidone, zotepine and aripiprazole. They have less EP effects.
Chlorpromazine has the greatest affinity for the alpha-receptor and thus causes hypotension.
The answer to this question is found in the following paragraph:
Hyperprolactinemia in women results in the amenorrhea-galactorrhea syndrome and infertility; in men, loss of libido, impotence, and infertility may result. Hyperprolactinemia may cause osteoporosis, particularly in women. If dose reduction is not indicated, or is ineffective in controlling this pattern, switching to an atypical agent that does not raise prolactin levels, eg, aripiprazole, may be indicated.
Katzung: Basic and clinical pharmacology, 15edition
The order of blockade by local anaethetics is?
A Pain, temperature, sympathetic, propioception and touch
B Sympathetic, pain, temperature, touch and propioception
C Sympathetic, propioception, pain, temperature and touch
D Pain, sympathetic, temperature, propioception and touch
B
Explanation
Sensitivity to block:
Sympathetic postganglionic, dorsal root pain (type C fibres) and preganglionic autonomic (type B fibres)=4 + sensitive
Type A fibres:
Pain and temp (delta fibres)=3+ sensitive
Muscle spindles (gamma fibres) and touch, pressure (beta fibres)= 2+ sensitive
Proprioception and motor (alpha fibres)= 1+ sensitive
Note: beginning with sympathetic transmission and progressing to temperature, pain, light touch and finally motor block. Extra: Spinal block reflects this - the most vulnerable components achieving greater dermatomal (cephalad) spread. Loss of cold sensation roughly two segments above analgesic level for pinprick (pain), which will in turn be roughly two segments above loss of light touch.
Which receptors do the tricyclic antidepressants NOT block?
A Serotonin receptors
B Histamine receptors
C Dopamine receptors
D Noradrenaline receptors
C
Explanation
TCA block the following receptors:
Noradrenaline, histamine, serotonin, muscarininc, alpha receptors. They also block sodium channels and in overdose lead to ventricular tachycardia and fibrillation.
Note: The MCQ option may include nicotinic receptors. A web-based search does report that TCA can block these receptors
They do not block dopamine receptors. The MCQ may offer GABA receptors- according to current web sources- they do antagonize the GABA receptor
Extra:
Tricyclic antidepressants impose their therapeutic effects by inhibiting presynaptic reuptake of norepinephrine and serotonin in the central nervous system (CNS). This effect in the CNS can cause seizures. TCAs are weakly basic, and an acidic environment facilitates the formation of the ionized form and potentiates this effect. In cases of toxicity, TCAs block a number of receptors, including peripheral alpha-adrenergic, histaminic, muscarinic, and central serotonin receptors. Blockade of alpha-adrenergic receptors can cause hypotension. Blockade of muscarinic receptors can cause signs of anticholinergic toxicity, such as tachycardia, fever, dry mouth and skin, decreased bowel sounds, and altered mental status. Blockade of histamine receptors can also cause altered mental status. TCAs can cause cardiac toxicity. Blockade of fast sodium channels in myocardial cells slows the action potential and provides a membrane stabilizing effect. The characteristic QRS prolongation seen in TCA overdose occurs secondary to prolongation of phase “0” of the myocardial action potential. This effect can lead to heart block and bradycardia. QT prolongation seen in cases of TCA overdose occurs due to potassium channel blockade that may potentially cause torsades de pointes. TCAs can also exert a quinidine-like toxic effect on the myocardium that can cause decreased cardiac contractility and hypotension
Source: Tricyclic Antidepressant Toxicity
Muhammad M. Khalid; Muhammad Waseem
Which neurotransmitter is NOT stored in preformed secretory granules?
A Serotonin
B Histamine
C Acetylcholine
D Noradrenaline
D
Explanation
Note: Difficult question. Not sure of the answer. A closer look at Histamine reveals that it is a neurotransmitter and a neuromodulator and in most tissues histamine is sequestered and bound in granules (vesicles) in mast cells or basophils
Looking through Ganong:
Norepipherine: is sequestrated into presynaptic vesicles
Ach: is transported into a storage vesicle. By definition, Ach is a neurotransmitter of the parasympathetic nervous system
Serotonin: is concentrated in vesicles. It is also found in the brainstem where cell bodies synthesise, store and release it
Histamine: It seems to be more of a stimulant of sensory nerve endings via H1, rather than being released form vesicles. Histamine is sequestrated into vesicles of mast cells, rather than vesicles of nerve endings. H3 agonists induce the release of ACH, amine and peptide transmitters (rather than acting as vesicle bound neurotransmitters themselves)
Extra: it may be noradrenaline as noradrenaline is stored as dopamine, and then converted to noradrenaline once inside the actual vesicle. I will let you decide.
From a subscirber…perhaps the answer is ACh… in the current TB it says about noradrenaline “it is found in characteristic small vesicles that have a dense core (granulated vesicles”) so Imaybe implies that vesicles are not in fact granules.
Extra: a thorough explanation for a subscriber
The answer is as you state Noradrenaline. The wording of the question is lacking, having seen this before and from the prescribed text, my feeling is that what is meant by the question is “ Which of these neurotransmitters is NOT stored, preformed, in secretory granules”. Grammar is everything. The answer would then be as stated. L Dopa is converted to Dopamine, dopamine is taken up into the secretory vesicle and then NA is FORMED in the vesicle itself, as opposed the the others where it is ACh, Histamine and Seretonin that are transported into the vesicle, with no additional steps whilst inside the vesicle itself. Agreed this is a poor question, however I believe your answer to be correct. I think they just got “in” and “preformed” the wrong way round in the question. Moreover, the nomenclture of granules is outdated, it is interchangeable with vesicle in this instance, it relates to chromatin granules in the adrenal medulla for example. The use of vesicle and granule are somewhat location dependent depending on nomenclature at the time of discovery and other factors. In regard neurotransmission the accepted current nomenclature in scientific text is: Small synaptic vesicles, SSV (which are clear cored) Large dense cored vesicles (LDCV) Small dense cored vesicles (SDCV) as evidenced by Merighi et al Front. Cell. Neurosci., 21 August 2018 | https://doi.org/10.3389/fncel.2018.00272 I believe, but don’t quote me on this, the dense vs clear is a related to their initial identification process, where the larger MW contents of SDCV / LDCV appeared darker as they have higher MW and proteinaceous content than the smaller monoamines.
ChatGPT: C
Acetylcholine (ACh): Unlike the other neurotransmitters listed, acetylcholine is not stored in preformed secretory granules. It is synthesized in the cytoplasm of the nerve terminal from acetyl-CoA and choline by the enzyme choline acetyltransferase and is then transported into vesicles for release. However, the vesicles are not considered “preformed secretory granules” like those seen with other neurotransmitters.
Serotonin, Histamine, Noradrenaline: These neurotransmitters are synthesized and stored in preformed secretory granules within the nerve terminal. These granules allow rapid release of neurotransmitter upon stimulation.
Antipsychotics exert their function by antagonising which receptor?
A D4
B D3
C D1
D D2
D
Explanation
It seems that there is no demonstrable antipsychotic effect after blocking any other receptor than the D2 (dopamine). D1, D3, D4 receptos have been tested with no antipsychotic effects. Most of the newer antispychotics agents and some of the traditional ones have a higher affinity for 5-HT2A receptor than D2, suggesting an important role for the serotonin system in the aetiology of schizophrenia and the action of these drugs.
Which dopaminergic systems are important for the understanding of schizophrenia
A Medullary-periventricular pathway
B Mesolimbic-mesocortical pathway
C Tuberoinfundibular pathway
D Nigrostriatal pathway
B
Explanation
Mesolimbic-mesocortical pathway= behaviour and psychosis
Nigrostriatal pathway= coordination of voluntary movement
Tuberoinfundibular pathway= inhibits prolactin form the anterior pituitary
Medullary-periventricular pathway= ?eating behaviour
Incertohypothalamic pathway= regulates the anticipatory motivational phase of copulatory behaviour in rats
Regarding Phenobarbitone, which is CORRECT?
A Is effective for absence seizure activity
B 20-30% of Phenobarbitone is excreted unchanged in the urine
C Has a pKa of 7.2
D It enhances GABA mediated opening of the Ca channel
B
Explanation
Phenobarbitone is the oldest of the current anti-seizure medications available. Due to its side effects, it is considered the first choice of anti-seizure medication only in infants. pKa is similar to that of plasma pH=7.4. Mechanism of action is through enhancement of inhibitory processes and diminution of excitatory transmission. At higher doses it suppresses high frequency repetitive firing in neurons through an action on Na conductance. It also enhances GABA receptor mediated prolonged opening of the Cl channel. Finally it plays a role in suppression of glutamate-mediated excitation. It is used in the treatment of partial and generalized seizures, but there is no evidence for its use in the management of absence seizures. All barbiturates are metabolised in the liver and then excreted in the urine. With the EXCEPTION of phenobarbitone (20-30%), only insignificant quantities of barbiturates are excreted unchanged in the urine
Regarding neuroleptic malignant syndrome: All are true except:
A It may occur after months on a stable drug regimen
B Clinical features may include mutism, dysarthria, dystonia, incontinence and delirium
C Results from blockade of dopaminergic neurotransmission in the basal ganglia and hypothalamus
D Specific treatments include cooling, bromocriptine and dantrolene.
E The syndrome characteristically develops over 60 mins and is usually fully blown by 4 hours
E
Explanation
Neuroleptic malignant syndrome (NMS) is a life threatening neurologic emergency associated with the use of neuroleptic agents. The aetiology of NMS remains controversial. Although a central deficiency of dopaminergic neurotransmission at nigrostriatal, mesolimbic and hypothalamic-pituitary pathways appears pivotal. The syndrome develops in 0.02-2.5% of people taking neuroleptic medication. The onset of NMS usually occurs over 24-72 hours. It presents with a triad of CNS, neuromuscular and autonomic changes.
CNS: Altered mental state (in 82% of patients) agitated delirium with confusion rather than psychosis. Catatonic signs and mutism can be prominent. Progression to stupor and eventual coma.
Neuromuscular: Increased tone with ‘lead-pipe’ rigidity, generalised bradykinesia or akinesia – Mutism and staring- Dysarthria – Dystonia and abnormal postures – Abnormal involuntary movements – Incontinence
Autonomic instability: Hyperthermia – Tachycardia – Hypertension – Respiratory irregularities – Cardiac dysrhythmias
Management: Attention to ABC with rapid sequence intubation if coma or hyperthermia >39.5 degrees celcius. Detect and correct hyperthermia with continuous core temperature monitoring from 38.5 and RSI with neuromuscular paralysis above 39.5.
Dantroline is indicated for severe muscle rigidity and fever. Bromocriptine is a dopamine agonist and can be given in moderate to severe cases to improve autonomic instability and fever. Hypertension and tachycardia may be initially treated with a parental vasodilator such as GTN or nitroprusside. Any agent with dopamine antagonist effects should be avoided.
Which of the following drug drug clases interact dangerously with Monoamine Oxidase Inhibitors (MAOI)
A Tetracyclic antidepressants
B Selective Serotonin reuptake inhibitors (SSRI)Correct Answer
C 5 HT2 antagonists
D Tricyclic antidepressants
B
Explanation
MAOIs are associated with a sever drug interaction when combined with SSRIs. Life threatening serotonin syndrome can develop. The serotonin syndrome is due to overstimulation of the 5-HT receptors in the central gray nuclei and the medulla. Symptoms range from mild to lethal and include a triad of cognitive (delirium and coma), autonomic (hypertension, tachycardia and diaphoreses) and somatic (myoclonus, hyperreflexia and tremor) effects. Most SSRI antidepressants should be discontinued for at least 2weeks before starting a MAOI. Fluoxetine, because of its long half-life, should be discontinued for 4-5weeks. Conversely, an MAOI must be discontinued for at least 2 weeks before starting a serotonin agent
Note: There is a potential for drug interaction with all antidepressants, but the most serious of these involve the MAOIs and to a lesser extent the TCAs
Sodium Valporate inhibits the metabolism of all of the following drugs EXCEPT?
A Olanzapine
B Phenytoin
C Carbamazapine
D Phenobarbitol
A
Explanation
Sodium valproate (SV) inhibits the metabolism (increasing concnetration) of phenobarbitol, phenytoin, ethosuximide and carbamazepine (epoxide metabolite), leading to higher steady state concentrations of these agents. SV dramatically decreases the clearance of lamotrigine, resulting in a two-threefold prolongation of its half-life.
SV may decrease the olanzapine plasma concentration-mechansim unknown-(implying a increase in metabolism). This may result in a insufficient effect of olnazapine when taken with SV
Which of the following pharmacokinetics of Lithium is CORRECT?
A Bioavailability is <50%
B Volume of distribution is 2.0L/Kg
C Plasma half life is 30hrs
D It is not metabolised
D
Explanation
Lithium is rapidly absorbed, and plasma conc. peak within one-half to three hrs following oral administrations.
Gastrointestinal absorption of lithium carbonate tablets or capsules appears to be virtually complete (95% to 100%).
The absorption of sustained-release lithium products is more variable, and ranges from (60% to 90%). Lithium solutions appears to be rapidly and completely absorbed and plasma conc. peak within 60 min(30min-2Hrs).
The usual volume of distribution for lithium is approximately (0.7 L/kg).
T1/2=20hrs, no plasma protein binding
It is NOT metabolised and excreted virtually entirely in the urine
Which of the following drugs reduce the clearance of lithium?
A Thiazide
B Aspirin
C Clozapine
D Paracetamol
A
Explanation
Renal clearance of lithium is reduced by 25% with thiazide diuretics and the dose may need to be reduced by a similar amount. A similar reduction occurs with the newer NSAIDS. There is no issue with Aspirin however. Paracetamol is also safe. All neuroleptics with the possible exception of clozapine may produce more severe extrapyradimal side effects when combined with lithium
Which of the following induction anaesthetics are contraindicated in a patient allergic to eggs?
A Midazolam
B Propofol
C Ketamine
D Thiopentone
B
Explanation
Propofol is formulated as an emulsion containing 10% soybean oil, 2.25% glycerol and 1.2% lecithin, the major component of the egg yolk phosphatide fraction
The risk of transient neurological symptoms is most likely to occur with which local anaesthetic?
A Lignocaine
B Bupivacaine
C Chloroprociane
D Prilocaine
A
Explanation
Transient neurological symptoms (TNS) is a rare but devastating neurological complication that can occur with neuraxial (spinal and epidural) administration of local anaesthetic. TNS is a syndrome of transient pain and or dysaesthesia. The pain expeirenced can often be worse than the pain induced by the surgery alone. Lignocaine seems to be the drug most likely to cause TNS. The risk of other local anaesthetic causing TNS varies. Procaine and mepivacaine reduces the risk of TNS slightly. Risk of TNS with bupivacaine, prilocaine and chloroprociane is negligible
Which of the following local anaesthetics is recommended for procedures during labour?
A Prilocaine
B Bupivacaine
C Ropivoaaine
D Lignociane
B
Explanation
Bupivacaine requires low concentrations (<0.25%) to achieve prolonged peripheral anaesthesia and analgesia for postoperative pain control and pain control during surgery. It is often the agent of choice for epidural infusions for postoperative pain control and for labour analgesia. It is regarded as a very safe spinal anaesthetic agent, with a relatively favourable therapeutic index with respect to neurotoxicity and the development of transient neurologic symptoms.
Which pharmacological agent is best prescribed for motion sickness
A 5-HT3 receptor blockers
B Anti-muscarinic agents
C Dopamine 2 blockers
D Anti-histamines
B
Explanation
Certain vestibular disorders respond to antimuscarininc drugs (and to antihistaminic agents with antimuscarinic effects). Scopolomine is one of the oldest remedies for seasickness and is affective as most other newer agents.
Not sure about this question. The textbook says both antimuscarinic drugs as well as first generation H1 antagonists are the most effective agents for motion sickness.
Which of the following analgesic medications is relatively contraindicated in patients who have a history of seizure activity?
A Indometacin
B Tramadol
C Codeine
D Morphine
B
Explanation
Tramadol-central acting analgesia, mechanism of action-blockade of serotonin reuptake. Toxicity includes association with seizures and the drug is relatively contraindicated in patients with a history of epilepsy and with use of other drugs that lower the threshold for seizures. Another serious risk is the development of serotonin syndrome, especially if combined with a SSRI antidepressant
Note: In Australia the most common drugs causing toxic seizure are venlefaxine, bupropion, tramadol and amphetamines
Which of the following is false with regards to the CNS effects of thiopentone?
A It provides neuroprotection from focal cerebral ischaemia
B They produce dose dependent analgesia
C It decrease cerebral blood flow
D It suppresses cerebral electrical activity
B
Explanation
Thiopentone produces dose dependent CNS depression ranging from sedation to general anaesthesia. They do NOT produce analgesia. Some evidence suggests that they cause hyperalgesia. It is a potent cerebral vasoconstrictor and produce predictable decrease in cerebral blood flow, cerebral blood volume and intracranial pressure. They decrease CMRO2. They may provide neuroprotecttion from focal cerebral ischaemia (CVA, surgical resection, temporary clips during aneurysm clipping) but not form global cerebral ischaemia (due to cardiac arrest). They suppress cerebral electrical activity-anticonvulsants
Which side effect is most common with chlorpromazine?
A Dry mouth
B Hypotension
C Nausea and vomiting
D Extra pyramidal side effects
B
Explanation
Chlorpromazine has strong anti alpha and 5HT2A effects, followed by anti dopamine 2 and 1. Clinical potency is low, extrapyramidal toxicity is moderate. Orthostatic hypotensive action is high. Sedative action is also high. Other anti alpha effects include failure to ejaculate and impotence.
From Katzung: chlorpromazine: many adverse side effects, especially automimic- orthostatic hypotension, impotence and failure to ejaculate.
Which of the following metabolites of benzodiazepines are INACTIVE?
A Lorazepam
B Diazepam
C Triazolam
D Alprazolam
A
Explanation
Diazepam is metablised into oxazepam (an active metabolite)
Alprazolam and triazolam are metabolised into alpha-hydroxy metabolites (active)
Chlordiazepoxide is metabolised into desmethylchlordiazepoxide (active)
Another way the question could (or should be asked): “Which of the following benzodiazepines have inactive metabolites?” (None of the benzodiazepines listed are inactive, but lorazepam is the only one listed with inactive metabolites.)
Which is false regarding the anaesthetic agent propofol?
A Propofol has desirable antiemetic properties
B Propofol causes most pronounced decrease in blood pressure compared to other induction drugs
C Propofol augments the neuromuscular blockade, allowing for lower doses of the neuromuscular blocker
D Due to greater reduction in upper airway reflexes, propofol allows easier placement of a LMA
C
Explanation
The organ system effects of propofol
CNS: hypnotic effects, no analgesia. Reduction in cerebral blood flow, reduction in basal cerebral metabolic rate for oxygen, reduction in intracranial and intraocular pressure. Burst suppression of the EEG
CVS: most pronounced decrease in blood pressure compared to other induction drugs. Vasodilation of both arteries and veins leading to reduction in preload and afterload. Inhibition of the baroreflex resulting in only a modest increase in heart rate
Rep: respiratory depression and apnoea. Greater reduction in upper airway reflexes (than Thiopentone) allowing easier placement of a LMA
Other effects: Propofol does not augment other neuromuscular blockade. Propofol has desirable antiemetic properties. Pain at site of IVI injection can be reduced with the co-administration of lignocaine, slow injection rate and larger veins.
Mechanism of action: potentiation of the chloride current mediated through the GABAa receptor complex
A patient with Parkinson’s disease presents to the ED with profuse vomiting. Which is the anti-emetic of choice?
A Prochlorperazine
B Domperidone
C Droperidol
D Metoclopramide
B
Explanation
Domperidone is extremely well tolerated. Because it does not cross the blood brain barrier to a significant degree, neuropsychiatric and extrapyramidal effects are rare.
Metoclopramide, the phenothiazine (prochlorperazine, promethazine) and the butyrophenones (droperidol) cause extrapyramidal side effects-restlessness, dystonia and parkinsonian symptoms.
What is the action of benzodiazepines at their receptor site?
A Allosteric modulator
B Inverse agonist
C Partial agonist
D Full agonist
A
Explanation
Benzodiazepines are allosteric modulators at the GABA-A receptor, where they increased chloride channel opening frequency.
A 23-year-old epileptic has drug concentrations measured and is found to be sub-therapeutic. Her dose is minimally increased and two weeks later on re-testing they are supratherapeutic. Which drug is she likely taking?
A Keppra
B Phenytoin
C Valproate
D Carbamazepine
B
Explanation
Phenytoin exhibits dose-dependent elimination, with a switch from first to zero order kinetics at increasing concentrations predisposing to toxicity. Carbamazepine is a CYP inducer and induces its own metabolism. Valproate undergoes hepatic metabolism with first order kinetics. Keppra is metabolized primarily in the blood and thus has minimal drug interactions.
Extra:
Most antiseizure drugs follow linear (first order) kinetics, in which a constant fraction per unit time of the drug is eliminated (elimination is proportional to drug concentration). In the case of phenytoin, as dose increases, there is saturation of metabolism and a shift from first order to zero order kinetics, in which a constant quantity per unit time is metabolised. A small increase in dose can result in a large increase in concentration.
Orally administrated gabapentin also exhibits zero-order kinetics, but in contrast to phenytoin where metabolism can be saturated , in the case of gabapentin, gut absorption, which is mediated by the large neutral amino acid system L transporter , is susceptible to saturation. The bioavailability of gabapentin falls at high dose as the transporter is saturated so that increase in blood levels do not keep pace with increase in dose.
In a patient on an anti-seizure medication, hyponatraemia is most likely a potential side effect with administration of which of the following medications?
A Valproate
B Carbamazepine
C Keppra
D Phenytoin
B
Explanation
Adverse effects of carbamazepine include CNS effects (nystagmus, diplopia, ataxia, sedation at high doses), GI upset, LFT derangement, benign leukopenia, erythematous skin rash, hyponatraemia. Overdose causes seizures and cardiac toxicity.
Which drug used in the treatment of glaucoma reduces aqueous humour secretion?
A Echothiophate
B Timolol
C Latanoprost
D Pilocarpine
B
Explanation
Beta-blockers decrease aqueous humour secretion.
Which of the following drugs is used to dilate pupils in the emergency department?
A Latanoprost
B Atropine
C Timolol
D Cyclopentolate
D
Explanation
Cyclopentolate is an anti-muscarinic which causes mydriasis (pupillary constrictor muscle depends on muscarinic cholinoceptor activation) and cycoplegia (weakened contraction of ciliary muscle)
Accurate measurement of refractive error in uncooperative patients, e.g., young children, require ciliary paralysis. Also, mydriases greatly facilitates ophthalmoscopic examination of the retina. Therefore, antimuscarinic drugs, administered topically as eye drops or ointment, are very helpful in doing a complete exam. For older adults and older children, the shorter acting drugs are preferable. For younger children, the greater efficacy of atropine is sometimes necessary, but the possibility of antimuscarinic poisoning is correspondingly increased. Interesting, antimuscarinic drugs should never be used for mydriasis unless cycloplegia or prolonged action is required. Alpha-adrenoceptor stimulant drugs e.g. phenylephrine, produce a short-lasting mydriasis that us usually sufficient for fundoscopy examination.
Antimuscarinic drugs (duration of effect)
Atropine 5-7 days
Scopolamine 3-7 days
Homatropine 12-24hrs
Cyclopentolate 3-6hrs
Tropicamide 15-60min
Which of the following best describes the order of metabolism of benzodiazepine medications?
A Hydroxylation, urinary excretion
B Hydroxylation, conjugation with glucuronides, urinary excretion
C Conjugation with glucuronides, urinary excretion
D Conjugation with glucuronides, hydroxylation, urinary excretion
B
Explanation
Hepatic metabolism accounts for the clearance of all benzodiazepines. Most benzodiazepines undergo microsomal oxidation (phase I reactions), including hydroxylation. The metabolites are subsequently conjugated (phase II reactions) to form glucuronides that are excreted in the urine
Which neurotransmitter is implicated in the reward response to cocaine?
A Noradrenaline
B Dopamine
C Glutamine
D Serotonin
B
Explanation
In the CNS, cocaine blocks the uptake of dopamine, serotonin and noradrenaline through their receptive transporters.The block of the dopamine transporter (DAT), by increasing dopamine concentrations in the nucleus accumbens, has been implicated in the rewarding effects of cocaine.
A patient presents to emergency department with a decreased GCS. You note that the patient has a severe lead-pipe rigidity. Which of the following overdoses might be responsible?
A Flucloxacillin
B Lithium
C Risperidone
D MNDA
C
Explanation
Risperidone has been shown to cause neuroleptic malignant syndrome. The initial symptom is marked muscle rigidity- a lead pipe rigidity. Muscle type creatine kinase are usually elevated, reflecting muscle damage.
A patient presents with overdose. They are tachycardic, dry mucus membranes, and in urinary retention with a broadening of QRS. Which drug is most likely to cause this?
A Olanzapine
B Amitriptyline
C Venlefaxine
D Fluoxetine
B
Explanation
Amitriptyline in overdose can cause anti-cholinergic features with quinidine-like depressant effects on cardiac sodium channel (slowed conduction with a wide QRS interval and depressed cardiac contractility)
Which antidepressant has an active metabolite?
A Paroxetine
B Fluoxetine
C Escitalopram
D Citalopram
B
Explanation
The prototype SSRI, fluoxetine, differs from other SSRIs in some important respects. Fluoxetine is metabolized to an active product, norfluoxetine, which may have plasma concentrations greater than those of fluoxetine. The elimination half-life of norfluoxetine is about three times longer than fluoxetine and contributes to the longest half-life of all the SSRIs. As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered to mitigate the risk of serotonin syndrome.
A known epileptic on medications, presents with a sodium of 120mEq/L. Which is the most likely medication to cause this?
A Levetiracetam
B Carbemazapine
C Valproate
D Phenytoin
B
Explanation
The most common dose-related adverse effects of carbamazepine are diplopia and ataxia. The diplopia often occurs first and may last less than an hour during a particular time of day. Rearrangement of the divided daily dose can often remedy this complaint. Other dose-related complaints include mild gastrointestinal upsets, unsteadiness, and, at much higher doses, drowsiness. Hyponatremia and water intoxication have occasionally occurred and may be dose related.
