Pharmacology
Inhaled & IV anesthetics, opioids, NMBDs, reversal agents, anti-emetics, vasoactive drugs, toxicology, drug interactions. ← All topics
Q1. Methemoglobinemia from prilocaine
A 4-year-old undergoing awake fiberoptic intubation receives topical prilocaine 600 mg via the EMLA pathway. Thirty minutes later, SpO₂ reads 84% on the pulse oximeter, but the arterial blood gas shows PaO₂ 320 mmHg on FiO₂ 1.0. Arterial blood is chocolate-brown. Which is the most appropriate next step?
A. Increase FiO₂ to 1.0 and add PEEP 10 cm H₂O to improve oxygen delivery
B. Administer methylene blue 1–2 mg/kg IV over 3–5 minutes to reduce methemoglobin
C. Administer hydroxocobalamin 5 g IV over 15 minutes to treat cyanide toxicity
D. Administer ascorbic acid 1 g IV as alternative reducing agent for methemoglobinemia
E. Initiate exchange transfusion immediately to remove methemoglobin-containing red blood cells
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Answer: B. This is classic methemoglobinemia from prilocaine, whose aminophenol metabolites oxidize hemoglobin iron from Fe²⁺ to Fe³⁺. The saturation gap—low SpO₂ (84%) with normal PaO₂ (320 mmHg)—is pathognomonic because methemoglobin absorbs light at 630 nm, falsely lowering the pulse oximeter reading. Chocolate-brown arterial blood confirms the diagnosis. Methylene blue 1–2 mg/kg IV over 3–5 minutes is first-line treatment; it acts as a cofactor for NADPH-methemoglobin reductase to reduce Fe³⁺ back to Fe²⁺. Ascorbic acid is an alternative reducing agent but is much slower and is reserved for patients with G6PD deficiency, in whom methylene blue is contraindicated because it requires NADPH from the hexose-monophosphate shunt and can cause hemolysis in G6PD-deficient red blood cells. Supplemental oxygen does not treat methemoglobinemia because methemoglobin cannot bind oxygen. Hydroxocobalamin treats cyanide toxicity, not methemoglobinemia. Exchange transfusion is reserved for severe refractory cases or when methylene blue is contraindicated and ascorbic acid fails.
Q2. Glucagon mechanism in β-blocker toxicity
A 68-year-old on chronic β-blocker therapy develops refractory hypotension after CPB despite epinephrine and norepinephrine. Which mechanism best supports the use of glucagon?
A. Direct α₁-adrenergic agonism independent of β-receptor signaling pathways
B. Inhibition of phosphodiesterase III leading to increased intracellular cAMP accumulation
C. Activation of adenylyl cyclase via a non-β-adrenergic G-protein–coupled receptor pathway
D. Stimulation of cardiac ryanodine receptors causing direct calcium release from sarcoplasmic reticulum
E. Blockade of muscarinic acetylcholine receptors resulting in unopposed sympathetic cardiac activity
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Answer: C. Glucagon works by binding to its own G-protein–coupled receptor on cardiac myocytes, which activates adenylyl cyclase independently of β-adrenergic receptors. This bypasses β-blockade and increases intracellular cAMP, producing positive inotropic and chronotropic effects. Glucagon is useful in β-blocker overdose, post-cardiopulmonary bypass low cardiac output states, post-myocardial infarction, and refractory anaphylaxis in patients on β-blockers. It is contraindicated in pheochromocytoma (may trigger catecholamine release) and insulinoma (suppresses insulin secretion).
Q3. Pseudocholinesterase deficiency interpretation
A 32-year-old undergoing C-section remains paralyzed 90 minutes after 1.5 mg/kg succinylcholine. Dibucaine number returns at 20. This indicates:
A. Acquired pseudocholinesterase deficiency from severe liver disease causing prolonged paralysis
B. Heterozygous atypical genotype with one normal and one abnormal allele present
C. Homozygous atypical genotype with two abnormal alleles causing enzyme dysfunction
D. Normal genotype with pregnancy-related reduction in total enzyme activity levels
E. Phase II block from excessive succinylcholine dosing causing desensitization paralysis
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Answer: C. The dibucaine number reflects the quality (not quantity) of pseudocholinesterase by measuring inhibition of the enzyme by dibucaine. Normal enzyme is inhibited approximately 80%, yielding a dibucaine number of 80 with typical recovery in 5-10 minutes. Heterozygous atypical genotype shows a dibucaine number of 40-60 with recovery in 20-30 minutes. Homozygous atypical genotype shows a dibucaine number of approximately 20 with prolonged paralysis lasting 4-8 hours, as seen in this patient. Pregnancy reduces total pseudocholinesterase activity by 25-30% but does not change the dibucaine number because the enzyme quality remains normal. Acquired deficiency from liver disease would reduce enzyme quantity but not alter the dibucaine number. Phase II block is not characterized by a low dibucaine number and typically occurs with much higher doses than 1.5 mg/kg.
Q4. Volatile anesthetic blood:gas coefficients
Which inhaled anesthetic has the lowest blood:gas partition coefficient?
A. Halothane, with a blood:gas partition coefficient of approximately 2.54
B. Isoflurane, with a blood:gas partition coefficient of approximately 1.46
C. Sevoflurane, with a blood:gas partition coefficient of approximately 0.69
D. Nitrous oxide, with a blood:gas partition coefficient of approximately 0.46
E. Desflurane, with a blood:gas partition coefficient of approximately 0.42
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Answer: E. Desflurane has the lowest blood:gas partition coefficient at 0.42, followed by nitrous oxide at 0.46, sevoflurane at 0.69, isoflurane at 1.46, and halothane at 2.54. The blood:gas partition coefficient represents the solubility of an anesthetic in blood relative to gas. Lower solubility means less anesthetic dissolves in the blood, allowing the partial pressure in blood to rise more quickly toward the alveolar partial pressure. This results in faster equilibration between alveolar and brain partial pressures, leading to faster induction and emergence from anesthesia. Desflurane's very low blood:gas coefficient makes it the volatile anesthetic with the most rapid onset and offset of action.
Q5. Nitrous oxide and vitamin B12
A 28-year-old with chronic kidney disease receives 70% nitrous oxide for a 6-hour procedure. Which metabolic process is impaired?
A. Acetylcholinesterase activity at the neuromuscular junction via cobalt oxidation
B. Methionine synthase activity via irreversible oxidation of the vitamin B12 cobalt atom
C. Hepatic cytochrome P450 3A4-mediated oxidation via heme iron inactivation
D. Plasma cholinesterase function via irreversible carbamylation of the active site
E. Coenzyme A acylation via pantothenic acid depletion in mitochondrial pathways
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Answer: B. Nitrous oxide irreversibly oxidizes the cobalt atom in the center of vitamin B12 (cobalamin), converting it from the active Co+ form to the inactive Co2+ or Co3+ form. This inactivates methionine synthase, which requires vitamin B12 as a cofactor, and subsequently impairs thymidylate synthetase activity needed for DNA synthesis. Prolonged nitrous oxide exposure can lead to megaloblastic changes in the bone marrow, and exposure for 4 days or longer can cause agranulocytosis. Patients with chronic kidney disease often have baseline elevated homocysteine levels due to impaired renal function, making them particularly vulnerable to further methionine synthase inhibition. It is therefore prudent to avoid or minimize nitrous oxide use in this population, especially for prolonged procedures.
Q6. Desflurane and CO production
Which combination most increases carbon monoxide production from CO₂ absorbents?
A. Sevoflurane with fresh soda lime at standard fresh gas flows
B. Desflurane with desiccated soda lime at standard fresh gas flows
C. Isoflurane with desiccated baralyme at standard fresh gas flows
D. Halothane with fresh calcium hydroxide at standard fresh gas flows
E. Nitrous oxide with desiccated soda lime at standard fresh gas flows
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Answer: B. Desflurane produces the most carbon monoxide of any volatile anesthetic when used with CO₂ absorbents. Carbon monoxide production is an exothermic reaction that is markedly increased by desiccated absorbents, high temperatures, and low fresh gas flows. The combination of desflurane with desiccated soda lime creates the highest risk for CO production. In contrast, sevoflurane produces the most heat during CO₂ absorption and generates Compound A, but it produces significantly less carbon monoxide than desflurane. Isoflurane produces intermediate amounts of CO, while halothane and nitrous oxide produce minimal to no carbon monoxide with absorbents.
Q7. Hepatic injury and volatile anesthetics
Which volatile is most associated with immune-mediated fulminant hepatic necrosis?
A. Sevoflurane, which undergoes minimal hepatic metabolism and rarely causes immune-mediated hepatic injury
B. Desflurane, which undergoes minimal hepatic metabolism and rarely causes immune-mediated hepatic injury
C. Isoflurane, which undergoes moderate hepatic metabolism and occasionally causes immune-mediated hepatic injury
D. Halothane, which undergoes extensive hepatic metabolism and classically causes immune-mediated hepatic injury
E. Nitrous oxide, which undergoes negligible hepatic metabolism and does not cause immune-mediated hepatic injury
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Answer: D. Halothane hepatitis is the classic immune-mediated fulminant hepatic necrosis associated with volatile anesthetics. Halothane undergoes approximately 20% hepatic metabolism via oxidative pathways, producing trifluoroacetylated protein adducts that trigger an immune response in susceptible patients. This can lead to fulminant hepatic failure with mortality rates exceeding 50%. Halothane also decreases hepatic arterial blood flow more than other volatile agents. In contrast, sevoflurane and desflurane undergo only 3-5% and less than 0.02% metabolism respectively, making them least likely to cause immune-mediated hepatic injury. Isoflurane undergoes intermediate metabolism (approximately 0.2%). Nitrous oxide is not metabolized hepatically and does not cause immune-mediated liver injury.
Q8. Halothane and arrhythmias
A pediatric patient under halothane anesthesia receives epinephrine for hemostasis and develops premature ventricular contractions progressing to ventricular tachycardia. The underlying mechanism is:
A. Direct β₁-adrenergic stimulation of the myocardium by halothane
B. Halothane-induced sensitization of the myocardium to catecholamines
C. Coronary steal phenomenon redistributing blood flow away from myocardium
D. Hypercalcemia induced by halothane increasing myocardial irritability
E. QT interval prolongation from halothane predisposing to torsades
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Answer: B. Halothane sensitizes the myocardium to catecholamine-induced dysrhythmias, particularly in the presence of hypercarbia or hypoxia. This mechanism explains why exogenous epinephrine administration during halothane anesthesia can precipitate ventricular arrhythmias, even at doses that would normally be safe. The sensitization effect is dose-dependent and is one reason sevoflurane has largely replaced halothane in pediatric anesthesia, as sevoflurane causes fewer arrhythmias and less bradycardia. Halothane does not directly stimulate β₁ receptors, cause coronary steal, induce hypercalcemia, or significantly prolong the QT interval.
Q9. Propofol mechanism
Propofol's hypnotic effect is primarily mediated through:
A. NMDA receptor antagonism in the central nervous system
B. Potentiation of GABAₐ receptors in the central nervous system
C. α₂-adrenergic receptor agonism in the central nervous system
D. μ-opioid receptor agonism in the central nervous system
E. Glycine receptor agonism in the central nervous system
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Answer: B. Propofol's hypnotic effect is primarily mediated through potentiation of GABAₐ receptors in the central nervous system. This mechanism leads to decreased cerebral metabolic rate of oxygen consumption (CMRO₂), cerebral blood flow (CBF), intracranial pressure (ICP), and intraocular pressure (IOP). Propofol causes the largest drop in systemic blood pressure of any intravenous induction agent. It has no analgesic properties but possesses strong antiemetic effects even at sub-hypnotic infusion doses. NMDA receptor antagonism is the mechanism of ketamine. α₂-adrenergic agonism is the mechanism of dexmedetomidine. μ-opioid receptor agonism is the mechanism of opioids like fentanyl. Glycine receptor agonism is not a primary mechanism of common anesthetic agents, though some volatile anesthetics may have minor effects at these receptors.
Q10. Propofol infusion syndrome
A 14-year-old with traumatic brain injury is sedated on propofol 6 mg/kg/hr for 36 hours. He develops metabolic acidosis, rhabdomyolysis, hyperkalemia, and new bradycardia. The mechanism is:
A. Allergic reaction to soybean oil emulsion causing mast cell degranulation and systemic inflammatory response
B. Impaired free fatty acid utilization and mitochondrial dysfunction causing cardiac and skeletal muscle injury
C. Direct propofol toxicity to cardiac conduction system causing progressive atrioventricular nodal blockade and arrhythmia
D. Soybean-derived endotoxin contamination causing systemic inflammatory response and multiorgan dysfunction with metabolic derangement
E. Carrier-induced renal tubular injury from EDTA chelation causing electrolyte wasting and secondary metabolic acidosis
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Answer: B. Propofol infusion syndrome occurs with high-dose propofol (greater than 4 to 5 mg/kg/hr) administered for prolonged duration (greater than 24 to 48 hours). The mechanism involves impaired cellular free fatty acid utilization and mitochondrial dysfunction, leading to cardiac and skeletal muscle damage. Clinical features include rhabdomyolysis, lactic acidosis, hyperkalemia, hypertriglyceridemia, and cardiac dysfunction including bradycardia and heart failure. Children are at higher risk than adults. Concurrent administration of catecholamines or corticosteroids increases the risk. Treatment involves immediate discontinuation of propofol and supportive care.
Q11. Ketamine receptor profile
Ketamine's analgesia at high doses (1–2 mg/kg IV) is primarily mediated through:
A. NMDA receptor antagonism, which predominates at lower analgesic doses
B. μ-opioid receptor agonism, which predominates at higher analgesic doses
C. α₂-adrenergic agonism, which predominates at higher analgesic doses
D. GABAₐ receptor potentiation, which predominates at higher analgesic doses
E. Voltage-gated sodium channel blockade, which predominates at higher doses
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Answer: B. Ketamine exhibits dose-dependent receptor activity. At low doses (75–250 mcg/kg), ketamine acts primarily at NMDA receptors to produce analgesia. At high doses (1–2 mg/kg IV), the μ-opioid receptor mechanism predominates for analgesic effects. Ketamine preserves airway reflexes and respiratory drive, increases CMRO₂, and produces indirect sympathetic stimulation via inhibition of norepinephrine reuptake. The other receptor mechanisms listed are not primary mechanisms of ketamine analgesia at any dose range.
Q12. Etomidate and the adrenal axis
A 72-year-old septic patient is induced with etomidate. Which complication is most concerning in the postoperative period?
A. Hypertensive crisis from sympathetic surge and catecholamine release
B. Adrenal suppression from 11-β-hydroxylase inhibition in the cortex
C. Coronary steal from peripheral vasodilation and redistribution of flow
D. Increased cerebral metabolic oxygen demand and intracranial pressure elevation
E. Prolonged neuromuscular blockade from pseudocholinesterase inhibition at the junction
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Answer: B. Etomidate inhibits 11-β-hydroxylase, causing adrenal suppression that is detectable even after a single induction dose. The clinical significance of this suppression remains debated in septic patients, though it is the most concerning complication in this population. Etomidate also causes pain on injection, myoclonus, postoperative nausea and vomiting, and can induce epileptiform activity, so it should be avoided in patients with seizure disorders. Etomidate does not cause hypertensive crises, coronary steal, increased cerebral metabolic rate, or prolonged neuromuscular blockade.
Q13. Methohexital paradox
In a patient undergoing electroconvulsive therapy, which IV anesthetic is preferred because it facilitates rather than suppresses seizure activity?
A. Propofol, which enhances GABA-mediated inhibition and suppresses seizure activity
B. Thiopental, which enhances GABA-mediated inhibition and suppresses seizure activity
C. Methohexital, which activates epileptic foci and facilitates seizure activity
D. Dexmedetomidine, which provides alpha-2 agonism and suppresses seizure activity
E. Diazepam, which enhances GABA-mediated inhibition and suppresses seizure activity
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Answer: C. Methohexital is unique among barbiturates because it activates epileptic foci rather than suppressing EEG activity like other barbiturates such as thiopental. This paradoxical property makes it the preferred agent for electroconvulsive therapy, where adequate seizure duration is therapeutic. Methohexital is also useful for ictal mapping during epilepsy surgery. Etomidate is an alternative that also lengthens seizure duration and may be preferred when hemodynamic stability is a concern. Propofol, thiopental, dexmedetomidine, and benzodiazepines like diazepam all suppress seizure activity and would be counterproductive for ECT.
Q14. Dexmedetomidine biphasic response
After a 1 mcg/kg IV bolus of dexmedetomidine over 1 minute, what hemodynamic pattern would you expect in the first 3–10 minutes?
A. Sustained hypotension and tachycardia throughout the observation period
B. Transient hypertension followed by bradycardia and hypotension
C. Sustained hypertension and bradycardia throughout the observation period
D. Tachycardia followed by reflex hypotension in the later phase
E. No significant hemodynamic change throughout the observation period
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Answer: B. Dexmedetomidine produces a characteristic biphasic hemodynamic response when given as a rapid IV bolus. The initial phase is caused by peripheral α₂B-mediated vasoconstriction, producing transient hypertension that peaks around 3 minutes. This is followed by the second phase, in which central α₂A-mediated reduction in sympathetic outflow leads to bradycardia and hypotension by approximately 10 minutes. Slow administration (over 10-15 minutes rather than 1 minute) mitigates the initial hypertensive phase. Dexmedetomidine has much higher α₂:α₁ selectivity (1600:1) compared to clonidine (200:1), which contributes to its more predictable hemodynamic profile.
Q15. Morphine metabolites in renal failure
A 65-year-old with ESRD on hemodialysis receives morphine for postoperative pain and develops myoclonus, prolonged sedation, and respiratory depression. The most likely culprit is accumulation of:
A. Normorphine, a minor demethylated metabolite that accumulates renally and causes neuroexcitation
B. Morphine-6-glucuronide, a potent μ-agonist metabolite that accumulates renally and causes respiratory depression
C. Norfentanyl, an N-dealkylated metabolite that accumulates renally and causes prolonged sedation
D. Hydromorphone-3-glucuronide, a neuroexcitatory metabolite that accumulates renally and causes myoclonus
E. Naloxone glucuronide, an inactive conjugate that accumulates renally and causes paradoxical opioid effects
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Answer: B. Morphine-6-glucuronide (M6G) is nearly 100 times more potent than morphine at μ-opioid receptors and is renally eliminated. In ESRD, M6G accumulates and causes profound respiratory depression, prolonged sedation, myoclonus, and potentially seizures. Morphine-3-glucuronide (M3G), which has lower μ-receptor affinity, also accumulates and contributes to neuroexcitatory effects including myoclonus and allodynia at high concentrations. Morphine should be avoided in patients with ESRD. Alternative opioids include hydromorphone (though hydromorphone-3-glucuronide can still accumulate and cause neuroexcitation) or fentanyl, which lacks active renally-cleared metabolites. Normorphine is a minor metabolite without significant clinical impact. Norfentanyl is inactive. Naloxone metabolites do not cause opioid effects.
Q16. Meperidine and SSRI
A patient on fluoxetine receives meperidine for postoperative shivering. He develops hyperthermia, agitation, and clonus. The mechanism is:
A. Anaphylaxis from meperidine causing mast cell degranulation and systemic inflammatory response
B. Serotonin syndrome from meperidine inhibition of serotonin reuptake when combined with fluoxetine
C. MAO-B substrate accumulation leading to excessive catecholamine levels and sympathetic hyperactivity
D. Direct dopaminergic stimulation in the nigrostriatal pathway causing extrapyramidal motor symptoms
E. Histamine release from meperidine triggering widespread vasodilation and compensatory tachycardia
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Answer: B. Meperidine is a serotonin reuptake inhibitor as well as a κ-opioid agonist. When coadministered with SSRIs like fluoxetine, it can precipitate serotonin syndrome, characterized by hyperthermia, agitation, clonus, hyperreflexia, and autonomic instability. Other drugs that can cause serotonin syndrome when combined with SSRIs include MAOIs, tramadol, and methadone. Meperidine's metabolite normeperidine is neurotoxic (causing seizures) and is renally excreted, which is an additional concern in patients with renal impairment but is not the mechanism in this clinical scenario.
Q17. Remifentanil metabolism
Remifentanil's ultra-short context-sensitive half-time is due to:
A. Hepatic metabolism by cytochrome P450 3A4 isoenzyme
B. Renal excretion of unchanged parent drug compound
C. Nonspecific tissue and plasma esterase hydrolysis metabolism
D. Plasma cholinesterase hydrolysis in the blood stream
E. Hofmann elimination through spontaneous molecular degradation pathway
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Answer: C. Remifentanil is hydrolyzed by nonspecific plasma and tissue esterases, which are independent of hepatic and renal function. This gives remifentanil a context-sensitive half-time of approximately 3 to 4 minutes regardless of infusion duration. Importantly, remifentanil is not metabolized by plasma cholinesterase (butyrylcholinesterase), so its metabolism is unaffected by pseudocholinesterase deficiency. This distinguishes it from drugs like succinylcholine, mivacurium, and ester local anesthetics. The ultra-short and predictable duration makes remifentanil ideal for cases requiring rapid titration and offset.
Q18. Alfentanil characteristics
The rapid onset of alfentanil relative to fentanyl is best explained by:
A. Higher lipid solubility allowing faster blood-brain barrier penetration
B. Higher unionized fraction at physiologic pH allowing faster blood-brain barrier penetration
C. Lower protein binding allowing greater free drug availability for receptor binding
D. Smaller volume of distribution allowing higher initial plasma and effect-site concentrations
E. Faster receptor binding kinetics allowing more rapid opioid receptor occupancy
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Answer: B. Alfentanil has the lowest pKa of the fentanyl family at approximately 6.5, resulting in roughly 90% of the drug existing in the unionized form at physiologic pH. This high unionized fraction allows rapid blood-brain barrier crossing and accounts for its fast onset. Interestingly, alfentanil is actually less lipid-soluble than fentanyl, which contributes to its shorter duration of action. A useful clinical memory aid is the Rule of 4s: alfentanil has approximately 4 times faster onset, one-quarter the duration, and one-quarter the potency compared to fentanyl. While higher lipid solubility does facilitate CNS penetration for drugs like fentanyl and sufentanil, it is the ionization status (determined by pKa) that primarily drives alfentanil's rapid onset.
Q19. Methadone unique properties
A 45-year-old with neuropathic pain after spinal surgery is started on methadone. Beyond μ-opioid agonism, which property contributes to its efficacy for neuropathic pain?
A. δ-opioid receptor agonism and modulation of descending pain pathways
B. NMDA receptor antagonism and serotonin/norepinephrine reuptake inhibition
C. α₂-adrenergic agonism and enhancement of inhibitory spinal interneurons
D. COX-2 inhibition and reduction of prostaglandin-mediated central sensitization
E. Sodium channel blockade and suppression of ectopic neuronal discharge
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Answer: B. Methadone possesses NMDA receptor antagonism and serotonin/norepinephrine reuptake inhibition in addition to its μ-opioid agonist properties. These dual mechanisms make it particularly useful for neuropathic pain and in patients with opioid tolerance. The NMDA antagonism helps prevent wind-up and central sensitization, which are key mechanisms in neuropathic pain. Important clinical considerations include QT prolongation with risk of torsades de pointes, especially when combined with CYP3A4 inhibitors. Methadone has an unpredictable plasma half-life ranging from 13 to 58 hours, though its analgesic effect typically lasts only 4 to 8 hours, requiring careful titration.
Q20. Butorphanol and biliary spasm
Compared with morphine, which opioid is least likely to cause biliary spasm and sphincter of Oddi contraction?
A. Fentanyl, a pure μ-agonist that causes dose-dependent sphincter of Oddi contraction
B. Hydromorphone, a pure μ-agonist that causes dose-dependent sphincter of Oddi contraction
C. Meperidine, a pure μ-agonist that causes dose-dependent sphincter of Oddi contraction
D. Butorphanol, a κ-agonist and partial μ-agonist that does not increase biliary pressure
E. Oxycodone, a pure μ-agonist that causes dose-dependent sphincter of Oddi contraction
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Answer: D. Butorphanol is a κ-agonist and partial μ-agonist that does not increase pressure in the common bile duct or cause sphincter of Oddi contraction. In contrast, morphine, fentanyl, hydromorphone, meperidine, and oxycodone are all pure μ-agonists that cause sphincter of Oddi contraction and increase biliary pressure in a dose-dependent manner. Butorphanol also has a ceiling effect on respiratory depression and is renally safe because it lacks active metabolites, making it useful in patients with renal impairment.
Q21. Naloxone half-life mismatch
A patient who took an overdose of long-acting morphine is given naloxone in the ED and is awake and breathing. Why is continuous infusion or repeat dosing necessary?
A. Naloxone is rapidly metabolized by pseudocholinesterase in the plasma and liver
B. Naloxone has a half-life of only 1–2 hours, shorter than most opioids
C. Naloxone induces upregulation of μ-receptors leading to increased opioid binding capacity
D. Naloxone undergoes enterohepatic recirculation resulting in unpredictable plasma levels over time
E. Naloxone is highly protein-bound and dissociates slowly from receptors over several hours
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Answer: B. Naloxone has a half-life of 1–2 hours, which is significantly shorter than many opioids, especially methadone and sustained-release formulations like long-acting morphine. This pharmacokinetic mismatch means that naloxone's antagonist effect wears off while the opioid agonist is still present in therapeutic concentrations. Renarcotization is the rule unless a continuous infusion is started or repeat boluses are given. Important side effects of abrupt opioid reversal with naloxone include severe pain, hypertension, and pulmonary edema. Naloxone is actually metabolized primarily by hepatic glucuronidation, not by pseudocholinesterase, and it does not undergo significant enterohepatic recirculation or cause receptor upregulation.
Q22. Succinylcholine contraindications
In which of the following is succinylcholine most contraindicated due to risk of hyperkalemic cardiac arrest?
A. Acute trauma 1 hour after injury with multiple long bone fractures
B. Burn injury 5 days post-injury covering 35% total body surface area
C. Hyperkalemia of 5.5 mEq/L from chronic ACE inhibitor use in renal disease
D. Family history of myasthenia gravis in first-degree relative without patient symptoms
E. Pregnancy at term with no complications and normal baseline potassium level
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Answer: B. Upregulation of immature extrajunctional acetylcholine receptors begins 24 to 72 hours after burn injury, denervation, prolonged immobility, or stroke, and peaks at 5 to 6 weeks. When succinylcholine depolarizes these widespread extrajunctional receptors, massive potassium efflux occurs, leading to life-threatening hyperkalemia and cardiac arrest. Succinylcholine should be avoided in burns older than 24 hours, denervating disorders such as multiple sclerosis, amyotrophic lateral sclerosis, and muscular dystrophies, and in patients with prolonged immobility. Acute trauma within the first 24 hours is generally still safe because receptor upregulation has not yet occurred. Baseline hyperkalemia of 5.5 mEq/L is a relative contraindication but does not carry the same extreme risk as the massive potassium release from extrajunctional receptors. Family history of myasthenia gravis without patient symptoms and uncomplicated pregnancy are not contraindications to succinylcholine use.
Q23. Succinylcholine in Duchenne muscular dystrophy
A 6-year-old boy with previously undiagnosed Duchenne muscular dystrophy receives succinylcholine for laryngospasm and develops bradycardia progressing to cardiac arrest. The most likely mechanism is:
A. Direct vagal stimulation by succinylcholine causing profound bradycardia and asystole
B. Massive hyperkalemia from rhabdomyolysis and upregulated extrajunctional acetylcholine receptors
C. Malignant hyperthermia triggered by succinylcholine exposure with metabolic crisis
D. Uncontrolled calcium release from sarcoplasmic reticulum causing contracture and arrest
E. Anaphylaxis to succinylcholine with histamine release and cardiovascular collapse
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Answer: B. Duchenne muscular dystrophy is an X-linked dystrophin deficiency that makes patients extremely vulnerable to succinylcholine-induced hyperkalemia. In these patients, succinylcholine causes massive potassium release through two mechanisms: rhabdomyolysis of fragile dystrophic muscle and the presence of upregulated immature (extrajunctional) acetylcholine receptors on the muscle membrane. This can lead to life-threatening hyperkalemia, bradycardia, and cardiac arrest. Volatile anesthetic agents can also trigger rhabdomyolysis in these patients. This risk is why the FDA issued a black box warning against routine use of succinylcholine in children, as undiagnosed myopathies like Duchenne are often not recognized until such an event occurs. Succinylcholine is essentially contraindicated in children with known or suspected myopathy.
Q24. Cisatracurium metabolism
Which property makes cisatracurium attractive in patients with hepatic and renal failure?
A. Plasma cholinesterase hydrolysis that is pH- and temperature-dependent
B. Hofmann elimination that is pH- and temperature-dependent
C. Renal excretion of unchanged drug without hepatic metabolism
D. Biliary excretion of glucuronide metabolite without renal clearance
E. Hepatic CYP3A4 metabolism that is independent of renal function
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Answer: B. Hofmann elimination is a non-organ-dependent degradation pathway that makes cisatracurium attractive in patients with hepatic and renal failure. This spontaneous chemical process is enhanced by alkalosis and hyperthermia. The breakdown product is laudanosine, which can precipitate seizures at very high cumulative doses. Because cisatracurium is more potent than atracurium, less laudanosine is produced at equivalent degrees of neuromuscular blockade. The other options all depend on organ function: plasma cholinesterase is synthesized by the liver, renal and biliary excretion require functioning kidneys and liver respectively, and CYP3A4 is a hepatic enzyme system.
Q25. Sugammadex dosing
A patient receives 1.2 mg/kg rocuronium for RSI. Five minutes later, the case is canceled. What sugammadex dose is required?
A. 2 mg/kg, appropriate for moderate neuromuscular blockade with train-of-four count of two or more
B. 4 mg/kg, appropriate for deep neuromuscular blockade with one to two post-tetanic counts
C. 8 mg/kg, appropriate for profound neuromuscular blockade immediately following induction with vecuronium
D. 16 mg/kg, appropriate for immediate reversal following high-dose intubating bolus of rocuronium
E. Sugammadex cannot reverse rocuronium within five minutes of administration regardless of dose
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Answer: D. Sugammadex 16 mg/kg is the rescue dose used to reverse rocuronium immediately after a high-dose intubating bolus, as in this scenario where only 5 minutes have elapsed. This is also known as immediate reversal. In contrast, 4 mg/kg is used for deep block (1–2 post-tetanic counts), and 2 mg/kg is used for moderate block (train-of-four count ≥2). Sugammadex dosing is based on actual body weight. Sugammadex is a selective relaxant binding agent that encapsulates aminosteroid neuromuscular blocking agents (rocuronium, vecuronium) but is ineffective against benzylisoquinolinium compounds such as cisatracurium and atracurium.
Q26. Neostigmine-glycopyrrolate dosing
For reversal of neuromuscular blockade with neostigmine, glycopyrrolate is preferred over atropine because:
A. Glycopyrrolate has a longer half-life and duration better matched to neostigmine's pharmacokinetic profile
B. Atropine causes paradoxical bradycardia at the low doses required for muscarinic blockade during reversal
C. Glycopyrrolate has minimal CNS penetration and causes less tachycardia than atropine at equipotent doses
D. Atropine is ineffective at blocking the peripheral muscarinic effects of neostigmine at standard reversal doses
E. Glycopyrrolate undergoes hepatic metabolism and is unaffected by renal function unlike atropine or neostigmine
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Answer: C. Glycopyrrolate is preferred over atropine for neuromuscular blockade reversal with neostigmine because it is a quaternary amine that does not cross the blood-brain barrier, resulting in minimal central nervous system side effects. Additionally, glycopyrrolate produces less tachycardia than atropine at equipotent antimuscarinic doses. The onset and duration of glycopyrrolate are also better matched to neostigmine's pharmacokinetic profile. In contrast, edrophonium (which has a faster onset) is better paired with atropine. Important exception: in pregnancy and pediatrics, atropine is preferred because glycopyrrolate does not cross the placenta while neostigmine does, which could lead to fetal bradycardia if glycopyrrolate is used.
Q27. Ondansetron side effect
Which side effect of ondansetron most concerns the anesthesiologist managing a patient on methadone?
A. Headache from serotonin receptor antagonism in the CNS
B. Constipation from peripheral serotonin receptor blockade in gut
C. QT prolongation and risk of torsades de pointes
D. Hepatotoxicity from cytochrome P450 enzyme system inhibition
E. Extrapyramidal symptoms from dopamine receptor antagonism centrally
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Answer: C. Ondansetron prolongs the QT interval in approximately 20% of patients. Methadone is also known to prolong the QT interval. When used together, there is cumulative risk for developing torsades de pointes, a potentially fatal ventricular arrhythmia. The anesthesiologist must be particularly vigilant about this interaction when managing patients on chronic methadone therapy. Other common anesthesia drugs that prolong QT include droperidol, haloperidol, amiodarone, and class III antiarrhythmics. While ondansetron can cause headache and constipation, these are minor concerns compared to the life-threatening arrhythmia risk in this clinical scenario. Ondansetron does not cause significant hepatotoxicity or extrapyramidal symptoms.
Q28. Droperidol mechanism
Droperidol's antiemetic effect is primarily through:
A. 5-HT₃ receptor antagonism
B. Dopamine D₂ receptor antagonism
C. NK1 receptor antagonism
D. Muscarinic receptor antagonism
E. Histamine H₁ receptor antagonism
Show answer
Answer: B. Droperidol is a butyrophenone that exerts its antiemetic effect primarily through dopamine D₂ receptor antagonism in the chemoreceptor trigger zone. The drug carries an FDA black-box warning for QT prolongation and torsades de pointes, though this was based on data from psychiatric doses (greater than 25 mg). The antiemetic doses used in anesthesia practice (0.625–1.25 mg) are still considered safe and effective for rescue therapy of postoperative nausea and vomiting.
Q29. Aprepitant
Aprepitant is most useful for the prevention of which type of PONV?
A. Early PONV occurring 0–2 hours postoperatively
B. Delayed PONV occurring 12–48 hours postoperatively
C. Motion-induced nausea occurring during patient transport
D. Chemotherapy-induced acute vomiting occurring within 24 hours
E. Opioid-induced nausea occurring with initial dosing
Show answer
Answer: B. Aprepitant is an NK1 (neurokinin-1) receptor antagonist with a 10-hour half-life that is particularly effective for delayed PONV occurring 12–48 hours postoperatively. It should be given preoperatively by the oral route. Substance P is the endogenous ligand that binds to NK1 receptors in the nucleus tractus solitarii, and aprepitant's antagonism at these receptors provides prolonged antiemetic coverage extending well into the delayed postoperative period. This makes it especially useful for procedures with high risk of delayed nausea and vomiting, whereas shorter-acting antiemetics like ondansetron are more effective for early PONV.
Q30. Scopolamine and physostigmine pitfall
A patient receives a scopolamine patch preoperatively and is on varenicline for smoking cessation. Postoperatively she develops agitation and is given physostigmine. Why is this concerning?
A. Physostigmine antagonizes varenicline at central nicotinic receptors, worsening agitation and potentially causing withdrawal symptoms
B. Physostigmine reversal of scopolamine combined with varenicline's nicotinic agonism causes central acetylcholine receptor overstimulation and seizures
C. Physostigmine causes severe refractory hypotension when combined with scopolamine due to excessive peripheral muscarinic receptor stimulation
D. Varenicline competitively blocks physostigmine at nicotinic receptors, preventing reversal of scopolamine and prolonging anticholinergic toxicity
E. Scopolamine prevents enzymatic breakdown of varenicline, leading to toxic accumulation and excessive nicotinic stimulation with seizure risk
Show answer
Answer: B. Physostigmine is a tertiary amine that crosses the blood-brain barrier and reverses central anticholinergic effects of scopolamine by inhibiting acetylcholinesterase. Varenicline is a partial α₄β₂ nicotinic receptor agonist used for smoking cessation. When physostigmine reverses scopolamine's antimuscarinic effects, the resulting increase in central acetylcholine combined with varenicline's nicotinic agonism leads to overstimulation of central acetylcholine receptors, which can precipitate seizures. Similar caution is warranted with other drugs affecting central cholinergic transmission, including bupropion, dextromethorphan, and NMDA antagonists.
Q31. Phenylephrine dose and onset
For an adult with sudden hypotension under spinal anesthesia, an appropriate IV bolus of phenylephrine is:
A. 5–10 mcg IV bolus with onset in 1 minute
B. 50–200 mcg IV bolus with onset in 1 minute
C. 500–1000 mcg IV bolus with onset in 1 minute
D. 2–5 mg IV bolus with onset in 1 minute
E. 10 mg IV bolus with onset in 1 minute
Show answer
Answer: B. Phenylephrine 50–200 mcg IV bolus is the appropriate dose for treating hypotension under spinal anesthesia in adults. The onset of action is approximately 1 minute, with a duration of 5–10 minutes. Phenylephrine is a pure alpha-1 adrenergic agonist that increases systemic vascular resistance and may cause reflex bradycardia. The 5–10 mcg dose is too small to be effective. The 500–1000 mcg dose and higher doses (2–5 mg, 10 mg) risk severe hypertension and excessive bradycardia. Note that IM phenylephrine 2–5 mg can be used when IV access is unavailable, with onset in 10–15 minutes.
Q32. Vasopressin in vasoplegic shock
A patient develops refractory hypotension after CPB despite high-dose norepinephrine. Vasopressin is added. Beyond V₁ receptor agonism, which property makes vasopressin useful in vasoplegia?
A. Direct β₁ receptor stimulation increasing cardiac contractility and output
B. Retained efficacy at acidotic pH where catecholamine receptors are desensitized
C. Inhibition of nitric oxide synthase reducing vasodilatory mediator production
D. Increased preload via venoconstriction augmenting venous return to heart
E. NMDA receptor antagonism preventing excitotoxic injury and vascular dysfunction
Show answer
Answer: B. Vasopressin retains efficacy in acidotic, catecholamine-desensitized vasoplegia (e.g., post-CPB, sepsis), making it particularly useful when catecholamine receptors are downregulated or desensitized by low pH. Vasopressin acts via V₁ receptors on vascular smooth muscle through the IP3 signaling pathway, independent of catecholamine receptors. This pH-independent mechanism explains its utility in refractory vasoplegic shock. Methylene blue (guanylate cyclase inhibitor) and hydroxocobalamin (NO scavenger) are last-line agents for refractory vasoplegia.
Q33. Dopamine receptor dose dependence
At which infusion range does dopamine predominantly act on α₁ receptors with generalized vasoconstriction and reduced cardiac output?
A. <1 mcg/kg/min with predominant dopaminergic receptor activation
B. 1–3 mcg/kg/min with predominant dopaminergic receptor activation
C. 3–10 mcg/kg/min with predominant beta-1 adrenergic receptor activation
D. >10 mcg/kg/min with predominant alpha-1 adrenergic receptor activation
E. Dose-independent with mixed receptor activation at all infusion rates
Show answer
Answer: D. Dopamine exhibits dose-dependent receptor activity. At low doses (≤3 mcg/kg/min), dopamine acts primarily on D₁ receptors causing renal and mesenteric vasodilation. At moderate doses (3–10 mcg/kg/min), β₁ receptor effects predominate, increasing contractility and heart rate via norepinephrine release. At high doses (>10 mcg/kg/min), α₁ receptor stimulation causes generalized systemic vasoconstriction and may reduce cardiac output. Dopamine is not recommended over norepinephrine in shock states due to higher rates of arrhythmia and increased mortality in cardiogenic shock.
Q34. Milrinone mechanism and contraindication
A patient with severe aortic stenosis develops low cardiac output. Why is milrinone not an ideal inotrope here?
A. Milrinone increases systemic vascular resistance, worsening the fixed left ventricular outflow obstruction
B. Milrinone causes profound bradycardia, reducing cardiac output through decreased heart rate
C. Milrinone reduces afterload through vasodilation, worsening the gradient across the stenotic valve
D. Milrinone is metabolized too slowly, causing prolonged hypotension in patients with hepatic dysfunction
E. Milrinone causes pulmonary hypertension through pulmonary vasoconstriction, increasing right ventricular afterload
Show answer
Answer: C. Milrinone is a phosphodiesterase-3 (PDE3) inhibitor that increases intracellular cAMP, resulting in positive inotropy, lusitropy, and both arterial and venous dilation (inodilator effect). In severe aortic stenosis, the left ventricle faces a fixed obstruction and depends on adequate afterload to maintain coronary perfusion pressure. The systemic vasodilation caused by milrinone reduces afterload, which worsens the pressure gradient across the stenotic valve and can precipitate hypotension and myocardial ischemia. This same principle applies to other fixed obstructive lesions like hypertrophic obstructive cardiomyopathy (HOCM). Milrinone is renally excreted (not hepatically metabolized), so dose adjustment is required in renal failure. Common side effects include tachycardia (not bradycardia), hypotension, and atrial fibrillation. It does not increase SVR or cause pulmonary hypertension; rather, it reduces both systemic and pulmonary vascular resistance.
Q35. Fenoldopam mechanism
Fenoldopam is useful in hypertensive emergencies particularly when:
A. Tachycardia must be avoided in the clinical setting
B. Renal preservation is a priority in the clinical setting
C. Pulmonary hypertension is present in the clinical setting
D. Severe aortic stenosis is present in the clinical setting
E. The patient has long QT syndrome requiring management
Show answer
Answer: B. Fenoldopam is a selective dopamine-1 (D₁) receptor agonist that causes vasodilation in coronary, peripheral, renal, and splanchnic vascular beds via increased cAMP production. It uniquely increases renal blood flow and glomerular filtration rate, making it particularly useful in hypertensive emergencies when renal perfusion is a concern or when renal preservation is a priority. Fenoldopam has no alpha-adrenergic or beta-adrenergic activity. It can cause reflex tachycardia due to its vasodilatory effects, so it would not be ideal when tachycardia must be avoided. It does not have specific benefits in pulmonary hypertension, severe aortic stenosis, or long QT syndrome.
Q36. Nitroprusside toxicity
A patient receives a sodium nitroprusside infusion at 8 mcg/kg/min for 12 hours. He develops metabolic acidosis, altered mental status, and a high mixed venous oxygen saturation. The mechanism is:
A. Methemoglobinemia from oxidation of hemoglobin iron, impairing oxygen delivery to tissues
B. Cyanide toxicity from nitroprusside metabolism, impairing mitochondrial oxidative phosphorylation
C. Coronary steal from excessive vasodilation, shunting blood away from ischemic myocardium
D. Carbon monoxide poisoning from hemoglobin binding, preventing oxygen release to tissues
E. Lactic acidosis from impaired hepatic perfusion, reducing lactate clearance and metabolism
Show answer
Answer: B. Sodium nitroprusside releases both nitric oxide and cyanide during metabolism. Cyanide binds to cytochrome oxidase in mitochondria, blocking oxidative phosphorylation and forcing cells into anaerobic metabolism. This produces metabolic acidosis with elevated lactate. Because tissues cannot extract oxygen, mixed venous oxygen saturation becomes paradoxically elevated despite tissue hypoxia. Altered mental status reflects cerebral dysfunction from impaired cellular respiration. Treatment includes hydroxocobalamin (preferred agent), or the combination of sodium thiosulfate with or without sodium nitrite. To prevent toxicity, limit infusions to less than 2 mcg/kg/min when used for more than 24 hours, or use alternative agents for prolonged hypotensive therapy.
Q37. Nitroglycerin vs nitroprusside
Compared with sodium nitroprusside, IV nitroglycerin is characterized by:
A. Predominant arteriolar dilation with balanced reduction in systemic vascular resistance
B. Predominant venodilation with reduction in preload via cGMP-mediated smooth muscle relaxation
C. Equal arteriolar and venous dilation with balanced effects on afterload and preload
D. Positive inotropic effect with increased myocardial contractility and cardiac output augmentation
E. Absence of tachyphylaxis with sustained hemodynamic effects during prolonged continuous infusion
Show answer
Answer: B. Nitroglycerin is a pure venodilator that works via cGMP-mediated smooth muscle relaxation, with preload reduction being its predominant hemodynamic effect. In contrast, sodium nitroprusside produces balanced arterial and venous dilation, affecting both preload and afterload. Nitroglycerin is clinically useful for angina through coronary vasodilation, for congestive heart failure through preload reduction, and as a tocolytic in obstetric emergencies such as retained placenta and uterine inversion. Nitroglycerin does not have inotropic effects and can develop tachyphylaxis with prolonged use.
Q38. Clevidipine
Clevidipine is most distinguished by:
A. Long duration of action via hepatic conjugation
B. Hepatic metabolism by the CYP3A4 enzyme system
C. Ultra-short half-life via hydrolysis by plasma esterases
D. Renal excretion of unchanged drug without metabolism
E. Direct β-blockade in addition to calcium antagonism
Show answer
Answer: C. Clevidipine is a dihydropyridine calcium channel blocker that is metabolized by plasma and tissue esterases, giving it an ultra-short half-life with onset of action within 1 minute and duration of 5 to 15 minutes. This rapid metabolism by esterases (not hepatic CYP enzymes or renal excretion) allows for precise titration and makes it particularly useful in situations requiring rapid blood pressure control such as neurosurgery, hypertensive emergencies, and aortic dissection. Like other dihydropyridines, it acts on vascular smooth muscle calcium channels and does not have direct beta-blocking properties. It does not undergo hepatic metabolism via CYP3A4, does not have a long duration of action, and is not renally excreted unchanged.
Q39. Esmolol pharmacology
Esmolol's short half-life is due to:
A. Hepatic metabolism by the cytochrome P450 3A4 enzyme system
B. Rapid renal excretion of unchanged drug in the urine
C. Hydrolysis by esterases located within red blood cells
D. Spontaneous degradation via Hofmann elimination at physiologic pH
E. Hydrolysis by plasma cholinesterase enzyme in the bloodstream
Show answer
Answer: C. Esmolol is hydrolyzed by red blood cell esterases, which accounts for its very short half-life of approximately 9 minutes. This rapid metabolism results in an onset of action within 1 minute and a duration of effect of approximately 10 minutes. Esmolol is a selective β₁ adrenergic blocker that is particularly useful for controlling acute tachycardia during laryngoscopy, electroconvulsive therapy, and intraocular surgery. The drug is not significantly metabolized by hepatic cytochrome P450 enzymes, does not undergo renal excretion as the primary route of elimination, does not undergo Hofmann elimination (a property of some neuromuscular blockers like atracurium), and is not hydrolyzed by plasma cholinesterase (which metabolizes succinylcholine and mivacurium).
Q40. Labetalol ratio
Which best describes labetalol's α:β blockade ratio with IV administration?
A. 1:1 (equal alpha and beta blockade)
B. 1:7 (beta blockade predominates significantly)
C. 1:4 (beta blockade predominates moderately)
D. 7:1 (alpha blockade predominates significantly)
E. Pure beta-blocker (no alpha blockade)
Show answer
Answer: B. Labetalol administered intravenously has an α:β blockade ratio of approximately 1:7, meaning beta-adrenergic blockade predominates significantly over alpha blockade. This contrasts with oral administration, which has a ratio closer to 1:3. The predominance of beta blockade makes labetalol useful in pregnancy-induced hypertension and aortic dissection, where controlled heart rate reduction is beneficial. It should be avoided in patients with bronchospasm or severe bradycardia. Carvedilol is the other commonly used combined α₁ and β-blocker.
Q41. Amiodarone toxicities
Long-term amiodarone therapy is most associated with which preoperative concern?
A. Thrombocytopenia, leukopenia, and bone marrow suppression
B. Pulmonary fibrosis, hypothyroidism, and hepatotoxicity
C. Renal failure, proteinuria, and tubular necrosis
D. Megaloblastic anemia, folate deficiency, and pancytopenia
E. Adrenal insufficiency, hypotension, and electrolyte disturbances
Show answer
Answer: B. Amiodarone is 40% iodine by weight and causes thyroid dysfunction (hypothyroidism or hyperthyroidism). Pulmonary toxicity manifests as interstitial pneumonitis progressing to fibrosis. Hepatotoxicity ranges from elevated transaminases to cirrhosis. Other important toxicities include optic neuropathy, blue-gray skin discoloration (hapten effect), peripheral neuropathy, bradycardia, heart block, and QT prolongation. Amiodarone is classified as Class III antiarrhythmic but exhibits Class I through IV effects. It does not cause thrombocytopenia, renal failure, megaloblastic anemia, or adrenal insufficiency.
Q42. Digoxin and hyperkalemia
A 78-year-old on digoxin develops nausea, confusion, and a serum K⁺ of 6.8 mEq/L after starting spironolactone. Why is hyperkalemia particularly worrisome in digoxin toxicity?
A. Digoxin causes intracellular potassium shift by blocking membrane transport proteins
B. Hyperkalemia indicates severe Na/K-ATPase inhibition and predicts worse digoxin toxicity
C. Hyperkalemia potentiates calcium binding at the digoxin receptor site directly
D. Digoxin acts directly on potassium channels to enhance extracellular potassium accumulation
E. Spironolactone displaces digoxin from albumin binding sites and increases free drug
Show answer
Answer: B. Digoxin inhibits the Na/K-ATPase pump, leading to extracellular potassium accumulation. The degree of hyperkalemia reflects the severity of Na/K-ATPase inhibition throughout the body. Hyperkalemia greater than 5.5 mEq/L in the setting of digoxin toxicity is an indication for digoxin immune Fab (Digibind) therapy. It is important to avoid calcium administration in digoxin toxicity because it can worsen cellular calcium overload and precipitate fatal arrhythmias. The combination of hyperkalemia and digoxin toxicity creates a particularly dangerous situation requiring prompt recognition and treatment.
Q43. TCA overdose and sodium bicarbonate
An adolescent presents with QRS widening, hypotension, and altered mental status after a tricyclic overdose. The most appropriate initial therapy is:
A. Lidocaine 1 mg/kg IV to stabilize cardiac sodium channels
B. Sodium bicarbonate 1–2 mEq/kg IV to reverse sodium channel blockade
C. Magnesium sulfate 2 g IV to correct electrolyte-mediated dysrhythmias
D. Norepinephrine infusion to restore mean arterial pressure and perfusion
E. Activated charcoal 1 g/kg PO to bind unabsorbed tricyclic agent
Show answer
Answer: B. Tricyclic antidepressants block cardiac fast sodium channels, causing QRS widening and dysrhythmias. Sodium bicarbonate is the most appropriate initial therapy because it raises serum pH, which favors the non-ionized form of the drug and reduces tissue binding, and it provides extracellular sodium that directly competes off the sodium channel blockade. Lidocaine and other sodium channel blockers worsen TCA toxicity by further blocking already-impaired channels. Norepinephrine may be needed for refractory hypotension but does not address the underlying sodium channel blockade. Magnesium is not indicated for TCA-induced dysrhythmias. Activated charcoal is useful only if given within 1–2 hours of ingestion and does not address acute cardiovascular toxicity.
Q44. Cyanide poisoning antidote of choice
A firefighter rescued from a structure fire is hypotensive with a lactate of 14 and a "cherry-red" skin. Carboxyhemoglobin is mildly elevated. Mixed venous oxygen saturation is 90%. The preferred antidote is:
A. Methylene blue, which reduces methemoglobin and restores oxygen-carrying capacity in cyanide poisoning
B. Sodium nitrite alone, which induces methemoglobin formation to bind cyanide and facilitate clearance
C. Hydroxocobalamin, which directly binds intracellular cyanide and forms cyanocobalamin for renal excretion
D. N-acetylcysteine, which replenishes glutathione stores and enhances hepatic detoxification of cyanide metabolites
E. Atropine plus pralidoxime, which reverses muscarinic effects and reactivates acetylcholinesterase inhibited by cyanide
Show answer
Answer: C. This firefighter has combined carbon monoxide and cyanide toxicity from smoke inhalation. The key diagnostic clue for cyanide poisoning is the elevated mixed venous oxygen saturation (90%), which reflects impaired cellular oxygen utilization due to cytochrome oxidase inhibition. The elevated lactate indicates severe lactic acidosis from anaerobic metabolism. Hydroxocobalamin is the preferred antidote because it directly binds intracellular cyanide to form cyanocobalamin (vitamin B12), which is then renally excreted. Critically, hydroxocobalamin does not impair oxygen-carrying capacity, unlike sodium nitrite, which induces methemoglobinemia. This is especially important in this patient who already has carbon monoxide poisoning with mildly elevated carboxyhemoglobin. Methylene blue treats methemoglobinemia, not cyanide toxicity. N-acetylcysteine is used for acetaminophen overdose. Atropine and pralidoxime treat organophosphate poisoning, not cyanide toxicity.
Q45. Organophosphate poisoning
A farmer presents with miosis, bradycardia, salivation, bronchorrhea, and muscle fasciculations. The most appropriate treatment is:
A. Atropine to reverse muscarinic effects and pralidoxime to regenerate cholinesterase before aging occurs
B. Physostigmine to reverse both muscarinic and nicotinic effects by inhibiting residual acetylcholinesterase activity
C. Edrophonium to diagnose cholinergic crisis and then atropine to reverse muscarinic receptor overstimulation
D. Glycopyrrolate to reverse muscarinic effects without crossing the blood-brain barrier or affecting nicotinic receptors
E. Activated charcoal alone to prevent further absorption if the exposure was recent and gastrointestinal
Show answer
Answer: A. Organophosphates irreversibly inhibit acetylcholinesterase, leading to accumulation of acetylcholine at both muscarinic and nicotinic receptors. The patient's miosis, bradycardia, salivation, and bronchorrhea reflect muscarinic overstimulation, while muscle fasciculations reflect nicotinic effects at the neuromuscular junction. Atropine is a competitive muscarinic antagonist that reverses secretions, bradycardia, miosis, and bronchospasm, but it does not address nicotinic effects. Pralidoxime is an oxime that regenerates acetylcholinesterase by cleaving the organophosphate-enzyme bond, but only if given before the bond "ages" (typically within 24 to 48 hours). Both agents are needed for complete treatment. Physostigmine is a cholinesterase inhibitor and would worsen toxicity. Edrophonium is a short-acting cholinesterase inhibitor used for myasthenia gravis diagnosis. Glycopyrrolate is a quaternary antimuscarinic that does not cross the blood-brain barrier and would not treat central effects. Activated charcoal may be useful as an adjunct for recent ingestions but is insufficient as sole therapy. Pyridostigmine is used for prophylaxis before exposure, not for acute treatment.
Q46. Acetaminophen toxicity
The antidote for acetaminophen toxicity works by:
A. Inhibiting CYP2E1 metabolism of acetaminophen to NAPQI
B. Replenishing glutathione stores to conjugate toxic NAPQI
C. Directly binding NAPQI to prevent hepatocellular protein damage
D. Enhancing renal excretion of acetaminophen and its metabolites
E. Blocking gastrointestinal absorption of remaining acetaminophen
Show answer
Answer: B. Acetaminophen is metabolized by CYP2E1 to NAPQI, a toxic intermediate that is normally conjugated with glutathione to form a safe, excretable product. In overdose, glutathione stores become depleted, allowing NAPQI to accumulate and bind to hepatocellular proteins, leading to fulminant hepatic necrosis. N-acetylcysteine (NAC) works by replenishing glutathione stores, thereby restoring the liver's capacity to detoxify NAPQI through conjugation. NAC does not inhibit CYP2E1, does not directly bind NAPQI itself, does not enhance renal excretion, and does not block absorption (though activated charcoal may be used for the latter purpose if given early).
Q47. Donepezil and succinylcholine
A 78-year-old on donepezil for Alzheimer disease receives succinylcholine for RSI. What is the expected effect?
A. Resistance to succinylcholine, requiring a larger dose for adequate paralysis
B. Prolonged duration of paralysis from reduced metabolism of succinylcholine
C. No effect on paralysis duration or depth of neuromuscular blockade
D. Profound bradycardia immediately upon administration of the succinylcholine bolus
E. Malignant hyperthermia triggered by interaction between donepezil and succinylcholine
Show answer
Answer: B. Donepezil is an acetylcholinesterase inhibitor that increases acetylcholine availability at the neuromuscular junction. Succinylcholine is metabolized by plasma cholinesterase (pseudocholinesterase), and acetylcholinesterase also contributes to its breakdown at the neuromuscular junction. By inhibiting acetylcholinesterase, donepezil reduces the metabolism of succinylcholine, leading to prolonged duration of paralysis from acetylcholine accumulation. This same mechanism causes resistance to non-depolarizing neuromuscular blocking drugs, as the increased acetylcholine competes with these agents at the receptor. Donepezil does not trigger malignant hyperthermia and while bradycardia can occur with succinylcholine, it is not specifically related to donepezil interaction.
Q48. Alpha-methyltyrosine indication
Alpha-methyltyrosine (metyrosine) is used preoperatively in patients with:
A. Pheochromocytoma to inhibit catecholamine synthesis preoperatively
B. Hyperthyroidism to inhibit thyroid hormone synthesis preoperatively
C. Carcinoid syndrome to inhibit serotonin synthesis preoperatively
D. Conn syndrome to inhibit aldosterone synthesis preoperatively
E. Acromegaly to inhibit growth hormone synthesis preoperatively
Show answer
Answer: A. Metyrosine (alpha-methyltyrosine) inhibits tyrosine hydroxylase, which is the rate-limiting step in catecholamine synthesis, and is used only in pheochromocytoma for preoperative preparation. Standard preoperative pheochromocytoma preparation also includes alpha-blockade with phenoxybenzamine or doxazosin, followed by beta-blockade once adequate alpha-blockade has been achieved. The other conditions listed use different preoperative management strategies: hyperthyroidism uses antithyroid drugs like methimazole or propylthiouracil; carcinoid syndrome uses octreotide; Conn syndrome (primary hyperaldosteronism) uses spironolactone or eplerenone; and acromegaly uses octreotide or pasireotide.
Q49. Thiazide diuretic effect on electrolytes
Hydrochlorothiazide therapy classically causes which electrolyte pattern?
A. Hyperkalemia, hypocalcemia, metabolic acidosis, hypermagnesemia
B. Hypokalemia, hyponatremia, hypercalcemia, metabolic alkalosis
C. Hyperkalemia, hypocalcemia, metabolic alkalosis, hyperphosphatemia
D. Hypokalemia, hypercalcemia, hyperphosphatemia, metabolic acidosis
E. Hypernatremia, hypokalemia, metabolic acidosis, hypocalcemia
Show answer
Answer: B. Hydrochlorothiazide causes the classic electrolyte pattern of hypokalemia, hyponatremia, hypercalcemia, and metabolic alkalosis. The mnemonic "HyperGLUC, hypoKMN" captures the full profile: hyperglycemia, hyperlipidemia, hyperuricemia, and hypercalcemia; hypokalemia, hyponatremia, hypomagnesemia, and metabolic alkalosis. The mechanism involves blocking the Na/Cl cotransporter in the distal convoluted tubule while also stimulating calcium reabsorption. Thiazides are contraindicated in patients with sulfa allergies.
Q50. Amiloride / triamterene
Amiloride and triamterene cause potassium retention by:
A. Aldosterone receptor antagonism in collecting duct principal cells
B. Blocking the epithelial sodium channel in collecting duct principal cells
C. Inhibiting carbonic anhydrase in proximal tubule epithelial cells
D. Blocking the Na/K/Cl cotransporter in thick ascending limb cells
E. Inhibiting 11-β-hydroxysteroid dehydrogenase type 2 in principal cells
Show answer
Answer: B. Amiloride and triamterene block the epithelial sodium channel (ENaC) in collecting duct principal cells, preventing sodium reabsorption. This eliminates the luminal-negative electrical gradient that normally drives potassium secretion into the tubular lumen, resulting in potassium retention. In contrast, spironolactone and eplerenone cause potassium retention through aldosterone receptor antagonism. Amiloride and triamterene are useful in treating Liddle syndrome, a genetic condition characterized by constitutively active ENaC channels.
Q51. NSAID mechanism for analgesia
NSAID analgesia is primarily mediated through:
A. Agonism of μ-opioid receptors in the central nervous system and spinal cord
B. Inhibition of cyclooxygenase leading to reduced prostaglandin synthesis and nociceptor sensitization
C. Antagonism of NMDA receptors in the dorsal horn of the spinal cord
D. Potentiation of GABAₐ receptors in the central nervous system and spinal cord
E. Blockade of voltage-gated sodium channels in the dorsal horn of spinal cord
Show answer
Answer: B. NSAIDs inhibit cyclooxygenase (COX) enzymes, which reduces the synthesis of prostaglandins, especially PGE₂. This decrease in prostaglandins reduces sensitization of peripheral nociceptors and decreases central pain transmission. COX-1 is constitutively expressed and maintains gastric mucosal integrity and platelet thromboxane A₂ production. COX-2 is inducible and mediates inflammation. COX-2 selective inhibitors spare platelet function but carry increased thrombotic risk compared to non-selective NSAIDs.
Q52. Gabapentin mechanism
Gabapentin's analgesic effect is mediated through:
A. Agonism at GABA-A and GABA-B receptors in the dorsal horn
B. Inhibition of α₂δ subunit of voltage-gated calcium channels in the dorsal horn
C. Blockade of voltage-gated sodium channels in peripheral sensory neurons
D. Antagonism at NMDA receptors in the spinal cord dorsal horn
E. Agonism at mu and kappa opioid receptors in the central nervous system
Show answer
Answer: B. Despite its name, gabapentin does not act on GABA receptors. It inhibits the α₂δ subunit of high-voltage-activated calcium channels, which decreases presynaptic release of excitatory neurotransmitters including glutamate and substance P, thereby reducing pain transmission. This mechanism makes it particularly useful for neuropathic pain conditions such as postherpetic neuralgia and diabetic neuropathy. The main side effects include sedation and ataxia, which are dose-dependent and typically improve with continued use.
Q53. Dantrolene mechanism
Dantrolene treats malignant hyperthermia by:
A. Blocking voltage-gated sodium channels on skeletal muscle membranes
B. Antagonizing the ryanodine receptor on the sarcoplasmic reticulum
C. Increasing calcium reuptake into the sarcoplasmic reticulum via SERCA
D. Blocking acetylcholine release at the neuromuscular junction presynaptically
E. Direct beta-adrenergic receptor blockade on cardiac and skeletal muscle
Show answer
Answer: B. Dantrolene antagonizes RYR1 (the ryanodine receptor) on the sarcoplasmic reticulum, which decreases calcium release into the cytoplasm and thereby reduces skeletal muscle contraction. This mechanism makes it the definitive treatment for malignant hyperthermia. Dantrolene is also used in neuroleptic malignant syndrome, severe spasticity, and has been used in serotonin syndrome and ecstasy overdose. Initial dosing is 2.5 mg/kg IV every 5 to 10 minutes up to 10 mg/kg total, followed by maintenance dosing of 1 mg/kg every 4 to 6 hours or 0.25 mg/kg/hr for 24 to 48 hours to prevent recrudescence.
Q54. Inhaled anesthetic effect on neuromuscular blockade
Which volatile most potentiates non-depolarizing NMB at 1 MAC?
A. Nitrous oxide, producing approximately 20% potentiation of neuromuscular blockade
B. Halothane, producing approximately 30% potentiation of neuromuscular blockade
C. Sevoflurane, producing approximately 40% potentiation of neuromuscular blockade
D. Isoflurane, producing approximately 40% potentiation of neuromuscular blockade
E. Desflurane, producing approximately 60% potentiation of neuromuscular blockade
Show answer
Answer: E. At 1 MAC, desflurane produces the greatest potentiation of non-depolarizing neuromuscular blockade at approximately 60%, followed by isoflurane and sevoflurane at approximately 40% each, halothane at approximately 30%, and nitrous oxide at approximately 20%. The mechanism involves direct skeletal muscle relaxation combined with synergistic effects at the neuromuscular junction. This potentiation is more pronounced with aminosteroid neuromuscular blockers (such as rocuronium and vecuronium) than with benzylisoquinolinium compounds (such as atracurium and cisatracurium). Clinically, this means that lower doses of neuromuscular blocking agents may be required when using potent volatile anesthetics, and recovery from blockade may be prolonged.
Q55. Antibiotics that prolong NMB
Which class of antibiotic most prolongs non-depolarizing NMB?
A. Cephalosporins
B. Aminoglycosides
C. Penicillins
D. Fluoroquinolones
E. Vancomycin
Show answer
Answer: B. Aminoglycosides are the antibiotic class that most significantly prolongs non-depolarizing neuromuscular blockade. They prolong NMB by inhibiting presynaptic acetylcholine release and depressing postjunctional receptor sensitivity at the neuromuscular junction. Other antibiotics that can prolong NMB include polymyxins, tetracyclines, lincomycin, and clindamycin, though aminoglycosides produce the most clinically significant effect. Calcium administration may partially reverse the neuromuscular blockade caused by aminoglycosides. Cephalosporins, penicillins, fluoroquinolones, and vancomycin do not have clinically significant effects on neuromuscular blockade.
Q56. Lidocaine maximum dose with epinephrine
The maximum infiltration dose of lidocaine with epinephrine is approximately:
A. 3 mg/kg
B. 4.5 mg/kg
C. 7 mg/kg
D. 12 mg/kg
E. 15 mg/kg
Show answer
Answer: C. The maximum infiltration dose of lidocaine with epinephrine is 7 mg/kg (maximum absolute dose 500 mg). Without epinephrine, the maximum dose is 4.5 mg/kg (maximum absolute dose 300 mg). The addition of epinephrine causes vasoconstriction, which slows systemic absorption and allows for higher dosing. For comparison, other local anesthetic maximum doses include: bupivacaine 2.5 mg/kg without epinephrine and 3 mg/kg with epinephrine; ropivacaine 3 mg/kg; and chloroprocaine 11 mg/kg without epinephrine and 14 mg/kg with epinephrine.
Q57. Local anesthetic onset, potency, duration determinants
Which property primarily determines local anesthetic potency?
A. pKa, which determines the fraction of unionized drug available for nerve membrane penetration
B. Lipid solubility, which determines the ability to penetrate lipophilic nerve membrane structures
C. Protein binding, which determines the duration of binding to sodium channels in nerves
D. Molecular weight, which determines the rate of diffusion through interstitial tissue to nerves
E. Vasoconstrictor co-administration, which determines the local tissue concentration achieved at target nerves
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Answer: B. Lipid solubility is the primary determinant of local anesthetic potency because it governs the ability of the drug to penetrate the lipophilic nerve membrane. In contrast, pKa determines onset of action: drugs with pKa closer to physiologic pH have a greater unionized fraction available for membrane penetration, resulting in faster onset. Adding bicarbonate to lidocaine raises pH and speeds onset by this mechanism. Protein binding determines duration of action by affecting how long the drug remains bound to sodium channels. Vasoconstrictor co-administration prolongs duration by slowing systemic absorption from the injection site.
Q58. Bupivacaine cardiotoxicity vs ropivacaine
Why is ropivacaine considered less cardiotoxic than bupivacaine?
A. Lower lipid solubility resulting in reduced myocardial tissue accumulation and decreased cardiac sodium channel blockade
B. Pure S-enantiomer formulation with faster dissociation kinetics from cardiac sodium channels compared to racemic bupivacaine
C. Higher pKa value leading to greater ionization at physiologic pH and reduced penetration into cardiac myocytes
D. Predominantly hepatic clearance with less active metabolite accumulation compared to bupivacaine's renal elimination pathway
E. Lower degree of plasma protein binding allowing for greater free drug availability and faster redistribution from myocardium
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Answer: B. Ropivacaine is a pure S(–) enantiomer that dissociates more rapidly from cardiac sodium channels than racemic bupivacaine, which contains both R(+) and S(–) enantiomers. This faster dissociation kinetics provides a wider safety margin in local anesthetic systemic toxicity (LAST). The R(+) enantiomer in bupivacaine binds more avidly to cardiac sodium channels and dissociates more slowly, contributing to greater cardiotoxicity. Both ropivacaine and bupivacaine are heavily protein-bound, which actually makes them safer in pregnancy than lidocaine because less free drug crosses the placenta. The stereoselective difference in sodium channel binding is the primary mechanism explaining ropivacaine's improved cardiac safety profile.
Q59. Lidocaine for ion trapping in fetus
Why is lidocaine particularly concerning in the setting of fetal acidosis?
A. Acidic fetal environment increases oxygen consumption and potentiates lidocaine cardiotoxicity
B. Acidic fetal serum ionizes and traps lidocaine, preventing back-diffusion across placenta
C. Acidic fetal environment enhances lidocaine binding to fetal cardiac sodium channels
D. Acidic fetal serum prolongs lidocaine elimination half-life and delays hepatic metabolism
E. Acidic fetal environment impairs placental glucose transport and potentiates lidocaine toxicity
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Answer: B. In fetal acidosis, lidocaine becomes ionized (protonated) in the acidic fetal environment and becomes trapped on the fetal side of the placenta because the ionized form cannot readily cross lipid membranes to return to maternal circulation. This ion trapping leads to accumulation and higher fetal drug levels, increasing the risk of toxicity. In contrast, ropivacaine and bupivacaine cross the placenta less readily due to their high protein binding, making them safer alternatives in this setting.
Q60. CYP3A4 induction and warfarin
Which medication is most likely to decrease the effect of warfarin via CYP3A4 induction?
A. Rifampin, a potent CYP3A4 inducer that accelerates warfarin metabolism and reduces anticoagulant effect
B. Fluconazole, a potent CYP3A4 inhibitor that decreases warfarin metabolism and increases anticoagulant effect
C. Ciprofloxacin, a moderate CYP3A4 inhibitor that decreases warfarin metabolism and increases anticoagulant effect
D. Amiodarone, a potent CYP3A4 inhibitor that decreases warfarin metabolism and increases anticoagulant effect
E. Omeprazole, a moderate CYP3A4 inhibitor that decreases warfarin metabolism and increases anticoagulant effect
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Answer: A. Rifampin is a strong CYP3A4 inducer that accelerates warfarin metabolism, thereby reducing INR and decreasing anticoagulant effect. Other important CYP inducers include phenytoin, carbamazepine, phenobarbital, St. John's wort, and chronic alcohol use. In contrast, fluconazole, ciprofloxacin, amiodarone, and omeprazole are all CYP inhibitors that decrease warfarin metabolism, leading to increased INR and enhanced anticoagulant effect with potential bleeding risk.
Q61. Codeine and CYP2D6
Codeine is converted to its active metabolite morphine by:
A. CYP3A4, which accounts for the majority of codeine metabolism
B. CYP2D6, which accounts for approximately 5–15% of codeine metabolism
C. CYP2C9, which accounts for minor pathways of codeine metabolism
D. UGT2B7, which accounts for the glucuronidation of codeine metabolites
E. Plasma esterases, which account for hydrolysis of codeine's ester
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Answer: B. CYP2D6 converts codeine to its active metabolite morphine, accounting for approximately 5–15% of codeine metabolism. This pathway has important clinical implications based on genetic polymorphisms. Ultra-rapid metabolizers can develop respiratory depression at standard doses, which is particularly relevant in nursing mothers whose breast milk can contain high morphine concentrations leading to infant respiratory arrest. Poor metabolizers obtain little to no analgesia from codeine because they cannot effectively convert it to morphine. The FDA contraindicates codeine use in tonsillectomy and adenoidectomy patients under 12 years of age due to risk of respiratory depression in ultra-rapid metabolizers.
Q62. Sevoflurane and Compound A
Compound A formation with sevoflurane is increased by which combination?
A. High fresh gas flow with fresh soda lime containing strong base
B. Low fresh gas flow with desiccated absorbent containing strong base
C. High fresh gas flow with desflurane and desiccated absorbent
D. Low fresh gas flow with sevoflurane at room temperature
E. High fresh gas flow with calcium hydroxide–only absorbent
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Answer: B. Compound A formation rises with low fresh gas flow, desiccated absorbents, strong bases (NaOH, KOH in traditional soda lime), and higher temperatures. The combination of low flow and desiccated absorbent with strong base maximizes Compound A production. High fresh gas flow dilutes and removes Compound A, reducing accumulation. Calcium hydroxide–only absorbents (such as Amsorb) lack strong bases and produce minimal Compound A. Desflurane does not produce Compound A. Room temperature does not enhance formation compared to the elevated temperatures in the CO2 absorbent canister. Compound A showed theoretical nephrotoxicity in animals, but humans appear less susceptible. Current recommendations remain fresh gas flow ≥2 L/min when using sevoflurane >2 MAC-hours to minimize exposure.