Introduction: Amyl nitrite is a volatile organic nitrite and an important vasodilator studied in pharmacology. B. Pharm students should understand its mechanism of action as a nitric oxide (NO) donor, rapid inhalational absorption, short onset and duration, clinical uses (acute angina relief and cyanide poisoning adjunct), characteristic adverse effects (methemoglobinemia, headache, hypotension, reflex tachycardia), interactions (notably with PDE5 inhibitors), and pharmacokinetics. Knowledge of chemical class differences between nitrites and nitrates, metabolism, antidotes for complications, and dosage forms is essential for safe therapeutic use. This review links theory to practice and exam-focused facts. ‘Now let’s test your knowledge with 30 MCQs on this topic.’
Q1. Which best describes the primary mechanism by which amyl nitrite causes vasodilation?
- Inhibition of angiotensin-converting enzyme (ACE)
- Activation of guanylate cyclase via nitric oxide (NO) increasing cGMP
- Blockade of beta-1 adrenergic receptors
- Calcium channel blockade at L-type channels
Correct Answer: Activation of guanylate cyclase via nitric oxide (NO) increasing cGMP
Q2. What is the usual onset and duration of action after inhalation of amyl nitrite?
- Onset 30 seconds; duration 2–5 minutes
- Onset 15 minutes; duration 4–6 hours
- Onset 2–4 hours; duration 24 hours
- Onset 5–10 minutes; duration 30–60 minutes
Correct Answer: Onset 30 seconds; duration 2–5 minutes
Q3. Which clinical use of amyl nitrite is historically well known and still relevant in emergencies?
- First-line treatment of chronic hypertension
- Adjunctive therapy in acute cyanide poisoning
- Long-term management of heart failure
- Treatment of bacterial endocarditis
Correct Answer: Adjunctive therapy in acute cyanide poisoning
Q4. Which adverse effect is most directly caused by the oxidizing action of amyl nitrite?
- Hyperkalemia
- Methemoglobinemia
- Hypoglycemia
- Neutropenia
Correct Answer: Methemoglobinemia
Q5. Why is concomitant use of amyl nitrite and sildenafil contraindicated?
- Increased risk of serotonin syndrome
- Severe and potentially life-threatening hypotension due to additive cGMP effects
- Increased risk of methemoglobinemia only when combined
- Enhanced renal toxicity leading to acute kidney injury
Correct Answer: Severe and potentially life-threatening hypotension due to additive cGMP effects
Q6. Which laboratory or clinical sign is characteristic of clinically significant methemoglobinemia?
- Bright red arterial blood that does not darken on standing
- Chocolate-brown colored blood with low pulse oximeter reading around 85%
- Marked leukocytosis and high fever
- Significant hematuria with red cell casts
Correct Answer: Chocolate-brown colored blood with low pulse oximeter reading around 85%
Q7. Which antidote is the treatment of choice for symptomatic methemoglobinemia caused by amyl nitrite (when not contraindicated)?
- Naloxone
- Methylene blue
- N-acetylcysteine
- Atropine
Correct Answer: Methylene blue
Q8. Which patient condition makes methylene blue less effective or potentially harmful for treating methemoglobinemia?
- G6PD deficiency
- Hypothyroidism
- Hyperlipidemia
- Hypokalemia
Correct Answer: G6PD deficiency
Q9. Which statement correctly contrasts organic nitrites (like amyl nitrite) and organic nitrates (like nitroglycerin)?
- Only nitrates produce NO; nitrites have no NO-related activity
- Nitrites act rapidly by inhalation and have very short duration; nitrates often require enzymatic biotransformation and have longer duration
- Nitrates cause methemoglobinemia commonly whereas nitrites do not
- Nitrites are prodrugs activated by mitochondrial aldehyde dehydrogenase (ALDH2)
Correct Answer: Nitrites act rapidly by inhalation and have very short duration; nitrates often require enzymatic biotransformation and have longer duration
Q10. How does amyl nitrite help in cyanide poisoning?
- It directly neutralizes cyanide by chemical decomposition
- It converts hemoglobin to methemoglobin, which binds cyanide ions, sequestering them away from cytochrome oxidase
- It increases renal excretion of cyanide
- It enhances hepatic detoxification of cyanide to thiocyanate
Correct Answer: It converts hemoglobin to methemoglobin, which binds cyanide ions, sequestering them away from cytochrome oxidase
Q11. Which physiological effect predominates after an inhaled dose of amyl nitrite?
- Preload reduction by venodilation more than afterload reduction
- Marked increase in cardiac contractility
- Selective renal vasoconstriction
- Direct increase in systemic vascular resistance
Correct Answer: Preload reduction by venodilation more than afterload reduction
Q12. Which enzyme is primarily responsible for bioactivation of organic nitrates like nitroglycerin but is not required for amyl nitrite action?
- Mitochondrial aldehyde dehydrogenase (ALDH2)
- Monoamine oxidase (MAO)
- Cytochrome P450 CYP3A4
- Glutathione S-transferase
Correct Answer: Mitochondrial aldehyde dehydrogenase (ALDH2)
Q13. Which of the following is a common acute adverse effect after inhalation of amyl nitrite?
- Persistent bradycardia for days
- Severe hyperglycemia
- Headache and facial flushing
- Prolonged QT interval leading to torsades de pointes
Correct Answer: Headache and facial flushing
Q14. Which monitoring parameter is most useful to detect clinically significant methemoglobinemia?
- Serum creatinine
- Co-oximetry measurement of methemoglobin fraction
- 24-hour urine sodium
- Serum troponin I
Correct Answer: Co-oximetry measurement of methemoglobin fraction
Q15. Which statement about tolerance to vasodilators is correct?
- Tolerance develops rapidly with continuous exposure to organic nitrates, and cross-tolerance can occur with other NO donors
- Tolerance does not occur with any nitrate or nitrite compounds
- Tolerance is only an issue with intravenous amyl nitrite
- Tolerance results in permanent loss of drug effect that cannot be reversed
Correct Answer: Tolerance develops rapidly with continuous exposure to organic nitrates, and cross-tolerance can occur with other NO donors
Q16. Which pharmacokinetic property best describes amyl nitrite?
- Poorly absorbed via lungs and requires oral dosing
- Rapid pulmonary absorption with very short systemic half-life
- Extensive enterohepatic recirculation leading to prolonged effect
- Exclusive renal excretion as unchanged drug
Correct Answer: Rapid pulmonary absorption with very short systemic half-life
Q17. Which contraindication is especially important when considering amyl nitrite use?
- Concurrent use of sildenafil or other PDE5 inhibitors
- History of migraine headaches
- Concomitant use of beta blockers
- Age over 65 years only
Correct Answer: Concurrent use of sildenafil or other PDE5 inhibitors
Q18. What is the immediate cardiovascular response to amyl nitrite inhalation?
- Bradycardia with hypertension
- Transient hypotension with reflex tachycardia
- Progressive heart block
- Marked increase in systemic vascular resistance
Correct Answer: Transient hypotension with reflex tachycardia
Q19. In forensic or recreational contexts, “poppers” refers to which class of compounds?
- Alkyl nitrites such as amyl nitrite
- Benzodiazepines
- Organophosphate pesticides
- Short-chain fatty acids
Correct Answer: Alkyl nitrites such as amyl nitrite
Q20. Which biochemical change in red blood cells occurs when methemoglobin forms?
- Heme iron is oxidized from Fe2+ to Fe3+, reducing oxygen-binding capacity
- Heme iron is reduced from Fe3+ to Fe2+, increasing oxygen delivery
- Globin chains are denatured and precipitate as Heinz bodies in all cases
- Hemoglobin is glycosylated causing increased oxygen dissociation
Correct Answer: Heme iron is oxidized from Fe2+ to Fe3+, reducing oxygen-binding capacity
Q21. Which of the following drugs can exacerbate methemoglobinemia risk when combined with amyl nitrite?
- Prilocaine
- Furosemide
- Warfarin
- Metformin
Correct Answer: Prilocaine
Q22. Which physiological change reduces oxygen delivery despite normal PaO2 in methemoglobinemia?
- Decreased cardiac output only
- Reduced hemoglobin oxygen-carrying capacity and left shift of oxyhemoglobin dissociation curve
- Increased 2,3-BPG levels causing right shift
- Increased dissolved oxygen in plasma compensates fully
Correct Answer: Reduced hemoglobin oxygen-carrying capacity and left shift of oxyhemoglobin dissociation curve
Q23. Which emergency step is appropriate immediately after suspected cyanide exposure when amyl nitrite is available?
- Administer oral activated charcoal
- Inhale amyl nitrite to induce methemoglobinemia as a temporizing measure
- Administer high-dose insulin
- Give intravenous calcium chloride
Correct Answer: Inhale amyl nitrite to induce methemoglobinemia as a temporizing measure
Q24. Which metabolic product is primarily responsible for the vasodilatory effect of amyl nitrite?
- Nitrite ion (NO2−) and subsequent nitric oxide (NO) formation
- Sulfate conjugates that stimulate cAMP
- Hydroxylated metabolites that block adrenergic receptors
- Glucuronide metabolites that increase calcium entry into smooth muscle
Correct Answer: Nitrite ion (NO2−) and subsequent nitric oxide (NO) formation
Q25. Which clinical situation is amyl nitrite least appropriate for?
- Immediate relief of an acute anginal attack in a monitored setting
- Adjunct in suspected cyanide poisoning while definitive therapy is arranged
- Chronic long-term management of stable angina as sole maintenance therapy
- Short-term reduction of severe peripheral vasospasm
Correct Answer: Chronic long-term management of stable angina as sole maintenance therapy
Q26. Which precaution should be taken when using amyl nitrite in elderly patients?
- No precautions—age has no impact on response
- Use caution because of increased susceptibility to orthostatic hypotension and syncope
- Double the dose because of decreased pulmonary absorption
- Administer only intravenously to avoid variability
Correct Answer: Use caution because of increased susceptibility to orthostatic hypotension and syncope
Q27. Which molecule inside vascular smooth muscle directly decreases cytosolic calcium to cause relaxation following NO stimulation?
- cGMP-dependent protein kinase (PKG) activation leading to reduced Ca2+ levels
- Increased IP3 production
- Activation of phospholipase A2
- Direct blockade of ryanodine receptors increasing Ca2+
Correct Answer: cGMP-dependent protein kinase (PKG) activation leading to reduced Ca2+ levels
Q28. Which test result would most specifically confirm a diagnosis of methemoglobinemia?
- Arterial blood gas showing low PaO2
- Co-oximetry showing elevated methemoglobin percentage
- Elevated D-dimer
- Low serum bicarbonate only
Correct Answer: Co-oximetry showing elevated methemoglobin percentage
Q29. Which statement about occupational or recreational exposure to amyl nitrite is true?
- Recreational inhalation poses no cardiovascular risk
- Repeated exposure can cause headaches, syncope, and chronic hematologic effects such as methemoglobinemia
- There is no abuse potential for inhaled nitrites
- Exposure is primarily associated with renal failure as the main chronic effect
Correct Answer: Repeated exposure can cause headaches, syncope, and chronic hematologic effects such as methemoglobinemia
Q30. In a patient with severe hypotension after inadvertent excess inhalation of amyl nitrite, which immediate measure is appropriate?
- Give a standard long-acting nitrate to counteract effects
- Place patient supine, provide oxygen, and manage with IV fluids and vasopressors if needed
- Administer high-dose oral beta blockers
- Induce emesis to remove the drug
Correct Answer: Place patient supine, provide oxygen, and manage with IV fluids and vasopressors if needed
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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