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Amyl Nitrite

Pronunciation

(AM il NYE trite)

Index Terms

  • Isoamyl Nitrite

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Liquid, for inhalation: USP: 85% to 103% (0.3 mL)

Pharmacologic Category

  • Antianginal Agent
  • Antidote
  • Vasodilator

Pharmacology

Relaxes vascular smooth muscle; decreases venous ratios and arterial blood pressure; reduces left ventricular work; decreases myocardial O2 consumption. When used for cyanide poisoning, amyl nitrite promotes the formation of methemoglobin which competes with cytochrome oxidase for the cyanide ion. Cyanide combines with methemoglobin to form cyanomethemoglobin, thereby freeing the cytochrome oxidase and allowing aerobic metabolism to continue.

Absorption

Inhalation: Readily absorbed through respiratory tract

Metabolism

In the liver to form inorganic nitrates (less potent)

Excretion

Urine (~33%)

Onset of Action

Angina: Within 30 seconds

Duration of Action

Angina: 3-15 minutes; Pharmacologic provocation of latent left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM): ~30 seconds (Reagan, 2005)

Half-Life Elimination

Amyl nitrite: <1 hour; Methemoglobin: 1 hour

Use: Labeled Indications

Coronary vasodilator in angina pectoris

Note: Given the widespread use of newer nitrate compounds, the use of amyl nitrite for patients experiencing angina pectoris has fallen out of favor.

Use: Unlabeled

Adjunct treatment of cyanide toxicity; produce changes in the intensity of heart murmurs; provocation of latent left ventricular outflow tract (LVOT) gradient during echocardiography in patients with hypertrophic cardiomyopathy (HCM)

Contraindications

Glaucoma; recent head trauma or cerebral hemorrhage; pregnancy

Dosing: Adult

Angina: Inhalation: 2 to 6 nasal inhalations from 1 crushed ampul; may repeat in 3 to 5 minutes

Cyanide toxicity (off-label use): Inhalation: 0.3 mL ampul crushed into a gauze pad and placed in front of the patient’s mouth (or endotracheal tube if patient is intubated) to inhale over 15 to 30 seconds; repeat every minute until sodium nitrite can be administered (Mokhlesi, 2003). Note: Must separate administrations by at least 30 seconds to allow for adequate oxygenation; each ampul will last for ~3 minutes. Amyl nitrite is a temporary intervention that should only be used until IV sodium nitrite infusion is ready for administration (ATSDR).

Pharmacologic provocation of latent left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM) (off-label use): Nasal inhalation: 3 to 4 deep inhalations from 1 crushed ampul over a 10 to 15 second period (Gersh, 2011; Nagueh, 2011; Reagan, 2005). Note: The use of more physiologic testing (eg, treadmill testing with Doppler echocardiography) may be preferred over amyl nitrite inhalation (Maron, 2003; Nagueh, 2011).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Cyanide toxicity (off-label use): Refer to adult dosing.

Administration

Administer nasally via inhalation. The patient should be lying down during administration. Crush the ampul in a gauze pad and place in front of patient’s mouth (or endotracheal tube if intubated) and allow patient to inhale for 15 to 30 seconds; repeat every minute until sodium nitrite can be administered. One ampul lasts for ~3 minutes.

Storage

Store in a cool place at 2°C to 8°C (36°F to 46°F). Protect from light. Contents are flammable; protect from open flame or spark.

Drug Interactions

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when nitric oxide is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the vasodilatory effect of Amyl Nitrite. Avoid combination

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Riociguat: Amyl Nitrite may enhance the hypotensive effect of Riociguat. Avoid combination

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Monitor therapy

Tetracaine (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Cerebral ischemia, facial flushing, hypotension, orthostatic hypotension, shock, syncope, tachycardia, vasodilatation

Central nervous system: Dizziness, headache, increased intracranial pressure, restlessness

Dermatologic: Dermatitis, diaphoresis, pallor, skin irritation

Gastrointestinal: Fecal incontinence, nausea, vomiting

Genitourinary: Urinary incontinence

Hematologic & oncologic: Hemolytic anemia, methemoglobinemia

Neuromuscular & skeletal: Weakness

Ophthalmic: Eye irritation, increased intraocular pressure

Warnings/Precautions

Concerns related to adverse effects:

• Hypotension: Amyl nitrite may cause severe hypotension resulting in diminished oxygen-carrying capacity; serious adverse effects may occur at doses less than the recommended therapeutic dose. Monitor for adequate perfusion and oxygenation; ensure patient is euvolemic. Use with caution in patients where the diagnosis of cyanide poisoning is uncertain, patients with preexisting diminished oxygen or cardiovascular reserve (eg, smoke inhalation victims, anemia, substantial blood loss, and cardiac or respiratory compromise) and in patients who may be susceptible to injury from vasodilation; the use of hydroxocobalamin is recommended in these patients.

• Methemoglobinemia: Amyl nitrite may cause methemoglobin formation resulting in diminished oxygen-carrying capacity; serious adverse effects may occur at doses less than the recommended therapeutic dose. Monitor for adequate perfusion and oxygenation. Use with caution in patients where the diagnosis of cyanide poisoning is uncertain, patients with preexisting diminished oxygen or cardiovascular reserve (eg, smoke inhalation victims, anemia, substantial blood loss, and cardiac or respiratory compromise), and in patients at greater risk for developing methemoglobinemia (eg, congenital methemoglobin reductase deficiency); the use of hydroxocobalamin is recommended in these patients. Use with caution with concomitant medications known to cause methemoglobinemia (eg, nitroglycerin, phenazopyridine).

Disease-related concerns:

• Aortic stenosis: Use with extreme caution or avoid in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia; considered by some to be a contraindication (Reagan, 2005).

• Cardiovascular disease: Use with caution in patients with coronary artery disease and patients with hypotension. Transient episodes of dizziness, weakness, syncope, and cerebral ischemia secondary to postural hypotension may occur.

• Increased intracranial pressure: Use with caution in patients with increased intracranial pressure; use is contraindicated in patient with recent head trauma or cerebral hemorrhage.

Special populations:

• Fire victims: Fire victims may present with both cyanide and carbon monoxide poisoning. In these patients, the induction of methemoglobinemia (due to amyl nitrite) is contraindicated until carbon monoxide levels return to normal due to the risk of tissue hypoxia. Methemoglobinemia decreases the oxygen-carrying capacity of hemoglobin and the presence of carbon monoxide prevents hemoglobin from releasing oxygen to the tissues. In this scenario, sodium thiosulfate may be used alone to promote the clearance of cyanide. Hydroxocobalamin, however, should be considered to avoid the nitrite-related problems and because sodium thiosulfate has a slow onset of action.

• Pediatric: Methemoglobin reductase, which is responsible for converting methemoglobin back to hemoglobin, has reduced activity in pediatric patients. In addition, infants and young children have some proportion of fetal hemoglobin which forms methemoglobin more readily than adult hemoglobin. Therefore, pediatric patients (eg, neonates and infants <6 months) are more susceptible to excessive nitrite-induced methemoglobinemia. Hydroxocobalamin will circumvent this problem and may be a more effective and rapid alternative.

• Pregnancy: Nitrites should be avoided due to fetal hemoglobin's susceptibility to oxidative stress.

Other warnings/precautions:

• Appropriate use: Cyanide poisoning: Due to the risk for serious adverse effects, use with caution in patients where the diagnosis of cyanide poisoning is uncertain. However, if clinical suspicion of cyanide poisoning is high, treatment should not be delayed. Treatment of cyanide poisoning should include external decontamination and supportive therapy. Consider consultation with a poison control center at 1-800-222-1222.

• Initiation of treatment: Collection of pretreatment blood cyanide concentrations does not preclude administration and should not delay administration in the emergency management of highly suspected or confirmed cyanide toxicity. Pretreatment levels may be useful as postinfusion levels may be inaccurate.

• Return of symptoms: Patients receiving treatment for acute cyanide toxicity must be monitored for return of symptoms for 24-48 hours; repeat therapy should be administered if symptoms return.

• Smoke inhalation: Use nitrites cautiously in patients with cyanide poisoning related to smoke inhalation because methemoglobinemia and carboxyhemoglobinemia may worsen oxygen-carrying capacity.

Monitoring Parameters

Monitor blood pressure and heart rate during therapy

Cyanide poisoning: Monitor for at least 24-48 hours after administration; blood pressure and heart rate during and after infusion; hemoglobin/hematocrit; co-oximetry; serum lactate levels; venous-arterial PO2 gradient; serum methemoglobin and oxyhemoglobin. Pretreatment cyanide levels may be useful diagnostically.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Because amyl nitrite significantly decreases systemic blood pressure and therefore blood flow to the fetus, use is contraindicated in pregnancy (per manufacturer). In addition, fetal hemoglobin may be more susceptible methemoglobin conversion (Valenzuela, 1986).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience loss of strength and energy, flushing, or headache. Have patient report immediately to prescriber severe dizziness, passing out, urinary or fecal incontinence, pale skin, blue skin or nails, shortness of breath, cold sweats, tachycardia, agitation, severe vomiting, or severe nausea (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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