Doxapram Hydrochloride

Respiratory stimulant Analeptic

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog IV 1-5 mg/kg (for anesthesia-induced respiratory depression) Single dose; may repeat in 5-10 minutes if needed Duration: Short-term use (minutes)
Notes: For neonates: 1-2 drops of 20 mg/mL solution on the tongue or 0.1-0.2 mg/kg IV.
Cat IV 1-5 mg/kg Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For neonates: 1-2 drops of 20 mg/mL solution on the tongue or 0.1-0.2 mg/kg IV.
Horse IV 0.5-1 mg/kg (foals) Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For adult horses: 0.5 mg/kg IV for respiratory stimulation.
Cattle IV 0.5-1 mg/kg (calves) Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For adult cattle: 0.5 mg/kg IV.
Small Ruminants (sheep, goats) IV 0.5-1 mg/kg Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For neonates: 0.1-0.2 mg/kg IV or sublingual.
Rabbit IV 1-2 mg/kg Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For neonates: 0.1-0.2 mg/kg IV or sublingual.
Bird/Poultry IV 1-2 mg/kg Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For neonates: 0.1-0.2 mg/kg IV or sublingual.
Exotic/Other (ferrets, guinea pigs) IV 1-2 mg/kg Single dose; may repeat in 5-10 minutes Duration: Short-term use
Notes: For neonates: 0.1-0.2 mg/kg IV or sublingual.

Clinical Indications & Species Uses

General Indications
  • Respiratory depression due to drug overdose (e.g., opioids, barbiturates)
  • Apnea in neonates
  • Post-anesthetic respiratory stimulation
Dog (Canine)
  • Respiratory depression associated with anesthesia (e.g., barbiturates, opioids)
  • Apnea in neonates (e.g., after cesarean section)
  • Post-anesthetic respiratory stimulation
  • Stimulate breathing in cases of drug-induced respiratory depression
Cat (Feline)
  • Respiratory depression associated with anesthesia
  • Apnea in neonates
  • Post-anesthetic respiratory stimulation
Horse (Equine)
  • Respiratory depression in foals (e.g., neonatal maladjustment syndrome)
  • Apnea during anesthesia
  • Stimulation of respiration in cases of drug-induced respiratory depression
Cattle (Bovine)
  • Respiratory depression in calves (e.g., after dystocia or anesthesia)
  • Apnea in neonates
  • Stimulation of respiration in cases of drug-induced respiratory depression
Small Ruminants (Sheep / Goat)
  • Respiratory depression in lambs and kids (e.g., after dystocia or anesthesia)
  • Apnea in neonates
Rabbit & Small Mammals
  • Respiratory depression during anesthesia (e.g., with opioids or barbiturates)
  • Apnea in neonates
Avian & Poultry
  • Respiratory depression during anesthesia (e.g., with isoflurane or sevoflurane)
  • Apnea in neonates
Exotic & Other Species
  • Respiratory depression in small mammals (e.g., ferrets, guinea pigs) during anesthesia
  • Apnea in neonates

Pharmacology & Mechanism of Action

Drug Class: Respiratory stimulant | Pharmacological Group: Analeptic

Mechanism of Action: Doxapram is a central and peripheral respiratory stimulant. It acts primarily by stimulating the peripheral carotid chemoreceptors, which in turn reflexively increase the activity of the respiratory center in the medulla. At higher doses, it also directly stimulates the medullary respiratory and vasomotor centers. The drug enhances tidal volume and respiratory rate, and also increases cardiac output and blood pressure via central sympathetic activation. It does not cause significant arousal of the cerebral cortex at therapeutic doses, making it useful for respiratory depression without excessive CNS excitation.

Pharmacodynamics: Doxapram produces a dose-dependent increase in respiratory rate and tidal volume. It also increases heart rate and blood pressure due to central sympathetic stimulation. The onset of action is rapid (within 20-40 seconds after IV administration) and the duration of effect is short (5-12 minutes). It can reverse respiratory depression caused by various drugs, including opioids and barbiturates, but is not effective against respiratory depression due to neuromuscular blockade. It also has a mild arousal effect, which can be beneficial in post-anesthetic recovery.

⚑ Pharmacokinetics Summary

Absorption: Doxapram is well absorbed after oral administration, but due to extensive first-pass metabolism, oral bioavailability is low. In veterinary medicine, it is typically administered intravenously, intramuscularly, or subcutaneously for rapid onset. After oral administration, peak plasma concentrations occur within 1-2 hours, but the drug is not commonly used orally in animals.
Distribution: Doxapram is widely distributed throughout the body. It crosses the blood-brain barrier and the placenta. It is highly lipid-soluble and has a large volume of distribution. Protein binding is approximately 40-50% in plasma.
Metabolism: Doxapram is extensively metabolized in the liver, primarily by oxidation and hydroxylation. The major metabolites are active and contribute to the pharmacological effects. The metabolism is rapid, and the drug has a short half-life.
Excretion: Doxapram and its metabolites are excreted primarily in the urine (about 60-70%) and to a lesser extent in the feces. The elimination half-life is short, approximately 2-4 hours in dogs and cats, but the duration of action is even shorter due to redistribution.
Half-Life: Dogs: ~2-4 hours; Cats: ~2-3 hours; Horses: ~1-2 hours; Cattle: ~1-2 hours (estimated).
Bioavailability: Oral bioavailability is low due to first-pass metabolism; IV administration provides 100% bioavailability.
Protein Binding: Approximately 40-50% in plasma.

Available Formulations & Strengths

Injectable Solution 20 mg/mL (20 mg/mL in 20 mL vials) (IV, IM, SC)
Oral Drops (for neonates) 20 mg/mL (used sublingually) (Sublingual)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to doxapram
  • Seizure disorders (may lower seizure threshold)
  • Severe hypertension or cardiovascular disease
  • Respiratory failure due to neuromuscular blockade (e.g., curare-like drugs)
  • Mechanical respiratory obstruction (e.g., foreign body)
  • Concurrent use with monoamine oxidase inhibitors (MAOIs) or sympathomimetics (risk of severe hypertension)
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment (metabolism/excretion may be reduced).
  • May cause arrhythmias; use with caution in animals with cardiac disease.
  • Do not use as a substitute for adequate ventilation; ensure airway patency.
  • In neonates, use with extreme caution; monitor for hyperventilation and acidosis.
  • May cause CNS excitation at high doses; avoid overdose.
  • Use with caution in animals with hyperthyroidism or pheochromocytoma.
  • In food animals, observe withdrawal times; not approved for use in food animals in some countries.

Adverse Effects & Reactions

Common:

  • Restlessness
  • Tachycardia
  • Hypertension
  • Arrhythmias (ventricular premature beats)
  • Hyperventilation
  • Muscle tremors
  • Vomiting (especially in cats)

Serious / Severe:

  • Seizures
  • Cardiac arrest
  • Severe hypertension
  • Pulmonary edema (rare)
  • Cerebral hemorrhage (in neonates with rapid administration)

Rare:

  • Laryngospasm
  • Bronchospasm
  • Hypersensitivity reactions (anaphylaxis)
  • Metabolic acidosis (with prolonged use)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Opioids (e.g., morphine, fentanyl) Doxapram may partially reverse opioid-induced respiratory depression, but may also increase opioid-induced CNS excitation. Moderate
Barbiturates (e.g., pentobarbital) Doxapram can reverse respiratory depression but may cause excessive CNS stimulation if used in high doses. Moderate
Sympathomimetics (e.g., epinephrine, dopamine) Additive cardiovascular effects (hypertension, tachycardia) may occur. High
Monoamine oxidase inhibitors (MAOIs) Risk of severe hypertensive crisis. High
Inhalant anesthetics (e.g., isoflurane, sevoflurane) Doxapram may increase anesthetic requirements and cause arrhythmias. Moderate
Neuromuscular blocking agents (e.g., atracurium) Doxapram is ineffective in reversing respiratory depression caused by these agents. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypertension
  • Tachycardia
  • Arrhythmias
  • Seizures
  • Hyperventilation leading to respiratory alkalosis
  • CNS excitation
  • Hyperthermia

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Discontinue the drug immediately. Provide adequate ventilation and oxygenation. Control seizures with diazepam or barbiturates (e.g., pentobarbital) if necessary. Manage arrhythmias with appropriate antiarrhythmic agents (e.g., lidocaine for ventricular arrhythmias). Monitor blood pressure and treat severe hypertension with vasodilators (e.g., nitroprusside) if needed. Supportive care includes fluid therapy and temperature management. In severe cases, consider activated charcoal if oral ingestion occurred (though rare).

Food Animal Withdrawal Times

πŸ₯© Meat: 7 daysπŸ₯› Milk: 3 days

Withdrawal times are not officially established for doxapram in food animals. The values provided are conservative estimates based on the drug's short half-life. However, doxapram is not approved for use in food animals in many countries; extra-label use requires veterinary oversight and adherence to local regulations. Always consult the label and regulatory authorities.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 15-30Β°C (59-86Β°F).

Handling & Special Conditions: Protect from freezing. Keep container tightly closed. Use only if solution is clear and colorless.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in dogs and cats for respiratory stimulation. Not approved for food animals in the US.

Extra-Label (Off-Label) Use: In the US, doxapram is not approved for use in food animals. Extra-label use in food animals is permitted under AMDUCA only with a valid veterinary-client-patient relationship and a withdrawal time established by the veterinarian. In companion animals, it is a prescription drug.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Doxapram is a valuable respiratory stimulant for emergency use in veterinary medicine, particularly for reversing respiratory depression caused by anesthetic agents or opioids. It is short-acting, so repeated doses or continuous infusion may be necessary. It is not a substitute for mechanical ventilation in cases of severe respiratory failure. In neonates, it can be administered sublingually for rapid absorption. Use with caution in animals with cardiac disease or seizure disorders. Always monitor vital signs closely during administration. In food animals, extra-label use requires careful consideration of withdrawal times and regulatory compliance.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)