Usage
Doxapram is a central respiratory stimulant primarily prescribed for the treatment of:
- Postanesthesia Respiratory Depression: Reversal of respiratory depression induced by general anesthesia following surgical procedures.
- Drug-Induced CNS Depression: Reversal of respiratory depression caused by drug overdose with central nervous system depressants.
- Acute Hypercapnia in Chronic Obstructive Pulmonary Disease (COPD): Short-term management of acute exacerbations of COPD associated with acute hypercapnia.
- Apnea of Prematurity (off-label): Although not FDA-approved, it’s sometimes used to treat apnea of prematurity when other treatments fail.
Pharmacological Classification: Central Respiratory Stimulant
Mechanism of Action: Doxapram stimulates respiration primarily by acting on peripheral carotid chemoreceptors, which are sensitive to changes in blood oxygen levels. This stimulation leads to an increase in tidal volume and respiratory rate. It also has a minor stimulatory effect on the central respiratory centers in the medulla.
Alternate Names
- Generic Name: Doxapram Hydrochloride
- Brand Name: Dopram
How It Works
Pharmacodynamics: Doxapram stimulates breathing by acting on the peripheral carotid chemoreceptors and, to a lesser extent, the medullary respiratory center. This results in increased tidal volume and respiratory rate. It can also cause a release of catecholamines, leading to a transient increase in blood pressure and heart rate.
Pharmacokinetics:
- Absorption: Rapidly absorbed following intravenous administration.
- Metabolism: Extensively metabolized in the liver, primarily by CYP450 enzymes.
- Elimination: Excreted mainly through the kidneys, with a small amount excreted in bile.
Mode of Action: Doxapram primarily acts on the carotid chemoreceptors by enhancing their sensitivity to hypoxia. This leads to increased afferent nerve impulses to the respiratory center in the brainstem, resulting in increased respiratory drive.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Doxapram’s primary mode of action is not through direct receptor binding but through modulation of carotid chemoreceptor activity. It does not directly inhibit or induce CYP450 enzymes, although it is metabolized by them.
Elimination Pathways: Primarily renal excretion following hepatic metabolism.
Dosage
Doxapram is administered intravenously (IV). Dosage and administration methods vary depending on the clinical indication.
Standard Dosage
Adults:
- Postanesthesia Respiratory Depression: 0.5-1.5 mg/kg IV, repeated every 5 minutes as needed, not to exceed 2 mg/kg total dose. Alternatively, an initial IV infusion of 2-5 mg/minute can be titrated to response, with the maintenance dose usually ranging from 1–3 mg/minute, maximum 4 mg/kg total dose.
- Drug-induced Respiratory Depression: Initial bolus dose of 1-2 mg/kg, followed by an infusion of 1-3 mg/minute, titrated to effect. Maximum daily dose: 3 grams.
- Acute Hypercapnia in COPD: 1-2 mg/minute IV infusion, titrated as needed. Maximum 3 mg/minute. Duration should not exceed 2 hours. Monitor arterial blood gases.
Children:
- Safety and efficacy have not been established in children under 12 years of age.
- For children over 12 years, follow adult dosing guidelines but with careful monitoring.
Special Cases:
- Elderly Patients: Use with caution due to increased risk of adverse effects. Lower doses and slower administration rates may be necessary.
- Patients with Renal Impairment: Use with caution. Dosage adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with caution as doxapram is metabolized by the liver. Dose reduction may be required.
- Patients with Comorbid Conditions: Careful monitoring is crucial, especially in patients with cardiovascular disease, hypertension, hyperthyroidism, or seizure disorders.
Clinical Use Cases
- Intubation: May be used as an adjunct to facilitate intubation in patients with respiratory depression.
- Surgical Procedures: Used postoperatively to reverse respiratory depression induced by anesthesia.
- Mechanical Ventilation: Doxapram should not be used concurrently with mechanical ventilation as this can increase the risk of respiratory alkalosis and other adverse events.
- Intensive Care Unit (ICU) Use: May be used in the ICU setting for short-term management of acute respiratory depression.
- Emergency Situations: May be used in certain emergency situations, such as drug overdose.
Dosage Adjustments:
- Renal/Hepatic Dysfunction: Dose reduction may be necessary.
- Metabolic Disorders/Genetic Polymorphisms: Careful monitoring is warranted.
Side Effects
Common Side Effects:
- Hypertension
- Tachycardia
- Headache
- Dizziness
- Nausea
- Vomiting
- Cough
- Dyspnea
Rare but Serious Side Effects:
- Seizures
- Arrhythmias (including ventricular fibrillation)
- Cerebral edema
- Respiratory distress syndrome
Long-Term Effects:
Limited data available on long-term effects.
Adverse Drug Reactions (ADR):
- Severe hypertension
- Cardiac arrhythmias
- Generalized seizures
Contraindications
- Hypersensitivity to doxapram
- Epilepsy or other seizure disorders
- Pulmonary embolism
- Mechanical ventilation
- Severe hypertension
- Conditions restricting chest wall movement or alveolar expansion (e.g., pneumothorax, flail chest, acute asthma)
- Head injury, stroke, or cerebral edema
- Significant cardiovascular impairment (e.g., severe coronary artery disease, uncompensated heart failure)
Drug Interactions
- Sympathomimetics: May potentiate cardiovascular effects, leading to severe hypertension and arrhythmias.
- MAO Inhibitors: Concomitant use can lead to hypertensive crisis.
- Volatile Anesthetics: May increase the risk of cardiac arrhythmias.
- Aminophylline/Theophylline: May increase CNS stimulation and other adverse effects.
- Neuromuscular Blocking Agents: Doxapram may temporarily mask the residual effects of these drugs.
- CYP450 Inhibitors/Inducers: Potential for altered doxapram metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Doxapram is classified as Pregnancy Category B. Animal studies have not shown harm to the fetus, but there are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: It is unknown if doxapram is excreted in human milk. Use caution when administering to nursing mothers.
Drug Profile Summary
- Mechanism of Action: Stimulates carotid chemoreceptors, increasing tidal volume and respiratory rate.
- Side Effects: Hypertension, tachycardia, headache, dizziness, seizures, arrhythmias.
- Contraindications: Hypersensitivity, epilepsy, pulmonary embolism, mechanical ventilation, severe hypertension, head injury, significant cardiovascular impairment.
- Drug Interactions: Sympathomimetics, MAO inhibitors, volatile anesthetics, aminophylline/theophylline, neuromuscular blocking agents.
- Pregnancy & Breastfeeding: Pregnancy Category B; use with caution during breastfeeding.
- Dosage: Variable depending on indication; generally 0.5–1.5 mg/kg for adults.
- Monitoring Parameters: Respiratory rate, blood pressure, heart rate, arterial blood gases, oxygen saturation.
Popular Combinations
Doxapram is not typically used in combination with other drugs for synergistic effects.
Precautions
- General Precautions: Evaluate patients for contraindications before administering. Monitor for adverse reactions, particularly cardiovascular and neurological effects.
- Specific Populations: Use cautiously in elderly patients, patients with renal or hepatic impairment, and pregnant/breastfeeding women. Not recommended for children under 12.
- Lifestyle Considerations: Advise patients to avoid alcohol and other CNS depressants.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Doxapram?
A: Dosage varies depending on the indication and patient’s response. See the “Dosage” section above for details on dosages for adults, children, and special populations.
Q2: How is Doxapram administered?
A: Doxapram is administered intravenously, either as an intermittent bolus injection or continuous infusion.
Q3: What are the common side effects of Doxapram?
A: Common side effects include hypertension, tachycardia, headache, dizziness, nausea, vomiting, cough, and shortness of breath.
Q4: When is Doxapram contraindicated?
A: Doxapram is contraindicated in patients with hypersensitivity to the drug, epilepsy, pulmonary embolism, mechanical ventilation, and several other conditions listed in the “Contraindications” section.
Q5: Can Doxapram be used in pregnant women?
A: Doxapram is Pregnancy Category B. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Q6: How does Doxapram interact with other medications?
A: Doxapram can interact with sympathomimetics, MAO inhibitors, volatile anesthetics, aminophylline/theophylline, and neuromuscular blocking agents. See the “Drug Interactions” section for more details.
Q7: What are the most serious side effects of Doxapram?
A: Seizures, arrhythmias (including ventricular fibrillation), cerebral edema, and respiratory distress syndrome are the most serious potential side effects.
Q8: What monitoring parameters are important when using Doxapram?
A: Monitor respiratory rate, blood pressure, heart rate, arterial blood gases, and oxygen saturation during Doxapram administration.
Q9: Can Doxapram be used in children?
A: Safety and efficacy have not been established in children under 12. For children over 12, adult dosing guidelines can be followed with cautious monitoring.
Q10: How long does it take for Doxapram to work?
A: Doxapram typically begins working within seconds to minutes following intravenous administration. The duration of effect is typically 5-12 minutes following a single bolus injection.
