DOXAPRAM HCL
Chemistry - Doxapram HCl is a white to off-white, odorless, crystalline powder that is stable in light and air. It is soluble in water, sparingly soluble in alcohol and practically insoluble in ether.
Injectable products have a pH from 3.5-5. Benzyl alcohol or chlorobutanol is added as a preservative agent in the commercially available injections.
Onset of effect in humans and animals after IV injection usually occurs within 2 minutes. The drugis well distributed into tissues. In dogs, doxopram is rapidly metabolized and most is excreted asmetabolites in the urine within 24-48 hours after administration. Small quantities of metabolitesmay be excreted up to 120 hours after dosing.Uses, Indications - The manufacturer of Dopram®-V lists the following indications:
For Dogs, Cats, and Horses: To stimulate respiration during and after general anesthesia and/or tospeed awakening and reflexes after anesthesia.
For Neonatal Dogs and Cats: Initiate or stimulate respirations following dystocia or cesareansection.
Doxopram also has been used for treatment of CNS depression in food animals (not approved) and has been suggested as a treatment of respiratory depression in small animals caused by reactions to radiopaque contrast media or for barbiturate overdosage (see precautions below).
Contraindications/Precautions - Doxapram should not be used as a substitute for aggressive artificial (mechanical) respiratory support in instances of severe respiratory depression.
Contraindications from the human literature include: seizure disorders, head trauma, uncompensated heart failure, severe hypertension, cardiovascular accidents, respiratory failure secondary to neuromuscular disorders, airway obstruction, pulmonary embolism, pneumothorax, acute asthma, dyspnea, or whenever hypoxia is not associated with hypercapnea. Doxapram should be used with caution in patients with history of asthma, arrhythmias, or tachycardias. It should be used with extreme caution in patients with cerebral edema or increased CSF pressure, pheochromocytoma or hyperthyroidism. Patients who have a history of hypersensitivity to the drug or are receiving mechanical ventilation should not receive doxapram. The above contraindications/precautions are not listed in the veterinary product literature provided by the manufacturer.
Avoid the use of a single injection site for a prolonged period of time or extravasation when administering intravenously. However, subcutaneous injection has been recommended for use in neonatal feline and canine patients.
Safety of doxopram has not been established in pregnant animals. The potential risks versusbenefits should be weighed before using.
Overdosage - Symptoms of overdosage include: hypertension, skeletal muscle hyperactivity, tachycardia, and generalized CNS excitation including seizures. Treatment is supportive. Drugssuch as short acting IV barbiturates may be used to help decrease CNS hyperactivity. Oxygentherapy may be necessary.
Doxapram may mask the effects of muscle relaxant drugs.
Doxapram may increase epinephrine release; therefore use should be delayed for approximately10 minutes after discontinuation of anesthetic agents (e.g., halothane, enflurane) that have beendemonstrated to sensitize the myocardium to catecholamines.
Injectable products have a pH from 3.5-5. Benzyl alcohol or chlorobutanol is added as a preservative agent in the commercially available injections.
Storage, Stability, Compatibility
Store at room temperature and avoid freezing solution. Do notmix with alkaline solutions (e.g., thiopental, aminophylline, sodium bicarbonate). Doxapram iscompatible with D5W or normal saline.Pharmacology - DOXAPRAM HCL
Doxapram is a general CNS stimulant, with all levels of the CNS affected. Theeffects of respiratory stimulation are a result of direct stimulation of the medullary respiratorycenters and possibly through the reflex activation of carotid and aortic chemoreceptors. Transientincreases in respiratory rate and volume occur, but increases in arterial oxygenation usually do notensue. This is because doxapram usually increases the work associated with respirations withresultant increased oxygen consumption and carbon dioxide production.Pharmacokinetics - DOXAPRAM HCL
Little pharmacokinetic data appears to be published for domestic animals.Onset of effect in humans and animals after IV injection usually occurs within 2 minutes. The drugis well distributed into tissues. In dogs, doxopram is rapidly metabolized and most is excreted asmetabolites in the urine within 24-48 hours after administration. Small quantities of metabolitesmay be excreted up to 120 hours after dosing.Uses, Indications - The manufacturer of Dopram®-V lists the following indications:
For Dogs, Cats, and Horses: To stimulate respiration during and after general anesthesia and/or tospeed awakening and reflexes after anesthesia.
For Neonatal Dogs and Cats: Initiate or stimulate respirations following dystocia or cesareansection.
Doxopram also has been used for treatment of CNS depression in food animals (not approved) and has been suggested as a treatment of respiratory depression in small animals caused by reactions to radiopaque contrast media or for barbiturate overdosage (see precautions below).
Contraindications/Precautions - Doxapram should not be used as a substitute for aggressive artificial (mechanical) respiratory support in instances of severe respiratory depression.
Contraindications from the human literature include: seizure disorders, head trauma, uncompensated heart failure, severe hypertension, cardiovascular accidents, respiratory failure secondary to neuromuscular disorders, airway obstruction, pulmonary embolism, pneumothorax, acute asthma, dyspnea, or whenever hypoxia is not associated with hypercapnea. Doxapram should be used with caution in patients with history of asthma, arrhythmias, or tachycardias. It should be used with extreme caution in patients with cerebral edema or increased CSF pressure, pheochromocytoma or hyperthyroidism. Patients who have a history of hypersensitivity to the drug or are receiving mechanical ventilation should not receive doxapram. The above contraindications/precautions are not listed in the veterinary product literature provided by the manufacturer.
Avoid the use of a single injection site for a prolonged period of time or extravasation when administering intravenously. However, subcutaneous injection has been recommended for use in neonatal feline and canine patients.
Adverse Effects, Warnings
Hypertension, arrhythmias, seizures, and hyperventilation leading torespiratory alkalosis has been reported. These effects are most probable with repeated or highdoses. The drug reportedly has a narrow margin of safety when used in humans.Safety of doxopram has not been established in pregnant animals. The potential risks versusbenefits should be weighed before using.
Overdosage - Symptoms of overdosage include: hypertension, skeletal muscle hyperactivity, tachycardia, and generalized CNS excitation including seizures. Treatment is supportive. Drugssuch as short acting IV barbiturates may be used to help decrease CNS hyperactivity. Oxygentherapy may be necessary.
Drug Interactions
Additive pressor effects may occur with sympathomimetic agentsDoxapram may mask the effects of muscle relaxant drugs.
Doxapram may increase epinephrine release; therefore use should be delayed for approximately10 minutes after discontinuation of anesthetic agents (e.g., halothane, enflurane) that have beendemonstrated to sensitize the myocardium to catecholamines.