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Doxapram HCl

The Elephant Formulary
© 2003-06 Susan K. Mikota DVM and Donald C. Plumb, Pharm.D.
Published by Elephant Care International -
www.elephantcare.org


Elephant specific information, if available, is in blue.

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.

 

Storage/Stability/Compatibility - Store at room temperature and avoid freezing solution. Do not mix with alkaline solutions (e.g., thiopental, aminophylline, sodium bicarbonate). Doxapram is compatible with D5W or normal saline.

 

Pharmacology - Doxapram is a general CNS stimulant, with all levels of the CNS affected. The effects of respiratory stimulation are a result of direct stimulation of the medullary respiratory centers and possibly through the reflex activation of carotid and aortic chemoreceptors. Transient increases in respiratory rate and volume occur, but increases in arterial oxygenation usually do not ensue. This is because doxapram usually increases the work associated with respirations with resultant increased oxygen consumption and carbon dioxide production.

 

Pharmacokinetics - 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 drug is well distributed into tissues. In dogs, doxopram is rapidly metabolized and most is excreted as metabolites in the urine within 24-48 hours after administration. Small quantities of metabolites may 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 to speed awakening and reflexes after anesthesia. For Neonatal Dogs and Cats: Initiate or stimulate respirations following dystocia or cesarean section.

 

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 to respiratory alkalosis has been reported. These effects are most probable with repeated or high doses. 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 versus benefits should be weighed before using.

 

Overdosage - Symptoms of overdosage include: hypertension, skeletal muscle hyperactivity, tachycardia, and generalized CNS excitation including seizures. Treatment is supportive. Drugs such as short acting IV barbiturates may be used to help decrease CNS hyper­activity. Oxygen therapy may be necessary.

 

Drug Interactions - Additive pressor effects may occur with sympathomimetic agents

Doxapram may mask the effects of muscle relaxant drugs. Doxapram may increase epinephrine release; therefore use should be delayed for approx­imately 10 minutes after discontinuation of anesthetic agents (e.g., halothane, enflurane) that have been demonstrated to sensitize the myocardium to catecholamines.

 

Doses -

Horses:

a)   0.5 - 1 mg/kg IV at 5 minute intervals (do not exceed 2 mg/kg in foals); For foal resuscitation: 0.02 - 0.05 mg/kg/min IV (Robinson 1987)

 

 

Elephants:

a) To stimulate respirations in a new born calf, calculate dose at 0.5 mg/kg. Give under the tongue or IV. Can repeat the dose or double the dose one time if necessary. 

200 lb (90 kg) calf = 45 mg (2.25 ml)

250 lb (113 kg) calf = 56 mg (2.8 ml)

300 lb (136 kg) calf = 68 mg (3.4 ml) (Schmitt, 2001).

 

b) 100 mg/ton IM or IV; authors’ personal experience (Cheeran et.al. 1995).

 

c) One African elephant immobilized with carfentanil and maintained on halothane experienced respiratory depression and was given two IV doses of doxapram at a dosage of 0.22 mg/kg (Jacobson et.al. 1988).

 

Elephant References:

a) Schmitt,D.L. 2001. Riddle’s Elephant and Wildlife Sanctuary Elephant Birth Protocol. www.elephantcare.org/protodoc_files/birthpro.pdf

b) Cheeran,J.V., Chandrasekharan,K., and Radhakrishnan,K., 1995. Principles and Practice of Fixing Dose of Drugs for Elephants . In: Daniel,J.C. (Editor), A Week with Elephants; Proceedings of the International Seminar on Asian Elephants. Bombay Natural History Society; Oxford University Press, Bombay, India pp. 430-438

 

c) Jacobson,E.R., Kollias,G.V., Heard,D.J., and Caligiuri,R. 1988. Immobilization of African elephants with carfentanil and antagonism with nalmefene and diprenorphine. Journal of Zoo Animal Medicine 19:1-7

Monitoring Parameters -

1)   Respiratory rate

2)   Cardiac rate and rhythm

3)   Blood gases if available and indicated

4)   CNS level of excitation

5)   Blood pressure if possible and indicated

 

Client Information- This agent should be used in an inpatient setting or with direct pro­fessional supervision.

 

Dosage Forms/Preparations/FDA Approval Status/Withholding Times -

 

Veterinary-Approved Products:

Doxapram HCl for Injection: 20 mg/ml; 20 ml multi-dose vial; Dopram-V®   (Fort Dodge); (Rx)  Approved for use in dogs, cats & horses

 

Human-Approved Products:-

Doxapram HCl for Injection: 20 mg/ml in 20 ml vial; Dopram®  (Robins); (Rx) ; generic, (Rx)

 

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