Doxapram uses, dose, brand name and its side effects

Description of Doxapram

Doxapram is a parenteral analeptic and respiratory stimulant indicated for postanesthesia respiratory depression or apnea other than that due to muscle relaxant drugs, drug-induced central nervous system (CNS) depression, and chronic obstructive pulmonary disease (COPD) associated with acute hypercapnia. The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. Doxapram is neither an antagonist to muscle relaxant drugs nor a specific opioid antagonist. Although opioid-induced respiratory depression is antagonized by doxapram, the analgesic effect is not affected. Modest to significant increases in blood pressure have been noted in some patients receiving doxapram. A pressor response may result after doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemia than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. An increased release of catecholamines has also been observed after doxapram administration.Therapy other than use of analeptic agents, such as noninvasive intermittent ventilation, is preferred in the treatment of respiratory depression arising from COPD.

Mechanism of Action of Doxapram

Doxapram is a central nervous system and respiratory stimulant and acts to stimulate respiration through both peripherally and centrally mediated mechanisms. Doxapram produces respiratory stimulation mediated through the peripheral carotid chemoreceptors. As the dosage level is increased, the central respiratory centers in the medulla are stimulated with progressive stimulation of other parts of the brain and spinal cord. At least some respiratory stimulant effects of doxapram are likely achieved through inhibition of acid sensitive potassium channels found in the carotid bodies and brain stem. The respiratory stimulant action is manifested by an increase in tidal volume associated with a slight increase in respiratory rate. Doxapram is neither an antagonist to muscle relaxant drugs nor a specific opioid antagonist. Although opioid-induced respiratory depression is antagonized by doxapram, the analgesic effect is not affected. A pressor response may result after doxapram administration. Provided there is no impairment of cardiac function, the pressor effect is more marked in hypovolemic than in normovolemic states. The pressor response is due to the improved cardiac output rather than peripheral vasoconstriction. An increased release of catecholamines has also been observed after doxapram administration.

Pharmacokinetics: Doxapram is administered intravenously. It is metabolized via ring hydroxylation to ketodoxapram, an active metabolite. After a single doxapram 1.5 mg/kg IV bolus and 6.5 mg/kg continuous IV infusion for 2 hours in healthy male volunteers, the mean terminal plasma half-lives were 5.9 and 7.5 hours, respectively. The mean Vd and clearance were 3,240 mL/kg and 5.93 mL/minute/kg after the bolus dose and 3,670 mL/kg and 5.61 mL/minute/kg after the 2-hour infusion.

Route-Specific Pharmacokinetics
Intravenous Route
The onset of respiratory stimulation after the recommended single intravenous injection of doxapram usually occurs in 20 to 40 seconds with peak effect at 1 to 2 minutes. The duration of effect may vary from 5 to 12 minutes.

Generic Name

Doxapram Hydrochloride

Brand Names

Dopram

Therapeutic Class

Stimulant, Respiratory

FDA-Label Indications

Chronic obstructive pulmonary disease – Hypercapnia, acute: Adult
Chronic obstructive pulmonary disease – Hypercapnia, acute: Pediatric: yes (age 12 y and older)
Complication of anesthesia – Respiratory depression: Adult
Complication of anesthesia – Respiratory depression: Pediatric: yes (age 12 y and older)
Drug-induced central nervous system depression: Adult
Drug-induced central nervous system depression: Pediatric: yes (age 12 y and older)

Common Effects

Dermatologic: Flushing, Pruritus
Gastrointestinal: Diarrhea, Nausea, Vomiting

Serious Effects

Cardiovascular: Cardiac dysrhythmia, Chest pain, Thrombophlebitis
Hematologic: Hemolysis
Respiratory: Dyspnea, Wheezing

Administration

Intravenous: contains benzyl alcohol, not for use in neonates
Intravenous: (repeat injections) give at 5 minute intervals
Intravenous: (infusion, postanesthetic) add 250 mg to 250 mL of D5W, D10W or NS and infuse at 5 mg/min initially until respiratory response is reached, maintain at a rate of 1 to 3 mg/min
Intravenous: (mild drug-induced CNS depression) infuse at a rate of 1 to 2 mg/kg/hr
Intravenous: (moderate drug-induced CNS depression) infuse at a rate of 2 to 3 mg/kg/hr
Intravenous: (COPD with acute hypercapnia) mix 400 mg with 180 mL of D5W, D10W, or NS to a concentration of 2 mg/mL and infuse at 1 to 2 mg/min, max 3 mg/min

How Supplied – Trade

Dopram: Intravenous Solution: 20 MG/1 ML

Adult Dose

Chronic obstructive pulmonary disease – Hypercapnia, acute: 1 to 2 mg/min IV continuous infusion (0.5 to 1 ml/min of a 2 mg/mL solution), may increase to 3 mg/min as needed; MAX infusion time 2 h
Complication of anesthesia – Respiratory depression: initial, 0.5 to 1 mg/kg IV, repeat every 5 min; MAX single dose 1.5 mg/kg, MAX total dose 2 mg/kg
Complication of anesthesia – Respiratory depression: initial, 0.5 to 1 mg/kg continuous IV infusion at a rate of 5 mg/min until response, maintenance 1 to 3 mg/min; MAX total dose 4 mg/kg
Drug-induced central nervous system depression: priming dose of 1 mg/kg IV, repeat in 5 min and every 1 to 2 h until sustained arousal OR following priming dose, 1 to 2 mg/kg/hr continuous IV infusion; discontinue if patient awakens or at end of 2 h; MAX 3 g/day
Drug-induced central nervous system depression: priming dose of 2 mg/kg IV, repeat in 5 min and every 1 to 2 h until sustained arousal OR following priming dose, 2 to 3 mg/kg/h continuous IV infusion; discontinue if patient awakens or at end of 2 h; MAX 3 g/day
Shivering, Postanesthesia: 0.18 mg/kg IV

Pediatric Dose