Dopram-V

Generic name: doxapram hydrochloride injection
Dosage form: FOR ANIMAL USE ONLY

NADA 34-879, Approved by FDA

Caution

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Each 1 mL contains:

Doxapram hydrochloride ..... 20 mg
Benzyl alcohol (as preservative) ..... 0.9 %
Water for Injection, USP ..... q.s.

Description

Dopram-V (doxapram hydrochloride) is a potent respiratory stimulant. It is unique in its ability to stimulate respiration at dosages considerably below those required to evoke cerebral cortical stimulation. In nonanesthetized animals the dose required to produce convulsions is some 70 to 75 times the dose required to produce respiratory stimulation. In anesthetized subjects, doxapram also exerts a marked arousal effect. Thus, by promoting the restoration of normal ventilation and producing early arousal following general anesthesia, doxapram minimizes or prevents the undesirable effects of post-anesthetic respiratory depression or hypoventilation and hastens recovery.

Chemistry1

The chemical name of doxapram hydrochloride is 1-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone hydrochloride hydrate.

The material is prepared as a clear, colorless, 2% aqueous solution with a pH of 3.5 to 5 and is stable at room temperature. Stability studies of 24 months’ duration have shown doxapram to have excellent stability characteristics. The preservative is benzyl alcohol, 0.9% and sterilization is accomplished by aseptic filtration technique. Doxapram is compatible with 5% and 10% dextrose in water or normal saline, but is physically incompatible with alkaline solutions, such as 2.5% thiopental sodium.

Species Variation2,5
The dog responds more dramatically to doxapram than other species. For example, arousal was not observed in the rat, and the cat responded poorly in comparison with the dog. Respiratory stimulation was slight in the rat, moderate in the cat and marked in the dog and horse.

Effect on EEG3
Studies show that while the drug acted selectively on respiratory centers of the brain, higher doses stimulated other parts of the neuraxis. The cortex appeared to be the most resistant part of the central nervous system to the action of the drug.

Effect on Cerebral Blood Flow4
The effect of doxapram on cerebral blood flow in anesthetized dogs was determined. Initially, the drug caused a transient increase in blood flow concomitant with rising femoral arterial blood pressure. Flow then diminished while the blood pressure remained elevated. The decreased flow appeared to coincide with marked respiratory stimulation; its occurrence, therefore, is consistent with the known vasoconstrictor