Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that the antiemetic neuroleptic drug, prochlorperazine, is a potent stimulant of the ventilatory response to hypoxia. To investigate whether or not this effect persisted in the presence of central depression of ventilatory drive, the effects on ventilatory control of morphine with and without prochlorperazine were studied in 12 normal humans. Measurement of resting ventilation and the ventilatory responses to progressive hypercapnia and to transient asphyxia were made before and 15 min after morphine (0.15 mg/kg) given intravenously. Prochlorperazine (12.5 mg) was then administered intravenously to 6 study subjects and saline to 6 control subjects. After a further 10 min, resting ventilation and chemoreceptor function were remeasured. After the administration of morphine, resting ventilation, the ventilatory response to hypercapnia, and the ventilatory response to asphyxia were all significantly decreased (p less than 0.01 in each case; mean effect in control and study group were, respectively, -16 and -17%, -50 and -32%, -46 and -55%). Administration of saline produced no significant additional changes in the 6 control subjects. By contrast, administration of prochlorperazine to the 6 study subjects markedly increased the ventilatory response to asphyxia to levels significantly greater than postmorphine values (p less than 0.005; 2.38 +/- 0.22 L . min-1 . % Sao2 versus 0.80 +/- 0.14 L . min-1; mean +/- SEM). Resting ventilation and ventilatory response to hypercapnia were not significantly affected by prochlorperazine. These results were not explained by differences in end-tidal PCO2 at which hypercapnic hypoxic tests were performed. It is concluded that prochlorperazine reverses the depression of the ventilatory response to asphyxia caused by morphine.
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PMID:The effects of combined morphine and prochlorperazine on ventilatory control in humans. 396 24

The effect of the dopamine-receptor blocking agent prochlorperazine on the ventilatory response to hypercapnic hypoxia was studied in six healthy adults. Repeated episodes of transient hypoxia were induced at the mixed venous PCO2 level by a nonrebreathing technique in five males and one female before and after an intravenous bolus injection of prochlorperazine mesylate (12.5 mg = 10 mg base). The ventilatory response to CO2 was also studied before and after drug administration. Prochlorperazine produced a modest (15%) increase in resting ventilation (P less than 0.05) but a marked increase in the ventilatory response to asphyxia such that the group mean response was double the control value [2.0 +/- 0.7 vs. 4.2 +/- 1.5 l . min-1 . % arterial O2 saturation (%SaO2); P less than 0.001]. Two-thirds of this change in ventilatory response was due to an increase in frequency response to hypoxia (0.34 +/- 0.20 vs. 0.81 +/- 0.52 breaths . min-1 . %SaO2; P less than 0.001). The position of the ventilatory response line, as judged by the computed ventilation at 95% SaO2, was increased by prochlorperazine (22.2 +/- 9.6 vs. 35.9 +/- 10.9 l . min-1; P less than 0.01) due to an increase in both tidal volume (P less than 0.05) and frequency of breathing (P less than 0.0125). The ventilatory response to CO2 was unchanged by drug injection. In separate experiments prochlorperazine was shown to 1) increase the ventilatory response to steady-state eucapnic hypoxia (P less than 0.01) demonstrating that the drug effect was not dependent on either the presence of hypercapnia or rapidly changing states of arterial oxygenation; and 2) reverse the depressant effect of intravenously infused dopamine hydrochloride (5 micrograms . kg-1 . min-1) on the ventilatory response to transient asphyxia (P less than 0.01). We conclude that prochlorperazine augments hypoxic responsiveness in humans. The mechanism may be blockade of dopaminergic receptors that modulate carotid body discharge.
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PMID:Augmentation of ventilatory response to asphyxia by prochlorperazine in humans. 712 85