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A controlled clinical trial of oral droperidol and droperidol plus diazepam for premedication in children.

In 87 children aged 2-9 yr, oral droperidol and oral droperidol plus diazepam were compared as premedicants in a controlled double-blind clinical trial. Atropine was given orally to all the patients. Droperidol was well absorbed and produced good sedation, associated with a low incidence of vomiting after operation. Droperidol plus diazepam did not appear to offer any advantage over droperidol alone. Anxiety and extrapyramidal effects were not observed and may have been obviated by the addition of atropine. Droperidol syrup was noted to be more palatable than other oral premedicants in use.

Administration, Oral

Specific alpha-adrenoceptor blocking effect of droperidol on isolated smooth muscles.

The present study was conducted so as to obtain more insight into the controversies concerning the alpha-adrenoceptor blocking properties of droperidol, a short-acting neuroleptic agent used in neuroleptanalgesia. The effect of droperidol on the vasoconstriction induced by norepinephrine, sympathetic nerve stimulation, histamine and potassium ions was studied on isolated, perfused ear arteries; its effect on norepinephrine-induced contraction was studied on isolated aorta, spleen and vas deferens. In addition, the onset and duration of action of droperidol was studied. Low doses of droperidol inhibit the vasoconstriction induced by norepinephrine and sympathetic nerve stimulation in the ear artery of the rabbit (3.3 X 10(-9) M and 1.3 X 10(-8) M respectively). At similar low doses, droperidol inhibits norepinephrine-induced contractions in the other tissues studied and has a potency comparable to that of phentolamine; its action is rapid in onset and of short duration. High doses of droperidol (10(-6) M) also inhibit the vasoconstriction of the ear artery induced by histamine and by potassium ions. These findings indicate that a low doses, droperidol has specific and competitive alpha-adrenoceptor blocking effects.

Adrenergic alpha-Antagonists

Effects of droperidol on activity of carotid body chemoreceptors in cat.

1 The effect of droperidol on the spontaneous activity of carotid body chemoreceptors and on their response to various stimuli was studied in 21 anaesthetized, paralyzed and artificially ventilated cats. Carotid body blood flow was controlled with a perfusion pump, and drugs were injected into the perfusion circuit. 2 In low doses, droperidol transiently increased the rate of spontaneous chemoreceptor activity, but in higher doses it depressed chemoreceptor activity after an initial stimulation. 3 Droperidol reduced or abolished the normal increase in chemoreceptor activity produced by stagnant asphyxia. This effect did not depend solely on the ability of droperidol to suppress spontaneously occurring impulses. Chemoreceptor responses to sodium cyanide, and to dopamine were also inhibited. 4 Dopamine antagonists other than droperidol were also studied for their effect on chemocreceptor activity. Chlorpromazine depressed spontaneous chemoreceptor activity and also reduced the chemoreceptor responses to sodium cyanide and dopamine, as did pimozide. The effects of these dopamine antagonists were much briefer and less marked than those of droperiodol. 5 Although the influence that we have shown droperidol to have on peripheral chemoreceptor activity has an uncertain basis, it may have important implications in human and veterinary medicine.

Animals

A comparison of droperidol, diazepam, and hydroxyzine hydrochloride as premedication.

A double-blind comparison of the efficacy and safety of droperidol (5 mg), hydroxyzine HCl (50 mg), diazepam (5 mg), and saline placebo, given concomitantly with meperidine (50 or 75 mg) for preoperative medication, was conducted in 280 female patients scheduled for minor gynecologic procedures. Droperidol proved to significantly superior to the other study drugs in alleviating apprehension (83% of patients calm versus 54, 46, and 34% for hydroxyzine, diazepam, and placebo, respectively). Some drowsiness, occurred in 68 percent of the droperidol-treated patients versus 31, 30, and 21 percent of the other 3 groups, respectively. Global evaluations were consistent with these findings. No clinically significant changes were observed in vital signs in any of the study-drug groups. Adverse reactions were unremarkable in all groups. Significantly less nausea occurred with droperidol than with other treatments, and signficantly less vomiting occurred with droperidol or hydroxyzine. Significantly fewer patients in the droperidol group than in the diazepam group required postoperative antiemetics.

Adolescent

Antagonism by droperidol of dopamine-induced relaxation in isolated dog arteries.

Dopamine caused a dose-related relaxation in helically cut strips of dog coronary and renal arteries treated with phenoxybenzamine andcontracted with prostaglandin F2 alpha. The dose-response curve to dopamine was shifted to the right by droperidol in concentrations above 3 X 10(-5) M. Adenosine-induced relaxations were not attenuated by droperidol. The dose--relaxation curve to isoproterenol was also shifted to the right by droperidol. Propranolol (10(-6) M) failed to significantly alter the dose response curve to dopamine, and in propranolol-treated preparations the antagonism by droperidol of dopamine actions was practically identical with that in control preparations. Droperidol appears to act as a reversible, surmountable antagonist to dopamine actions on dog arterial smooth muscles, and such evidence supports the hypothesis of specific dopamine receptors in dog arteries.

Animals

Diazepam and droperidol as i.v. premedicants.

The effects of i.v. diazepam and droperidol both alone and in combination administered as premedication were studied in 240 patients. Relief of anxiety, sedation, lack of recall, acceptance by both patient and physician and side-effects were evaluated. Overall, the combination of droperidol 2.5 mg with diazepam 5 mg produced better ratings of these variables than could be achieved with either droperidol 10 mg or diazepam 10 mg alone. Larger doses of droperidol with diazepam produce an increased frequency of anxiety; larger doses of diazepam with droperidol may cause over-sedation.

Adolescent

Has droperidol an atropinic effect?

The action of droperidol on the tachycardia produced by atropine and on the serum concentration of cholinesterases was observed during balanced anaesthesia. Without atropine, the mean heart rates of patients who received fentanyl plus droperidol were similar. Atropine increased heart rate only in the presence of droperidol (P less than 0.001) (fentanyl v. fentanyl plus droperidol: P less than 0.05). Droperidol inhibited serum cholinesterases (P less than 0.05); this effect was independent of atropine.

Adult

Effects of droperidol in management of vestibular disorders.

The chemo-therapy of vestibular disease has involved a wide spectrum of pharmacological agents insofar as their mode of action is concerned. In our experience, however, droperidol is one pharmaceutical agent which is remarkably effective in depressing vestibular disturbance regardless of etiology. This medication (also called Inapsine) belongs to a relatively new class of compounds known as butyrophenones and its pharmacological action can best be described as a dopa blocking agent. The activity of droperidol on the nervous system first became evident when it was used in combination with the potent analgesic fentanyl citrate in order to produce an anesthetic condition that has been termed neuroleptanalgesia. This mixture (also called Innovar) is rapid in action and results in complete suppression of vestibular activity of both normal subjects and those with Ménière's disease as described by Dowdy, et al., in a preliminary report. These impressive results have prompted us to evaluate the effectiveness of this medication in the treatment of different disorders of the labyrinth. The patients chosen for evaluation were referred for vestibular examination at the Toronto General and St. Michael's Hospitals. Electronystagmography was used to record objectively the effects of the drugs being tested while subjective symptoms including side effects were also noted. These studies involved 20 patients receiving Innovar while 12 patients were tested with Inapsine. Innovar administered in a single dose (droperidol 5 mg, fentanyl 0.1 mg) to patients undergoing acute episodes of vestibular disease (vestibular neuronitis and Ménière's disease) was found effective in the following symptoms and/or signs: nausea, vertigo, nystagmus, the positive past-pointing test and the Romberg test. Innovar appeared to be effective in the amelioration of vomiting although the population was too small to demonstrate statistical significance in this regard. The drug mixture appeared to have no effect on improving auditory acuity and had no significant effects on tinnitus. Adverse reactions to the drug combination were unusual, and, occurring in three patients, were mild as manifested by drowsiness. Since the above findings confirmed the marked effectiveness of the fentanyl-droperidol mixture in the management of vestibular disease, it was decided to determine the relative effectiveness of the droperidol component alone and this was determined by comparing the effectiveness of the drug with placebo in a double-blind study. Review of our findings involving this double-blind study indicates significant responses to Inapsine. This therapy clearly provided the statistically significant response (p less than 0.1, Fisher's Exact Test). This was particularly apparent at the 60-minute evaluation point. While some of the patients receiving Inapsine had recovered earlier, by 60 minutes none of the placebo patients but all of the Inapsine patients had recovered from the vestibular symptoms of Ménière's disease...

Acute Disease

Droperidol, its alpha-adrenergic blocking action on the aortic strip and inhibitory action on norepinephrine uptake of the adrenergic terminal of the left atrial strip of rabbit.

In aortic strips, the dose-response curves for phenylephrine were obtained before and after addition of droperidol. Droperidol caused a parallel shift of the curves dose-dependently toward the right side and its grade of the shift was greater than caused by phentolamine at the same concentration. In the left atrial strip, the potentiation of contraction by tyramine was markedly depressed by droperidol. In the reserpinized preparation, the effect of tyramine was depressed markedly and there was no norepinephrine fluorescence. After incubation with norepinephrine they were restored to the same level as in non-reserpinized preparations. However, incubation with droperidol before norepinephrine blocked the restoration. It is postulated that droperidol may have both alpha-adrenergic blocking action and inhibitory action on norepinephrine uptake by adrenergic terminals.

Adrenergic alpha-Antagonists

Inhibiting effect of droperidol compared with verapamil on the myocardial fiber calcium exchange determined by a simple physiological procedure.

A simple procedure was employed in order to quantify myocardial calcium antagonism by the neuroleptic agent droperidol. Droperidol blocked recovery of excitability induced by isoproterenol in isolated rabbit hearts depolarized by KCl. This was also observed with verapamil, a known calcium inhibitor, though at much lower concentrations. Considering that isoproterenol excites depolarized tissue by favouring calcium conductance and that droperidol as verapamil lack beta-adrenergic blocking properties, it is infered that droperidol hinders myocardial membrane permeability to calcium ions in a manner similar to that of verapamil. This action of droperidol, together with its known inhibiting effect on the rapid Na entrance, may explain the mechanism by which it affects cardiac chronotropism.

Animals

Antiemetic effect of droperidol after ophthalmic surgery.

Postoperative nausea with emesis is an undesirable side effect of general anesthesia in patients who have undergone ophthalmic surgery. The antiemetic effect of intravenous droperidol (Inapsine) was measured in a double-blind, controlled study of 78 patients undergoing general (enflurane [Ethrane]) anesthesia for a variety of ophthalmic procedures. There was a significant difference in the incidence of postoperative nausea and/or emesis in the droperidol-treated group, 13 of 78 (16%) as compared with the control population (37 of 87 [42%]). No complications of droperidol administration were observed. Droperidol may be an effective antiemetic drug if used prophylactically in patients who receive general anesthesia for ophthalmic surgery.

Adolescent

Mechanism of the hypertensive effect of droperidol in pheochromocytoma.

Droperidol is used in the anaesthetic management of pheochromocytoma because of its sedative, anti-dysrhythmic and alpha-adrenoreceptor blocking properties. However, droperidol when used in pheochromocytoma, has been reported to produce a paradoxical hypertensive response. In vitro experiments with perfused rabbit ear arteries using a histochemical fluorescence technique, showed droperidol to be an inhibitor of noradrenaline uptake into sympathetic nerve endings, and this uptake inhibition was dose related. The uptake inhibition effect did not, however, produce pressor changes in experiments simulating pheochromocytoma in cats. The hypertensive response to droperidol may be due to blockade of presynaptic alpha-adrenoreceptors and this possible mechanism of action is discussed.

Adrenal Gland Neoplasms

Comparison of domperidone, droperidol, and metoclopramide in the prevention and treatment of nausea and vomiting after balanced general anesthesia.

Women (185) undergoing elective orthopedic surgery under balanced general anesthesia were given 5 or 10 mg of domperidone, 1.25 mg of droperidol, 10 mg of metoclopramide, or a saline placebo intravenously in a double-blind random fashion 5 minutes before the end of anesthesia to prevent postoperative vomiting. Administration of the same antiemetic was repeated intramuscularly during the first 24 hours postoperatively if the patient complained of nausea or retched or vomited. Sigificantly (p less than 0.05 to p less than 0.001), fewer of the patients given droperidol were nauseated (25%) or vomited (17%) in comparison with patients given saline (incidence of nausea was 55% and vomiting 40%). Incidences of nausea and vomiting were similar in patients given domperidone, metoclopramide, or saline. Furthermore, 39 to 45% of the patients given domperidone, metoclopramide, or saline needed additional doses of the same drug, whereas only 22% of the patient given droperidol required a second dose. It is concluded that droperidol is effective in the prevention and treatment of postoperative nausea and vomiting after balanced general anesthesia but that domperidone or metoclopramide are not.

Adult

The effect of diazepam, flunitrazepam and droperidol with an analgesic on blood pressure and heart rate in man.

The effects of i.v. diazepam (0.3 mg/kg), droperidol (5 mg) and a new benzodiazepine, 5-(a-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one (flunitrazepam, Ro 5-4200) (0.03 mg/kg) on blood pressure and heart rate was studied in 62 healthy volunteer students. Observations were made after each drug alone, after diazepam and flunitrazepam each combined with pethidine (1 mg/kg), and after droperidol combined with fentanyl (0.2 mg). The doses of the benzodiazepines were halved in those subjects given pethidine but the dose of droperidol was the same with and without fentanyl. The blood pressure was measured by auscultation and the heart rate by counting the radial pulse. The systolic and diastolic blood pressure was regularly decreased by not more than 20 and 11 mmHg, respectively. Changes in the heart rate were slight. Flunitrazepam did not have greater effects than diazepam or droperidol through the combination of flunitrazepam and pethidine seemed to induce a greater fall in systolic blood pressure than did the combination of diazepam and pethidine. None of the changes observed was clinically significant.

Adult

Electrophysiological effects of droperidol on sinoatrial nodal fibers.

The influence of 1 and 5 mg/l of droperidol on rabbit sinus node intracellular recordings was evaluated. At 1 mg/l the drug merely prolonged the spontaneous basic cycle by reducing phase 4 slope of the action potential. At the higher concentration, droperidol induced a more pronounced effect of these variables and after 20 min perfusion, it also decreased the upstroke velocity and the threshold potential. Further exposure continued to reduce spontaneous rate, until irregular failure of impulse initiation and subthreshold oscillations appeared. After 45 min exposure to droperidol, only subthreshold oscillations could be recorded. Isoproterenol (0.2 mg/l) rapidly restored normal action potentials, while acetylcholine (0.5 mg/l) caused an immediate arrest leaving a stable level of membrane potential. The activity of droperidol in 1 mg/l concentration could be dependent on a partial blockade of the sodium leakage current, while at higher concentrations of 5 mg/l the drug seems to provoke a total blockade of Na--Ca slow channels. Subthreshold oscillations could be explained by changes in K conductance together with a remanent of the sodium leakage current.

Acetylcholine

Comparison of droperidol, haloperidol and prochlorperazine as postoperative anti-emetics.

The results of this study demonstrate that prochlorperazine, haloperidol and droperidol are all effective post-operative anti-emetic compounds when compared to saline but vary in onset of activity and duration of action. Haloperidol has the shortest onset of action, being effective within 30 minutes of intravenous administration. Prochlorperazine has an intermediate onset of action and droperidol is the slowest of the three compounds but the only one to provide significant anti-emesis 4-24 hours following administration. Our data suggest that a combination of haloperidol and droperidol may be more effective as an anti-emetic than any one of the compounds used alone.

Droperidol

The effects of droperidol and fentanyl on intracranial pressure and cerebral perfusion pressure in neurosurgical patients.

The effects of droperidol and fentanyl on the intracranial pressure (i.c.p.) and cerebral perfusion pressure (c.p.p.) were studied in eight anaesthetized normocapnic patients with intracranial space-occupying lesions. The infection of droperidol resulted in a small and not significant increase in i.c.p. from 24.0 to 27.2 mm Hg, while c.p.p. decreased from 75.9 mm Hg to 57.8 mm Hg, as a result of a decrease in systemic arterial pressure. The addition of fentanyl produced no change in i.c.p., but a further decrease in arterial pressure decreased c.p.p. from 60.4 mm Hg to 47.8 mm Hg. In four patients values of c.p.p. less than 40 mm Hg were obtained. C.p.p. was was increased by hyperventilation in all but one of these patients. It is concluded that droperidol and fentanyl should be used in patients with intracranial hypertension only if hypocapnia has been established and when the arterial pressure is normal or increased.

Adult