Intravenous Administration Of Chlorpromazine Research Articles

Ultrasound-guided phrenic nerve block for intraoperative persistent hiccups: a case report

BackgroundContinuous hiccups during surgery not only affect the surgical procedure, they can also cause adverse effects for the patient. Apart from active investigation of the cause of the hiccups, their timely termination is also necessary.Case presentationWe reported a case of a 70-year-old woman with continuous intraoperative hiccups that appeared during vaginal hysterectomy under low continuous epidural anesthesia. After the ineffectiveness CO2 repeated inhalation and intravenous administration of chlorpromazine and methoxychlorpromide, we performed unilateral phrenic nerve block under ultrasound guidance. Hiccups were terminated without any related complications.ConclusionsDuring intraoperative continuous hiccups, ultrasound guided phrenic nerve block may be a suitable treatment option when physical methods and drug therapy are not effective. However, given the absence of a vital risk related to hiccups, this block should imply the complete absence of any respiratory contraindication and a prolonged postoperative respiratory monitoring.

Cardiovascular effects of phenothiazines

Phenothiazines have significant electrophysiologic and cardiocirculatory effects. The electrophysiologic effect of these drugs is similar to that reported for quinidine. Phenothiazines decrease the rate of rise of phase 0 of the action potential, decrease the duration and amplitude of phase 2, and prolong phase 3. The surface ECG changes produced by phenothiazines are lengthening of the QTC interval, ST-T wave changes, increased size of U waves, and prolongation of the PR interval. The degree of repolarization abnormalities secondary to phenothiazines seems to be dose-related. Various arrhythmias have been attributed to the effect of phenothiazine therapy and numerous cases of sudden death as a result of fatal arrhythmia have been described. Paradoxically, phenothiazines such as chlorpromazine and thioridazine also have been shown to have significant antiarrhythmic properties. Chlorpromazine shows a powerful vasodilatory effects which is caused by alpha-adrenergic receptor blockade, a central action, and a direct effect on the vascular wall. In addition, the drugs also have a direct depressant effect on the myocardium. As a result of peripheral vasodilatation and negative inotropic effects, hypotension is the most common adverse reaction of phenothiazines in patients with no evidence of congestive heart failure. Experimental studies have demonstrated significant reductions in systemic and pulmonary vascular resistance as well as systemic blood pressure following intravenous administration of chlorpromazine. These hemodynamic changes were accompanied by significant increase in cardiac output in one study and by no change in cardiac output in another study. The vasodilatory effect of chlorpromazine resulted in increased renal and mesenteric blood flow and prolongation of survival time in dogs following hemorrhagic hypotension. Chlorpromazine was found effective in relieving abnormal vascular tonus and improving the circulation in patients undergoing cardiopulmonary bypass surgery. In patients with myocardial infarction complicated by congestive heart failure, intravenous administration of chlorpromazine caused significant hemodynamic improvement and a considerable degree of sedation. The drug was found effective in reducing the vasoactive response in patients with cardiogenic shock which resulted in improved tissue perfusion and metabolism.

A spinal sympatho-inhibitory action of chlorpromazine and haloperidol in the cat.

Abstract Intravenous administration of chlorpromazine (0.03–l.0 mg/kg) or haloperidol (0.03–1.0 mg/kg) resulted in a dose-dependent inhibition of spinally-evoked electrodermal responses (EDRs) in the anesthetized spinal cat. These findings suggest that chlorpromazine and haloperidol act at the level of the spinal cord to depress activity in the sympathetic-cholinergic electrodermal system. Neither drug had a significant effect on pre- or postganglionically-evoked EDRs, further indicating their central action.

GI pharmacology of polyethyleneimine II: motor activity in anesthetized dogs.

The effects of orally and intravenously administered doses of polyethyleneimine were observed in 18 chloralose-urethan-anesthetized dogs. Polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions, a copious flow of gastric mucus, increased segmenting and propulsive activities of the small and large intestines, and occasional micturition and defecation. The gastric corpus and fundic regions became relaxed and enlarged. These events were associated with the prompt appearance of retching. The retching response to oral administration could only be abolished by bilateral vagotomy or bilateral sympathectomy. The skeletal muscle component of retching was blocked by tubocurarine. Intravenous administration of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine. Either oral or intravenous administration of polyethyleneimine produced no detectable changes in the lead II ECG but was associated with marked transient reductions in both mean and pulsatile arterial blood pressures. These depressor effects showed clear tachyphylaxis. In all cases where GI effects were noted, respiration was augmented and erratic in a manner associated with the retching responses.

Hypothermic action of chlorpromazine in monkeys.

1 In the conscious monkey (Macaca cyclopis) intravenous administration of chlorpromazine 0.1-8.0 mg/kg produced a fall of rectal temperature of 0.3 to 3.5 degrees C after a latency of 3.5 to 10.8 minutes. The course of hypothermia lasted from 125 to 600 min or more. 2 Direct injection of chlorpromazine 100-800 mug into the lateral or fourth cerebral ventricle produced a similar fall of 0.3 to 2.0 degrees C but with shorter latency (2 to 3.5 min) and with a duration of 94 to 375 minutes. 3 Two distinct structures in the brain stem, namely, the preoptic anterior hypothalamus (POAH) and medulla oblongata, responded to direct injection of chlorpromazine 200 mug. The sensitivity was slightly higher in the POAH than in the medulla. Structures in between were not sensitive. 4 The results suggest that chlorpromazine works principally through the central nervous system, i.e. the POAH and medulla oblongata, to mediate its hypothermic effect.

The effect of chlorpromazine on plasma renin activity and aldosterone in man.

The response of plasma renin activity (PRA) and aldosterone to the intravenous administration of chlorpromazine was determined in schizophrenic patients while they were supine and on a normal sodium diet. In all subjects PRA and aldosterone increased during chlorpromazine administration with little or no change in blood pressure. The maximum PRA and aldosterone levels occurred 60 min after the higher dose of chlorpromazine. These data suggest that chlorpromazine affects the renin-angiotensin-aldosterone system and it may interfere with the evaluation of this system in patients receiving this drug.

Effects of chlorpromazine on the metabolism of catecholamines in dog brain.

1. The effect of chlorpromazine (CPZ) on the metabolism of dopamine and 5-hydroxytryptamine in dog brain was investigated by following the concentrations of the acid metabolites of these amines, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid, in the ventricular cerebrospinal fluid (C.S.F.) of dogs over a period of 5 hr after intravenous administration of CPZ (2.5, 5, 10 and 15 mg/kg), using the technique of serial sampling of lateral ventricular C.S.F. "Low" doses (2.5-10 mg/kg) produced a rise in the concentration of homovanillic acid and smaller increases in the concentrations of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid. "High" doses (10-15 mg/kg) had a lesser effect on the concentration of homovanillic acid and had no effect on, or decreased, the concentrations of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid. The concentration of 3,4-dihydroxyphenylacetic acid was maximal in the ventricular C.S.F. 2 hr after CPZ 5 mg/kg and was unaltered from the control level 2 hr after 15 mg/kg.2. The effects on the metabolism of brain amines of CPZ (5 mg/kg), doses which the serial sampling of C.S.F. experiments had indicated as producing maximal and minimal effects on dopamine metabolism in brain tissue, were studied by estimating the concentrations of adrenaline, noradrenaline, dopamine, metanephrine, methoxydopamine, homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid in the hypothalamus, midbrain, thalamus, hindbrain, cortex, globus pallidus and caudate nucleus of control dogs and of dogs treated with CPZ intravenously 2 hr before killing. The concentrations of homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid were estimated in samples of ventricular C.S.F. withdrawn from these dogs 2 hr after the injection of CPZ (i.e., immediately before death).3. The following changes in concentrations were observed. Dopamine: CPZ 5 mg/kg produced no change in the concentration in the caudate nucleus, globus pallidus and midbrain and increased the concentration in the thalamus; CPZ 15 mg/kg appeared to cause a reduction in the concentration of this amine in the caudate nucleus and globus pallidus. Homovanillic acid and 3,4-dihydroxyphenylacetic acid: CPZ 5 mg/kg increased the concentrations of both acids in the caudate nucleus and had no effect on the concentrations of the acids in the globus pallidus, hypothalamus and thalamus; CPZ 15 mg/kg produced no change in the concentrations of the acids in any area of the brain. Methoxydopamine: CPZ 5 mg/kg and 15 mg/kg reduced the concentration in the caudate nucleus. Noradrenaline: The concentrations in the hypothalamus, midbrain, thalamus and hindbrain were slightly increased by CPZ 5 mg/kg and 15 mg/kg. Only in the thalamus was a statistically significant increase in noradrenaline observed.4. It was concluded that the actions of chlorpromazine on catecholamine synthesis and metabolism in the brain of the dog are dose dependent. A dose of CPZ 5 mg/kg was postulated to have the following actions: (i) to increase dopamine synthesis; (ii) to activate mitochondrial monoamine oxidase. A dose of CPZ 15 mg/kg was postulated to act as follows: (i) to decrease dopamine synthesis; or (ii) to release dopamine from its storage sites.5. The ratios of the concentrations of homovanillic acid, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindolylacetic acid in the caudate nucleus to the concentrations of these acids in the ventricular C.S.F. were the same in the control dogs as in the dogs treated with CPZ (5 mg/kg and 15 mg/kg). It was concluded that the levels of the acid metabolites of dopamine in lateral ventricular C.S.F. reflect the levels of these acids in the caudate nucleus.

Comparison of T-wave changes in the dog following intravenous administration of chlorpromazine and fluphenazine.

As early as 1954, flattening of the T-wave following chlorpromazine administration to anaesthetized dogs was reported by Moyer et al.1. Marked T-wave changes were also noted by Melville2 in 1958 following the administration of chlorpromazine to dogs under similar conditions. Other investigators have noted electrocardiographic alterations in man after parenteral administration of chlorpromazine. Undesirable effects on the electrocardiogram and ballistocardiogram by chlorpromazine were observed by Eliakim et al.3. Kupatz4 recommended that chlorpromazine should not be used to tranquillize children prior to electrocardiogram determinations because the compound induced changes in the T-wave. Minor T-wave changes in the electrocardiograms of several patients treated with chlorpromazine were noted by Moyer et al.1.

EFFECTS OF CHLORPROMAZINE AND BROMOLYSERGIC ACID DIETHYLAMIDE ON GASTRIC SECRETION OF ACID INDUCED BY HISTAMINE IN RATS.

In anaesthetized rats in which the lumen of the stomach was perfused with 0.001 to 0.00025 N-sodium hydroxide solution and the pH of effluent fluid was recorded continuously, intravenous administration of chlorpromazine caused transient inhibition of acid secretion. After acid secretion had returned to the control level the responses to histamine were greater than those before chlorpromazine was given. Aminoguanidine, iproniazid and bromolysergic acid diethylamide also potentiated the effect of histamine on acid secretion but the initial inhibition was absent. Indirect evidence from experiments in which mixtures of aminoguanidine with chlorpromazine or bromolysergic acid diethylamide and of iproniazid with chlorpromazine or bromolysergic acid diethylamide were given, suggests that chlorpromazine and bromolysergic acid diethylamide enhance responses to histamine by inhibition of imidazole-N-methyl transferase.

Effect of Chlorpromazine on Cerebral Hemodynamics and Cerebral Oxygen Metabolism in Man

Cerebral blood flow frequently decreases following the intravenous administration of chlorpromazine, apparently a result of the reduction in arterial blood pressure. If arterial blood pressure does not decrease, cerebral blood flow is not altered. Chlorpromazine does not exert a depressant effect on cerebral oxygen consumption as morphine does.

Effect of chlorpromazine upon epileptic and normal monkeys.

Conclusions1. The rapid intravenous administration of chlorpromazine (2-10 mg/kg) to epileptic and normal monkeys produced prompt profound behavioral changes characterized by hypokinesia, flaccidity, diminished responsiveness, reduced aggressiveness, lethargy and somnolence. 2. High amplitude slow wave activity (2-5 second) became dominant in the EEG up to several hours after intravenous injection of chlorpromazine; epileptic monkeys showed, in addition, increased high amplitude spike and sharp wave forms. 3. Epileptic monkeys under the acute influence of chlorpromazine retained their clinical convulsive responsiveness to intramuscular Met-razol (16 mg/kg or less). Clinical epileptic response to vigorous prodding was not significantly changed. 4. Normal control monkeys under the acute influence of chlorpromazine did not exhibit clinical convulsions and remained refractory to treatment with intramuscular Metrazol (32 mg/kg) and to vigorous prodding stimulation.