Cardiovascular depression

Methohexital [18652-93-2] (Brevital), C 4H gN202, (2) is a barbiturate iv anesthetic iaduction agent that has a slightly faster onset than thiopentone and less accumulation. The recovery from anesthesia is also slightly faster and better. However, iaduction is associated with an iacreased iacidence of excitatory phenomena. Methohexital also causes respiratory and cardiovascular depression and is unstable ia solution, necessitating reconstitution before use (99). 

Morphine has certain undesirable side effects. Among these are respiratory depression, nausea, and vomiting, depression of the cough reflex, cardiovascular depression and hypotension, smooth muscle contraction (constipation), and histamine release (93). Morphine s onset of action, duration, and low therapeutic indices have prompted a search for a more effective opiate iv anesthetic. Extreme simplification of the complex morphine molecule has resulted in anilido —piperidines, the fentanyl class of extremely potent opiate iv anesthetics (118,119). 

A preliminary report on rauwolscine by Chakravarti indicates that it is a cardiovascular depressant, shows hypotensive action and a relatively high toxicity. Koepfli s rauwolfine produces a fall in blood pressure, and stimulation of respiration in frogs it has a curare-like action. The rauwolfine of van Itallie and Steenhauer has been examined by Hartog and by de Boer, especially in regard to its cardiac action. According to Raymond-Hamet, it reverses the action of adrenaline. 

The thiazide diuretics possess antihypertensive properties, in part consequent upon electrolyte and plasma-volume changes but mainly resulting from a direct cardiovascular depressant effect. This is clearly illustrated by the non-diuretic thiazide, diazoxide, which is an effective hypotensive [326b, c]. It is not therefore, surprising that both these properties should be found (in varying proportions) in other, structurally related, compounds. One particular line of research, aimed at modification of the thiazide heterocycle (the o-chlorobenzenesulphonamide moiety was untouched as it was believed essential to activity-the subsequent advent of ethacrynic acid questions this belieO examined first the corresponding... 

The main indication for etomidate is induction of anesthesia. It has no analgesic properties. It has little respiratory and cardiovascular depressant properties. However it can seriously suppress adrenal function. 

Thiopental remains the most popular IV induction agent. Its rapid and pleasant induction of anesthesia and its relatively low cost are among the reasons for its high acceptance rate by both the patient and the practitioner. Also, it does not induce obstructive secretions in the airway, produces little or no emesis, and does not sensitize the myocardium to endogenous catecholamines that may be released in response to the stress of surgery. It can, however, cause cardiovascular depression. 

Cardiovascular depression may occur after the administration of barbiturates by IV bolus. The hemodynamic changes are transient in the healthy patient with good cardiovascular reserve, but they may be prolonged... 

Although serious adverse reactions to lidocaine are uncommon, high dosage by any route may produce cardiovascular depression, bradycardia, hypotension, arrhythmias, heart block, cardiovascular collapse, and cardiac arrest,... 

It also produces the respiratory and cardiovascular depression as with halothane but bradycardia is more prominent. 

Isoflurane has a dose-dependent depressant effect on the myocardium. In vitro studies indicate that it reduces myocardial contractility to a similar extent as halothane. In vivo, isoflurane appears to be less of a cardiovascular depressant than other volatile agents. 

Nitrous oxide has both a direct depressant and sympthomimetic effect on the myocardium. In healthy patients these tend to counterbalance each other, the resultant effect being minimal cardiovascular depression. In patients with car-diovascular disease or who are taking conconcurrent medication with, e.g. 3 blockers, its depressant effect may be more obvious. Nitrous oxide supplementation of high-dose opioid-based anaesthesia may result in a reduction in cardiac output and heart rate although the mechanism of this is unclear. Nitrous oxide may have a venoconstrictor effect resulting in increased pulmonary vascular resistance, particularly in the presence of pulmonary hypertension. 

The combination of pethidine with monoamine oxidase inhibitors (MAOIs) can cause serious adverse reaction, which can present in two distinct forms. The excitatory form is characterised by sudden agitation, delirium, headache, hypo- or hypertension, rigidity, hyperpyrexia, convulsions and coma. It is thought to be caused by an increase in cerebral 5-HT concentrations because of inhibition of monoamine oxidase. This is potentiated by pethidine, which blocks neuronal uptake of 5-HT. The depressive form, which is frequently severe and fatal, consists of respiratory and cardiovascular depression and coma. It is the result of the inhibition of hepatic microsomal enzymes by the MAOI, leading to accumulation of pethidine. Phenoperidine should also be avoided in patients taking MAOI drugs but other opioids appear to be safe. 

At doses up to those causing hypnosis, no significant effects on the cardiovascular system are observed in healthy patients. However, in hypovolemic states, heart failure, and other diseases that impair cardiovascular function, normal doses of sedative-hypnotics may cause cardiovascular depression, probably as a result of actions on the medullary vasomotor centers. At toxic doses, myocardial contractility and vascular tone may both be depressed by central and peripheral effects, leading to circulatory collapse. Respiratory and cardiovascular effects are more marked when sedative-hypnotics are given intravenously. 

Thiopental Rapid onset and rapid recovery (bolus dose) —slow recovery following infusion Standard induction agent causes cardiovascular depression avoid in porphyrias... 

Nearly all opioids induce bradycardia (Bowdle, 1998), most likely mediated via central stimulation of the vagus nerve. Cardiovascular depression associated with most opioids is moderate and only the stronger opioids of the fentanyl group induce a more severe effect. Morphine and some of its analogs induce a non-opioid receptor-mediated release of histamine, which can result in a decrease in blood pressure and compensatory... 

A number of industrial chemicals have been linked to cardiotoxicity. Aldehydes and primary alcohols that can be metabolically oxidized to aldehydes have exhibited cardiodepressant effects. Acute exposure to ethanol has caused arrhythmia. Isopropyl alcohol (2-propanol), a widely used industrial chemical and personal care product, may cause cardiovascular depression and excessively rapid heartbeat. Some halogenated hydrocarbons, including chloroform, ethyl bromide, and trichlo-rofluoromethane, have been implicated in cardiovascular disorders, including arrhythmia. 

Phencyclidine (PCP) was developed in late 1950 as an intravenous anesthetic agent. PCP produces anesthesia and analgesia with respiratory or cardiovascular depression. However, postoperatively, the drug produced psychotomimetic effects (e.g., delirium and hallucinations) and was subsequently withdrawn from the market. 

Chloroform pleasant odor, nonflammability, hepatotoxin, cardiovascular depressant... 

Lebeaux M (1975) Sheep a model fortesting spinal and epidural anesthetic agents. Laboratory Animal Sci 25 629-633 Raner C, Biber B, Lundberg J et al. (1994) Cardiovascular depression by isofluorane and concomitant thoracic epidural anesthesia is reversed by dopamine. Acta Anesthesiol Scand 36 136-143... 

Enflurane is a structural isomer of isoflurane. It is more soluble than isoflurane. It causes more respiratory depression than the other volatile anaesthetics and hypercapnia is almost inevitable in patients breathing spontaneously. It causes more cardiovascular depression than isoflurane and is occasionally associated with cardiac arrythmias. Two percent of enflurane is metabolised and prolonged administration or use in enzyme-induced patients generates sufficient free inorganic fluoride from the drug molecule to cause polyuric renal failure. There have been a few cases of jaimdice and heptatoxicity associated with enflurane but the incidence of about one in 1-2 million anaesthetics is lower than with halothane. 

Hyperkalemia, acidosis, severe hypoxia, and myocardial ischemia increase the cardiovascular depressive effects of bupivacaine. 

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