Hypotension with barbiturates

Mercier el al. (330) administered i.v. infusions of sodium salicylate to dogs and determined the lethal dose to be 1 g/kg. Simultaneous administration of papaverine resulted in a slight increase in the toxicity. Lettr6 et al. (331) studied the synergism of mitotic poisons and found that papaverine intensified the mitotic effect of colchicine on the growth of fibroblasts in vitro. The spasmolytic effect of khelline was augmented by small doses of papaverine (332). Therapeutic doses of khelline did not produce a hypotensive effect upon dogs, but in combination with barbiturates and papaverine a hypotensive effect was observed. 

Atropine - emergency treatment of hypotension with bradycardia Azathioprine - immunosuppressant cancer chemotherapy, rheumatoid arthritis Baclofen - skeletal muscle relaxant spasticity Barbiturate - hypnotic (little therapeutic use)... 

Toxicity management of mild to moderate toxicity usually requires only supportive care. Management of severe toxicity may require more aggressive intervention. Monitor the need for airway management, including endotracheal intubation in patients with CNS depression or recurrent seizures. Treat seizures with IV benzodiazepines and barbiturates. Treat hypotension with fluids and vasopressors. Atropine maybe used to treat hypotension associated with bradycardia. 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

With BZ administration, a brief period of cardiorespiratory depression (less than 1 minute) may occur and can necessitate assisted ventilation or require intubation, especially if BZs are used with a barbiturate. Hypotension may occur with high doses of BZs. 

Clinical reports of patients who underwent chloroform anesthesia indicated that premedication with morphine caused serious respiratory depression when chloroform was co-administered. Thiopentone (thiopental Na, an ultra-short-acting barbiturate anesthetic) was associated with increased incidences of hypotension in chloroform-anesthetized patients (Whitaker and Jones 1965). 

Fatalities due to acute BZD overdose alone are extremely rare. Nevertheless, fatal overdoses with triazolam in the elderly have been reported ( 192, 193). Even with ingestion of massive doses, recovery appears to be rapid and without serious complications or aftereffects ( 194, 195, 196 and 197). Combined ingestion of BZDs with other CNS depressants (alcohol, barbiturates, narcotics, orTCAs), however, may result in severe CNS and respiratory depression or hypotension. Severity of symptoms appears to depend more on the type and quantity of the other drugs than on the BZD plasma level (194, 195, 196 and 197). 

There is a broad spectrum of signs and symptoms associated with acute short-acting barbiturate toxicity. Lethargy, ataxia, nystagmus, diplopia, amnesia, slurred speech, confusion, hypotonia, hypotension, hypothermia, hypoglycemia, coma, respiratory depression, and death have been reported. Comatose patients may develop erythematous or hemorrhagic bullous skin lesions primarily over areas of pressure (e.g., elbows and knees). These lesions are commonly referred to as barb burns . Doses of 3-5 mg kg of most short-acting barbiturates will cause toxicity in children. The estimated potentially fatal dose in nondependent adults is 3-6 g. 

Concomitant use with other CNS depressants (narcotic analgesics, general anesthetics, antihistamines, phenothiazines, barbiturates, benzodiazepines, sedative-hypnotics, tricyclic antidepressants, alcohol, and muscle relaxants) potentiates respiratory and CNS depression, sedation, and hypotensive effects. 

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