Glucagon

If calcium infusion provides inadequate clinical response, glucagon should be tested next. Glucagon is capable of inducing an immediate and remarkable positive chronotropic and inotropic response in mild to moderate toxicity. Glucagon binds to at least one specific membrane receptor, which is distinct from the b-adrenergic receptor. The glucagon receptor activates the stimulatory G-protein, leading to an elevation in cytosolic cyclic adenosine monophosphate (cAMP). The increased cAMP signals for the activation of protein kinases that phosphorylate the cytosolic domain of the L-channel. Channel phosphorylation increases the probability of channel opening, even if an organic CCB is bound to the channel. However, the degree of recruitment in channel opening is entirely dependent on the proportion of channels that have CCB bound to them. If binding is widespread, then the net increase in channel opening will be very low, even with maximal cAMP-protein kinase stimulation. Thus, with severe CCB poisoning, glucagon may be ineffective.

Glucagon should be diluted in normal saline, as opposed to using the phenol provided in the package, and a 0.1 mg/kg intravenous test bolus should be administered. In general, one of two responses occurs with glucagon injection with CCB overdose. The patient may show immediate evidence of improvement, both on ECG and in blood pressure. Alternatively, the patient may vomit, and deteriorate. —I4 andi5 If a benefit is observed, a constant infusion of glucagon should be initiated, starting at 0.1 mg/kg/h. The infusion rate should be minimized to maintain sinus rhythm or a systolic blood pressure above 100 mmHg with urine production above 1 mL/kg/h. Note that wholesale cost of glucagon is about $20/mg.

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