Toxicity : Beta Blockers

• The common feature of beta-blocker toxicity is excessive blockade of the beta-receptors resulting in bradycardia and hypotension.
• goal of antidote is to restore perfusion to critical organ systems by increasing cardiac output.
• accomplished by improving myocardial contractility, increasing heart rate or both.  

Glucagon

• high-dose glucagon is considered the first-line antidote.
• enhance myocardial contractility, heart rate and atrioventricular conduction; many authors consider it the drug of choice for beta blocker toxicity.
• rapid onset of action and a short duration of effect, rarely longer than 15 minutes.
• The endpoints for discontinuing glucagon infusions are not clear; however, it is reasonable that once a patient is hemodynamically stable for a minimum of 6 hours, a slow taper of a single agent at a time can be employed.
• Evidence suggest that once therapy is discontinued, close observation is necessary for a minimum of 12 hours.

Insulin

• High-dose insulin has long been reported to be an inotrope.
• As HIET is particularly effective in improving myocardial contractility, the early administration of HIET may avoid the need for vasopressors or allow the use of lower doses, thereby reducing the potential for ischemic consequences. Insulin therapy may be considered if the patient has failed to respond to the traditional antidotes or if hyperglycemia is present.

DRUG	DOSING & ADMINISTRATION	STABILITY
Glucagon	Initial bolus dose of 50–150 mcg/kg should be administered i.v. over 1 to 2 minutes. The initial dose should be followed by a continuous i.v. infusion at a rate of 2–5 mg/hr (maximum: 10 mg/hr) diluted in 5% dextrose injection (if benefit is seen). If improvement is not seen with the initial bolus dose, consider increasing the initial dose. Reconstitution requires adding 1 mL of sterile diluent to a vial containing 1 mg of the drug, to provide solutions containing 1 mg of glucagon/mL. http://www.ajhp.org/content/ajhp/63/19/1828.full.pdf?sso-checked=true IV bolus of 5-10 mg (adult) or 0.05mg/kg (pediatric) over 1-5 minutes, followed by a continuous infusion of response dose per hour. http://www.mdpoison.com/media/SOP/mdpoisoncom/healthcareprofessionals/antidote-facts/glucagon%20antidote%20facts.pdf	The bolus dose can be administered using the provided diluent or sterile water for injection. The prepared solution should be used immediately after reconstitution but may be kept at 5° C for up to 48 hours if necessary.
Insulin	1U/kg of an insulin bolus followed by continuous infusion of 1-10U/kg /h, but boluses of up to 10U/kg and continous infusions as high as 22U/kg/h has been used with good outcomes and minimal adverse events (Medscape) IV loading dose of 1 U/kg of regular insulin followed by an infusion of 0.5–1 U/kg/hr.The infusion dosage can be increased every 20–30 minutes. Doses of 2.5–3 U/kg/hr have been used depending on the response. http://www.medscape.com/viewarticle/757588_3	4 weeks after opening

REFERENCES

1. http://www.mdpoison.com/media/SOP/mdpoisoncom/healthcareprofessionals/antidote-facts/glucagon%20antidote%20facts.pdf
2. http://www.ajhp.org/content/ajhp/63/19/1828.full.pdf?sso-checked=true
3. http://emedicine.medscape.com/article/813342-treatment
4. http://www.medscape.com/viewarticle/757588_3