Beta-2 Agonist side effects & overdose

I was chatting with my AT preceptor today and we got to talking about albuterol. We ended the conversation wondering what side effects would be in general, whether the Pt needed it or not. So I'm thinking, Beta-2 agonist means bronchodilation due to relaxing the smooth muscle, and some increase in skeletal muscle contractility which causes the tremors.

First question to y'all is, are there any more side effects other than those?

As well, how does overdosing on a Beta-2 agonist work? I'm reading that it can be fatal, but I can't find a real physiological reason other than "fatal" and for some reason liver failure. My thought process here is that it is only beta 2, so it is not effecting the heart or really the vascular system. Sure it could cause liver failure, but that would be the same physiology as any other overdose/alcohol consumption, no? What happens as the Pt receives an increasingly over-the-top dose? How much are we talking? Certainly an MDI wouldn't accomplish permanent damage by itself. Thoughts?

Thanks guys!

Hyperglycemia due to activation of glycolysis and gluconeogenesis. Far from an issue in an otherwise healthy individual.

teedubbyaw said:

Hyperglycemia due to activation of glycolysis and gluconeogenesis. Far from an issue in an otherwise healthy individual.

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I see why that would be a situational but real problem, but why is glycolysis even involved here?

The stimulation of beta receptors in the liver (part of the sympathetic autonomic response) causes glucose to be released. But hyperglycemia from it will normally only occur in diabetics.

In non-diabetics, the extra glucose released will cause an increase in insulin production, which will draw potassium into the cells alongside the glucose, and can cause hypokalemia.

Beta-2 agonists also activate beta-1 receptors in higher doses. This is why they cause tachycardia and hypertension when used in large doses, and this is also why an overdose could be fatal.

Ok, I see what you mean. It is a bit indirect, but can still happen. Now, what kind of dosage are we talking for tachycardia, hypertension, and possible hypokalemia? Even in general, ie, 10mgs vs 100 mgs.

Thanks!

To cause hypokalemia to the point of causing a cardiac arrest would require massive amounts.

I wouldn't even be willing to venture a guess.

Edit: a few things I found searching "LD50 Albuterol" on Google indicated ~2000mg/kg in rats and mice, couldn't find anything on humans.

Found this: http://www.ncbi.nlm.nih.gov/m/pubmed/8067892/

Roger that, so a legitimate OD is not reasonable. Thanks for the help!

teedubbyaw said:

Hyperglycemia due to activation of glycolysis and gluconeogenesis.

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Also from moderation of insulin release from the pancreas and decreased insulin sensitivity of the skeletal muscles.

Grimes said:

Roger that, so a legitimate OD is not reasonable. Thanks for the help!

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Depends on what you mean by "OD". Repeated doses of albuterol can probably cause increased Mv02 sufficient to cause problems in susceptible individuals, perhaps especially on those upregulated due to beta antagonist therapy.

As I recall, hypokalemia secondary to albuterol was more of an issue for peds. We were encouraged to consider Xopenex -- a different isomer of the same drug.