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Pharmacology

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Autonomic Nervous Systems

Question
46 out of 75
 

Which one of the following is a side effect of beta 2 agonist?



A Hypoglycemia
B Hypomagnesemia

C Hypophosphatemia
D Hypokalemia

Ans. D Hypokalemia

a. β2 agonist cause hypokalemia by enhancing K + uptake into muscles, thus used in hyperkalemic familial periodic paralysis.

b. Beta-adrenoceptor agonists (β-agonists) bind to β-receptors on cardiac and smooth muscle tissues. They also have important actions in other tissues, especially bronchial smooth muscle (relaxation), the liver (stimulate glycogenolysis) and kidneys (stimulated renin release).

c. Beta-adrenoceptors normally bind to norepinephrinereleased by sympathetic adrenergic nerves, and to circulating epinephrine.

d. Therefore, β-agonists mimic the actions of sympathetic adrenergic stimulation acting through β-adrenoceptors. Overall, the effect of β-agonists is cardiac stimulation (increased heart rate, contractility, conduction velocity, relaxation) and systemic vasodilation. Arterial pressure may increase, but not necessarily because the fall in systemic vascular resistance offsets the increase in cardiac output.

e. Therefore, the effect on arterial pressure depends on the relative influence on cardiac versus vascular β-adrenoceptors. β-agonists cause β-receptor down-regulation, which limits their therapeutic efficacy to short-term application. Beta-agonists, because they are catecholamines, have a low bioavailability and therefore must be given by intravenous infusion.

Drug

Receptor Selectivity

Clinical Use

Comments

Epinephrine

β1 = β2 > α1* = α2*

Anaphylactic shock; cardiogenic shock; cardiac arrest

Low doses produce cardiac stimulation and vasodilation, which turns to vasoconstriction at high doses. *At high plasma concentrations, α = β selectivity.

Norepinephrine

β1 = α1 >
β2 = α2

Severe hypotension; septic shock

Reflex bradycardia masks direct stimulatory effects on sinoatrial node.

Dopamine

β1 = β2 > α1*

Acute heart failure, cardiogenic shock and acute renal failure

Biosynthetic precursor of norepinephrine; stimulates norepinephrine release. *At low doses, it stimulates the heart and decreases systemic vascular resistance; at high doses, vasodilation becomes vasoconstriction as lower affinity α-receptors bind to the dopamine; also binds to D1 receptors in kidney, producing vasodilation.

Dobutamine

β1 > β2 > α1

Acute heart failure; cardiogenic shock; refractory heart failure

Net effect is cardiac stimulation with modest vasodilation.

Isoproterenol

β1 = β2

Bradycardia and atrioventricular block

Net effect is cardiac stimulation and vasodilation with little change in pressure.

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