Wed3November0903PM 13

A 75-year-old woman is admitted to the coronary care unit with cardiogenic shock following an acute myocardial infarction. Full haemodynamic monitoring is employed and a dobutamine infusion is commenced.

The following haemodynamic data are collected over the next four days:

Day1 Day2 Day3 Day4

Infusion rate of dobutamine (mcg/kg/min) 5 10 15 25

Cardiac output (L/min) 3.4 3.2 3.1 3.2

Pulse rate (beats per min) 110 112 105 100

Blood pressure (mmHg) 80/60 75/61 83/60 81/56

Which one of the following options is the most likely explanation for the haemodynamic changes in response to treatment?

(Please select 1 option)

Degradation of beta1 receptors

Increased metabolism secondary to induction of hepatic catechol-O-methyl-transferase Incorrect answer selected

Tolerance by down-regulation of beta1 receptors This is the correct answer

Increased renal excretion of dobutamine

Tachyphylaxis secondary to depletion of neurotransmitters

Explanation

Tachyphylaxis is the rapid decrease in response to a drug over a short period of time (minutes to hours). It usually results from the acute depletion of neurotransmitters.

Examples include a decrease in response to indirectly acting catecholamines such as ephedrine or the ganglion blocker, trimetaphan.

Tolerance or desensitisation is the gradual reduction in activity of a drug over a period of days or weeks.

Beta1 receptors are subject to "down-regulation". This is the acute reduction in the number of receptors and subsequent reduction of affinity of the agonist. The mechanisms are:

Internalisation or endocytosis of receptors into the cell membrane

Eventual degradation of the receptors.

This process is faster than de novo synthesis of new receptors.

Other examples include:

Nitrates (depletion of sulphydryl groups in smooth muscle)

Opioids (down-regulation of opioid receptors)

Barbiturates (liver enzyme induction).

Dobutamine is considered a direct beta1-adrenergic agonist. It also has mild beta2- and alpha1-adrenergic effects at therapeutic doses. These effects tend to balance one another and cause little direct effect on the systemic vasculature. In contrast to dopamine, dobutamine does not cause the release of norepinephrine. It has relatively mild chronotropic, arrhythmogenic, and vasodilative effects.

Answer Statistics

1

4%

2

6%

3

56%

4

2%

5

33%

Times answered: 273