QUESTION NO.1

A man who has been “surfing the Web” in search of an aphrodisiac or some other agent to enhance “sexual prowess and performance” discovers yohimbine. He consumes the drug in excess and develops symptoms of toxicity that require your intervention. You consult your preferred drug reference and learn that yohimbine is a selective  α2-adrenergic antagonist.

Which of the following should you expect as a response to this drug?

a. Bradycardia

b. Bronchoconstriction

c. Excessive secretions by exocrine glands (salivary, lacrimal, etc.)

d. Hypertension

e. Reduced cardiac output from reduced left ventricular contractility

ANSWER

The answer is d.

(Brunton, pp 166t, 174, 264, 264f, 271; Craig, pp 94,787t; Katzung, pp 81, 84, 146, 189.) Whether you memorize that yohimbine is a selective  α2 antagonist is up to you, but you should know what the main effects of a selective α2 antagonist are. That, of course, depends on knowing what α2 receptors—at least in the peripheral autonomic nervous system—do in the physiological sense. Recall that the preponderance of physiologically important α2 receptors are located on adrenergic nerve terminals (or nerve “endings”). When stimulated by a suitable agonist, the response is a turning off of further NE release. Because NE is the neurotransmitter released from adrenergic nerves and it is an excellent  α agonist, the presynaptic α2 receptors upon which NE acts serve as the main physi-ologic mechanism for regulating neurotransmitter release. So, when we block those receptors with yohimbine, we enhance the  apparent overall activity of the sympathetic nervous system on its effectors by interfering with NE’s ability to turn off its own release. Of the responses listed, only hypertension (owing to the vasoconstrictor effects of NE on postsynaptic α-adrenergic receptors) occurs as a result of yohimbine (or of NE excess). The other main effects you should anticipate would be cardiac stimulation (rate, contractility, electrical impulse conduction rates; all  β1-mediated effects) and, probably of less clinical consequence, mydriasis (α). In terms of the aphrodisiac effects, the drug probably increases arousal via an action in the CNS, but the mechanism isn’t known for sure; and it increases the vigor of ejaculation, which is predominantly an  α-mediated effect. (Recall that erection primarily involves muscarinic-cholinergic vascular effects, mediated by enhanced production of endothelium-derived relaxing factor . . . i.e., nitric oxide.)