Autonomic ganglion-blocking drugs

The concentration of FA inside the Nation membrane is very sensitive to the presence of other cations. Figure 2 shows cyclic voltammograms observed with the Nafion-coated GC electrode with 7.2 x 10" M FA and different concentrations of hexamethonium (autonomic ganglionic blocking drug) in the electrolyte solution. The addition of hexamethonium resulted in a decrease in the peak current for FA. This phenomenon clearly demonstrated that some FA initially trapped inside the Nation membrane is replaced by hexamethonium added to the electrolyte solution (Figure 3). 

Because the effector cell receptors (muscarinic, <, and 6) are not blocked, patients receiving ganglion-blocking drugs are fully responsive to autonomic drugs acting on these receptors. In fact, responses may be exaggerated or even reversed (eg, norepinephrine may cause tachycardia rather than bradycardia), because homeostatic reflexes, which normally moderate autonomic responses, are absent. 

Trimethaphan camsylate is a ganglionic-blocking drug that inhibits both sympathetic and parasympathetic autonomic activities. It has a rapid onset and brief duration of action and must be admiifistered by continuous intravenous infusion with constant monitoring of blood pressure. Trimethaphan camsylate is particularly useful in aortic dissection because it can be titrated carefully to permit smooth control of blood pressure and because it decreases cardiac output and left ventricular ejection rate. Tachyphylaxis... 

In conclusion, the incorporation of an acetylenic moiety into a benzylamine structure conferred completely novel biochemical and therapeutic properties on an otherwise inert phenylalkylamine. Outstanding in this respect are the potent MAO-inhibitory, antihypertensive, and antidepressant effects of this new drug. The potent autonomic side effects normally encountered with the ganglionic blocking type antihypertensive agents are much less pronounced with this drug and a definite advance has been scored toward achieving selectivity of action. 

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

Trimethaphan is an antagonist at nicotinic ganglionic synapses. The drug thus blocks transmission of information through autonomic pathways in a dose-dependent manner. 

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