Ganglionic+Blockers

__General Pharmacology__ The sympathetic adrenergic nervous system plays a major role in the regulation of arterial pressure. Activation of these nerves to the heart increase the heart rate (positive chronotropy), contractility (positive inotropy) and velocity of electrical impulse conduction (positive dromotropy). The norepinephrine-releasing, sympathetic adrenergic nerves that innervate the heart and blood vessels are postganglionic efferent nerves, whose cell bodies originate in prevertebral and paraveterbral sympathetic ganglia. Preganglionic sympathetic fibers, which travel from the spinal cord to the ganglia, originate within the medulla of the brainstem. Within the medulla are located sympathetic excitatory neurons that have significant basal activity, which generates a level of sympathetic tone to the heart and vasculature even under basal conditions. The sympathetic neurons within the medulla receive input from other neurons within the medulla (e.g., vagal neurons), from the nucleus tractus solitarius (receives input from peripheral baroreceptors and chemoreceptors), and from neurons located in the hypothalamus. Together, these neuronal systems regulate sympathetic (and parasympathetic) outflow to the heart and vasculature. Sympatholytic drugs can block the sympathetic adrenergic system are three different levels. First, **peripheral sympatholytic drugs** such as alpha and beta receptor antagonists block the influence of norepinephrine at the effector organ (heart or blood vessel). Second, there are **ganglionic blockers** that block impulse transmission at the sympathetic ganglia. Third, there are drugs that block sympathetic activity within the brain. These are called **centrally acting sympatholytic drugs**. Neurotransmission within the sympathetic and parasympathetic ganglia involves the release of acetylcholine from preganglionic efferent nerves, which binds to nicotinic receptors on the cell bodies of postganglionic efferent nerves. Ganglionic blockers inhibit autonomic activity by interfering with neurotransmission within autonomic ganglia. This reduces sympathetic outflow to the heart thereby decreasing cardiac output by decreasing heart rate and contractility. Reduced sympathetic output to the vasculature decreases sympathetic vascular tone, which causes vasodilation and reduced systemic vascular resistance, which decreases arterial pressure. Parasympathetic outflow is also reduced by ganglionic blockers. __Therapeutic Indications__ Ganglionic blockers are not used in the treatment of chronic hypertension in large part because of their side effects and because there are numerous, more effective, and safer antihypertensive drugs that can be used. They are, however, occasionally used for hypertensive emergencies. __Specific Drugs__ Several different ganglionic blockers are available for clinical use; however, only one (**trimethaphan camsylate**) is very occasionally used in hypertensive emergencies or for producing controlled hypotension during surgery. __Side Effects and Contraindications__ Side effects of trimethaphan include prolonged neuromuscular blockade and potentiation of neuromuscular blocking agents. It can produce excessive hypotension and impotence due to its sympatholytic effect, and constipation, urinary retention, dry mouth due to it parasympatholytic effect. It also stimulates histamine release.
 * Ganglionic Blockers**