Drugs affecting adrenergic function

• Regulation of physiologic processes in the autonomic nervous system (ANS) is managed by oppositional or complementary stimulation by the sympathetic (adrenergic) and parasympathetic (cholinergic) nervous systems. • To effect an action, a neurotransmitter needs to bind with an appropriate receptor site on the effector organ or tissue. • The primary neurotransmitter of the sympathetic nervous system (SNS) is norepinephrine (NE). Additionally, epinephrine and dopamine stimulate adrenergic receptors. • The SNS, commonly referred to as the fi ght-or-fl ight system, increases cardiovascular and respiratory function, increases metabolism, diverts blood to muscles, and decreases GI activity. • SNS receptors with pharmacological relevance are subdivided into alpha-1, alpha-2, beta-1, and beta-2 subtypes. Alpha-1, beta-1, and beta-2 receptors are located on the post-synaptic side of the synapse, while alpha-2 receptors are located on the pre-synaptic side of the synapse. Stimulation of alpha-2 receptors acts as a negative feedback and shuts off the fl ow of NE, stopping sympathetic stimulation. • Adrenergic agonists stimulate the adrenergic receptors, whereas adrenergic antagonists block adrenergic receptors within the SNS, preventing endogenous neurotransmitters from attaching to the receptor. There are multiple terms for these categories of drugs. • Alpha-1 agonists, such as phenylephrine, stimulate alpha-1 receptors directly. They are most commonly used as nasal decongestants and in ophthalmology to achieve mydriasis. They may also be used as vasopressors to treat vascular failure and related shock. • Alpha-2 agonists such as clonidine shut off the sympathetic release of NE and sympathetic stimulation. They are used in the treatment of substance abuse to prevent withdrawal symptoms and have a minor use in the treatment of hypertension. • Nonselective adrenergic agonists, such as epinephrine, are used to treat anaphylactic shock, asthma, hemorrhage, and ventricular fi brillation. The nonselective activity stimulates all four adrenergic subtypes. • Dopamine, a vasopressor, is used to correct the hemodynamic imbalances present in shock. Dopamine is a naturally occurring catecholamine and a precursor to norepinephrine. It stimulates alpha and beta receptors directly and indirectly (by releasing the stored epinephrine). It also has dopaminergic effects, including increased renal perfusion, increased cardiac output, increased or decreased peripheral resistance (depending on the dose), and increased blood pressure. • Drugs that are relatively selective for beta-2 stimulation are used to treat asthma. • Fenoldopam, a dopamine-1 agonist, is used in the management of acute hypertension for rapid reduction of blood pressure. • Alpha-1 antagonists, such as prazosin, cause vasodilation and are used to treat hypertension and benign prostatic hyperplasia (BPH). • Beta-blockers, such as metoprolol, are relatively selective for beta-1 receptors in the heart; in larger doses they also have effects on beta-2 receptors. They are used to treat hypertension, angina, controlled chronic heart failure, cardiac arrhythmias, hyperthyroidism, and migraine headache.