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6.5:

Adrenergic Agonists: Direct-Acting Agents

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JoVE Central Pharmacology
Adrenergic Agonists: Direct-Acting Agents

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Polar endogenous catecholamines are potent adrenoceptor stimulants. However, they are nonselective and orally ineffective due to inactivation by metabolic enzymes. Adrenergic agonists or sympathomimetics are synthetic drugs with better bioavailability that elicit a sympathetic response directly, indirectly, or via mixed action. Direct-acting sympathomimetics act on postsynaptic adrenoceptors without interfering with the presynaptic neuron. They are classified as either selective or nonselective agents based on either considerable, partial or no selectivity for a particular adrenoceptor subtype. Nonselective direct-acting agonists such as oxymetazoline —a decongestant, and isoprenaline possess no subtype selectivity. Selective direct-acting agents generate a therapeutic response based on the targeted adrenoceptor type. For instance, ɑ1- and ɑ2- selective agonists like phenylephrine and clonidine, respectively, have cardiovascular actions.  ꞵ1-selective agonists like dobutamine increase cardiac output, while ꞵ2- selective agonists like terbutaline are used to treat asthma. 

6.5:

Adrenergic Agonists: Direct-Acting Agents

Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.

These agents can be classified based on their selectivity to specific adrenoceptor types. Non-selective agents, like oxymetazoline, have diverse effects. Selective direct-acting agonists target specific adrenoceptors, avoiding unwanted side effects. Examples include α1-selective agents (e.g., phenylephrine) that enhance cardiovascular function, α2-selective agents that inhibit it, ꞵ1-selective agents (e.g., dobutamine) that increase heart rate and cardiac output, and ꞵ2-selective agents (e.g., salbutamol, terbutaline) that act as bronchodilators and uterine relaxants. Additionally, ꞵ3-selective agents like mirabegron are used to treat urinary incontinence by acting on the detrusor muscle of the bladder.