Adrenergics

• Remember, these drugs have sympathetic effects

• Direct activation of adrenergic receptors, stimulate release/inhibition of reuptake, and reflex homeostatic mechanism (e.g. heart)

a-b Agonists

• Refer to chart below for cardiovascular effects

• Causes general vasoconstriction, relaxation of smooth muscle, i GI motility and bronchorelaxation.

  1. Epinephrine – used for glaucoma, anaphylactic shock, asthma. Hits a1 a2 b1 b2 receptors, diabetogenic effects (decreased insulin, increased lipolysis).

  2. Norepinephrine – used for hypotension and neurogenic shock. No b2, vagal reflex overrides direct effect, vasodilates cardio/pulmonary vessels.

  3. Dopamine – [renal] used as "renal drug" causing vasodilation in kidneys; also for cardiogenic and septic shock. Inotropic in low doses; chronotropic in high doses; no to CNS; tolerance.

a 1 Agonists

• Effects smooth muscle (vasculature, visceral and sphincters)

•  BP associated with sinus bradycardia

• Adverse effects: hypertension, anginal pain, headache, anxiety and rebound congestion

• Not degraded by COMT therefore longer lasting

  1. Methoxamine, phenylephrine – use for orthostatic hypotension, nasal decongestant and mydriatics (p).

a 2 Agonists

• Effects presynaptic terminals and pancreatic beta cells; hits a 2 and/or imidazoline receptors

• Cause a decrease in central adrenergic tone

• Adverse effects: sedation, xerostomia, drowsiness, dizziness, impotence, (hypertension)

  1. Clonidine and apraclonidine – used for withdrawal from tobacco, alcohol and opiods; second drug of choice for hypertension; glaucoma, preoperative sedative, ADD; modulates release of norepinephrine hits a 2 and imidazoline receptors.

  2. Guanabenz, guanafacine, tizanidine – use for spinal cord spasticity; hits a2 receptors.

  3. Methoxamine and rilmenidine – use for neurogenic shock.

Nonselective b Agonists

• Activates b1 b2 b3 receptors

• Vagal reflex adds to direct effect of drug (see chart above)

• Net effect: pronounced HR; vasodilation of all vascular beds.

  1. Isoproterenol – [heart] used for Torsade de pointes (ventricular tachycardia) and b-blocker overdose; less hyperglycemia than epinephrine since no 2 insulin inhibition

b 1 Adrenergic Agonists

• Effects myocardium and renin producing juxtaglomerular cells of kidneys

• Inotropic cardiovascular effect (Increased contractility and conduction)

• Adverse effects: fear, anxiety, tremors, hypertension, palpitations, anginal pain, arrhythmias, pulmonary edema, hyperglycemia, tolerance

1. Dobutamine – [heart] used for in emergencies for cardiac failure and cardiogenic shock.

b 2 Adrenergic Agonists

• Effects visceral and vascular smooth muscle and liver

• Bronchodilation and enhanced mucociliary clearance (mucous secretion is increased)

• Tolerance due to receptor down regulation

• Adverse effects: headache drowsiness, dizziness, anxiety, tachycardia, palpitations; hypokalemia (stimulates K⁺ reentry into skeletal muscle); hyperglycemia and hypoxemia ( ventilation/perfusion ratio; asthma)

1. Albuterol, terbutaline, metaproterenol, salmeterol – used for asthma and chronic obstructive pulmonary disease (COPD); aerosol administration.

2. Ritodrine – used as a uterine relaxant in premature labor

Indirect Acting Adrenergics

• Stimulates release of norepinephrine, dopamine and seratonin from peripheral and CNS

• Effects similar to norepinephrine; enters CNS; tolerance to central effects

• Toxicity includes hypertension, negative psychic effects, nausea and vomiting, dependence.

1. Amphetamine, methamphetamine, methylphenidate – used for narcolepsy (no tolerance) and attention–deficit hyperactivity disorders.

Other Indirect/Mixed Action Adrenergics

1. Tyramine, methyldopa – used for hypertension (m); false neurotransmitters which are taken up by adrenergic neurons then transformed into octopamine which displaces norepinephrine form adrenergic vesicles; causes sympathetic effects if administered with MAO inhibitor (prolonging effect of norepinephrine)

2. Cocaine – used as anesthetic; indirect acting adrenergic drug that blocks catecholamines uptake.

3. Ephidrine – used for asthma, COPD; enhances release of norepinephrine; less potent than epinephrine.

Category: Pharmacology Notes