Adrenergic Drugs PDF

Adrenergic Drugs Prof. Murat Oz Faculty of Pharmacy Kuwait University Epinephrine acts as a hormone, whereas norepinephrine acts as a neurotransmitter Sympathomimetic amines that contain the 3,4-dihydroxybenzene group (such as epinephrine, norepinephrine, isoproterenol, dopamine,...

Adrenergic Drugs Prof. Murat Oz Faculty of Pharmacy Kuwait University Epinephrine acts as a hormone, whereas norepinephrine acts as a neurotransmitter Sympathomimetic amines that contain the 3,4-dihydroxybenzene group (such as epinephrine, norepinephrine, isoproterenol, dopamine, and dobutamine (synthetic)) are called catecholamines. Catecholamines potently activate α or β receptors Catecholamines are metabolized by catechol-O-methyltransferase (COMT) in the synaptic space and by MAO intraneuronally, by COMT. Thus, very brief effect parenterally and no effect orally Catecholamines are polar and, therefore, do not penetrate the CNS Noncathecolamines (phenylephrine, ephedrine, amphetamine) lacking the catechol hydroxyl groups are not inactivated by COMT have longer half-lives Indirect-acting agonists block the reuptake (cocaine) or cause the release of norepinephrine from the cytoplasmic pools or vesicles of the adrenergic neuron (amphetamine). Ephedrine and its stereoisomer, pseudoephedrine, both stimulate α and β receptors directly and enhance release of norepinephrine from the adrenergic neuron (mixed action)  Tyramine is a normal byproduct of tyrosine metabolism in the body. It can enter the nerve terminal and displace stored norepinephrine and acts as indirectly acting sympathomimetic. Tyramine can be produced in high concentrations in protein rich foods by decarboxylation of tyrosine during fermentation (Beer, Cheese, Sausage, Salami, Pepperoni, Smoked or pickled fish) In patients treated with MAO (MAO-A) inhibitors (antidepressant drugs), the sympathomimetic effect of tyramine may be greatly intensified, leading to marked increases in blood pressure. Directly acting sympathomimetics: Oxymetazoline is a direct-acting synthetic agonist on both a1 and α2 receptors. Phenylephrine is α1 agonist. It is not inactivated by COMT and has a longer duration of action than the catecholamines and raises blood pressure, and also used as nasal decongestant. Midodrine is selective α1-receptor agonist and used in treatment of orthostatic hypotension α2 selective agonists are clonidine, methyldopa, guanfacine, guanabenz are useful in the treatment of hypertension. Clonidine, guanfacine are also used for treatment of attention deficit disorders as well. Sedation is a major side effect of these drugs, and newer α2 agonists (moxonidine, rilmenidine) with fewer CNS side effects are available for the treatment of hypertension Some of the adverse effects observed with nonselective adrenergic agonists Epinephrine causes bronchodilation through β2. Epinephrine causes hyperglycemia through increased glycogenolysis in the liver (β2), increased release of glucagon (β2), and a decreased release of insulin (α2). Epinephrine causes lipolysis through increased cAMP and activation of hormone sensitive lipase in adipose tissue, which hydrolyzes triglycerides to free fatty acids and glycerol. Epinephrine is used in treatment of 1) Bronchospasm 2) Anaphylactic shock 3) Cardiac arrest 4) Local anesthesia 5) lntraocular surgery (mydriasis). Dopamine activates β1 in the heart and dilates renal and splanchnic arterioles by activating dopamine receptors. It is used for cardiogenic and septic shock and is also used to treat hypotension, severe heart failure, and bradycardia. Fenoldopam is an agonist of peripheral D1 receptors and used as a rapid-acting vasodilator to treat severe hypertension Dobutamine is a synthetic, direct-acting catecholamine that acts as β1 agonist Albuterol, levalbuterol, metaproterenol, and terbutaline are short-acting β2 agonists bronchodilators. Tremor is common side effect of these drugs, and they should not be used concomitantly with MAO inhibitors. Salmeterol, formoterol, arformoterol, and indacaterol are long-acting β2 agonists, but they are not used as monotheraphy Mirabegron is a β3 agonist that relaxes the detrusor smooth muscle and increases bladder capacity. It is used for patients with overactive bladder. THANKS