Transcript Document
59-291 Section 2, Lecture 4 Adrenergic Receptor Agonists • Termed sympathomimetic drugs • Divided into three groups • Direct-acting agonists – Catecholamines – Noncatecholamines • Indirect-acting agonists • Mixed acting agonists 1 Catecholamines • Naturally occurring: – NE: endogenous sympathetic neurotransmitter – EP: The principle hormone of adrenal medulla – Dopamine: Precursor to EP and NE • Synthetic: Isoproterenol, dobutamine • Structure: catechol moiety, ethylamine side chain • Inactivation: COMT, MAO; found in the gut, liver and other tissues • Low oral bioavailability, short plasma half-lives • Must be administered parenterally for systemic actions; Anaphylactic shock 2 Mechanisms and Effects • Cathecolamines differ in their affinities and specificities for receptors • Size of alkyl substitution on the amine nitrogen determines the relative affinity for a and b receptors • Larger alkyl group, higher affinity for breceptors; Isoproterenol 3 Ethylamine NE: Constricts all blood vessels EP: Constricts some blood vessels but dilates the others Dopamine: stimulates release of NE from sympathetic nerves (Direct and indirect agonist) 4 Drug Pharmacologic Effect (and Receptor) Direct-acting catecholamines Dobutamine Cardiac stimulation (β1) and vasodilation (β2) Dopamine* Renal vasodilation (D1), cardiac stimulation (β1), and increased blood pressure (β1 and α1) Epinephrine Vasoconstriction and increased blood pressure (α1), cardiac stimulation (β1), and bronchodilation (β2) Isoproterenol Cardiac stimulation (β1) and bronchodilation (β2) Norepinephrine Vasoconstriction and increased blood pressure (α1) 5 Drug Clinical Use Direct-acting catecholamines Dobutamine Cardiogenic shock, acute heart failure, and cardiac stimulation during heart surgery Dopamine* Cardiogenic shock, septic shock, heart failure, and adjunct to fluid administration in hypovolemic shock Epinephrine Anaphylactic shock, cardiac arrest, ventricular fibrillation, reduction in bleeding during surgery, and prolongation of the action of local anesthetics Isoproterenol Asthma, refractory atrioventricular block, and refractory bradycardia Norepinephrine Hypotension and shock 6 Sys, Dias., MeanArt. P 7 Adverse effects: -excessive vasoconstriction leading to ischemia -reduces blood flow to vital organs such as kidneys; cause excessive cardiac stimulation leading to myocardial ischemia or arrythmias -b-adrenergic agonists: hyperglycemia undesirable in diabetics Indirect-Acting Amphetamine- induces the release of NE Cocaine-prevents reuptake of NE 8 Mixed-Acting: the name says it all! Direct and Indirect acting adrenergic agonists activate both α and b receptors Ephedrine and Pseudoephedrine vasoconstriction via a1 receptors; useful as nasal decongestants; via b bronchodilate Adverse effects: tachycardia, hypertension, urinary retention 9 Practice Questions • Which of the following drugs does stimulate mainly b receptors – – – – NE EP Isoproterenol Dopamine 10 • Which of the following catecolamines may cause reflex bradycardia due to stimulation of a1 receptors? – – – – NE EP Dopamine Isoproterenol 11 • What is the treatment of choice for anaphylactic shock – – – – NE EP Isoproterenol Dobutamine 12