1 Adrenergic Receptor Agonists Termed sympathomimetic drugs Divided into three groups Direct-acting agonists –Catecholamines –Noncatecholamines Indirect-acting agonists Mixed acting agonists Section 2, Lecture 4

2 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

3 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  and  receptors Larger alkyl group, higher affinity for  receptors; Isoproterenol

4 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) Ethylamine

5 DrugPharmacologic Effect (and Receptor) Direct-acting catecholamines DobutamineCardiac stimulation (β 1 ) and vasodilation (β 2 ) Dopamine*Renal vasodilation (D 1 ), cardiac stimulation (β 1 ), and increased blood pressure (β 1 and α 1 ) EpinephrineVasoconstriction and increased blood pressure (α 1 ), cardiac stimulation (β 1 ), and bronchodilation (β 2 ) IsoproterenolCardiac stimulation (β 1 ) and bronchodilation (β 2 ) NorepinephrineVasoconstriction and increased blood pressure (α 1 )

6 DrugClinical Use Direct-acting catecholamines DobutamineCardiogenic 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 EpinephrineAnaphylactic shock, cardiac arrest, ventricular fibrillation, reduction in bleeding during surgery, and prolongation of the action of local anesthetics IsoproterenolAsthma, refractory atrioventricular block, and refractory bradycardia NorepinephrineHypotension and shock

7 Sys, Dias., MeanArt. P

8 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 -  -adrenergic agonists: hyperglycemia undesirable in diabetics Indirect-Acting Amphetamine- induces the release of NE Cocaine-prevents reuptake of NE

9 Mixed-Acting: the name says it all! Direct and Indirect acting adrenergic agonists activate both α and  receptors Ephedrine and Pseudoephedrine vasoconstriction via  1 receptors; useful as nasal decongestants; via  bronchodilate Adverse effects: tachycardia, hypertension, urinary retention

10 Practice Questions Which of the following drugs does stimulate mainly  receptors –NE –EP –Isoproterenol –Dopamine

11 Which of the following catecolamines may cause reflex bradycardia due to stimulation of  1 receptors? –NE –EP –Dopamine –Isoproterenol

12 What is the treatment of choice for anaphylactic shock –NE –EP –Isoproterenol –Dobutamine