Section 2, Lecture 4 Adrenergic Receptor Agonists -termed sympathomimetic 3 Groups: Direct-acting Indirect-acting mixed-acting Direct-acting Subdivided into: -catecholamines -non catecholamines

2 Catecholamines Naturally occuring- NE, E, dopamine Synthetic- isoproterenol and dobutamine These are rapidly inactivated by 2 enzymes found in the gut and liver and in many other tissues: monoamine oxidase (MAO) and catechol- o-methyltransferase (COMT); low oral bioavailabilities and short t ½ therefore must be administered parenterally.

3 Mechanisms and Effects Catecholamines differ wrt affinities and specificities for the receptors Draw relative response vs log [Catecholamine] plots for the agonists in the box.

4

5

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 ar arrythmias -  -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! activate both α and  receptors Ephedrine and Pseudoephedrine vasoconstriction via  1 receptors; useful as nasal decongestants; via  bronchodilate Adverse effects: tachycardia, hypertension, urinary retention