Adrenergic Agonists.pdf

Adrenergic Agonist Agents Norepinephrine Release at Effector Tissue/Organ (Remember this is post-ganglionic synapses) Adrenergic Agonist Drugs Act on receptors stimulated by epinephrine and norepinephrine Major effects mediated by β receptors β2 β1 Tachycardia Increased myocardial contractility Incr...

Adrenergic Agonist Agents Norepinephrine Release at Effector Tissue/Organ (Remember this is post-ganglionic synapses) Adrenergic Agonist Drugs Act on receptors stimulated by epinephrine and norepinephrine Major effects mediated by β receptors β2 β1 Tachycardia Increased myocardial contractility Increased lipolysis Vasodilation Slight decrease in peripheral resistance Bronchodilation Increased glycogenolysis (liver and muscle) Increased Glucagon release Relaxation of uterine smooth muscle Activation of Alpha Adrenoreceptors Adrenergic Agonist Actions Direct Acting Adrenergic Agonists Endogenous/Natural Occurring Epinephrine Norepinephrine Dopamine Synthetic Dobutamine Isoproterenol Epinephrine Interacts with alpha and beta receptors Low dose/levels higher affinity for beta receptors beta receptor activity predominates (vasodilation by beta 2 receptor activity) High dose higher affinity for alpha receptors alpha receptor predominates (vasoconstrictor by alpha 1 receptor activity) Epinephrine Pharmacokinetics Rapid onset but brief duration: IV, SC Orally ineffective Metabolites excreted in urine (Metanephrine & Vanillylmandelic Acid) Adverse effects CNS disturbances Intracerebral hemorrhage cardiac arrhythmias (digitalis) pulmonary edema Interactions Hyperthyroidism Cocaine Actions of Epinephrine Cardiovascular system (+) inotropic and chronotropic (B1) Peripheral vasoconstriction with decrease renal blood flow (A1) Peripheral vasodilation (B2) Actions of Epinephrine Respiratory system - Bronchodilation (B2) Liver - Glycogenolysis (B2) Pancreas - Insulin (A2) Adipose tissue - Lipolysis (B3) Therapeutic use of Epinephrine Bronchospasm (SC) Anaphylactic shock Type I hypersensitivity reactions (Anaphylaxis) Glaucoma open angle (2% sol) intraocular pressure by increase uveoscleral outflow Anesthetics – increased duration of local anesthetic effect due to vasoconstiction Norepinephrine Affects mostly alpha receptors Actions - Cardiovascular - vasoconstriction *Endogenous NE is reduced with baroreceptor reflex (stretching of baroreceptors due increased BP which cause decrease in sympathetic flow and thus NE levels) Therapeutic use - Acute hypotension in a hemodynamically unstable patient - It can be use as atropine pre-treatment for acute hypotension (if given after atropine it will cause tachycardia) - Cardiac arrest (adjunct Tx) Isoproterenol Non-selective B1and B2 agonist Therapeutic use Actions Bronchial Asthma - Cardiovascular Heart block or cardiac (+) inotropic (+)chronotropic arrest Decrease peripheral resistance - Pulmonary - Bronchodilation Dopamine A1 and B1 receptors activity D receptors activity - Dopamine 1 receptors subserve vasodilation, especially in the renal, coronary, mesenteric, and cerebral vascular beds - Dopamine 2 receptors have been located at the endings of postganglionic sympathetic nerves; upon activation inhibits norepinephrine release Actions - Cardiovascular (+) inotropic (+)chronotropic (B1) vasoconstriction (A) - Vasodilation of dilation of renal and splanchnic beds Therapeutic use – primarily used for cardiogenic shock and acute HF Adverse effects – short lived arrhythmias and nausea Other Direct Acting Agents Fenoldopam Phenylephrine (A1) Oxymetazoline (A) Nasal decongestant Ophthalmic (Upneeq) Clonidine (A2) Essential hypertension due to CNS action (diminish central adrenergic outflow) IV D1 and A2 Rapid vasodilation for severe hypertension in hospitalized patients Dobutamine (B1) + inotropic Use in congestive heart failure to  C.O. Other Direct Acting Agents Beta -2 agonist (bronchodilators) Metaproterenol Albuterol Pirbuterol Salmeterol and formoterol – long acting Terbutaline – also for tocolysis (bronchodilator  uterine contractions in premature labor (delay labor) Indirect Acting Adrenergic Agents Amphetamines (“ups’ ”) Causes release of norepinephrine from presynaptic terminals and increases NE release Central stimulation  Blood pressure and heart rate Tyramine – an AA Not a clinically useful drug found in cheese and Chianti wine Cocaine - local anesthetic that blocks Na / K pump required for reuptake of norepinephrine enhancing its sympathetic activity. Mixed - Action Adrenergic Agents Induce norepinephrine release from presynaptic terminals and activate adrenergic receptors in postsynaptic membranes Ephedrine Enhance contractility and improve motor function in Myasthenia Gravis Metaraminol Alternative drug for shock treatment May be used to treat acute hypotension Adrenergic Agonists Side Effects Arrhythmias Headache Hyperactivity Insomnia Nausea Tremors