BSN Adrenergic Drugs 2023 PDF

Adrenergic Agonists or Sympathomimetic Drugs Ramzi Sabra , MD, MHPE  Learning Outcomes Classify sympathomimetic drugs according to their chemical nature (catecholamines or not) and their mode of action (direct or indirect action on receptors) Discuss the effect of pre-tre...

Adrenergic Agonists or Sympathomimetic Drugs Ramzi Sabra , MD, MHPE  Learning Outcomes Classify sympathomimetic drugs according to their chemical nature (catecholamines or not) and their mode of action (direct or indirect action on receptors) Discuss the effect of pre-treatment with either cocaine or reserpine on the responses to the different drugs based on their mode of action Differentiate among the sympathomimetic drugs as to their potency, mode of action, receptor selectivity, route of administration, duration of action, and penetration into the CNS. Discuss the pharmacological and therapeutic effects of the drugs based on their interaction with the alpha1, aloha2 beta-1 and beta-2 adrenergic receptors. Indicate the major adverse effects associated with each of thee mechanisms.  THE SYMPATHOMIMETIC DRUGS or AMINES Classification – Catecholamines Natural: epinephrine, norepinephrine, dopamine Synthetic: isoproterenol, dobutamine – Non-catechol sympathomimetic amines Directly acting: Indirectly acting (enter through uptake-1 and displace NE in vesicles) Mixed: ephedrine Chemistry C C N – derivatives of phenylethylamine  Sympathomimetic Agents Catecholamines Non-Catecholamines All directly acting Direct Action Indirect Action- Natural: Synthetic Methoxamine (α1) like NE Norepinephrine Isoproterenol Phenylephrine (α) Tyramine Epinephrine Dobutamine Clonidine (α2) Mephentermine Dopamine Dobutamine (β1) Terbutaline (β2) Effect abolished Oxymetazoline (α) By reserpine and cocaine Mixed Ephedrine  Sympathomimetic drugs Contain a catechol nucleus: The catecholamines: OH OH at 3 & 4 of benzene ring HO NH2 HO NH2 HO Norepinephrine OH H HO N HO CH3 Dopamine HO OH Epinephrine H OH N H HO HO N CH3 CH3 H3C CH3 HO HO Isoproterenol Dobutamine  OH Sympathomimetic Amines: Noncatecholsympathomimetic H amines Non-catecholamines N CH3 CH3 NH2 Ephedrine CH3 OH H N Amphetamine HO CH3 H N Phenylephrine CH3 H3C NH2 CH3 Mephentermine HO Tyramine  Differences among Drugs 1. Selectivity to receptors 2. Route of administration 3. Duration of action 4. Potency 5. Direct versus indirect effect  Demonstration of receptor selectivity Effect of catecholamines on the CV system Heart Blood vessels 1 2 1 2 D1 E + + + + 0 NE + 0 + + 0 I + + 0 0 0 D + + + + +  Differences Catecholamines Noncatecholamines Not by COMT and Metabolism by Yes: so not less by MAO: so MAO and COMT effective orally Can be given orally Half-life Short half life Longer half life Polarity High – do not Low: enter CNS enter CNS Potency High Lower Mode of action Direct Direct or Indirect or Mixed EFFECTS AND THERAPEUTIC USES OF SYMPATHOMIMETIC AGENTS  Effects and Therapeutic Uses I. Alpha-1 Receptor Activation 1. Vasoconstriction Control superficial bleeding (skin and mucus membranes) Decongestant: use for short periods because rebound congestion can happen – local: phenylephrine, naphazoline; oral: pseudoephedrine Delay absorption of local anesthetics to prolong effect: epinephrine, norepinephrine Hypotensive shock:– not first choice, Better treat cause of hypotension; norepinephrine, phenylephrine, 2. Mydriasis (radial muscle of iris)  Toxicity of Alpha-1 effects Hypertension - excessive vasoconstriction Necrosis - vasoconstriction induced ischemia  Which is the presynaptic receptor that causes negative feedback on NE release? a) Alpha-1 b) Alpha-2 c) Beta-1 d) Beta-2  II. Alpha-2 Receptor Agonists Decreasing sympathetic outflow from CNS – effective as antihypertensive drugs; e.g. Clonidine Adverse effect: – hypotension – withdrawal syndrome – rebound effect Methyldopa: (also antihypertensive) Converted to methyl-NE – an alpha-2 agonist III. Cardiac Use of Beta-1 Agonists In heart failure: inotropic effect (increase contractility): norepinephrine, dopamine, dobutamine. In Shock – to maintain blood flow to organs by increasing cardiac output. In atrio-ventricular block – stimulate conduction through the A-V node Restore cardiac rhythm after arrest: epinephrine  Adverse Effects of Beta-1 Agonists Tachycardia or arrhythmias Angina – due to increased oxygen demand by the heart - especially in patients with atherosclerosis of coronary arteries  IV. Beta-2 agonists Bronchodilation – treatment of asthma; albuterol, sulbutamol, metaproterenol. Administration by inhalation – reduces systemic adverse effects Pre-term labor: inhibition of uterine contractions. Adverse Effects of Beta-2 Activation Hyperglycemia – in diabetic patients not normal Tremors – decreases with time High doses- lose selectivity and activate Beta-1  tachycardia  Other Therapeutic uses of Sympathomimetic Drugs 1. Allergies – Anaphylactic reactions: epinephrine (Epipen auto-injector) acting on alpha-1 (vasoconstriction increases BP, decreases glottal edema); beta-1 increases CO and BP; and beta-2  bronchodilation 2. Ophthalmic uses – Glaucoma: epinephrine 3. CNS – Narcolepsy: amphetamine – ADHD children: amphetamine  Non-catechol Sympathomimetic Amines Drugs with CNS effect 1. Amphetamine Peripheral effects: like NE - indirect action CNS effects: motor stimulation  convulsions; psychic stimulation  psychosis; decreased appetite Drug of abuse Useful in ADHD and narcolepsy 2. Ephedrine Peripheral effects: like E, direct and indirect CNS: weak stimulation Therapeutic use: bronchodilator  Non-catechol Sympathomimetic Amines Tyramine: found in foods (aged cheeses & meats, wine...) 1. pure indirect effect – release NE from vesicle 2. Metabolized by MAO: interaction with MAO Inhibitors- which are used as antidepressant drugs so if patient taking MAO inhibitors  exaggerated effects  potential hypertensive crisis  Adverse Effects Alpha Beta Alpha-1 Beta-1 – Hypertension – Cardiac stimulation: – Necrosis tachycardia, arrhythmias angina Alpha-2 – Hypotension Beta-2 – Sudden withdrawal – Hyperglycemia – in diabetic syndrome – Tremors – less with time Selectivity is never absolute