PNS DRUGS P.2.docx

PNS DRUGS: ADRENERGIC AGONIST/ANTAGONIST [ADRENERGIC AGONIST OVERVIEW] Referred to as sympathomimetics. Has two classes: 1. Catecholamines (Epi/norepi, isoproterenol, dopamine and dobutamine) a. Contain a catechol group and amine group b. Metabolized by the enzymes MAO and catechol-...

PNS DRUGS: ADRENERGIC AGONIST/ANTAGONIST [ADRENERGIC AGONIST OVERVIEW] Referred to as sympathomimetics. Has two classes: 1. Catecholamines (Epi/norepi, isoproterenol, dopamine and dobutamine) a. Contain a catechol group and amine group b. Metabolized by the enzymes MAO and catechol-O c. Epi/norepi, isoproterenol, dopamine and dobutamine. d. They cannot be admin orally, brief duration of action, they CANNOT cross the BBB 1. Non catecholamines e. Does not have catechol group f. Not substrates for COMT and metabolize slowly by MAO half lives are much longer g. They do not undergo rapid degradation by MAO and COMT can be given orally h. Can cross the BBB [RECEPTOR SPECIFICITY] Albuterol B2 low doses. B1 & 2 at high doses Isoproterenol B1 & 2 Epinephrin acts on all 4 adrenergic receptor subtypes A and B Selectivity is relative NOT absolute. Selectivity depends on dose: at low doses = maximal selectivity. As dose increases = selectivity declines - Alpha 1 - Therapeutic use: hemostasis, nasal congestion, adjunct to local anesthesia, elevation of bp, and mydriasis - AE: HTN, necrosis of tissue, bradycardia sec to baroreceptor - Alpha 2 - Beta 1 - Therapeutic uses: heart failure, shock, AV block and cardiac arrest - AE: tachycardia and dysrhythmias - Beta 2 - Therapeutic uses: asthma, delay of preterm labor - AE: hyperglycemia in DM, tremors - Dopamine receptors - Therapeutic uses: shock [ADRENERGIC AGONIST DRUGS] +-----------------------------------+-----------------------------------+ | Epi- all receptors | \- Uses: delaying absorption of | | | local anesthetics, control | | Topical or injection | superficial bleeding, inc bp, | | | overcome AV heart block, restore | | Short half life and absorption | cardiac function, | | | bronchodilation, tx anaphylactic | | | shock | | | | | | \- AE: HTN crisis, dysrhythmias, | | | angina, necrosis following | | | extravasation, hyperglycemia | +===================================+===================================+ | Norepi- A1/2, B1 | \- uses: hypotensive states, | | | cardiac arrest | | Catecholamine | | | | \- AE: tachydysth, angina, HTN, | | | local necrosis | +-----------------------------------+-----------------------------------+ | Isoproterenol- B1/2 | \- Uses: AV block, cardiac | | | arrest, inc CO | | | | | | AE: tachyarrhythmias, angina, | | | hyperglycemia in DM | +-----------------------------------+-----------------------------------+ | Dopamine- dose dependent | \- Uses: shock, HF | | | | | D @ low doses, B1 @ moderate, A1 | \- AE: tachy, dysrhy, anginal | | @ high | pain | | | | | Catecholamine | | +-----------------------------------+-----------------------------------+ | Dobutamine- B1 | \- Uses: HF | | | | | | \- AE: tachy | | | | | | \- should not be taken with MAOIs | +-----------------------------------+-----------------------------------+ | Phenylephrine- A1 | \- locally to reduced nasal | | | congestion | | Non-catecholamine | | | | \- parenterally to inc bp | | | | | | \- eye drop to dilate | | | | | | \- admin with local anesthetics | | | to delay anesthetic absorption | +-----------------------------------+-----------------------------------+ | Albuterol- B2 | \- Uses: asthma through | | | bronchodilation | | \@high B1 | | | | \- AE: tremor and tachy | +-----------------------------------+-----------------------------------+ | Ephedrine- all receptors but poor | \- uses: asthma through | | selectivity | bronchodilation, shock, | | | anesthesia induced hypotension | | Indirect and direct | | | | \- AE: HTN, dysrhythmias, angina, | | | hyperglycemia in DM | | | | | | crosses BBB and causes insomnia | +-----------------------------------+-----------------------------------+ [ADRENERGIC ANTAGONISTS] All adrenergic antagonists produce reversible competitive blockade. More selective than agonists thus alpha and beta antagonists blocking groups - Alpha blocking agent: - Uses: **HTN**, reversal of toxicity from alpha agonist, BPH, pheochromocytoma and Raynaud disease - AE: orthostatic hypotension, reflex tachy sec to baroreceptor reflex, nasal congestion, inhibition of the ejaculation, NA retention - AE of A2: reflux tachy. release of NE will increase +-----------------------------------+-----------------------------------+ | Alpha 1 Blocking Agent | | +===================================+===================================+ | Prazosin- protype, A1 | \- "first dose" effect of sev | | dilation/relaxation | postural hypotension 1^st^ dose | | | should be no more than 1mg | | Doxazosin, tamsulosin, alfuzosin, | | | and silodosin BPH only | | | | | | Tamsulosin/silodosin: can cause | | | abnormal ejaculation and inc risk | | | for rhinitis | | | | | | Alfuzosin: prolong QT. do not | | | give with inhibitors of CYP | | +-----------------------------------+-----------------------------------+ | Alpha 2 Blocking Agent | | +-----------------------------------+-----------------------------------+ | Phentolamine- noncompetitive | Uses: pheochromocytoma, | | | prevention of tissue necrosis | | | after extravasation, reversal of | | | soft tissue anesthesia | +-----------------------------------+-----------------------------------+ | Phenoxybenzamine- noncompetitive, | Uses: only pheochromocytoma | | receptor blockade is NOT | | | reversible | | +-----------------------------------+-----------------------------------+ - Beta blocking agent: - Uses: anti-anginal therapy, HTN, dysrhythmias, MI, HF, hyperthyroid, migraine, pheochromocytoma, stage fright, intraocular pressure (contraindicated with AV block) - AE: - B1: bradycardia - Special considerations: taper 1-2 weeks rebound excitation. - B2: bronchoconstriction for asthma pts, hypoglycemia in DM a B1 selective agent is preferred +-----------------------------------+-----------------------------------+ | Beta Blocking Agent | | +===================================+===================================+ | Propranolol- 1^st^ generation | \- suppression of renin, | | non-selective | bronchoconstriction, | | | vasoconstriction, reduced | | Blocks B1/2 | glycogenolysis | | | | | Cross BBB and eliminated | \- highly lipid soluble. Excreted | | hepatically (same as below) | in the urine | | | | | | \- contra: allergy, DM, cardiac, | | | respiratory, psych, and neonates | +-----------------------------------+-----------------------------------+ | Metoprolol | \- can mask signs of hypoglycemia | +-----------------------------------+-----------------------------------+ | Labetalol/carvedilol- block alpha | postural hypotension | | and beta | | | | Atenolol, metoprolol, nadolol, | | Esmolol: emergency IV for SVT | and timolol BBW: abrupt | | | discontinuation and risk for | | Sotalol: vent dysrhy and | angina increase risk of MI | | maintenance of SR for afib pts | | +-----------------------------------+-----------------------------------+ [INDIRECT-ACTING ANTI-ADRENERGIC AGENTS] - Clonidine - Indication: HTN, pain, ADHD - A2 adrenergic agonist that causes selective activation of A2 receptors in the CNS - Causes bradycardia and dec CO - Lipid soluble - AE: drowsiness, xerostomia, rebound HTN w/draw slowly over 2-4 days, constipation, impotence, gynecomastia, adverse CNS effects - Not recommended for pregnancy. - Guanfacine (same as above) - Methyldopa - Oral antihypertensive by acting on CNS sites - s/e: hemolytic anemia and hepatic necrosis - GREAT FOR PREGNANCY - Methyldopate - IV - HTN - AE: + combs test, hemolytic anemia, hepatic toxicity, xerostomia, sexual dys, orthostatic hypotension, and CNS effets