Lecture 9: sympatholytics B blockers Flashcards
Beta blocker uses
-angina
-arrhythmia
-post-MI
-HTN
-heart failure
Beta blocker use for angina
-reduces myocardial oxygen need
-decrease HR and contractility
Beta blocker use for cardiac arrhythmia
-slow AV nodal conduction
Beta blocker use for post-myocardial infraction
-reduce myocardial oxygen need
-slow AV nodal conduction
Beta blocker use for HTN
-decrease CO
-inhibibit renin secretion
beta blocker use for congestive heart failure
-decrease chronic overstimulation/toxicity of compensatory catecholamines
Aryloxypropanolamines
-Beta ANTAgonists
-O side chain
-OH
-NH
-bulky alkyl group
Aryloxypropanolamines structure
-right half (-OH, -NHR) resembles B AGONIST
-left half (aromatic ring) more lipophilic and pimary determinant of ANTAgonist activity. may also b determinant in B-1 selectivity
Nonselective B ANTAgonists
-propranolol
-Nadolol
-Timolol
-Pindolol
-Carteolol
Propranolol
-nonselective B ANTAgonist
-lipoPHILIC
-extensive first pass hepatic metabolism
-local anesthetic properties
-blockade is activity-DEPENDENT
Propranolol effects
-decrease CO and HR
-reduce renin release
-increase VDL
-decrease HDL
-inhibit lipolysis
-inhibit compensetory glyconeogensis and glucose release in response to hyperglycemia
-increase bronchial airway resistance
Therapeutic use of B ANTAgonists
-HTN
-agina
-arrhythmia
-migraine
-stage fright
-thyrotoxicosis
-glaucoma
-congestive heart failure
Nadolol
-non selective B-ANTAgonist
-less lipophillic than propranolol
-20 hour half life
-mostly excreted unchanged in urine
-oral admin
Nadolol uses
-HTN
-agina
-migraine
Timolol
-non-selective B ANTAgonist
-thiadiazole nucleus with morpholine ring
-oral, ophthalmic admin
Timolol uses
-glaucoma
-HTN
-angina
-migraine
How will B-blockers affect pupil size?
Timolol use in glaucoma
-decrease intraocular pressure
-target ciliary epithelium
Pindolol
-nonselective B-ANTAgonist
-possess intrinsic sympathomimetic activity (ISA)
-PARTIAL agonist
-less likely to cause BRADYcardia and lipid abnormalities
-oral admin
Pindolol uses
-HTN
-angina
-migraine
-good for patients with severe BRADYcardia or little cardiac reserve
What would a pindolol dose-response curve look like?
-doesnt achieve full receptor activation
Carteolol
-Non-selective
-ISA
-PARTIAL agonist
-less likely to cause BRADYcardia and lipid abnormalities
-oral or opththalmic admin
Carteolol uses
-HTN
-glaucoma
Selective B-1 ANTAGONISTs
-metaprolol and bisoprolol
-atenolol
-esmolol
Metoprolol and Bisoprolol
-selective B1 ANTAgonists
-para phenyl derivatives
-cardioselective
-less bronchoconstriction
-moderate lipophilicity
-3-4hour half life
-big first pass metabolism
-oral or parenteral admin
Metoprolol and Bisprolol uses
-HTN
-agina
-antiarrythmic
-congestive heart failure
-oral and parenteral admin
Atenolol
-selective B-1 ANTAgonist
-cardioselective
-less bronchoconstriction
-LOW lipophilicity (“water soluble metoprolol)
-6-9 hour half life
Atenolol uses
-HTN
-agina
-oral and parenteral admin
Esmolol
-B1 ANTAgonist
-9 min half life
-rapid hydrolysis by ESTERASE in RBCs
-incompatible with sodium bicarbonate
Esmolol uses
-supraventricular TACHYcardia
-atrial fibrilation
-perioperative HTN
-parenteral admin
-note compatible with sodium bicarbonate
Side effects of B-blockers
-BRADYcardia
-AV block
-sedation
-symptoms of hypoglycemia
-withdrawal syndrome
Contraindications of Beta-blockers
-asthma
-COPD
-congestive heart failure (type IV)
Mixed Adrenergic ANTAgonists
-Labetalol
-cavedilol
Labetalol
-phenylethanolamine derivative
-mixed adrenergic receptor ANTAGONIST
-2 chiral carbons
-racemic mix
Labetalol R isomer
-nonselective B-antagonist
-activity prevents reflex TACHYcardia associated with a1 ANTAgonists
Labetalol SR isomer
-a1 ANTAgonist
-vasoDILATION
=prevents BRADYcardia associated with the B ANTAgonist
Carvedilol
-Both enantiomers antagonize a1 receptors
-only S enantiomer B-ANTAgonist
Carvedilol S enantiomer
-non-selective B-ANTAgonist
-prevents reflex TACHYcardia associated with a1 ANTAgonists
Carvedilol use
-HTN
-congestive Heart failure
-oral admin
Indirect-acting sympatholytics
-Metyrosine
-Bretylium tosylate
-reserpine
Metyrosine
-indirect sympatholytic
-inhibits NE synthesis
-inhibits tyrosine hydroxylase
-depletes catecholamines everywhere
Metyrosine clinical use
-perioperative management of pheochromocytoma (adrenal medulla tumor that results in excessive NE and epinephrine synthesis and release)
Metyrosine problems
-depletes catecholamines everywhere
Bretylium Tosylate
-aromatic quarternary ammonium
-mech unknown
-displace and release NE and prevent further release
-so does Guanethidine
Bretylium tosylate use
-reduce storage/release of NE
-antiarrhytmic (ventricular fib)
-parenteral admin
Reserpine
-indole alkaloid from root
-block vesicular monoamine transporters (VMAT)
-deplete vesicular pool of NE
-slow onset
-sustained effect (weeks)
Reserpine action
-VMAT IRREVERSIBLE inhibitor
-depletes stored NE
Reserpine use
-HTN but rarely bc bad effects
-may precipitate depression
Reserpine problems
-orthostatic hypotension
-increased GI activity
-CNS effects: sedation, depression, suicide
