Sympatholytics Flashcards
Types of cholinergic receptors and sites of action
1) Nicotinic: ganglia and skeletal muscle
2) Muscarinic: glands (lacrimal, salivary, gastric), smooth muscle (bronchial, GI, bladder, and vessels), and heart (SA and AV node)
All preganglionic neurons release what neurotransmitters? Is it excitatory or inhibitory?
Acetylcholine. Excitatory.
What is the rate-limiting step in the synthesis of epi and norepi in the adrenal medulla?
tyrosine hydoxylase
Ratio of Epi/norepi synthesis in the adrenal medulla
80/20
What neurotransmitter precedes the synthesis of norepinephrine?
dopamine
Metabolism of norepi and epi
Metabolic degradation by MOA and COMT. However, 80% is reuptake.
Beta-1 selective antagonists
atenolol, esmolol, and metoprolol
Beta-blockers with alpha effects
labetalol and carvedilol
Phentolamine MOA and SE
nonselective reversible IV alpha-blocker. Produces vasodilation. Produces baroceptor-mediated increases in CO and HR. May cause dysrhythmias and angina, as well as hyperperistalsis, abdominal pain, and diarrhea due to the predominance of parasympathetic activity.
Clinical uses for phentolamine
Intraop management of pheochromocytoma, autonomic dysreflexia (SCI), and extravasation of IV sympathomimetic.
Phenoxybenzamine MOA and SE
nonselective IRREVERSIBLE alpha-blocker. Profound hypotension in the presence of hypovolemia, blood loss, vasodilators, and inhalation agents. Noncardiac effects include miosis, nasal stuffiness, and sedation.
Phenoxybenzamine clinical uses
Preoperative management of pheochromocytoma, inoperable adrenal tumors, Raynaud’s diseases (more effective in cutaneous vasoconstriction rather than skeletal muscle flow)
Preoperative management of pheochromocytoma with phenoxybenzamine
0.5-1 mg/kg PO beginning two weeks prior to surgery. Make sure intravascular volume is adequate. Prazosin as an alternative.
Yohimbine MOA
Selective presynaptic alpha-2 antagonist. Enhances the release of norepinephrine.
Yohimbine clinical uses
idiopathic orthostatic hypotension, former treatment for impotence.
Prazosin MOA
selective post-synaptic alpha-1 antagonist. Dilates both arterioles and veins. Reflex tachycardia less common because drug has no inhibitory effect on alpha-2 receptors.
Prazosin clinical uses
HTN, Raynaud’s, BPH
Vasodilators are often combined with which drug and why?
beta-blockers to minimize baroreceptor mediated increases in heart rate and cardiac output.
beta-blockers for the management of CHF
metoprolol, carvedilol, and bisoprolol
Which beta-blocker increases the risk of amide local anesthetic toxicity and why?
Propranolol. Propranolol induced decreases in hepatic metabolism decrease the clearance of amide LA.
Most selective beta-blocker
Atenolol
Which type of beta-blocker is preferred in diabetics? Why?
Selective beta-blockers, because they do not potentiate insulin-induced hypoglycemia seen with nonselective beta-blockers (think beta-2 effects).
How is esmolol metabolized?
rapid hydrolysis by plasma esterases. Ultra-short acting. Elimination half-life 9 minutes. Return of HR to predrug levels within 10-30 minutes.
DOC for treating massive beta-adrenergic antagonist overdose
glucagon
Percentage of B1 and B2 receptors in the heart
75% beta-1 and 20% beta-2
Which beta-blocker is highly protein-bound?
Propranolol
What drug decreases the pulmonary first-pass uptake of fentanyl?
Chronic administration of propranolol results in 2-4 times as much fentanyl being injected into the systemic circulation. Both are basic lipophilic amines.
Nonselective beta-blockers should not be used in what type of patients?
Patients with reactive airway disease, peripheral vascular disease, and those who are prone to hypoglycemia.
Useful in the management of perioperative thyrotoxicosis, pregnancy-induced HTN, and epinephrine or cocaine-induced cardiotoxicity.
Esmolol because of its rapid onset and it is short-acting.
Beta-blockers can affect the serum concentration of what electrolyte?
Potassium, serum concentrations are increased due to the inhibition of insulin release.
What receptors does labetalol work on?
alpha 1, beta 1, beta 2. Decreases SVR (alpha 1 blockade) with attenuation of reflex tachycardia by simultaneous beta-blockade.
Which common beta-blocker depends on the kidneys as its primary route of elimination?
Atenolol
Common beta-blocker with intrinsic sympathomimetic activity
Labetalol
alpha 1 receptor stimulation effects
mydriasis, bronchoconstriction, vasoconstriction, uterine contracture, contraction of sphincters of GI/GU tract
alpha 2 receptor stimulation effects
Decreased NE release, decreased sympathetic outflow resulting in peripheral vasodilation and decreased BP, sedation, inhibition of insulin release, platelet aggregation
Beta 1 receptor stimulation
positive chronotropic, dromotropic, and inotropic effects
Beta 2 receptor stimulation
Smooth muscle relaxation (bronchodilation, vasodilation, uterus/bladder/gut), glycogenolysis, lipolysis, gluconeogenesis, insulin secretion, activation of Na/K pump (K goes intracellular, can produce hypokalemia and dysrhythmia)
contraindications to beta-blockade
sinus or AV node dysfunction, heart block, hypotension, decompensated heart failure, severe reactive airway disease.
Clinical uses for esmolol
HTN & tachycardia in response to intraop noxious stimulation & intubation, ECT, pheo, thyrotoxicosis, PIH, epi or cocaine-induced cardiac toxicity.
Which beta-blocker does not cross the BBB/placenta?
esmolol due to its poor lipid solubility
Most common SE of labetalol
orthostatic hypotension
