Exam 2: Beta Blockers Flashcards

Question

Prazosin

Answer 1

* Selective Alpha-1 antagonist (*less SEs than non-specific agents*) * Less likely to cause tachycardia * Dilates both arterioles and veins * Uses: * Pre-op preparation of patients with pheochromocytoma * Essential HTN (combined with thiazides) * Decreasing afterload in patients with heart failure * Raynaud phenomenon * Pt may be taking it * Control BP in pheochromocytoma * Selective alpha 1 blocker (minimal alpha 2) * Less reflexive tachycardia (remember alpha 2 is inhibitory to NE release)

Answer 2

* Alpha 2 selective blocker * Increases the release of Norepi from post-synaptic neuron * Used w/orthostatic hypotension, impotence * *Don’t see much anymore*

Answer 3

alpha antagonists - pts may be taking them for BPH * Long-acting, both are selective alpha -1a particularly effective in prostatic smooth muscle relaxation * But Tamsulosin is even more specific for **alpha 1a subtype** and so it acts mainly on the urogenital tract * Vary in elimination half times * Orthostatic hypotension is biggest concern (less for Tamsulosin)

Answer 4

(Class II antiarrhythmics, act on phase 4) * *Decreasing workload, increasing perfusion time for coronary arteries* * Disallow sympathomimetics from provoking a beta response on the: * Heart * Bradycardia * Decreased contractility * Decreased conduction velocity * Improve O2 supply and demand balance * Airway * bronchoconstriction and can provoke bronchospasm in patients with asthma or COPD – need to use cardioselective B-blocker * Blood vessels * Vasoconstriction in skeletal muscles; PVD symptoms ↑ * Juxtaglomerular cells * ↓ renin release – indirect way of ↓BP * Pancreas * Fight or flight – gluconeogenesis and glyogenolysis (double check this) – increase in glucose. So this will block it. * Decreased stimulation of insulin release by epi/norepi at B2 and then masked symptoms of hypoglycemia B1 * Derivatives of the beta agonist isoproterenol thus possessing some sympathomimetic effects Substitution on the benzene ring

Answer 5

* Mechanism of action * Selective binding to beta receptors (influence inotropy, chronotropy) – *no covalent bonding for B-blockers* * Competitive and reversible inhibition-large doses of agonists will completely overcome antagonism * Chronic use is associated with increase in the # of receptors (up-regulation) * So what happens if we stop them suddenly perioperatively???? Exaggerated response to catecholamines * Classification: * Non selective (beta 1 & 2) * propranolol, nadalol, timolol, pindolol * Cardioselective (beta 1 only) * metoprolol, atenolol, acebutolol, betaxolol, esmolol * Large doses lose selectivity * Selecting B-blockers * Note: * Selectivity * Elimination ½ life * Bioavailability

Answer 6

* Clinical uses of b-blockers * Treatment of HTN * Management of Angina * Decrease mortality in treatment of post MI pts * Used periop and preop for pts at risk for MI * Suppression of tachyarrythmias * Prevention of excessive sympathetic nervous system activity * Relative Contraindications * Pre-existing AV heart block or cardiac failure * Reactive Airway Disease * Diabetes Mellitus (without BG monitoring) 0 mask sx’s of hypoglycemia * Hypovolemia – *their compensatory response is to* *↑ HR, so you’re taking that away*

Answer 7

* Side effects of b-blockers * CV System-decrease HR, Contractility, BP * Exacerbation of peripheral vascular disease (block of beta - 2 vasodilation) * Airway resistance-bronchospasm * Metabolism-alter carbohydrate and fat metabolism, mask hypoglycemic ↑ in HR * Distribution of extracellular potassium-inhibit uptake of potassium into skeletal muscles * Interaction with anesthetics-may have ↓ BP with IAs * Nervous system-fatigue, lethargy * Nausea, vomiting and diarrhea * Eye –reduction in IOP (esp if patient has glaucoma) due to decreased aqueous humor production * Decreased concentrations of HDLs have been seen with chronic use that may increase risk for CAD (mechanism not understood and undergoing research)

Answer 8

B-blocker prototype * Non-selective (about equal B1 and B2 prototype for Beta-blockers * CV: decreased HR and contractility (B1) and increased vascular resistance (B2) * *Can increase vascular resistance in the lungs bc of b2 blockade* * Undergoes extensive 1st pass effect * Limited use in current anesthesia practice. * Concerns with patients who have been treated chronically with propranolol: * Decreased clearance of amide local anesthetics * Decreased pulmonary clearance of fentanyl (both are basic lipophilic amines) * **Administered with a goal of 55-60 bpm** * Cardiac effects: * Decreased HR, contractility, decreased CO * The above effects are especially prominent during exercise and sympathetic outflow * Blockade of b2 receptors - increased PVR, increased coronary vascular resistance * However due to decreased HR and CO oxygen demand is lowered, opposing the above effects * Reduction in Renin release (mainly through B1 antagonism) * Pharmacokinetics: * Goes thru significant first-pass effect (90-95%) * Oral dose much larger than IV dose * 0.05mg/kg IV or 1-10mg (give slowly 1mg q 5 min) – *we’re not really giving this IV anymore* * Protein bound (90-95%) * Metabolized in liver, E1/2t of 2-3hrs (will be ↑in low hepatic blood flow states) * Decreases clearance of amide LAs due to a decrease in hepatic blood flow inhibiting metabolism in the liver –risk of systemic toxicity of amide local anesthetics

Answer 9

* Beta 1 selective (inotropic and chronotropic) * Selectivity is dose related – *higher doses, **lose cardioselectivity*** * About 60% goes thru first pass effect * PO 50-400mg * IV 1-15 mg (Max dose) * Metabolized in the liver E1/2t of **3-4hrs*, but start to see effects in 3-4 minutes (so pretty quick)*** * Available IV * Beta 2 receptors remain intact: * Bronchial dilation * Vasodilation * Metabolic effects * What kind of patients would benefit from this selectivity? * *5 mg/mL, usually giving 5 mg or less in OR*

Answer 10

* **Most** selective beta 1 antagonist and thought to have the least CNS effects * E1/2t is 6-7hrs * Not metabolized in liver, excreted via renal system, therefore E1/2t is increased markedly in pts with renal disease * Advantageous to those who need beta 2 receptor activity – lung dz * Oral drug given to treat HTN * Long lasting antihypertensive effects (once a day dosing)

Answer 11

* Rapid onset and short duration Beta-1 selective beta blocker * Available IV only * **Onset of action = 60 seconds** * E1/2t is 9 minutes * **Duration of action 10-30 minutes** * Metabolized by plasma esterase (less than 1% of drug is excreted unchanged in the urine) * Poor lipid solubility dose not cross the BBB or placenta * Useful in treating HTN and tachycardia associated with laryngoscopy * Useful in treating hyper dynamic effects of: * Pheochromocytoma * Thyrotoxicosis * Thyroid storm * Rapidly hydrolyzed by plasma esterases * Not the same esterases as plasma cholinesterases responsible for metabolism of succinylcholine, therefore no effect on succinylcholine metabolism or duration of action * *Might use this one for induction bc you only what a transient effect! Can use for CAD pts*

Answer 12

* Timolol * Non-selective beta blocker * Used to tx glaucoma-decreases intraocular pressure by ↓ production of aqueous humor * Eye drops can cause ↓BP, ↓HR and ↑ airway resistance * Nadolol - "*Nada-metabolizer? Just eliminated."* * Non-selective beta blocker * No significant metabolism (renal/biliary elimination) * E1/2t of 20-40hrs take 1X daily * *Maybe used in esophageal varices?* * Betaxolol * Cardioselective beta 1 blocker * E1/2t is 11-22hrs * Single dose daily for HTN * Topical useful for glaucoma, with less risk of bronchospasm as seen with timolol, so good alternative choice in asthmatics with glaucoma * *"betta(x) for glaucoma but asthmatics! (Timolol is nonselective).*

Answer 13

LABETALOL * *Will see a little more peripheral relaxation bc of alpha1 blockade* * Combined Non-Selective antagonists * alpha 1 and beta 1 and 2 receptors * IV Beta to Alpha Blockade 7:1 * PO Beta to Alpha Blockade 3:1 * Metabolism conjugation of glucuronic acid; \<5% drug recovered unchanged in the urine * E1/2t of 5-8 hrs, prolonged in liver dz not affected by renal dysfunction * Max drop in BP 5-10 minutes after IV administration * Dose 0.1-0.5 mg/kg * *Dr. tola might give 2.5-5 mg at a time, and just wait and see how the pt tolerates* * Usually 5 mg at a time for mild HTN in the OR * Decreases systemic blood pressure (alpha-1) and **attenuates** reflex tachycardia (Beta 1 blockade) * ↓ BP, SVR, HR. CO is unaffected * Used to treat intraoperative HTN and hypertensive crisis * Can be used in hypotensive technique without an increase in HR (don’t really do this often anymore) * Can cause orthostatic hypotension, bronchospasm, heart block, CHF, bradycardia * Formerly used to decrease blood loss – re-do hip surgery, jaw surgery, shoulder procedure/arthroscopy, spine surgerry * Can cause **blindness**, prone position in back surgery and gets hypotension * Sitting position hypotension – blood to the brain * Can use this technique at 20% below normal, and this would give you a longer effect than with like esmolol. * Only use this technique with younger pts, or have no comorbidities * *Ex: use at the end of neuro cases when they want the pt’s BP to stay nice and low*

Answer 14

* According to recent findings**, perioperative application of beta- blockers still plays a pivotal role in cardiac surgery**, as they can substantially reduce the high burden of supraventricular and ventricular arrhythmias in the aftermath of surgery. Their influence on mortality, Acute MI, stroke, congestive heart failure, hypotension and bradycardia in this setting remains unclear. * **In non-cardiac surgery, evidence from low risk of bias trials shows an increase in all-cause mortality and stroke with the use of beta- blockers**. * As the quality of evidence is still low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and AMI in this setting seems to be offset by the potential increase in mortality and stroke.

Answer 15

* MOA: Reduce sympathetic outflow from vasomotor centers in the brain stem. Centrally acting selective partial alpha-2 adrenergic agonist * Site of action: CNS non-adenergic binding sites and a2 receptor agonism * Clinical Uses * Hypertension * Induce sedation – *the sedative property dissipates over time bc they get used to it* * Decrease anesthetic requirements * Improve peri-operative hemodynamics * Analgesia * Drugs in this category: Clonidine

Answer 16

* MOA: Reduce sympathetic outflow from vasomotor centers in the brain stem. Centrally acting selective partial alpha-2 adrenergic agonist * Site of action: CNS non-adenergic binding sites and a2 receptor agonism * Result in: * BP reduction from decreased CO due to decreased HR and peripheral resistance * **Rebound hypertension with abrupt cessation** – must be weaned!!! * Side Effects * Bradycardia * Sedation * Xerostomia (Dry mouth) * Impaired concentration * Nightmares * Depression * Vertigo * EPS * Lactation in men * Pharmacokinetics * Available as PO or transdermal patch * 50/50 hepatic metabolism and renal excretion * Withdrawal Syndrome * Occurs with doses of \>1.2mg/day * Occurs 18 hours after acute discontinuation of drug * Lasts for 24-72 hours * Treatment rectal or transdermal clonidine

Answer 17

Treatment of HypotensionSympathomimetics Ephedrine Phenylephrine Vasopressin – Dr. Tola will send us more info about this Epinephrine Norepinephrine Dopamine Dobutamine

Answer 18

* Arginine vasopressin = antidiuretic hormone (ADH) * Arginine vasopressin is an endogenous hormone * Produced in hypothalamus stored in posterior pituitary * Controls osmoregulation → release stimulated by increased osmolality and hypovolemia * Potent vasoconstrictor, but dilates renal afferent, pulmonary and cerebral arterioles * Three types of vasopressin receptors: * V1 – mediates vasoconstriction * V2 – mediates water reabsorption in the renal collecting ducts * V3 – found in the CNS and stimulate modulation of corticotrophin secretion * Multiple uses * Post cardiopulmonary bypass shock * Refractory hypotension * Reduce bleeding in von Willebrand’s disease * Anti-diuresis in diabetes insipidus * Treatment of enuresis (involuntary urination, esp by children at night)

Answer 19

* Dose * Low dose infusion 0.03-0.04 units/min; up to 0.1units/min * 1-2 units bolus * Onset 1-5 min. * Peak 5 min * DOA 10-30 min. * Complications * Seen at \> 0.04 units/min * Gastrointestinal ischemia * Decreased cardiac output * Skin or digital necrosis