Vasodilating Versus First-Generation -βblockers for Cardiovascular ProtectionScott Morgan MSIIINovember 2012

Introduction

• Hypertension (HTN)• Defined as BP >140/90 mmHg• Prevalence in US adults is 29% or approximately 59 million• Risk factor for several diseases:• Cardiovascular (CV) • Cerebrovascular • Renovascular

• β-blockers • Discovered in mid 1960s• Were first-line HTN treatment previously• Currently falling out of favor due to side effects

-blocker Classesβ

Generation Properties Examples

First Nonselective w/o Vasodilation Propanolol, pindolol, nadolol, tindolol, sotalol

Second β1-selective w/o Vasodilation Atenolol, bisoprolol, metoprolol

Third Nonselective w/ Vasodilation

β1-selective w/ Vasodilation

Carvedilol, bucindolol, labetalol

Nebivolol

Vasodilating Effects

• First and Second-Generation (older generation)• No vasodilation

• Third-Generation• Nonselective w/ Vasodilation• Block vascular α-receptors• Carvedilol, bucindolol, labetalol

• β1-selective w/ Vasodilation• Increase NO• Nebivolol

1st Generation Pharmacology• Inhibits catecholamines acting on β1-receptors in heart• Decreases HR and contractility• Leads to decrease CO (SV x HR) and BP• Decreases cardiac work and oxygen demand

• Inhibits β1-receptors on juxtaglomerular apparatus in kidneys• Decreases renin release• Leads to decreased activation of renin angiotensin

aldosterone system (RAAS)

• Inhibits presynaptic transmission in CNS• Decreases catecholamine release

Older Gen Clinical Indications• Coronary heart disease• Heart failure• Reduce mortality by 30% in HF w/o preserved ejection

fraction• Post-myocardial infarction• Prevent catecholamine arrhythmogenic effects such as

ventricular tachyarrhymias• Chronic stable angina• Reduction in cardiovascular events• PTs with• advanced age• LV dysfunction• Anterior MI

Older Gen for Blood Pressure

Compliance Issues• Lethargy• Drowsiness• Depression• Peripheral vascular effects• Cold extremities

• Sexual side effects• Erectile dysfunction• Orgasmic dysfunction

• Can worsen• Diabetes mellitus• Decreased insulin release by block β2 receptors in pancreas

• COPD• PVD

Nonselective 3rd Gen β-blockers• Carvedilol, bucindolol, metoprolol• Block vascular α-receptors

• Decreased PVR and increased glucose delivery to muscles• Increases insulin sensitivity• Normally vasodilates by NO, but vasoconstricts by SNS• Diabetes and HTN blunt NO effects allowing SNS to increase PVR

• Can raise HDL and lower LDL levels• Increases renal blood flow • Less activation of RAAS• Reduces microalbuminuria• No negative BUN/creatinine effects

Carvedilol• Better tolerated in elderly• Body already has β-blocker like effects

• Decreased β-adrenergic response and increased catecholamine levels

• Less β-blocking effects and more vasodilation

• Less sympathetic activation• Fewer adverse effects• More compliance

• Most common side effects• HA• Dizziness• Orthostatic hypotension

Nebivolol

β-blocker Properties

Summary• Third generation β-blockers are more effective at controlling

HTN than traditional

• More favorable metabolic effects• Better choice with multiple comorbid conditions• Safer in elderly and black populations

• Fewer side effects

• Older generation β-blockers are still useful for treatment of other cardiovascular diseases

Citation

• Fares, Hassan et al. Vasodilating Versus First-Generation β-blockers for Cardiovascular Protection. Postgraduate Medicine. Volume 124; Issue 2: 7-14. March, 2011.