Hypertension Medication Information

For hypertension, when we target alpha 1, what do we target?

Vascular SMCs

For hypertension, when we target alpha 2, what do we target?

Central sympathetic neurons

For hypertension, when we target beta 1, what do we target?

Working cardiomyocytes

For hypertension, when we target beta 2, what do we target?

Bronchiolar SMCs

What is the MOA for beta-1 selective beta blockers?

Binds to the preferably to the beta-1 cells in central sensory neurons → Blocks NE and Epi → Reduced Gs - cAMP - PKA signaling → Reduced pacemaker activity and calcium-dependent contractility → Reduced heart rate and force of contraction

What does reduced B1-adrenergic signaling reduce?

CO, MAP, renin release, calcium-dependent contractility

What does beta-1 selective mean?

All betas are very similar, but the beta-1 selective have better binding affinity and reduced undesired signaling

What is the MOA for alpha-1 blocker?

Binds to alpha-1 in vSMC → blocks NE from activating → Reduces Gq-PLC mediated signaling → Decrease IP3-dependent calcium release → Reduced MLCK →Reduces contraction and increase vessel tone

What does alpha-1 blocker reduce?

Reduced vasoconstriction and SVR

AP has heart failure and COPD controlled with Advair and albuterol. Considering the patient's PMH, which antihypertensive agent would you recommend? Carvedilol or Metoprolol

Metoprolol

What does RyR-mediated signaling do?

Release Ca2+ from intracellular stores into cytosol

What does BPH?

Benign prostatic hyperplasia

Patient has a hypertension and BPH, what drug class would be desired?

Non-selective alpha-1 blocker

What is the MOA for alpha-2 blockers?

Stops NO and Epi → Inhibit Go/Gi -mediated signaling → Decrease cAMP + PKA → Decrease HR + BP

What is the MOA for calcium channel blockers, DHP?

Binds to L-type Ca channels in vSMCs, cardiomyocytes → Inhibits inward flux of extracellular Ca → Decrease nodal depolarization → Promotes vasodilation & reduced myocardial contractility

What is the MOA for calcium channel blockers, non-DHP?

Binds to L-type Ca channels in pore regions , cardiomyocytes → Inhibits inward flux of extracellular Ca → Decrease nodal depolarization → Promotes vasodilation & reduced myocardial contractility

What does non-DHP mean?

Works centrally by slowing heart contractility

What are the two non-DHP calcium channel blocker?

Verapamil and diltiazem

Why can diltiazem lower BP and slow AV-nodal conduction, while amlodipine is used mainly for its vascular effect?

Both inhibit L-type channels, but diltiazem has prominent direct cardiac effects as well as vascular effect; amlodipine acts predominantly on arteriolar smooth muscle

What hypertension class raises SVR?

Calcium channel blocker

What does excess action at SA/AV-nodal cells?

Bradycardia; slowed AV conduction

What does excess vascular smooth muscle cause?

Hypotension