Vasodilators & ACE Inhibitors / ARBs Flashcards Preview

CVPR - CV Unit 1 > Vasodilators & ACE Inhibitors / ARBs > Flashcards

Flashcards in Vasodilators & ACE Inhibitors / ARBs Deck (11):

Nitrates - Mechanism

Venous vasodilators that act by donating a NO group; in the VSMCs, NO activates guanylate cyclase, which produces cGMP; cGMP activates PKG which phosphorylates SERCA, activating it; reduced intracellular Ca2+ leads to smooth muscle relaxation

PKG also inhibitors LTCC resulting in decreased Ca2+ entry; less Ca2+ is available to bind CaM and activate MLCK; reduced phosphorylation of myosin heads results in less cross-bridge cycling

o increase venous capacitance, thereby decreasing venous return to the heart (pre-load); reduce LV diastolic pressures & pulmonary congestion



Arterial dilator that works by reducing systemic vascular resistance (afterload), permitting increased ventricular muscle fiber shortening during systole resulting in increased stroke volume

Does not generally reduce BP because drop in peripheral resistance is compensated for by a rise in cardiac output


ACE Inhibitors

Balanced venous/arterial dilators; inhibit the production of AII, preventing it from causing vasoconstriction; also decreases aldosterone levels which increases sodium elimination and reduces intravascular volume, improving systemic and pulmonary congestion

Anti-remodeling effect


Angiotensin II Receptor Blockers (ARBs)

Block the action of AII at its receptor; generally considered to be as effective as ACE Inhibitors

Used when common ACE inhibitors are not tolerated due to common side effects, most often cough


Isosorbide Dinitrate + Hydralazine (H-ISDN)

Added to therapy for patients with persistent symptoms despite ACEI/ARB and B-blocker

Particularly effective in blacks NYHA class III-IV

Arterial dilation (hydralazine) reduces afterload & cardiac work; venous dilation (isosorbide) decreases pre-load


ACE Inhibitors - Mechanism

Inhibits ACE-mediated conversion of AI to AII, blocking AII-induced vasoconstriction (decreased preload & afterload)

Decreases AII-induced release of aldosterone, reducing myocardial hypertrophy & remodeling

Decreases bradykinin inactivation, increasing vasodilation


Lisinopril - Pharmacokinetics

Well absorbed orally, eliminated by kidney (requires renal dosing)


ACE Inhibitors - Adverse Effects

Acute Renal Failure
Not used in pregnancy


Losartan - Mechanism & Uses

Selective inhibitor of AII receptor; similar effects as ACE Inhibitors; provides potential for more complete inhibition of AII than ACEIs

Used for treatment of heart failure in patients who cannot tolerate ACEIs; some potential for benefit in combo use of ACEIs and ARBs


Losartan - Pharmacokinetics

Oral administration with 2x/daily dosing

Requires adjustment in hepatic dysfunction



Vasoconstrictor peptide produced by vascular endothelium as a precursor and cleaved to its active form by endothlin converting enzyme (ECE)

Endothelin binds to EC receptors in VSMCs, which are Gq coupled; Gq activates PLC which produces IP3 and DAG; IP3 increases intracellular Ca2+, producing contraction of the VSMCs