ACE inhibitors If cough is intolerable, switch to an ARB or just use an ARB instead. Development of angioedema or significant hyperkalemia requires discontinuation of the drug. All generic drug names end in –pril. Angiotensin II AT1 Receptor Blockers (ARBs) (first-line) Molecular Mechanism Competitive antagonism of angiotensin II at the AT1 receptor* Physiological Mechanisms Block of angiotensin II-mediated vasoconstriction* Reduced norepinephrine release by block of angiotensin II-mediated enhancement Reduced sympathetic outflow from the brain stem Slightly reduced aldosterone secretion* Block of angiotensin II-mediated arterial and left ventricular remodeling* No change in bradykinin levels Much lower risk of dry cough than with ACE inhibitors* Much lower risk of angioedema than with ACE inhibitors* As teratogenic as ACE inhibitors* Hyperkalemia (in the absence of diuretic)* AT1 receptor blockers Efficacy is equivalent to that of ACE inhibitors. Useful in patients who cannot tolerate ACE inhibitors. Use of ARBs is increasing as generic versions become available. All generic drug names end in Once again, do not combine an ACE inhibitor with an ARB. There is –artan. no advantage to the combination compared with either single drug alone. Calcium Channel Blockers (amlodipine and other vascular-specific blockers are first line; verapamil and diltiazem are used in special circumstances) Molecular Mechanisms Reversible block of L-type Ca2+ channels in vascular smooth muscle cells* Reversible block of L-type Ca2+ channels in cardiac muscle cells* (verapamil, diltiazem only) Physiological Mechanisms Reduced sympathetically-mediated vasoconstriction due to block of Ca2+ action potentials and Ca2+-mediated Ca2+ release from sarcoplasmic reticulum* Reduced inotropy, cardiac output* (verapamil, diltiazem only) Other Actions Reflex tachycardia (risk in ischemic heart disease; avoid using rapidly-acting calcium channel blockers)* Reduced inotropy and chronotropy (verapamil, diltiazem only)* Edema from precapillary dilatation with reflex postcapillary constriction (all)
ACE inhibitors If cough is intolerable, switch to an ARB or just use an ARB instead. Development of angioedema or significant hyperkalemia requires discontinuation of the drug. All generic drug names end in –pril. Angiotensin II AT1 Receptor Blockers (ARBs) (first-line) Molecular Mechanism Competitive antagonism of angiotensin II at the AT1 receptor* Physiological Mechanisms Block of angiotensin II-mediated vasoconstriction* Reduced norepinephrine release by block of angiotensin II-mediated enhancement Reduced sympathetic outflow from the brain stem Slightly reduced aldosterone secretion* Block of angiotensin II-mediated arterial and left ventricular remodeling* No change in bradykinin levels Much lower risk of dry cough than with ACE inhibitors* Much lower risk of angioedema than with ACE inhibitors* As teratogenic as ACE inhibitors* Hyperkalemia (in the absence of diuretic)* AT1 receptor blockers Efficacy is equivalent to that of ACE inhibitors. Useful in patients who cannot tolerate ACE inhibitors. Use of ARBs is increasing as generic versions become available. All generic drug names end in –artan. Once again, do not combine an ACE inhibitor with an ARB. There is no advantage to the combination compared with either single drug alone. Calcium Channel Blockers (amlodipine and other vascular-specific blockers are first line; verapamil and diltiazem are used in special circumstances) Molecular Mechanisms Reversible block of L-type Ca2+ channels in vascular smooth muscle cells* Reversible block of L-type Ca2+ channels in cardiac muscle cells* (verapamil, diltiazem only) Physiological Mechanisms Reduced sympathetically-mediated vasoconstriction due to block of Ca2+ action potentials and Ca2+-mediated Ca2+ release from sarcoplasmic reticulum* Reduced inotropy, cardiac output* (verapamil, diltiazem only) Other Actions Reflex tachycardia (risk in ischemic heart disease; avoid using rapidly-acting calcium channel blockers)* Reduced inotropy and chronotropy (verapamil, diltiazem only)* Edema from precapillary dilatation with reflex postcapillary constriction (all)