Vasodilators in Angina Flashcards
Major determinant of myocardial O2 supply is
Coronary Blood flow- blood flow during diastole is decreased during tachycardia (also decreased by increased LVEDP)
Myocardial O2 supply is inversely proportional to
coronary vascular resistance- damage to endothelium can alter ability of vasculature to dilate. Vascular control by metabolites (autoregulation) is most important.
Determinants for myocardial oxygen demand
1) Contractile state
2) Heart rate
3) LV pressure and ventricular volume
Drug that increase coronary blood flow
Nitrates and CCBs
Preload decreased by
Nitrates
Afterload decreased by
CCBs
-dipines properties (SA-AV Node(HR), Cardiac Muscle contractility and afterload)
CCBs. Inc, none to dec, dec
Diltiazem (SA-AV Node(HR), Cardiac Muscle contractility and afterload)
CCB. Dec, none to dec, dec
Verapamil (SA-AV Node(HR), Cardiac Muscle contractility and afterload)
CCB. Dec, Dec, Dec
Drugs that decrease demand
Beta-blockers
Nitrates
Calcium Channel Blockers
Drugs that reduce thrombosis
Antiplatelet Agents - Anticoagulants
Beta-blockers – Nitrates – CCBs
Drugs that prevent vasospasm
Nitrates
Calcium Channel Blockers
Variant (Prinzmetal) Angina
Caused by coronary vasospasm with or without atheromatous plaque. Occurs commonly at rest.
Variant Chronic Pharmacotherapy
Reversing or preventing vasospasm and increasing supply with vasodilators (nitrates or Ca++ channel blockers)ion
Nitrate Pathway
Nitrates to NO to inc cGMP to Vasodilation
Nitroprusside
converts to NO and affects venules and aterioles (causing decreased BP)
Increased cGMP results in
reduction of LVEDP and systemic vascular resistance
Transdermal (ointment or patch), Sublingual/lingual and IV all bypass
First pass effect! (much higher doses for oral)
Nitrate Adverse Rxns
Throbbing headache Orthostatic hypotension Reflex Tachycardia Facial Flushing (due to vasodilation) Tachyphylaxis (tolerance- need nitrate free interval of 6-14 hours)
Dihydropyridines effects (nifedipine)
greater ratio of vascular (dilation) to cardiac (rate-conduction-contractility) effects
Verapamil and Diltiazem (effects)
prominent effects at cardiac nodal tissue (phase 0 at SA and AV node) and on cardiac muscle (phase 2)
Rapid onset -dipines may rapidly lower…?
BP! causes reflex activation of the SNS which leads to tachycardia, exacerbation of angina and increased risk for MI
CCB Properties
1) Variable Oral bioavailability
2) Extensively protein bound
3) Metabolized by cytochrome P450
CCB Use in Angina
Long-lasting decrease in peripheral vascular resistance
Reduced heart O2 requirement
Reduced coronary arterial tone (aid in vasospastic angina)
CCB other uses
Arrhythmias
Hypertension
Subarachnoid hemorrhage
Inhibition of Premature labor
Verapamil/diltiazem vs Dihydropyridines
Dyhydropyridines greatly increase vasodilation while not having Negative inotropic effect and suppressing AV node conduction
CCB Adverse Rxns (verapamil/diltiazem more)
Cardiac arrest
Bradycardia
AV block
Congestive heart failure)
B-Blocker Uses in Angina
Decreased O2 demand
Can block reflex tachycardia from use of nitrates
NOT vasodilators -> no use in variant angina
B-Blocker Use
Angina patients with concomitant hypertension or arrhythmias responsive to β-blockers
B-Blocker Contraindications
Asthma
Peripheral vascular disorders
Abrupt withdrawal precipitates SNS overactivity
Failure of Late Na+ Current Inactivation causes
Ischemia! Decreased O2 supply and increased demand. Caused by increased extravascular compression and diastolic wall tension.
What drug blocks Failure of Late Na+ Current Inactivation?
Ranolazine. Administered bid.
Ranolazine Adverse Rxns
Can Prolong QT interval
Cardiovascular effects (~ 5%): bradycardia, hypotension, palpitations, edema
Ranolazine Use
Add-on to standard anti-anginal therapy
Reduces symptoms of chronic stable angina and increases exercise capacity
Can substitute for beta-blockers if not tolerated or contraindicated
