Angina and Heart Failure - PPT II - Final Exam

What are the three main drug classes used for angina?

-nitrates

-calcium channel blockers

-beta blockers

What are the two strategies of antiginal drugs?

reduce oxygen demand and increase oxygen supply to myocardium

What are the nitrate agents?

-amyl nitrate

-nitroglycerin

-isosorbid dinitrate

-isosorbide mononitrate

What is the dosage form of amyl nitrate?

inhaled

What are the dosage forms of nitrogylcerin?

-sublingual

-oral

-IV

What are the dosage forms of isosorbide dinitrate?

-sublingual

-oral

What is the dosage form of isosorbide mononitrate?

oral

What is the MOA of nitrates?

-increase concentration of NO in vascular smooth muscle

-NO activates guanylyl cyclase to produce cGMP

-cGMP facilitates the dephosphorylation of myosin light chains, preventing interaction with actin

What is the net result of the MOA of nitrates?

vascular smooth muscle relaxation

What are the therapeutic uses of nitrates?

angina

How do nitrates treat angina?

-decrease cardiac preload

-decrease cardiac afterload

-decrease myocardial oxygen demand

-increase myocardial oxygen supply by dilating large epicardial arteries

How are oral nitrates metabolized?

rapidly by hepatic reductase

What are the fastest acting preparations of nitrate?

-inhaled amyl nitrate

-IV nitroprusside

What nitrate is not suitable for maintenance or chronic therapy?

sublingual nitroglycerin

What are the adverse effects of nitrates?

-acute toxicity may cause pronounced vasodilation resulting in orthostatic hypotension

-reflex tachycardia

-throbbing headaches

-development of tolerance for vasodilating action with prolonged use

What are the contraindications of nitrates?

-synergistic hypotension with phosphodiesterase type 5 inhibitors like sildenafil

-known hypersensitivity

-hypotension

What is the MOA of calcium channel blockers?

-blocks voltage dependent L-type calcium channels of cardiac and vascular smooth muscle

-reduce intracellular Ca2+ which causes relaxation in arteriolar smooth muscles (vasodilation)

-cause long-lasting relaxation of vascular smooth muscles and reduce cardiac contractility

What are the therapeutic uses of calcium channel blockers?

-angina

-HTN

What is the MOA of beta blockers?

-decrease HR

-reduced cardiac contractility

-reduced BP

-decreases myocardial oxygen requirements at rest and during exercise

What are the therapeutic uses of beta blockers?

treatment of classic angina

What is the therapeutic use of ranolazine?

-chronic stable angina

-prophylaxis of angina

What is the MOA of ranolazine?

-block excessive prolongation of the late phase of sodium current in heart cells

-decreases diastolic wall tension, improves diastolic subendocardial perfusion, and reduces oxygen consuption

-has no effect of HR and BP

What are the adverse effects of ranolazine?

-mild dizziness

-headache

-nausea

-constipation

What is the MOA of ivabradine?

reduces heart rate by blocking the funny sodium channels in the SA node

What are the therapeutic uses of ivabradine?

chronic stable angina in patients who cannot take beta blockers

What are the adverse effects of ivabradine?

-bradycardia

-visual brightness

-mild dizziness

-headache

-nausea

-constipation

What medications are used for erectile dysfunction disorder?

-sildenafil

-tadalafil

What is the MOA of sildenafil and tadalafil?

selectively inhibit phosphodiesterase type 5 in male corpus cavernosum which increases cGMP to prolong smooth muscle relaxation and increase blood flow in the corpus cavernosum

What percentage of diabetes or prostate cancer patients do not respond to sildenafil and tadalafil?

50%

What are the adverse effects of sildenafil and tadalafil?

-headache

-flushing

-transient visual abnormalities

-priapism

What erectlie dysfunction medications are longer acting?

-vardenafil

-tadalafil

What are the contraindications of drugs for erectil dysfunction?

-elderly males with cardiovascular disease especially if they are receiving nitrate therapy for angina or CHD

-extreme hypotension that is sometimes fatal

What is alprostadil?

PGE1 analog that can be injected directly into CC

What is the MOA of alprostadil?

-acts through smooth muscle relaxation in penile tissue

-vasodilator and avalible as urethral suppository

What are the adverse effects of alprostadil?

-mild/moderate penile pain

-irritation

-painful erection

-urethral bleeding

What drugs are used for heart failure?

-angiotensin-converting enzyme inhibitor

-angiotensin receptor blockers

-neprilysin inhibitor

-natriuretic peptide

-vasodilators

-beta adrenoceptor blockers

-aldosterone receptor antagonists

-diuretics

-positive inotropic drug

-phosphodiasterase-3 enzyme inhibitor

-adrenergic receptor antagonists

What is the neprilysin inhibitor?

sacubitril

What is sacubitril?

a prodrug available in 1:1 combination with valsartan in Entresto

What is sacubitril converted to and by what?

sacubitrilat by plasma esterase

What is the MOA of sacubitril and valsartan?

-prevent degradation of BP lowering natriuretic peptides

-block angiotensin II receptor

-increase vasodilation

What is the typical responsibility of neprilysin?

degrade atrial natriuretic peptide and ventricular natriuretic peptide (BP lowering peptides)

What is the therapeutic use of sacubitril?

heart failure with reduced ejection fraction

What are the adverse effects of sacubitril/valsartan?

-hypotension

-hyperkalemia

-cough

-dizziness

-renal failure

What are the contraindications of Entresto?

with ACEIs

What are the natriuretic peptides?

nesiritide

What is nesiritide?

-synthetic form of endogenous peptide

-human B-type natriuretic peptide obtained from E coli using recombinant DNA technology

What is the MOA of natriuretic peptides?

-increases cGMP in vascular smooth muscle and endothelial cells

-cGMP acts as a second messenger to dilate arterial and venous smooth muscle

What are the therapeutic uses of natriuretic peptides?

-acute (not chronic) heart failure

-treatment of patients with acutely decompensated heart failure who have shortness of breath at rest

What are the adverse effects of natriuretic peptides?

hypotension

What is the MOA of digoxin for positive ionotrpic effects?

-in CHF, digoxin begins with inhibition of NA/K ATPase

-intracellular increase in Na+ concentration

-decreased expulsion of intracellular Ca2+

-increased intracellular Ca2+

-increased actin-myosin interaction by intracellular Ca2+

-increased force of myocardial contraction

What is the MOA of digoxin for negative chronotropic effects to decrease heart rate?

-produced bradycardia by decreasing sympathetic tone

-stimulates vagus nerve and decrease HR

-decrease automaticity, prolong refractory period, and slow AV node conduction

What are the therapeutic uses of digoxin?

-congestive heart failure to increase contractility

-rapid ventricular rate in atrial fibrillation doesn't reduce mortality but reduces rehospitalization

What are the gastrointestinal adverse effects of digoxin?

-anorexia

-nausea

-vomiting

-diarrhea

-abdominal discomfort

-side effects disappear a few day after discontinuing

What are the most dangerous side effects of digoxin?

cardiac effects

What are the cardiac side effects of digoxin?

-arrhythmias

-sinus bradycardia

-ectopic ventricular beats

-AV block

What is the most common cause of death with digoxin?

ventricular fibrillation

What should you monitor with digoxin?

-routine ECG

-serum digoxin

-serum potassium

What are the CNS side effects of digoxin?

-headache

-fatigue

-malaise

-drowsiness

-mental symptoms

What are the adverse effects of digoxin in the elderly?

-disorientation

-hallucinations

What are the other adverse effects of digoxin?

-color and visual distrubances

-skin rashes

-eosinophilia

-gynecomastia

What should be used to treat digoxin toxicity?

digoxin immune fab and discontinuation of digoxin

How does digoxin immune fab work?

-IV

-reverse digoxin toxicity rapidly

-binds to digoxin

What are the phosphodiesterase enzyme 3 inhibitors?

milrinone

What is the MOA of PDE3 inhibitors?

inhibits PDE3 present in cardiac muscle by increasing the concentration of cAMP in myocytes

What is the typical action of PDE3?

inactivate cAMP

What is the therapeutic use of PDE3s?

short term management of acute heart failure in patients who are not responsive to other drugs

What are the adverse effects of PDE3s?

-long-term use can cause thrombocytopenia and ventricular arrhythmias

-hypotension

What are the adrenergic receptor agonists?

dobutamine

What is dobutamine?

selective beta-adrenoreceptor agonist used in short term managment of acute heart failure and cardiogenic shock

What is the MOA of adrenergic receptor agonists?

selectively stimulates cardiac contractility and usually causes less tachycardia than other beta agonists

How are adrenergic receptor agonists administered?

IV infusion and high doses may increase mortality

What are the adverse effects of adrenergic receptor agonists?

arrhythmias