Heart Failure Drugs

Question 1

What is the goal of Treatment of Heart Failure?

Answer 1

1.Drugs that increase contractility
2.Drugs that decrease preload
3.Drugs that increase afterload
4.Drugs that reduce edema

Question 2

What are the drugs used for HF? (There are five different classes)

Answer 2

1.Positively Inotropic drugs Digitalis Glycoside: Digoxin Adrenoreceptor Agonist: Dobutamine Phosphodiesterase inhibitors: Milrinone
2. Vasodilators
ACE Inhibitors: Enalapril, Lisinopril ARB: Valsartan, Candesartan Other Vasodilators:
Hydralazine, Isosorbide, Nesiritide
3. Aldosterone Antagonists Spironolactone, Eplerenone
4. Beta Adrenoreceptor Blocker: Carvedilol, Metoprolol, Bisoprolol
5. Diuretic
Furosemide, bumetanide and torsemide

Question 3

Irene came with decrease in heart contractility. What drug will you give her and what is the MOA?

Answer 3

1. Digoxin also known as cardiac glycosides
   Mechanism of Action:
   It inhibits the Na+/K+ ATPase pump

Question 4

What is the direct and indirect of Digoxin?

Answer 4

Direct Effect:
Inhibits Na+/K+ ATPase pump leading to increase intracellular Na+ Ca++ Force of contraction
AV node digoxin decreases conduction velocity

Indirect Effect:
Inhibition of Neuronal Na+/K+ ATPase: 1.Activates cholinergic system Heart rate 2.Activates sympathetic system Contractility

Question 5

What is the clinical use of Digoxins

Answer 5

1.CHF
2.Supraventricular tachycardia except WPW syndrome

Question 6

Digoxin is displaced by what other drugs

Answer 6

Amiodarone, Propafenone, Quinidine and verapamil

Question 7

What is the side effects of Digoxin

Answer 7

GI: Anorexia, nausea, vomiting and diarrhea
CNS: Headache, disorientation and visual halos
CVS: PVCs, AV block, sinus bradycardia and Inverted T waves

Question 8

Digitalis Toxicity:

Answer 8

Triggered by:
Hypokalemia, hypomagnesemia, and hypercalcemia

Question 9

What is the Antidote to digitalis Toxicity:

Answer 9

DigiFab (digibind)
Supportive therapy (electrolytes and antiarrhythmic drugs)

Question 10

Drugs that cause Digitalis toxicity:

Answer 10

Loop diuretics, thiazide diuretics, quinidine, verapamil NSAIDS, amiodarone, and erythromycin

Question 11

What are Bipyridines, clinical use?

Answer 11

Drugs ending in “rinone”
Inamrinone and Milrinone
Mechanism of action:
Inhibits PDE causing increase in cAMP——>Positive inotropy
increase in cGMP——>Vasodilation
Clinical use: Short term Rx of CHF Adverse effects: Hypotension Inamrinone: Thrombocytopenia

Question 12

ER Treatment of Heart failure:

Answer 12

1.Sympathomimetic drug: Dobutamine
Indicated in acute decompensated heart failure
2. Diuretics: Loop and Thiazides
Reduction of congestion and edema
Spironolactone reduced mortality when combined with ACEI 3. ACE inhibitors: Lisinopril
4. CCB: Amlodipine and verapamil
5. BB: Carvedilol has proven to decrease mortality
Metoprolol increase survival in patients with CHF
6. Nesiritide: Recombinant B type natriuretic peptide (rhBNP) Increases cGMP leading to smooth muscle relaxation
Increases Natriuresis and decreases preload
Clinical use: To relieve dyspnea at rest in severe decompensated CHF

Question 13

Pulmonary Hypertension and Core Pulmonale:

Answer 13

WHO classification of pulmonary HTN
Group 1: Idiopathic
Group 2: secondary to left-sided heart failure Group 3: Secondary to hypoxemia of lung diseases Group 4: Secondary to chronic thromboembolism Group 5: Secondary to other causes

Question 14

Management of Pulmonary Hypertension

Answer 14

1.Treatment of underlying condition
2.CCB

Question 15

Drugs used in Pulmonary Hypertension:

Answer 15

1.Endothelin Receptor Antagonists: Bosentan: Blocks ETa/ETb receptors Ambrisentan: Blocks Eta only Contraindicated in pregnancy
Side effects : Hypotension and flushing
2. PDE 5 inhibitors
Sildenafil and Tadalafil
Increase cGMP Vasodilation
3. Prostacyclin Analogs
Epoprostenol IV
Iloprost and Treprostinil given by inhalation
4. Oral soluble guanylate cyclase activator
Riociguat causing vasodilation

Question 16

Pivotal drug for acute heart failure

Answer 16

1. Carvedilol
2. Furosemide
3. Dobutamine
4. Lisinopril

Question 17

Newly approved drugs in Heart Failure

Answer 17

Ivabradine
Sacubitril/Valsartan

Question 18

What is the drug for treatment of HF, MOA,

Answer 18

Use: Heart failure: Reduce the risk of hospitalization
For patients with EF< 35% in sinus rhythm with heart rate > 70 MOA: Inhibits F-channels with the SA-node leads to decrease (If) ion and reduce heart rate.

Question 19

Sacubitril/Valsartan MOA for HF?

Answer 19

Neprilysin inhibitor/ARB
Use: Heart failure in place of ACEI or ARB
MOA:
Sacubitril: Inhibits Neprilysin (neutral endopeptides) NEP leading to increase Natriuretic peptide
Valsartan: Direct antagonist of Angiotensin II receptors

Question 20

Electrophysiology of the Heart (List 4)

Answer 20

1.Responsiveness
Capacity of a cell to depolarize
Depends on the # of channels in ready state
2. Conductance
Rate of spread of an impulse (conduction velocity) Depends on Vmax, threshold potential and resting Membrane potential
3. Automaticity
Ability to spontaneously depolarize
4. Refractoriness
The inability to respond to a stimulus

Question 21

Class 1: ________ Channel blockers

Answer 21

Na+

Question 22

List of the drugs Class 1A

Answer 22

Quinidine, Procainamide and Disopyramide

Question 23

What is the anticholinergic effect and Alpha blocking effect of Quinidine

Answer 23

Anticholinergic effect: Increase heart rate and conduction Alpha blocking effect: Vasodilation and reflex tachycardia

Question 24

What is the side effects of Class 1A drugs

Answer 24

Cinchonism: Tinnitus, loss of hearing, GI upset, diplopia Increase QT interval (Torsades de pointes)
Displaces Digoxin from tissue binding sites VD Antacids will increase its absorption and toxicities

Question 25

What is the side effects of Procainamide, what class is it ?

Answer 25

Less anticholinergic No alpha blocking activity Active metabolite NAPA (N-Acetyl procainamide)

Question 26

In Class 1A is the most anticholinergic?

Answer 26

Disopyramide

Question 27

What are the Class IB?

Answer 27

Lidocaine, Tocainide, Mexiletine

Question 28

What class of drug of the Antiarrhythmia preference of ischemic tissue

Answer 28

Class IB

Question 29

Winnie the Pooh comes in to ER with Vtac after MI what do you give him and what is the side effects?

Answer 29

Lidocaine Adverse effects: Drowsiness Paresthesia Convulsions in toxic doses

Question 30

What is the name of the drugs in Class IB, which ones are orally given?

Answer 30

Lidocaine Tocainide orally Mexiletine orally

Question 31

What class of drugs is Flecainide, Propafenone, Moricizine, MOA, clinical sue, and side effects

Answer 31

Class IC Work on both Na+ Channels Marked decrease of Vmax, but no effect on APD Clinical use: Life threatening Vtac and Vfib Refractory SVTs Adverse effects: Proarrhythmic effect: can worsen existing arrhythmia Can increase in sudden death and cardiac arrest by decrease LV function after MI

Question 32

What are Class II drugs, MOA, clinical use, side effects?

Answer 32

Class II: Beta Blockers Metoprolol, Propranolol, Acebutolol and Esmolol SA and AV nodal conduction Decrease the slope of phase 4 depolarization Clinical use: Prophylaxis for ventricular arrhythmias Post MI Rx of SVTs Adverse effects: Proarrhythmic: can cause AV block Esmolol has a t1/2 of 8 minutes Given IV for emergency Rx of SVT

Question 33

What are class 3 Antiarrhythmic drug, MOA, Clincial use, side effects

Answer 33

Amiodarone, Dofetilide, Ibutilide, Sotalol, dronaderone APD and ERP Prolong repolarization and lengthen Phase 2 Amiodarone Mimics Class 1, 2, 3, and 4 Binds to Na+ Channel (inactivated) Blocks K+ and Ca++ channels Non-competitive inhibitor of Beta receptors Long t1/2: 25 – 60 days Clinical use: Atrial fibrillation Ventricular Tachycardia Adverse effects: Pulmonary fibrosis Hepatotoxicity Smurf skin (bluish discoloration of skin) Hypothyroidism 5% and Hyperthyroidism 25 May cause Torsades de pointes

Question 34

Selectively block outward potassium channel Ibutilide and Dofetilide?

Answer 34

Selectively block outward potassium channel called delayed rectifier potassium channels. Prolong Ventricular Repolarization and increase the QT interval Used for pharmacological cardioversion of atrial fibrillation and flutter

Question 35

Which class 3 drug is a beta and K+ blocker, clinical use, side effects

Answer 35

Sotalol Beta blockers and K+ channel blocker Class 2: Decrease heart rate and AV conduction Class 3: Prolongs APD and ERP Clinical use: Atrial fibrillation and life-threatening Ventricular arrhythmias Adverse effects Torsades de pointes Headache, depression and impotence Caution with asthmatics

Question 36

What class 4 Antiarrhythmic? Clinical use? Side effects, MOA?

Answer 36

Diltiazem and Verapamil SA and AV nodal conduction Slope of phase 4 Clinical Use: PSVT due to AV nodal re-entry Adverse effects: Orthostatic hypotension Reduce cardiac output Lower extremity edema Constipation Verapamil displaces digoxin, increasing its toxicity Proarrhythmic AV block if used with beta blockers Caution: Atrial tachycardia due to WPW

Question 37

What is adenosine MOA, clinical use, side effects

Answer 37

Adenosine Miscellaneous drugs Rapid acting AV nodal blocker when given IV T1/2 is less that 30 seconds Adenosine receptors: A1: Gi coupled, decrease SA, AV nodal rate A2a: Gs-coupled, vasodilate A2b: Gq-coupled, bronchoconstriction Clinical use: Drug of Choice for PSVT Antagonist: Theophylline Adverse effects: Flushing, shortness of breath, burning sensation in the chest.

Question 38

What is the digoxin use for

Answer 38

Digoxin Used in heart failure Control ventricular rates in afib and aflutter. Torsades de pointes Arrhythmias caused by drugs that cause prolongation of QT intervals such as Amiodarone, quinidine, sotalol, thioridazine And Tricyclic antidepressants Management 1.Discontinue the offending drug 2.Administer magnesium sulfate and potassium