Drugs for heart failure 2

Question 1

Patients with HFpEF may benefit from which inhibitors

Answer 1

ARNI and SGLT2 inhibitor.

Question 2

List the stepwise treatment of CCF: STGs and EML

Answer 2

1. Diuretic PLUS ACEI
2. Add 3rd agent: carvedilol OR Spironolactone
3. Add 4th agent: Carvedilol OR Spironolactone
4. Add 5th agent: Digoxin

Question 3

MoA of carvedilol

Answer 3

MOA: Non-selective β-receptor antagonist with additional α1-blocking activity

Question 4

Were is carvedilol excreted

Answer 4

Bile

Question 5

Carbedilol Metabolised where

Answer 5

Extensive metabolism in the liver with large first-pass effect (lipophilic)

Question 6

Dosing for carvedilol

Answer 6

Dosing for CCF (max doses: 25mg bd – if weight is >85kg 50mg bd)

Question 7

How to start giving Carvedilol in patients with CCF

Answer 7

Preferred in CCF (dose responsive reduction in mortality)
* Introduce cautiously…start at low dose (3.125mg bd): worsening of CF or
fluid retention may occur during up titration of carvedilol – increase diuretics,
do not increase carvedilol dose until clinically stable

Question 8

contra-indications for carvedilol

Answer 8

• Contraindications:
• NYHA Class IV decompensated heart failure requiring ionotropic support, AV
  block, sick sinus syndrome cardiogenic shock, bradycardia,
• Use with caution in patients on digoxin
• Asthma & COPD,
• Liver impairment

Question 9

adverse effects for carvedilol

Answer 9

Adverse effects: (as with other β-blockers) postural hypotension, dizziness, oedema of the legs

Question 10

list b blockers in HF

Answer 10

Carvedilol, metoprolol and bisoprolol

Question 11

Explain the use of B blockers in HF

Answer 11

• Prolong survival, decrease hospitalizations, reduce the need for
  transplantation, and promote “reverse remodelling” of the left
  ventricle.
• These agents are recommended for all patients with HFrEF unless
  contraindicated.
• Therapy must be instituted at low doses, with slow upward titration
  to the target dose.

Question 12

Explain the benefins of spironolactone

Answer 12

Aldosterone antagonists
* Prolong survival and decrease hospitalizations in patients with HFrEF.
* Considered to reduce the risk of hospitalization in patients with HFpEF.

Question 13

Digoxin is unique in its ability because?

Answer 13

Digoxin is unique in its ability to strengthen cardiac contraction while decreasing heart rate.

Question 14

List the effects of Digoxin

Answer 14

Digitalis glycoside positive inotropic effect (an increase in the force of contraction), a negative chronotropic effect (a decrease in the heart rate), and a negative dromotropic
effect (a decrease in conduction velocity).

Question 15

Use Digoxin in patienst with HFrEF becauses

Answer 15

Used in select patients with HFrEF (symptomatic & in sinus rhythm)to improve symptoms or reduce the risk of hospitalization

Question 16

MoA of Digoxin

Answer 16

Mechanisms by which digoxin exerts its positive inotropic effect on the heart. Digoxin inhibits the sodium pump
(ATPase) in the sarcolemma and increases the concentration of intracellular sodium. The high sodium concentration increases the
activity of the sodium-calcium exchanger (Ex), thereby causing more calcium to enter or remain inside the cardiac myocyte. Calcium
activates muscle fiber shortening and increases cardiac contractility, which in turn increases stroke volume at any given fiber length
(preload).

Question 17

Explain the Electrophysiologic and electrocardiographic effects of Digoxin

Its alot but recall what you can

Answer 17

Digoxin causes an increase in parasympathetic (vagal) tone and a decrease in sympathetic tone. These actions slow the heart rate by decreasing sinoatrial (SA) node
automaticity. The increased vagal tone and decreased sympathetic tone also slows the atrioventricular (AV) node conduction velocity while increasing the AV node refractory period. The reduced AV conduction velocity increases the PR interval on the electrocardiogram.

In ventricular tissue, digoxin shortens the action potential
duration, and this decreases the QT interval. Toxic
concentrations of digoxin may evoke afterdepolarizations
throughout the heart and thereby cause extrasystoles
and tachycardia. Digoxin also causes ST-segment
depression, which gives rise to the so-called “hockey stick
configuration” on the electrocardiogram.

Question 18

Digoxin: pharmacokinetics
1. Rate of absorption
2. Bioavailability
3. Onset of action
4. Half-life
5. NTI
6. Dosiing

Answer 18

• Rate (but not extent) of absorption decreased by food
• Bioavailability varies between preparations (no generic substitution)
• Onset of action 0.5-2 hours (effects last for 6 days)
• Half-life prolonged in renal failure; elimination is renal (50-70%
  unchanged)
• Narrow therapeutic index: Therapeutic serum concentrations 0.65-
  1.1nmol/L
• Individualised dosing

Question 19

Adverse effects of Digoxin

Answer 19

• Most common adverse effects of digoxin are gastrointestinal, cardiac, and neurologic reactions.
• Earliest signs of toxicity are anorexia, nausea, and vomiting.
• Arrhythmias, most serious manifestation of digoxin toxicity, atrial tachycardia with AV block is one of the most common types of digitalis-induced arrhythmia, but digoxin can also cause ventricular arrhythmias. Hypokalaemia can precipitate arrhythmias.
• Neurologic effects: blurred vision and yellow, green, or blue chromatopsia (a condition in which objects appear unnaturally colored). Severe digoxin toxicity can precipitate seizures

Question 20

Explain the toxicity of digoxin

Answer 20

Hypokalaemia, hypomagnesaemia, and hypercalcaemia predispose to toxicity
* Monitoring samples of steady-state serum concentration should be taken 6-8 hours after last dose
* Patients should be aware of and report signs of toxicity: anorexia, nauseas and vomiting. CNS signs, headache, drowsiness, facial pain, depression, mental confusion, disturbed vision