pharm management of acute and chronic heart failure - Lee

Question 1

how can diabetes contribute to heart failure?

Answer 1

• high blood glucose levels –> increase advanced glycation end products (AGE)
• measure AGE by looking at HbA1C levels

Question 2

systolic vs diastolic HF

Answer 2

1. systolic
   - reduced EF** (HFrEF)
   - EF < 40%
   - due to pump failure (ex. LV dilation)
2. diastolic
   - preserved EF** (HFpEF)
   - EF >40%
   - due to stiff heart –> inadequate filling (ex. restrictive heart)

therapeutic treatment for both is different
-no direct treatment for diastolic HF –> treat HTN, diabetes, and monitor for diuretics

Question 3

acute vs chronic HF

Answer 3

1. acute
   - sudden change in heart function due to unexpected damage
   - + sympathetics and RAAS
2. chronic
   - gradual decline in heart function
   - remodeling (ex. hypertrophy, dilation)

Question 4

consequences of heart failure

Answer 4

1. tissue hypoperfusion and inadequate O2 delivery
2. pulmonary venous HTN
3. systemic venous HTN

Question 5

treatment principle of systolic HF

Answer 5

slide 11

-most drugs used to treat systolic heart failure*

Question 6

beta blockers and HF*****

Answer 6

-OPPOSITE**

• decrease HR and contractility even with low CO*
• resets everything to normal set point*** –> reverse heart failure gene program –> increase LV EF and reduce sudden cardiac death
• administered at low doses (slow dose escalation) and over period of time**
• lets heart have time to adapt and find new equilibrium

Question 7

neurohormonal modulalation of systolic HF

Answer 7

• ACE inhibitors
• ARBs
• beta blockers
• angiotensin receptor + neprilysin inhibitor (combo)

new –> aldosterone antagonist

Question 8

afterload reducing agents

Answer 8

-nitrates (previous lectures)

Question 9

spironolactone - DIURETIC and anti-hypertensive med

Answer 9

• aldosterone (mineralcorticoid) receptor antagonist**
• see hyperkalemia (Na+/K+ pump)
• lose water and Na+
• reduces aldosterone induced remodeling of heart

MOA
-competitive binding with aldosterone in collecting tubule**

indications
-treat CHF

contraindications

• renal impairment
• hyperkalemia
• pregnancy –> antiandrogenic/estrogenic effects**

adverse effects

• gynecomastia***
• agranulocytosis (rare)

drug interactions

• severe hyperkalemia when combined with other drugs
• NSAIDs reduce effectiveness of diuretics
• increases half life of digoxin*

Question 10

beta agonists

Answer 10

• also for systolic HF
• increase HR, contractility, conduction, velocity
• bronchodilation

Question 11

other Positive inotropes for systolic HF

Answer 11

1. cardiac glycosides (digitalis/digoxin)***
   - inhibits Na+/K+ ATPase –> build up of Na+ and Ca2+ in cell –> increase contractility and EF
   - can cause atrial tachycardias and AV block
   - contraindicated with hypokalemia, WPW, reduced renal function
2. Catecholamines (Epi, NE)
   - increase HR and contractility
3. PDE inhibitors
   - milrinone and enoximone (PDE3)
   - sildenafil and tadelafil (PDE5)
   - vasodilate, increase HR and contractility

Question 12

Ivabradine*****

Answer 12

-used as last resort for chronic HF*

MOA

• inhibition of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels aka Na+ funny channels***
• prolongs diastolic depolarization –> decrease HR
• decreases CO and demand on heart

indications
-CHF and EF =35% who are already on beta blockers or have contraindications for beta blockers*

contraindications

• sick sinus syndrome patients
• CYP3A4 inhibitors

adverse effects

• luminous phenomena*** –> brightness in visual field
• bradycardia
• AV block
• headache

Question 13

drug of choice for diastolic heart failure**

Answer 13

-thiazide diuretics –> reduce HTN to normalize BP