Heart Failure

Question 0

How does calcium enter and exit the cytosol?

Answer 0

Sources: extracellular plus mitochondria and SR.

Removal: reuptake into SR; extrusion from cell via Ca/Na exchange (then Na/K atpase restores Na balance)

Question 1

What phase of cardiac muscle action potential do calcium channels open?

Answer 1

Phase 2, plateau

Question 2

Three major compensatory mechanisms of a failing heart

Answer 2

Hypertrophy, increased sympathetic activity, increased RAAS activation

Question 3

6 classes of drugs for HF

Answer 3

Inotropes, beta blockers, diuretics, raas inhibitors, direct vasodilators, aldosterone anagonists

Question 4

Agents of choice for HF

Answer 4

ACEIS

Question 5

Pharmacokinetics of ACEIs

Answer 5

• adequate absorption via oral intake (take on empty stomach)
• need activation via hepatic hydrolysis (except captopril)
• renal elimination important

Question 6

Adverse effects of ACEIs

Answer 6

Postural hypotension, renal insufficiency, dry cough, hyperk, angioedema

Fetotoxic

Question 7

MOA of ARBs

Answer 7

Potent competitive antagonist of angiotensin type 1 receptor

More complete blockade than ACEIs

Also reduce morb and mort of hypertension

Question 8

Pharmacokinetics of ARBs

Plus how losartan is different

Excretion

Answer 8

Orally active
Once a day dosing

Losartan undergoes extensive first pass metab, converted to active metabolites (other drugs have inactive metabs)

Eliminated via urine and feces

Question 9

Beta blockers recommended for all patients with heart disease except

Answer 9

Those at high risk but with no sx

Those in acute HF

Question 10

Describe selectivity of metoprolol and carvedilol

Answer 10

Carvedilol- nonselective beta plus also blocks alpha adrenoreceptors

Metoprolol - selective b1 antagonist

Question 11

Thiazide diuretics lose effectivity when

Answer 11

crea clearance is less than 50mL/min

Question 12

How diuretics help in heart failure

Answer 12

Decrease plasma volume and preload (decreased workload and oxygen demand)

Also decrease afterload becase of dec plasma volume; thus decrease BP

Question 13

3 examples of direct vasodilators for HF

Answer 13

Hydralazine

Isdn

Sodium nitroprusside

Question 14

Antihypertensive drug to avoid in HF

Answer 14

Calcium channel blockers

Their negative inotropic effects cab exacerbate the dse

Question 15

Action of direct vasodilators in HF

Answer 15

Decrease in cardiac preload by increasing venous capacitance

Decrease afterload by reducing arteriolar resistance

Question 16

3 subclasses of inotropic agents for HF

Answer 16

Digitalis, beta adrenergic antagonists, phosphodiesterase inhibitors

Question 17

Mechanism of cardiac glycosides

Answer 17

Regulation of cytosolic Ca conc: inhibit na/k exchange by na:k atpase. Thus conc of intracellular na increases and there is decreased gradient across the membrane –>inhibit ability of cardiac myocyte to pump na out of the cell via the Na/Ca exchanged

Therefore increased contractility of cardiac muscle

Decrease in end diastolic volume, improve EF, thus reduced sympathetic activity, reduced PVR, lower heart rate

Question 18

Indication of digoxin in HF and where not indicated

Answer 18

Major: HF with AFib
Severe LVD alreading tx with ACEI and diuretics

Not indicated in diastolic HF

Question 19

Pharmacokinetics of digoxin

Answer 19

Renally eliminated intact
Long half life 36 hours
Narrow margin of safety

(Vs digitoxin which has longer half life and is more metab by the liver)

Question 20

Describe digoxin toxicity

Answer 20

Cardiac - arrhythmia (slowed AV conduction, atrial arryth) usually ppt by decreased serum K
GI effects - anorexia, nausea, vomiting
CNS - fatigue, headache, confusion, blurred vision, alteration of color perception, halos on dark objects

Question 21

Factors predisposing to dig toxicity

Answer 21

HypoK (like in use of thiazide and loop diuretics)
HypoCa
HypoMg
Drugs: quinidine, verapamil, amiodarone (displace dig from binding sites and competing with dig for renal excretion)
Hypothy, hypoxia, renal failure, myocarditis

Question 22

Patients who should not receive ACEIs

Answer 22

Bilateral renal artery stenosis
History of angioedema
Renal dysfxn: crea >2.5mg/dL

Question 23

When shouldn’t you use ARBs for pts who cant use ACEIs?

Answer 23

Renal art stenosis and angioedema. Just use ismn and hydralazine, a reasonable alternative

Question 24

benefits: ACEIs vs ARBs

Answer 24

Arbs may be equivalent to ACEIs but not more effective

Arbs have less mortality benefit but improvement in exercise tolerance may be greater

Question 25

Updates on digoxin

Answer 25

NOT ESSENTIAL in chf but don’t discontinue if present

• weak intrope, no effect on mortality, modest effect on hospitalization (Digitalis investigation group 1997)
• ssx recur rapidly if discontinued

Question 26

Mechanism of action of b adrenergic agonists dopamine and dobu

Answer 26

Activates adenylyl cyclase –> more cAMP produced –> activates protein kinase which phosphorylates a Ca channel –>increased Ca flow into cell.

P

Question 27

Examples of phosphodiesterase inhibitors and moa

Answer 27

Amrinone
Milrinone

Increase intracellular cAMP by decreasig conversion to AMP

Question 28

Why we don’t use phosphodiestrase inhibitors long term

Answer 28

Assoc with inc mortality

Question 29

Is spironolactone potassium sparing or what?

Answer 29

It is not. Pts on spironolactone should not be taking supplements

Question 30

When to start BBs

Answer 30

In pts on ACEIs for structural dse without symptoms, start then titrate up

If with ssx, ACEIs and BBs for all

Question 31

Spironolactone adverse effects

Answer 31

HyperK, gastric disturbances like gastritis and peptic ulcer, lethargy, confusion, gynecomastia, inc libido, menstrual irreg

(Antiandrogenic: inhibits 5a reductase, 17a hydroxylase and 17,20-desmolase plus increased peropheral conversion of testosterone to estradiol)

Question 32

Diabetic drug to avoid in CHF plus updates

Answer 32

Metformin - increased use of lactic acidosis in CHF

Though in 2007 in BMJ: review of evidence shows maybe not if isolated HF with no renal failure