Heart Failure Flashcards
How does calcium enter and exit the cytosol?
Sources: extracellular plus mitochondria and SR.
Removal: reuptake into SR; extrusion from cell via Ca/Na exchange (then Na/K atpase restores Na balance)
What phase of cardiac muscle action potential do calcium channels open?
Phase 2, plateau
Three major compensatory mechanisms of a failing heart
Hypertrophy, increased sympathetic activity, increased RAAS activation
6 classes of drugs for HF
Inotropes, beta blockers, diuretics, raas inhibitors, direct vasodilators, aldosterone anagonists
Agents of choice for HF
ACEIS
Pharmacokinetics of ACEIs
- adequate absorption via oral intake (take on empty stomach)
- need activation via hepatic hydrolysis (except captopril)
- renal elimination important
Adverse effects of ACEIs
Postural hypotension, renal insufficiency, dry cough, hyperk, angioedema
Fetotoxic
MOA of ARBs
Potent competitive antagonist of angiotensin type 1 receptor
More complete blockade than ACEIs
Also reduce morb and mort of hypertension
Pharmacokinetics of ARBs
Plus how losartan is different
Excretion
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
Beta blockers recommended for all patients with heart disease except
Those at high risk but with no sx
Those in acute HF
Describe selectivity of metoprolol and carvedilol
Carvedilol- nonselective beta plus also blocks alpha adrenoreceptors
Metoprolol - selective b1 antagonist
Thiazide diuretics lose effectivity when
crea clearance is less than 50mL/min
How diuretics help in heart failure
Decrease plasma volume and preload (decreased workload and oxygen demand)
Also decrease afterload becase of dec plasma volume; thus decrease BP
3 examples of direct vasodilators for HF
Hydralazine
Isdn
Sodium nitroprusside
Antihypertensive drug to avoid in HF
Calcium channel blockers
Their negative inotropic effects cab exacerbate the dse
Action of direct vasodilators in HF
Decrease in cardiac preload by increasing venous capacitance
Decrease afterload by reducing arteriolar resistance
3 subclasses of inotropic agents for HF
Digitalis, beta adrenergic antagonists, phosphodiesterase inhibitors
Mechanism of cardiac glycosides
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
Indication of digoxin in HF and where not indicated
Major: HF with AFib
Severe LVD alreading tx with ACEI and diuretics
Not indicated in diastolic HF
Pharmacokinetics of digoxin
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)
Describe digoxin toxicity
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
Factors predisposing to dig toxicity
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
Patients who should not receive ACEIs
Bilateral renal artery stenosis
History of angioedema
Renal dysfxn: crea >2.5mg/dL
When shouldn’t you use ARBs for pts who cant use ACEIs?
Renal art stenosis and angioedema. Just use ismn and hydralazine, a reasonable alternative
