05 Heart Failure Flashcards
(46 cards)
what is the major cause of Heart failure?
coronary artery disease (main cause, 60-70%)
-in Afro Americans, hypertension is a major cause
what two types of heart failure are there?
- compensated heart failure: fine at rest but not during exercise
- Congestive heart failure (CHF, decompensated):
- resting cardiac function inadequate - venous pooling → edema esp. lungs - shortness of breath (dyspnea)
- ‘neurohumoral storm’
- ejection fraction of less than 40%
what drug can cause heart failure?
adriamycin
what happens to the BP in CHF?
BP is well maintained
how is the BP maintained in CHF?
-Sympathetic, parasymp etc
- increased sypathtic tone (tachycardia)
- decr. parasympathtic tone
- activation of renin-angiotensin system
- incr. vasopressin release
- incr. blood volume
what class of drugs is generally containdicated in the treatment of heart failure?
Calcium channel blockers, bc they decrease cardiac function
What is Heart failure?
it’s a supply and demand problem, the demand from the body is not met by the CO of the heart
what are the general consequences of cardiac failure?
bc CO is less, blood flow is less, renin flow is less, thus the renin agiontensin II system increases, increasing aldosterone, increasing sodium and water retention, leading to edema
- this decr. force of contraction
- decr. CO, incr. TPR, decr Stroke volume, =cardiac hypertrophy
what is the “hormonal storm” /cycle of heart failure?
- activation of sympathetic nerve system and of renin-angiotensin-aldosterone axis
- ->heart tissue reodeling (hypertrophy)
- ->pumping function disrupted
- ->additional neuro-humoral activation promoted
- -> then it starts over again
What do Cardiac Glycosides do to the heart physiology?
They inhibit the Na+/K+ ATPase
- take Na from inside the cell and exchange it for K outside the cell
- Na out, K in
what is the other “pump” that’s important for ion concentrations inside the heart cells?
the Na+/Ca++ exchange, takes Ca inside the cell and exchanges it for Na outside the cell
(Ca out, Na in)
Cardiac glycoside example
-Digoxin*** and Digitoxin, they inhibit the Na/K atpase in the heart cells
What do cardiac glycosides bind to, and what is the structure?
they bind to a membrane bound transporter (Na/K ATPase)
-it has two alpha and two beta subunits
how can the binding of a cardiac glycoside be stabilized?
by phosphorylation of cytosol alpha subunit (on Na/K ATPase)
-this can occur by a DECREASE in extra cellular K, so drug combination with a thiazide would enhance a cardiac glycoside and combination with and ACEI would decrease effectiveness of card. glyc.
Mechanism of cardiac glycosides
inhibition of Na/K ATPase leads to:
- increased intracellular Na
- causing the Na/Ca exchange to work in reverse (now pumping Na out and Ca in)
- the increased Ca in the cell is then stored in the sarcoplasmic reticulum
- this increases contractile force (inotropic effect)
what is the Inotropic effect
- it’s an increase in contractile force
- this is what cardiac glycosides do, increase force=increased CO
what are the toxic effects of cardiac glycosides (Digoxin)
tachycardia
- also it has a very narrow therapeutic index so the toxic effects are close to the effective dose
- delirium, fatigue, dizziness, VISUAL DISTURBANCES (halo effect, mostly yellow and green)
what is a large contributor to the binding of cardiac glycosides?
potassium concentration (K) -hypokalemia=increased cardiac glycoside binding=diuretics (thiazide and loop)
what combination drugs would decrease the effectiveness of cardiac glycosides?
ACE Inhibitors/ARBs, and K-sparing
what heart failure medications work by increasing the cardiac output? (CO)
the cardiac glycosides and the catecholamines (Dobutamine and phosphodiesterase III inhibitors)
Dobutamine
used for acute emergency heart failure (iv)
- increases cAMP–> incre. in Ca influx–>incre. force of contraction (CO)
- it is a catecholamine (so are Phosphodiesterase III inhibitors)
Milrinone, Amrinone
- Phosphodiesterase III inhibitor
- this makes it so the cAMP inside the cardiac cell isn’t broken down increasing Ca and thus increasing heart contraction (incr. CO)
- can be used for chronic heart failure, but not that common bc of increased mortality
if a patient has heart failure and diabetes what drug(s) would you give them?
the ACE Inhibitors/ARBs/or Renin inhibitor(Alikiren)
when are ACE inhibitor contraindicated
during pregnancy and renal artery stenosis
