Heart Failure Pharmacology Lecture
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- Describe the body's extrinsic compensatory mechanism in Heart Failure. This leads to what reflex being reset?
- With decreased Cardiac output and decreased contractility, the body stimulates the SNS and the Renin-Angiotensin-Aldosterone system. Baroreceptor reflex is reset due to increased SNS output.
- Describe the initial effect of the SNS stimulation in HF.
- Initially, SNS stimulation leads to Tachycardia with increased cardiac contractility, increased vascular tone resulting in increased cardiac output.
- Describe the effect of the R-A-A system on HF.
- Angiotensin II production further increases afterload via Na+ and water retention. This leads to worsening HF.
- Describe the intrinisc compensatory mechanisms involved in HF.
- Myocardial hypertrophy cuased by increased heart activity and elevated AII level.
- TRUE/FALSE - Oral administration of cardiac glycosides (e.g. digitalis,digoxin) has a narrow therapeutic index.
- True
- Describe the mechanism of caridac glycosides.
- Potent Inhibitor of Na/K ATPase which leads to increased Calcium intracellular concentration (increased intracellular Na impairs Na/Ca exchanger). This leads to increased cardiac contractility.
- Bipyridines (e.g. Inamrinone, milrinone) are relatively toxic and work by what 2 mechanisms? What is their physiologic effect?
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1. Bipyridines inhibit PDE 3 isozyme (cAMP) in cardiac and smooth muscle, leading to increased inward flux of Ca during AP (increase contractility(PKA);
2.vasodilation via PKA activation, which promotes muscle relaxation via diminished myosin phosph. & increased Ca sequesteration - What is the later effect of prolonged SNS stimulation in HF?
-
Since the Heart is unable to handle the increasing
Afterload. Prolonged HF leads to decreased ejection fraction, cardiac output decrease, & renal perfusion decrease. - Beta 1 selective agonists (e.g. dobutamine) work by what mechanism in HF?
- Increased Cardiac contractility/cardiac output via protein kinase A and increased [Ca2+]in.
- Describe the mechanims of Diuretics (e.g. sprinolactone) in HF.
- Diuretics increase urine volume, reduce venous pressure and therefore Preload.
- What are the physiologic benefits of diuretics in HF?
- Reduce edema, cardiac size, improves cardiac efficiency
- Describe the mechanism and physiologic effects of ACE inhibitors.
- Mechanism is the blockage of AII production. This leads to decreases in AL, PL, and PVR.
- TRUE/FALSE - Vasodilators (e.g. nitrates, nitrites, CCBs) can dilate veins & arterioles and increase contractility.
- False - No positive inotropic effects
- Beta blockers (e.g. bisoprolol, carvedilol, metoprolol) inprove mortalitiy in HF. What effect do these drugs have on HR and CTY?
- Negative inotropic and chronotropic effets.
- TRUE/FALSE - Only 1/2 of patients with HF survive after 5 years even with standard of care therapy.
- TRUE
- Is digitalis + a diuretic, the current standard of care for treating HF?
- In the past, both were standard of care. Now, digitalis is reserved for those who do not respond to diuretics + ACE In + Beta blockers.