Ostrom Flashcards
What factors determine heart work and O2 supply?
- Work: heart rate, cardiac contractility, wall tension (afterload)
- O2 supply: coronary vascular resistance, perfusion pressure, collateral blood flow, heart rate and mechanics
- Therapies can either decrease demand, increase supply, or both
What does combo diuretic therapy typically look like? What are the associated toxicities and interactions?
- Combo: loop diuretic + metolozone, loop + spirono 25-50mg/day
- Toxicity: electrolyte disturbances, hypokalemia, hyponatremia, hypochloremic metabolic alkalosis, azotemia (abnormally high levels of nitrogen-containing compounds, i.e., urea, creatinine, etc.), dehydration, hypotension, ototoxicity (tinnitus, hearing loss; loop diuretics)
- Interaxns: NSAID’s reduce efficacy of diuretics by promoting fluid retention
What is Nesiritide? What are its benefits and MOA’s?
- Recombinant human BNP; FDA approved for IV tx of decompensated Class IV CHF
-
MOA’s: binds BNP receptor in vascular smooth muscle, veno- and vasodilation (via cGMP) -> reduces preload and afterload
1. Dilation of afferent renal glomerular arterioles INC GFR, filtration fraction, and DEC sodium reapsorption (natriuresis)
2. Suppresses renin-angiotensin and SNS - Benefit comparable to IV nitroglycerine, but hypotension may persist longer -> use should be limited to those who do not respond to nitroglycerine
Which drugs decrease preload?
- Furosemide
- Nitrates
- ACEI (also DEC afterload)
- ARB (also DEC afterload)
- Spironolactone
- Nesiritide (also DEC afterload)
Which drugs are anti-mitogenic?
- ACEI
- ARB
- Spironolactone
- Nesiritide
- B-blocker
What are the general approaches to treating angina?
- Increase coronary blood flow
- Reduce myocardial oxygen consumption (mvo2) by:
1. NEGATIVE CHRONOTROPIC EFFECT *HR
2. NEGATIVE INOTROPIC EFFECT *contractility
3. Decreased ventricular workload (wall stress):
a. Reduced preload (venodilation)
b. Reduced afterload (vasodilation) - Prevent platelet deposition/aggregation: ASA
What drugs are effective in preventing CHD, MI death in patients with angina?
- BB: reduce CHD events
- CCB: variable effect
- Aspirin: all patients w/CHD should receive ASA tx unless contraindicated -> reduces reinfarction, CHD, and stroke after unstable angina or MI
- ACEI: improve survival post-MI w/LV dysfunction; reduce MI in high-risk pts
- Thrombolytic therapy: DEC mortality in first year post-MI (can also do revascularization)
- Statins: reduce recurrent MI; may acutely stabilize coronary plaque
- HDL/TG drugs: reduce recurrent CHD/MI
What are the ACA/NYHA stages?
- Stage A: preventive measures + ACEI/ARB
- Stage B (NY 1): preventive measures + ACEI/ARB + beta blocker
- Stage C (NY 2, 3): PM + ACEI/ARB + BB + diuretic (2)/ Digoxin/ Spironolactone
- Stage D: PM + ACEI/ARB + BB + diuretic/ Digoxin/ Spironolactone + transplant/IV inotropes
What are the deleterious effects of chronically high levels of NE, E?
- BB’s attenuate deleterious effects of chronically high levels of NE and E, which cause:
1. B-AR down-regulation
- Arrhythmias (leading cause of death in class II, III CHF)
- INC myocardial O2 consumption/ischemia
- Myocyte apoptosis, followed by cardiac fibrosis
What are the effects of Spironolactone in CHF?
- DEC preload
- Anti-mitogenic
- Secondary diuresis
- Survival benefit
What vasodilators are NOT effective in CHF?
- Prazosin
- Minoxidil
- Dihydropiridine Ca-channel blockers
Why are nitrates used in advanced CHF?
- EX: Nitroprusside
- IV: veno- and vasodilation reduces preload and afterload (alone, or with vasodilator)
- Reduce pulmonary artery pressure and pulmonary congestion (via reduced preload)
- Reduce left ventricular filling pressure and wall stress
Which drugs increase inotropy?
- Digoxin
- Milrinone
- Dobutamine
- Beta-blockers (INC and DEC)
What are the three types of angina?
-
Unstable (pre-infarction, crescendo) angina
1. Recurrent angina assoc with minimal exertion
2. Prolonged and frequent pain
3. Due to fissuring of atheroscelortic plaques, and subsequent platelet aggregation
4. High correlation with myocardial infarction -
Variant (vasospastic, Prinzmetal’s) angina
1. Direct result of reduction in coronary flow due to vasospasm, not an increase in myocardial oxygen demand
2. Normal coronary angiograms – Excellent prognosis -
Exertional (exercise-induced) angina
1. Due to fixed coronary vascular obstruction (sx revascularization, angioplasty may be beneficial)
How do CCB’s treat angina?
- Non-dihydropyridine: Verapamil, Diltiazem
1. Direct effects to reduce heart work (demand): DEC HR & contractility, slowed AV conduction
2. Prevents, reverses vasospasm (coronary vasodilation) - Dihydropyridine: Nifedipine, Felodipine, etc
1. Potent vasodilation, reduces MvO2 by reducing afterload
2. Coronary vasodilation (increased supply)
3. Reflex cardiac stimulation: HR, contractility can increase reflexively
4. AV node conduction unaffected
5. Only use in combination with ß-blocker!
What are the contraindications for BB use in CHF?
- Heart block
- Bradycardia
- Decompensated CHF/need for IV inotropes (i.e., dobutamine)
- Volume overload
What are the effects of the beta-blockers in CHF?
- DEC/INC inotropy
- Anti-mitogenic
- Secondary natriuresis
- Survival benefit
Why does it matter that the heart is perfused during diastole (for drug therapy)?
- Any therapy that reduces contractility will reduce the amount of squeezing during systole
- Decreasing HR will increase amount of time spent in diastole, increasing amount of blood delivered to myocardium
What is aldosterone escape?
- Inability of ACEI therapy to reliably suppress aldosterone release
- Usually manifested by increased salt and water retention (refractory hyperaldosteronism)
What are ANP and BNP? What are their hemodynamic effects?
- Released from atria (ANP) and ventricles (BNP) in response to volume/pressure expansion
- Naturally elevated in CHF
- Promote vaso/venodilation and natriuresis
-
Hemodynamic effects:
1. Reduce ventricular filling pressure (preload)
2. Inhibit renin/aldosterone release
3. Inhibit Na reabsorption in proximal convoluted tubule
4. Selective afferent arteriolar vasodilation
What are the effects of the nitrates in CHF?
DEC preload