Ostrum Day I Lecture Flashcards
Why is it beneficial to block a1 receptors as well as B receptors in CHF?
prevent reflexive vasoconstriction via baroreceptor activation and nor release
What is the primary goal of pharmacotherapy in patients with early stage (A and B) CHF?
reign in the over-activation of neurohumoral mediators such as catecholamines and AngII
This is the ONLY thing that slows the progression of the disease. Any hemodynamic effects are only managing systems
Overview of treatment preferences in CHF by stage
Stage A (at risk)-D- preventative measures and ACEIs/ARBs
Stage B (I)- add BBs (withdraw at end-stage)
Stage C (II and III)- add diuretic, digoxin, spirolactone
Stage D (IV)- consider IV inotropes, transplant
What are the effects of angioII?
not only a hemodynamic effect of vasoconstriction, but they also mediate left ventricular hypertrophy and remodeling (so ACEIs/ARBS etc are used just as much to combat this effect as they are to promote vasodilation)
What is the end effect of hypertrophy of ventricles caused by angII release in CHF?
eventually as the ventricles enlarge they cannot receive adequate blood/oxygen supply and die (apoptosis), leading to an uncompensated state
A patient with a history of CHF has been taking losartan and metoprolol daily for 4 yrs. They present to you complaining of swollen ankles and mild dyspnea when walking up a few stairs. What additional treatment would you suggest?
A. Hydrocholothiazide B. Furosemide C. Digoxin D. Spirolactone E. Dobutamine
want a diuretic and typically for heavy edema you want a loop-diuretic
Thiazides are a little safer than loop-diuretics because they have more of a ceiling on their maximal effect of diuresis so A may not be appropriate here b/c not strong enough (okay if edema is very mild)
Spirolactone is potassium sparing via inhibition of aldosterone AND it has an advantage in EARLY CHF of preventing remodeling via aldosterone of ventricular muscle similar to ACEIs
B OR D are good answers
What is the main use of dobutamine?
emergency situations in end-stage CHF to keep a patient alive via a last-ditch inotropic response. Can overcome BBs with high dose
Why are BBs effective in treating class I-IV CHF?
because they block catecholamine-induced overdrive in the heart in response to early CHF and
restore B-adrenergic receptor function that have been down-regulated in response to high catecholamine release in CHF
Why is it counter-intuitive that BBs could actually help CHF?
because you would think that they would block B1 which would decrease CO
Why do BBs actually help CHF?
early CHF causes massive release of catecholamines which act on B1s in the heart to increase CO (compensatory effect). Eventually, the heart will down-regulate/desensitize these receptors (and degraded) in response to chronic high levels of these molecules, leading to arrhythmias in class II and III (can cause death) - BBs attenuate this
So what is the effect of BBs in CHF?
In short-term use you see reduced CO and reduced BP due to increased blockage of B1/B2 receptors (may see an initial worsening of symptoms). HOWEVER, in the long term, you see up regulation of B1 receptors and increased CO and decreased LV end diastolic pressure
How do Beta receptors respond to acute signaling?
catecholamine binding to receptor activated adenylyl cyclase, converting ATP to cAMP, which activated PKA. PKA phosphorylates L-type Ca channels which results in increased calcium influx during depolarization= stronger contraction, faster depolarization and relaxation. These effects require a high receptor number
How do Beta receptors respond to chronic signaling?
When the receptors are occupied for a long period, you see activation of PKA which causes activates CREB which causes gene re-programming and Epac is activated and it also causes gene re-programming that promotes hypertrophy (more sensitive)- lower receptor numbers required here to induce these changes
so BBs will get rid of this low-level chronic stimulation and promote recycling of the receptors to the surface, but not affect the acute effects of signaling so CO is increased
What are the primary BBs approved for CHF?
- carvedilol
- bisoprolol
- metoprolol
When are BBs indicated for CHF?
typically class II and up since they will only be effective once you have chronic stimulation of Beta receptors as a result of initial decreased CO
Why are BBs withdrawn from the treatment regimen at end-stage?
cant block progression anymore so there is no effect. ACEIs only help through hemodynamic effects at this point
Which of the following BBs would be least likely to induce increased TPR caused by reflex vasoconstriction?
Carvedilol- a1 blockage
When a CHF patient enter Stage C or Stage III failure due to appearance of dyspnea with minimal exertion, which of the following drug therapies should be initiated?
Digoxin
A patient with a history of CHF presents to you complaining of blurred vision with yellow-green halo. Which drug is responsible?
Digoxin
A patient with Stage D CHF has had 3 recent hospitalizations due to worsening dyspnea and pulmonary congestion. PMH is significant for lisinopril, carvedilol, and spirolactone taken daily. What additional drug would you suggest?
A. Bumetanide B. Transdermal nitrate C. Verapamil D. Nilrinone E. Dobutamine
not certain its end-stage without ejection fraction
Bumetanide (a diuretic) and Transdermal nitrate would be appropriate- decrease in after load and preload
Milrinone is a late-stage inotropic agent similar to Dobutamine which result in increased O2 demands which will eventually kill the patient
What is end-stage CHF defined as?
ejection fraction drops too low
Which anti-HTN should never be given to pregnant or nursing women?
Valsartan (ACEIs/ARBs)
By which mechanisms does digoxin increased cardiac contractility?
Inhibiting the Na/K+ ATPase, increasing intracellular Na+, altering the activity of the Na+/Ca2+ exchanger to increase intracellular Ca2+
What could increase the sensitivity of contractile machinery to Ca2+?
phosphorylation of troponin I
