Ostrum Day I Lecture

Question 1

Why is it beneficial to block a1 receptors as well as B receptors in CHF?

Answer 1

prevent reflexive vasoconstriction via baroreceptor activation and nor release

Question 2

What is the primary goal of pharmacotherapy in patients with early stage (A and B) CHF?

Answer 2

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

Question 3

Overview of treatment preferences in CHF by stage

Answer 3

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

Question 4

What are the effects of angioII?

Answer 4

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)

Question 5

What is the end effect of hypertrophy of ventricles caused by angII release in CHF?

Answer 5

eventually as the ventricles enlarge they cannot receive adequate blood/oxygen supply and die (apoptosis), leading to an uncompensated state

Question 6

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

Answer 6

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

Question 7

What is the main use of dobutamine?

Answer 7

emergency situations in end-stage CHF to keep a patient alive via a last-ditch inotropic response. Can overcome BBs with high dose

Question 8

Why are BBs effective in treating class I-IV CHF?

Answer 8

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

Question 9

Why is it counter-intuitive that BBs could actually help CHF?

Answer 9

because you would think that they would block B1 which would decrease CO

Question 10

Why do BBs actually help CHF?

Answer 10

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

Question 11

So what is the effect of BBs in CHF?

Answer 11

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

Question 12

How do Beta receptors respond to acute signaling?

Answer 12

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

Question 13

How do Beta receptors respond to chronic signaling?

Answer 13

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

Question 14

What are the primary BBs approved for CHF?

Answer 14

• carvedilol
• bisoprolol
• metoprolol

Question 15

When are BBs indicated for CHF?

Answer 15

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

Question 16

Why are BBs withdrawn from the treatment regimen at end-stage?

Answer 16

cant block progression anymore so there is no effect. ACEIs only help through hemodynamic effects at this point

Question 17

Which of the following BBs would be least likely to induce increased TPR caused by reflex vasoconstriction?

Answer 17

Carvedilol- a1 blockage

Question 18

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?

Answer 18

Digoxin

Question 19

A patient with a history of CHF presents to you complaining of blurred vision with yellow-green halo. Which drug is responsible?

Answer 19

Digoxin

Question 20

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

Answer 20

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

Question 21

What is end-stage CHF defined as?

Answer 21

ejection fraction drops too low

Question 22

Which anti-HTN should never be given to pregnant or nursing women?

Answer 22

Valsartan (ACEIs/ARBs)

Question 23

By which mechanisms does digoxin increased cardiac contractility?

Answer 23

Inhibiting the Na/K+ ATPase, increasing intracellular Na+, altering the activity of the Na+/Ca2+ exchanger to increase intracellular Ca2+

Question 24

What could increase the sensitivity of contractile machinery to Ca2+?

Answer 24

phosphorylation of troponin I