Congestive heart failure, adrenergic and angiotensin drugs

Question 1

Congestive heart failure pathophys definition

Answer 1

A condition in which the heart is no longer able to pump an adequate supply of blood to meet the metabolic needs of tissues.

Question 2

CHF clinical definition

Answer 2

Ventricular dysfunction causes reduced exercise capacity

Question 3

Drugs that target the heart in HF

Answer 3

Inotropes (cardiac glycosides, catecholamines), beta blockers, ACEI/ARBs

Question 4

Drugs that target blood vessels in HF

Answer 4

vasodilators, ACEI/ARB

Question 5

Drugs that target Kidney in HF

Answer 5

Diuretics, vasodilators, ACEI/ARB

Question 6

Most important categry of drugs used in HF

Answer 6

Vasodilators

Question 7

Vasodilators- drugs

Answer 7

Nitrates, ACEI, ARBs

Question 8

General effects of vasodilators

Answer 8

Decrease systemic vascular resistance (SVR), LV chamber size, and myocardial oxygen consumption (MVO2). Sympathetic outflow may be increased or decreased by their use. May target arteries or veins, or both

Question 9

Venodilators

Answer 9

nitroglycerin and isosorbide dinitrate (ISDN)

Question 10

Arterial dilators

Answer 10

Hydralazine, minoxidil and nifedipine

Question 11

Functions of ACE

Answer 11

Converts Angiotensin I to Angiotensin II AND causes degradation of the vasodilator bradykinin.

Question 12

Functions of Angiotensin II

Answer 12

Vasoconstriction, mitogenic (cardiomyocyte hypertrophy) via G protein signal transduction, elevates aldosterone, vasopressin, endothelin, Activates SNS

Question 13

Describe AngII signal transduction

Answer 13

Ang II binds to AT1 receptor which is coupled to Gq G protein. This activates PLC creating IP3 and DAG. IP3 increases intracellular Ca and DAG stimulates PKC

Question 14

Venous and arterial dilators

Answer 14

ACE inhibitors- captopril, enalapril and lisinopril

Question 15

Compare different ACEIs

Answer 15

Potency and dosage schedules differ, but no therapeutic differences. Enalapril (oral) is pro-drug for enalaprilat (IV)

Question 16

Possible side effect of ACEI

Answer 16

Increase serum K. Ang II increases aldosterone, which saves Na+ at the expense of K+. Thus, when Ang II
levels are lowered by ACE inhibition, there is less aldosterone leading to increases in potassium. Caution must be used if ACEI used with K-sparing diuretics. Also coughIncrease serum K. Ang II increases aldosterone, which saves Na+ at the expense of K+. Thus, when Ang II
levels are lowered by ACE inhibition, there is less aldosterone leading to increases in potassium. Caution must be used if ACEI used with K-sparing diuretics. Also cough

Question 17

When should ACEI be used in the course of HF?

Answer 17

Post-MI (but delayed a few days after the attack) and as early as possible in asymptomatic patients with compromised LV function

Question 18

ARB examples

Answer 18

Candesartan, irbesartan, losartan, and valsaran

Question 19

Clinical use of ARBs

Answer 19

Used to treat hypertension

Question 20

Beta blockers examples

Answer 20

1st gen- Propranolol. 2nd gen- Metoprolol. 3rd gen. Carvedilol.

Question 21

How do beta blockers work?

Answer 21

In HF, high conc of NE. B-blockers block NE from binding to receptor and this reduces metabolic demands. Also resensitizes signal transduction pathway.

Question 22

Beta blockers and inotropy

Answer 22

1st gen B-blockers decrease inotropy, but 2nd and 3rd gen have less of an effect on inotropy.

Question 23

Distinguish btw B-blocker generations

Answer 23

1st gen is nonselective. 2nd gen is selective for B1 or B2 AR (Metoprolol is B1 selective). 3rd gen are selective or nonselective with favorable pharmacology (Carvedilol is alpha-AR, B1 and B2 blockade with anti-oxidant properties and guanin-nucleotide modulatable binding and tight binding)

Question 24

Clinical effects of beta blockers

Answer 24

Increase CO, ejection fraction and submaximal exercise tolerance, reduced pulmonary artery and LV end-diastolic pressures. Over time, reduces ventricular dimensions

Question 25

Contraindications to use of B-blockers

Answer 25

Class IV HF with limited cardiac function- inability to up-titrate to the dose necessary.

Question 26

How long does it take for full effect of B-blockers

Answer 26

3-12 months due to cardiac remodeling