Congestive heart failure, adrenergic and angiotensin drugs Flashcards
Congestive heart failure pathophys definition
A condition in which the heart is no longer able to pump an adequate supply of blood to meet the metabolic needs of tissues.
CHF clinical definition
Ventricular dysfunction causes reduced exercise capacity
Drugs that target the heart in HF
Inotropes (cardiac glycosides, catecholamines), beta blockers, ACEI/ARBs
Drugs that target blood vessels in HF
vasodilators, ACEI/ARB
Drugs that target Kidney in HF
Diuretics, vasodilators, ACEI/ARB
Most important categry of drugs used in HF
Vasodilators
Vasodilators- drugs
Nitrates, ACEI, ARBs
General effects of vasodilators
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
Venodilators
nitroglycerin and isosorbide dinitrate (ISDN)
Arterial dilators
Hydralazine, minoxidil and nifedipine
Functions of ACE
Converts Angiotensin I to Angiotensin II AND causes degradation of the vasodilator bradykinin.
Functions of Angiotensin II
Vasoconstriction, mitogenic (cardiomyocyte hypertrophy) via G protein signal transduction, elevates aldosterone, vasopressin, endothelin, Activates SNS
Describe AngII signal transduction
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
Venous and arterial dilators
ACE inhibitors- captopril, enalapril and lisinopril
Compare different ACEIs
Potency and dosage schedules differ, but no therapeutic differences. Enalapril (oral) is pro-drug for enalaprilat (IV)
Possible side effect of ACEI
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
When should ACEI be used in the course of HF?
Post-MI (but delayed a few days after the attack) and as early as possible in asymptomatic patients with compromised LV function
ARB examples
Candesartan, irbesartan, losartan, and valsaran
Clinical use of ARBs
Used to treat hypertension
Beta blockers examples
1st gen- Propranolol. 2nd gen- Metoprolol. 3rd gen. Carvedilol.
How do beta blockers work?
In HF, high conc of NE. B-blockers block NE from binding to receptor and this reduces metabolic demands. Also resensitizes signal transduction pathway.
Beta blockers and inotropy
1st gen B-blockers decrease inotropy, but 2nd and 3rd gen have less of an effect on inotropy.
Distinguish btw B-blocker generations
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)
Clinical effects of beta blockers
Increase CO, ejection fraction and submaximal exercise tolerance, reduced pulmonary artery and LV end-diastolic pressures. Over time, reduces ventricular dimensions
Contraindications to use of B-blockers
Class IV HF with limited cardiac function- inability to up-titrate to the dose necessary.
How long does it take for full effect of B-blockers
3-12 months due to cardiac remodeling
