12. Drugs for Heart Disease Flashcards
What are the 8 classes of drugs for congestive heart disease (CHD)?
- ACE Inhibitor (analapril, lisinopril) use 1 or 3
- β1-blocker (atenolol, metoprolol) use 2 or 4
- Ang II receptor blocker (ARB, losartan)
- α/β adrenergic blocker (carvedilol, labetalol)
- Tailored diuretics- decrease edema (loop diuretic) furosemide + K sparing (spironolactone)
- Digoxin (inhibits Na pump (NaK ATPase) barrow therapeutic window
- Vasodilators (hydralazine and nitrates)
- Donuts mine (β1 agonist, milrinone)
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What is congestive heart failure?
Symptoms?
Reduced cardiac output relative to the body’s needs (failure of heart to provide adequate CO) Systolic emptying (EF<45%) Diastolic filling (preserved EF)
Symptoms- dyspnea on exertion, then at rest, orthopnea
Difficulty in breathing- shortness of breath when lying flat
Fatigue
Edema reduced renal function
Heart- big on x ray (mainly in systolic HF)
Echocardiogram (reduced EF, diastolic function)
Slides 4-5
What are the antecedents (precursors) to congestive heart failure (CHF)?
Increased workload- hypertension, aortic stenosis, mitral regurgitation, pregnancy, hyperthyroid
Decreased muscle- coronary artery disease (infarction), myocarditis, cardiomyopathy
What are the 3 most common precipitating causes of heart failure?
Hypertension
Coronary artery disease
Diabetes
What are the factors (compensatory mechanisms) that come into play with congestive heart failure (CHF)?
⬇️CO ⬇️BP ⬆️SNS activity ⬆️sweating ⬇️renal blood flow ⬆️renin release ⬆️ANG II ⬆️aldosterone ⬆️TPR ⬆️Na retention ⬆️blood volume ⬆️edema ⬆️venous pressure ⬆️work load ⬆️demand on heart ⬆️preload ⬆️afterload
Slide 7
What is afterload and contractility’s effect from heart failure?
Afterload- increases so lowers stroke volume
Contractility- since preload afterload increase and CO decreases, to compensate the heart muscle stretches to enhance contractility
Unable to compensate, the heart quits (systematic & pulmonary congestion sets in resulting in decreased blood supply to all organs) resulting in edema and CHF
Slide 9
What are the 2 compensatory mechanisms in heart failure?
Sympathetic nervous system (extrinsic control system)- increase contractility, sympathetic is a result of some of symptoms of heart failure like tachycardia and sweating and increase renin levels
Frank starling law of the heart (local control system)- increase contractility
Goal is to reduce preload afterload edema congestion enlarged heart and restore/enhance cardiac output
Why is preload and afterload increased?
Preload is increased because of incomplete emptying of the heart
Afterload is increased because of elevated SNS activity and activation of the renin-angiotensin-aldosterone system (RAAS)
What are the role of diuretics in CHF?
Rationale for combining furosdemide + spironolactone
Relieve congestion - edema first decrease preload
Thiazides used more as antihypertensives
Loop diuretics furosemide mainly for CHF
Problem: AE: hypovolemia, hypokalemia
Add spironolactone (K sparing diuretic) to overcome hypokalemia, blocks aldosterone action on heart remodelling & cardiac fibrosis
Slide 12
What is cardiac output?
It’s affect in CHF?
CO= HR x SV
SV is proportional to preload, afterload, contractility
Despite increase preload and increase left ventricular end diastolic pressure (venous return), strike volume elevation is lower in heart failure
Slide 8
What are the drugs that decrease afterload?
ACE inhibitors and ARBs decrease ANG II effect which decreases TPR and blood pressure
The vasodilators hydralazine and nitrates
Hydralazine is arteriolar dilator
Nitrates are veno and arteriolar dilators
If dry cough is a serious problem, use ARBs
Slide 13-14
What drugs increase contractility?
Digoxin, milrinone, β agonists
Digoxin inhibits Na-K ATPase (Na pump)
Increases [Na]i, increases Na-Ca exchange, increase [Ca2+]i, increase contractility, no O2 consumption, no increase work load on heart
Causes depolarization, reduced phase 0 slope, reduced conduction velocity, causes A-V block
Increase BP, increases vagal tone
Low therapeutic index
Slide 15
What are the 4 steps of cardiac contractility initiated by β1 and β2 receptor kinked adenylate cyclase activation?
- Binding of β-adrenergic agonist (dopamine/dobutamine) activates adenylyl cyclase, which produces cAMP
- cAMP activates protein kinase, which in turn phosphorylates a calcium channel
- Phosphorylation of a calcium Chen el increases calcium flow into the cell causing increases force of contraction of heart muscle
- Phosphodiesterase inhibitors prevent hydrolysis of cAMP and, thus, prolong the action of protein kinase
Slide 16
What are the 3 steps of digoxin increasing contractility?
- Digoxin inhibits Na/K exchange by Na/K ATPase
- The concentration of intracellular Na increases, and the concentration gradient across the membrane decreases
- Increased Na decreases the driving force for the Na/Ca exchanger, so there is decreased extrusion of Ca into the extracellular space
Slide 17
What are the 5 steps of positive ionotropic mechanism of digoxin?
- Digoxin blocks Na pump, Na can’t move out
- Na moves out through the bidirectional Na-Ca exchanger, Ca comes in exchange
- Ca triggers massive Ca release
- Elevated [Ca]i promotes cardiac contraction
- Without energy utilization, no consumption of ATP
Digoxin causes a secondary increase/release of Ca from the intracellular SR calcium stores and elevate [Ca] triggered by Ca coming through the Na-Ca exchanger
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