Heart Failure Drugs Flashcards
Compensatory Responses to Heart Failure Cycle
Compensatory responses lead to a cycle; start with decreased CO causing constriction from NE, AII, and ET-1 leading to increased afterload due to constriction leading to reduction in EF, which means more decreased CO then happens over and over again.
Loop Diuretics
Furosemide, bumetanide, torsemide
As sodium, K, and Cl move into the cell out of the urine and reabsorbing it; this causes a positive potential to recycle Mg and Ca2+
This causes fluid retention; the medication prevents fluid retention by inhibiting the NKCC2
25% of the Na and Cl is reabsorbed here – target will reduce absorption by 25%
High capacity diuretic = water pill
Thiazide Diuretics (DCT)
Hydrochlorothiazide (metolazone – action is the same)
Block Na/Cl channel and inhibits their reabsorption thus reducing water reabsorption
Often used in combination with loop diuretics
K+ wasting
5% of reabsorption occurs here
Diuretics
Controlling the symptoms without affecting the heart contractility
Decrease NaCl and KCl reabsorption
Increase H2O excretion
Decrease volume and cardiac preload and afterload
Decreases pulmonary and peripheral edema - suggested use only when these occur
Diuretic Side Effects
Water loss will decrease L ventricular filling so low as to decrease CO
Low K and Mg = arrhythmias
Diuretic Drug Interactions
Digitalis (increase loop diuretic and thiazide activity)
NSAIDs (decrease diuretic response)
Thiazide diuretics increase loop diuretic activity and vice versa
Quinidine + Thiazide = low K and risk of torsades de pointes
Aldosterone Antagonists
Sodium will not be reabsorbed by directly antagonizing mineralocorticoid receptors
Will not see much K loss = hyperkalemia is risk
Eplerenone- less activity on sex hormones and more selective for mineralocorticoids compared to Spironolactone
Significant reduction in morbidity and mortality when combined with a diuretic
Beta Blockers
Metoprolol and Atenolol
Counter intuitive because negative on inotropy and contractility, but are useful for tx of heart failure
Immediate effects: reduce systolic function, but recovers within a couple months
High NE increases apoptosis, so beta blockers may be blocking this
L ventricular geometry changes – decreases chamber size to increase EF
Increase expression of beta receptors
Lower HR
Need to be cautious due to negative inotropic effects
ACE Inhibitors and ARB
ACE Inhibitors: Captopril, Lisinopril
ARBs: Losartan, Valsartan
ACE: Prevent AI to AII resulting in reduced peripheral resistance to reduce afterload
Reduce water and salt retention
If reducing AII, it will decrease aldosterone thus reducing preload
Reducing sympathetic activity
Increase bradykinin levels to help with vasodilation
ARBs: work on AI receptor so same effects; reduced afterload and preload; reserved for those that cannot tolerate ACE inhibitors
Side Effects of ACE Inhibitors
Dry cough
Angioedema – potentially life threatening
Hyperkalemia
Can impair auto-regulation of glomerular perfusion pressure in patients with decreased renal blood flow
Side Effects of ARBs
Hypotension
Renal dysfunction
Hyperkalemia
Angioedema (rare; use caution if ACE inhibitor-associated angioedema in history)
Beta Agonists
Increase cAMP in the cell, and activate protein kinase A which phosphorylates the L type Ca channel to increase Ca influx into the cell; PKA also phosphorylate other substances like Ca channel on SR to cause Ca into cytoplasm; overall it causes an increase in contractility and CO
Beta agonists are IV only and used in acute heart failure while hospitalized; rapid development of tolerance within a few days
Beta Agonist Side Effects
Dobutamine –
mixed beta receptor agonist; cardiac effects through β1; β2 stimulation may decrease SVR and MAP
Tachycardia
Supraventricular or ventricular arrhythmias
Bipyridines
Inhibit PDE, which prevent hydrolysis of cAMP, and by preventing the breakdown it is increasing the time cAMP is present so it prolongs the actions of PKA and increases Ca2+ and contractility
Dilates resistance vessels to decrease preload and afterload
IV only in acutely ill hospitalized patients
Bipyridines Side Effects
Milrinone is the only PDE3 inhibitor used in acute heart failure in the US
Side effects:
Arrhythmias
Less bone marrow and liver toxicity than inamrinone
Inotropic Agents and Risk of Hospitalization and Death
Use of inotropic agents that increase cardiac cell cAMP are consistently associated with ↑ risk of hospitalization and death
Digoxin
Inhibit N/K exchange to increase Na in the cell which will decrease force for Na/Ca exchanger to keep Ca in, thus increasing free Ca2+ in the cell to increase contraction and EF, but decrease CO
Digoxin Side Effects
If you already have low K, low Mg, or high Ca = these effects will be increased as a side effect Arrhythmias Nausea Blurred or yellow vision Disturbances in cognitive function
Drug Interactions with Digoxin
It will have interactions with other drugs like quinidine
Increased digitalis concentration can occur when using these drugs = cardio toxicity
Thiazide, furosemide, corticosteroids – decrease K in blood, so increase cardio toxicity
Increase PR interval and decrease QT interval on EKG
Isosorbide Dinitrate
Isosorbide dinitrate: direct vasodilator Organic nitrate Enzymatic biotransformation to NO Short acting Reduces preload by increasing peripheral venous capacitance
Sodium Nitroprusside
Sodium nitroprusside: direct vasodilator
Direct NO donor (quickly metabolized to generate NO)
Vasodilation
IV only; effect occurs within 30 seconds and disappears within 3 minutes of discontinuation of drug
Hydralazine
Hydralazine: direct vasodilator
Change in Ca2+ balance, membrane hyperpolarization from opening K channels but mechanism is not clear
Vasodilation of arterioles and reduces resistance
Reduces SVR and LV preload
Not used by itself (usually with nitrate), only in combination with isosorbide dinitrate especially for those that do not tolerate ACE/ARBs
Acute vs. Chronic HF Medications
Acute: diuretics are drug of choice especially if pulmonary or peripheral edema, vasodilators, beta agonists, bipyridines (PDE inhibitors), natriuretic peptide
Chronic: diuretics, aldosterone antagonists, ACE inhibitors, ARBs, beta blockers, cardiac glycosides, vasodilators
Effects of Multi Drug Therapy
Just a diuretic: reduce ventricular filling pressure from reduction of preload by reducing volume, but does nothing for SV
Inotropic agent: contractility increases as well as CO
Vasodilator: lower filling pressure and higher SV, but no where close to normal
Therefore, people need a combination to be maintained vs. just one drug alone
