Drugs used in heart failure

#acute/severe; systolic/diastolic HF

#drop in contractility and force-> activation of Symp.NS (increased HR, increased contractility, incerasing peripheral R, increase in afterload, increase in preload) & RAAS activated (angiotensin II incerase, aldosterone incerase); angiotensin II also incerases afterload and preload-> heart remodeling (hypertophy)-> ilness progression up to mortaliy

Aims of treatment:

-reducing symptoms (diuretics, digitalics)

-decreasing mortality and morbidity (ACE inhibitors, beta blockers)

Drug that acts both on symptoms and morbidity is a drug acting to prevent heart remodelling mainly (?)

Drugs for heart failure:

a) chronic HF

#decreasing emodelling/prev.of ilness/ reducing symptoms

-beta blcokers (carvedilol, bisoprolol, metoprolol, nebivolol)

-RAAS inhibitors (ACE inh,; AT1receptor blockers, mineralocorticosteroid recpetor blcokers (spironolactone, eplerenon)

# reducing symptoms

-diuretics (loop diuretics, sometimes thiazides)

-digitalis (+ inotrops=cardiac glicozydes)

# ivabradine (non for acute or chronic?)

B)acute HF: iv

#positive inotrops

a)cAMP increase : beta agonists (dopamine, dobutamien); PDE inhibitors (inamrinon, milrinon)

b)cardiac glicozydes

1) Positive inotropic drugs

a)cardiac glicozydes

Digitalis purpura (pol. naparstnica): from this plant majority of cardiac glicozydes is derived

*DIGOXIN: inhibits Na+/K+ ATPase sodium pump and increases intracellular Na+, decreasing Ca2+ expulsion and increasing cardiac contractility; used in HF, nodal arrythmias (used in atrial fibrillation)!!; used orally or parenteral, duration 40h; is arrythmiogenic!!!, may also cause nausea, vomiting, diarrhea, visual chnges

-apart from the heart efct it also increases symp.activity

-negative chronotropic affect

-inhibition of AV conduction (negative domotropic effect)-> arrythmias

Limited use: because the drug inhibits symptoms but does not improove survival!!! problem with drug toxicity (narrow therapeutic window)

b)phosphodiesterase inhibitors

* INAMRINON, MILRINON : inhibit phosphodiesterases[PDE} ( inactivating cAMP &cGMP), their action is mainly due to vasodilating effects, increase contractility, used orally and parentrally, duration 3-6h

c)beta agonists

*DOBUTAMINE: beta1 selective agonist, increases cAMP synthesis; increases cardiac contractility and output; used in acute decompensated HF, intermittent therapy in chronic failure reduces symptoms; used iv only, duration a few minutes; may cause arrhythmias; additive to other sympatomimetics

*DOPAMINE : dopamine receptor agonist, higher doses activate beta and alpha adrenoreceptors; increases renal blood flow, higher doses increase cardiac force and BP; used in acute decompensated HF and shock; used iv only, duration few minutes; may cause arrythmia; may interact with other symphatomimetics (additive)

2)Vasodilators

- paradoxically they're the firs-use drugs in HF; most freqently used are diuretics, angiotensin receptor blockers (ARBs), beta blockers, ACE inhibitors

a) nitroprusside(combined arteriolar and venodilator): releases NO spont., activates guanylyl cyclase; causes marked vasodilation, reduces preload and afterload; used in acute cardiac decompensation, hypertensive emergencies (malignant hypertension); used iv only, duration 1-2 min, mau cause excessive hypotension, thiocyanate and cyanide toxicity, may be additive with other vasodilators

b)nitrates:

*NITROGLYCERINE: improoves heart perfomance, vasodilating effect of coronary vessels

c)hydralazine(arteriolar dilators): probably increases NO synthesis in endothelium; reduces BP and afterload , results in increased CO; hydralazine + nitrates reduce mortality; used orally, duration 8-12h, may cause tachycardia, fluid retention, lupus like syndrome

d)diuretics

-in hypertension: thiazides are more important

-in HF: furosemide is more important

* FUROSEMIDE (loop diuretic): decreases NaCl and KCl reabsorption in thick ascending loop of Henle; increases excretion of salt and water, reduces cardiac preload, reduces pulmonary and peripheral edema; used in acute and chronic HF&severe hypertension, edematous condition; used orally and iv, duration 2-4h; may cause hypovolemia, hypokalemia, orthostatic hypotension, ototoxicity, sulfonamide allergy

other loop diuretics: Bumetamide, torsemide,

*HYDROCHLOROTHIAZIDE (thaizide): decreases NaCl reabsorption in the distal convuluted tubule, effect same as furosemide but less efficaicious; used in very mild chronic HF, mild to moderate hypertension, hypercalciuria, has not been shown to reduce mortality; orally used only, duration 10-12h; may cause hyponatremia, hypokalemia, hyperglycemia, hyperuricemia, hyperlipidemia, sulfonamide allergy

-can be used with loop diuretic in severe cases (SYNERGISTIC EFFECT!!!)

e) aldosterone antagonists

(diuretic effect: no cause effect of heart moddeling- nie jest bezposrednio powiązane!!) jakby by było pytanie.

SPIRONOLACTONE: antagonist of aldosterone in kidney (blocks cytoplasmic aldosterone receptors in collecting tubules od nephron) plus poorly understood reduction in mortality, possible membrane effect; increased salt and water excretion, reduces remodeling!!!-> aldosterone can prode cardiac and vessel 'fibrogenesis?' (powoduje zwłóknienia), reduces mortality; used in chronic HF, aldosteronism, hypertension; used orally, duration 24-72h; may cause hypokalemia, antiandrogen action

f)ACE inhibitors

-used FIRSTLY!! BEFORE AT1 rec.blockers

--cough cause of bradykinin increase (but bradykinin produses also desired vasodilation-so its not only negative!)

-decreasing preload and afterload: improoving heart action ( by decreasing vascular peripheral R)

-inhibit heart remodelling

*CAPROPRIL: blocks ACE, reduces A II levels, decreases vascular tone and aldosterone secretion; used in HF, hypertension, diabetes; used orally, short half life but large doses, duration 12-24h

*BENAZEPRIL

*ENALAPRIL

*FOSINOPRIL

*LISINOPRIL

g)AT1 receptor blcokers[ARBs] (Angiotensin II influencing AT1)

-used when patient doesn't tolerate ACE inhibitors!

-dilation results from blocking AT1, but also from not blocking AT2!!

* CANDESARTAN

*LOSARTAN

*OLMESARTAN

*VALSARTAN

Contradication for ARBs and ACE inbs. : pregnancy, renal artery stenosis

H)Nesiritide: syntetic form brain natriuretic peptide, ; increases cGMP level in smooth mm., decreases tension of venous and arteries

3)Other drugs for chronic failure

Loop diuretic, ACE inhibitors, nesirtide ,

a)beta blockers: NEGATIVE INOTROPIC EFFECT! should be taken from the small doses not to exagerrate the neg.ino.effect; slowing down heart, decreasing catecholamine level, drop in BP, drob in oxygene consumption, drop in renin production, delaying HR, decreasing mortality, up regulation of heart ( bu cutting of adrenergic stimulation of the heart by the mean og catecholamines elimination); used if ACE inhs. and diuretics don't work

Prescriptions:

1) for chronic HF always!!!!: beta blocker

Rp. Bisoprolol 1.25mg

tab.

Lag.orig.No1

D.S. take one tablet

orally once daily

(initial dose)

2) diuretic for HF: furosemide (20 mg once daily) / if you have a fantasy: prescribing thiazide: we must write WHY!!/spironolactone is a BIG MISTAKE!!!!

3) digoxin

Rp. Digoxin 125 mcg

tab.

Lag.orig.No1

D.S. take one tablet

orally once daily

4) ACE inhibitor

Rp. Quinapril 5mg

tab.

Lag.orig.No1

D.S. take half a tablet

orally once daily

(initial dose)

Rp. Quinapril 10 mg

tab.

Lag.orig.No1

D.S. take one tablet

orally once daily

(maintainence dose)