Drugs for HF Flashcards
(89 cards)
1
Q
Main list of Drugs for Heart failure
A
• ACE inhibitors: captopril and other \_\_prils • angiotensin receptor blockers (ARBS): losartan and other \_\_sartans – valsartan/sacubitril(adds neprilysininhibitor) • carvedilol • spironolactone • diuretics: loop, thiazide, K+-sparing • direct vasodilators: nitroglycerin/isosorbide dinitrate, nitroprusside, hydralazine • digoxin • dobutamine, dopamine • milrinone
2
Q
What are the two types of Left sided Heart failure?
A
systolic = HFrEF≡ Heart Failure reduced Ejection Fraction
–
failure of the pump function of the heart (ejection fraction < 45%, normal = 60 –70%) typically due to dysfunction or destruction of cardiac myocytes or their molecular components
–
usually has progressive chamber dilation with eccentric remodeling
diastolic = HFpEF≡vHeart Failure preserved Ejection Fraction
–
occurs when the ventricular capacitance is diminished and/or when the ventricle becomes “stiff“ and cannot fully relax during diastole
–
diagnosis is now fairly common, especially among older women
–
typically due to concentric ventricular hypertrophy (e.g.,from chronic hypertension) or connective tissue diseases (e.g., amyloidosis)
3
Q
what are the changes in Pressure Volume loops for Systolic failure?
A
Decreased ESPVR slope
increased ESV and EDV
decrease SV and EF
Ventricular dilation
Loss of Inotropy
4
Q
what are the changes in pressure volume loops for Diastolic Failure?
A
increased EDPVR Slope
decreased EDV
Increased EDP
decreased compliance
5
Q
in diastolic HF what can worsen the prognostics?
A
increasing the MAP which can raise left atrial pressure leading to angina with wheezing, shortness of breath and cause a life threatening flash Pulmonary edema
6
Q
what is poorly tolerated in DHF?
A
atrial fibrillation
tachycardia
7
Q
what is the overall goal we are trying to prevent after an MI event?
A
Remodeling of the heart
8
Q
what are the main Heart Failure Vicious cycles that lead to Cardiac Remodeling?
A
Renin System (angotensin I, II, aldosterone)
Increased sympathetic activity (vasoconstriction leading to increased cardiac filling pressures
Renal Na+ and H20 retention
9
Q
How does ACE inhibitors and ARBs help in Heart failure?
A
Less Angiotensin II leads to:
decreased Vasoconstriction (decreased afterload)
Less aldosterone secretion and less sodium/water
Decreased cell proliferation and remodeling
10
Q
MOA, Effects and Clinical Applications of Captopril
A
MOA: ACE inhibitor (competitive
Effects: lowers levels of angiotension II, increases plasma renin activity and decreases aldosterone secretion
-lowers BP
Applications:
- Hypertension
- acute hypertension
- HFrEF (systolic)
- Diabetic Nephropathy
- off label aldosteronism
11
Q
Pharmokinetics and toxicities of Captopril
A
Pharmokinetics: rapidly absorbed
ecreted in urine
-CYP2D6
half life is 1.7 hours
Toxicities:
- BB = Fetal toxicity
- angioedema
- cough
- hypotension
- cholestatic jaundice
- drowsiness
12
Q
What is Enalapril?
A
another early ACEI that has a prodrug form and available for IV
13
Q
what is benazepril?
A
now widely used ACE inhibitor that has a longer half life for 1x/day dosing
14
Q
what is lisonopril
A
now widely used ACEI longer half life now permitting 1X day dosing
15
Q
MOA, Effects and Clinical application of Losartan
A
Competitive nonpeptide angiotensin II receptor antagonist (AT1 more than AT2)
Effects:
- blocks Vasoconstriction and aldosterone secreting effects
- does not effect response to bradykinin
- more complete inhibition of RAAS
Clinical:
- diabetic nephropathy with increased SCr and proteinuria in DM and HT
- HTN
- CKD
- HF if intolerant of ACE inhibitors
- Off-label Marfan syndrome
16
Q
Pharmacokinetics and TOxicities of Losartan
A
Pharmacokinetics: Extensive first pass metabolism to get to active metabolite
-half life 2 hours
Toxicities: -adverse effects more in diabetic nephropathy -hypotension -fatigue -anemia BB = fetal toxicity -hypoglycemia -hypokalemia
17
Q
What is Valsartan?
A
ARBs that has a half life of 6-10 hours that is not a prodrug
18
Q
what is Candesartan?
A
half life is 5-9 hours and is noteworthy for its relatively irreversible binding
19
Q
when should ARBs and ACEI not be used in heart failure?
A
- Not tolerated (cough, angioedema, try ARB)
- Pregnant
- Hypotensive
- Serium creatinine > 3mg/dL
- Hyperkalemia
20
Q
what are the affects of ANP/BNP?
A
causes natriuresis and diuresis
increase GFR decrease renin secretion decrease aldosterone -decrease Na and H20 water reabsorption -decreased ADH secretion and ADH effects in collecting duct
21
Q
what can BNP and NT-proBNP be used for?
A
BNP made by the ventricles and can be used as a biomarker
NT-proBNP is inactive until it is cleaved off
22
Q
what is the MOA, Effects, Clinical applications of Valsartan/sacubitril
A
MOA: Sacubitril is a prodrug that inhibits the Neprilysin (neutral endopeptidase)
- Valsartan is an ARB
- these drugs co crystalized
Effects:
-increase ANP and BNP
clinical applications:
-Heart failure
23
Q
Pharmokinetics and Toxicities of Valsartan/sacubitril
A
Pharmokinetics:
- twice daily dosing
- half life of 9-11 hrs
Tocicites:
- Hypotension
- hyperkalemia
- increased sCr
- angioedema
- cough
- renal failure
- decreased Hct, Hgb
24
Q
what makes Carvedilol beneficial in HF
A
Inverse antagonist thus preventing the downstream signaling rather than being an antagonist
others that are beneficial that are not inverse:
- metoprolol
- bisoprolol
25
Carvedilol MOA, effects, Clinical application
MOA: racemic mixture of nonselective beta and alpha adrenergic blocker
-b more than a
Effects:
-in HT decreased cardiac output and increased levels of ANP
in CHF decreased pulmonary pressure
-increased stroke volume index
Clinical applications:
-if stable, used in recent or remote history of MI and in HFrEF prevent symptomatic HF
off label: rate control in afib, chronic stable angina, gastroesophageal varices
26
what are the pharmacokinetics and toxicities of Carvedilol
Pharmacokinetics:
- rapid and extensive absorption
- half life 7/10 hours
- metabolized by liver
```
toxicities:
-allergy
-dizziness weight gain
swelling of legs
-SOB
-Bradycardia
-angina and heart attack if abruptly discontinued
```
27
What is use of Labetalol
another alpha/beta blocker used primarily for severe hypertension and hypertensive emergiencies
28
general use of Carvedilol
Prevent down regulation of the B1 adrenergic receptors in the Heart due to excessive sympathetic stimulation
Keeps heart responsive to sympathetic drive
- protects against dysrhythmias
- reduces renin secretion
- reduces myocardial O2 consumption
- limits heart remodeling
given at low doses initially and cautioned in a stable patient
given to patients with diastolic HF
and symptomatic of CHF and LVEF<40%
29
what is the big black box warning for Beta blockers
Beta blocker therapy should not be withdrawn abruptly (particularly in patients with CAD) but gradually tapered to void acute tachycardia, hypertension, and/or ischemia
30
MOA, effects and Clinical appication of Ivabradine?
MOA: specific inhibition of the hyperpolarization-activated cyclic nucleotide gated (HCN) channels (If cannels) within the SA node
-prolongs diastole and slows HR
Clinical applications:
- treatment of resting HR greater than 70 in stable and chronic HF with EF<35% who are sinus rhythm with:
- maximally tolerated doses of beta blockers
- contraindications to beta blocker use
off label: stable angina
31
Pharmokinetics and toxicites of and recomendations for ivabradine?
Given PO due to intestinal and hepatic metabolism
-half life 6hrs
TOxicities:
- bradycardia
- hypertension
- increased risk of atrial fib
- heart block
Contraindicted in:
- acute decompensated HF
- Hypotension
- bradycardia
- pacemaker dependance
- hepatic impairment
- strong CYP3A4 inhibitors
beneficial to reduce HF hospitilizations with stable chronic HFrEF (<35%)
32
MOA, effects and CLinical applications of Spoironolactone
MOA: competitive antagonist of aldosterone receptors
effects: K+sparing diuretic by preventing Na K+ exchange in collecting ducts
Clinical app:
- counteracts K+ loss induced by other diuretics in treatment of HF
- treat hyperaldosteronism
- ascites in cirrhosis
reduced fibrosis in HFrEF and post MI heart failure
treatment of androgenic alopecia in females
33
Pharmacokinetics and toxicities of Spironolactone
drug has active metabolites
-steroid effects are slow on and slow off so single dose
Toxicities:
- Hyperkalemia
- amenorrhea, hirsutism, gynecomastia, impotence
- tumorigen
34
what is eplerenone
more selective aldosterone antagonist, approved for use in Post MI heart failure and alone or in combination for treatment of hypertension
35
what are the general benefits from the use of Spironolactone
block Aldosterone
- prevent Na+ and water retention
- prevent K+ loss
- prevent Mg++ loss
- increase the baroreceptor reflex
- prevent cardiac fibrosis
- prevent ischemia
- decrease sympathetic activation
36
what is the common clinical reasons for administering a diuretic?
Essential hypertension
Edema associated with:
- congestive heart failure
- liver failure
- kidney failure
37
what are the K+ sparing diuretics?
–
triamterene, amiloride… Na+ channel blockers
–
spironolactone… aldosterone antagonist
38
what are the K+ losing diuretics?
–
thiazides… Na+Cl- co transporter blockers
–
loop diuretics… Na+K+2Cl-cotransporter blockers
–
carbonic anhydrase inhibitors (seldom used)
–
osmotic diuretics… non reabsorb able solutes
39
what are the locations of K+ losing diuretics?
PCT
THick segment ascending limb of heneles loop
Early distal Convoluted tubule
40
what are the locations of the K+ sparing diuretics
Late convoluted tubule and collecting duct
41
Hyperkalemic effects on the heart
```
•
tall T waves
•
prolonged PR interval
•
widened QRS interval
•
flattened P waves
•
arrhythmias including bradycardia, ventricular tachycardia or fibrillation
•
sinus arrest or nodal rhythm with possible asystole
```
much easier to fire AP since the resting membrane is depolarized
42
what are the effects of Hypokalemia on the heart
```
•
flattened T waves
•
ST segment depression
•
prolonged QT interval
•
tall U waves
•
atrial arrhythmias
•
ventricular tachycardia or ventricular fibrillation
```
harder to get AP because membrane is hyperpolarized
43
what diuretic causes the highest ceiling of diuresis
Furosemide
- works on the thick ascending limb of henle
- considered a loop diuretic
44
MOA, Effects, and clinical applications of furosemide
inhibits Na+ K+ 2Cl- cotransporter at the TAL preventing sodium and chloride reabsorption
-indirectly inhibits reabsorption of Ca and Mg due to loss of K+
effects: massive fluid removal and excretion of Na K+ Cl, Mg, Ca and H20
Clinical application:
-management of edema associate with HF, hepatic disease, and renal disease
acute pulmonary edema
-decreases preload and decreases EDV, rapid dyspnea relief
treatment of HTN and works in patients with a low GFR
45
Pharm kinetics and Toxicities of Furosemide
half life .5-2hrs
eliminated primarily as unchanged drug in urine
Ototoxicity
Sulfonamide (hypersensitivity)
- Hypokalemia
- Hyponatremia
- Hypocalcemia (decreased kidney stone risk)
- Hypomagnesemia
- Hypochloremic metabolic alkalosis
- Hyperglycemia
- Hyperurcemia
- increased cholesterol and tryglycerides
46
what is torsemide?
sulfonamide similar to furosemide with a longer T1/2 and better oral absorption and some evidence it works better in HF
47
what is bumetanide
similar to furosemide but more predictable oral absorption
48
what is ethacrynic acid
Non-sulfaonamide loop diuretic reserved for those with a sulfa allergy
49
what are some major drug interactions of Loop diuretics
–
digoxin: frequent since both drugs are often used to treat heart failure and the risk of digoxin toxicity is increased by low potassium due to the diuretic
–
ototoxic drugs: increased chance of hearing loss if combined with drugs having similar toxicity (e.g., gentamicin)
–
potassium-sparing diuretics can counter balance potassium-wasting effects
–
can also increase lithium toxicity, potentiate effects of other antihypertensive agents and have diuretic effects antagonized by NSAIDs
50
what are the benefits from diuretics in the aspect of congestion?
Relieve congestion
get rid of excess volume to allow for the return of ventricular fiber length for more optical range
51
MOA, effects, and clinical applications of Hydrochlorothiazide
MOA: inhibits sodium reabsorption in the Distal tubules via blockade of Na+ Cl- cotransporter
effects: increase excretion of Na and H20
- K+ losing as well
Clinical applications:
- management of HTN alone or in combination with other drug
- not effective in patients with low GFR
- treat edema
- off label calcium nephrolithiasis
52
Pharmokinetics and toxicities of HCTZ
well absorbed
half life 6-15 hours
excreted in urine
Toxicities:
- Hypotension
- hypokalemia
- hypomagnesemia
- hyponatremia
- hypochloremic metabolic alkalosis
sulfonamide drug
53
what are the characteristics of chlorothiazide, and chlorthalidone
Chlorothiazide: poor oral absorption
Chlorthalidone: much longer half life
54
what is the characteristics of Metolazone
Another long acting thiazide diuretic that is favorite of cardiologists for use as adjunct in the treatment of congestive HF
55
what can cause Diuretic Failure during HF treatment
Decreased renal perfusion and glomerular filtration rate
- via excessive volume depletion
- decline in CO
NSAIDS
Renal pathology
Reduced or impaired diuretic absorption
56
Benefits of Isosorbide dinitrate
Beneficial in African Americans
dilate veins and decrease preload and is given with hydralazine that dilates arteries and decreases afterload
57
MOA, effects, and CLinical applications of nitroglycerin
MOA: forms NO that activates guanate cyclase to produce more cGMP that will dephosphorylate myosin light chains and cause relaxation
effects:
- Vasodilation more in veins
- decrease preload
- moderately decrease afterload
- dilates coronary bloodflow and collateral flow
Clinical applications:
- treat angina
- acute decompensated HF especially in MI
- preoperative hypertension
- induce hypotension
- help with anal fissure
58
Pharmacokinetics and toxicities of Nitroglycerin
half life 1-4 min
but can be given anyway for how fast and long want to work
TOxicities:
- reflex tachycardia
- headache
- paresthesia
- dyspnea
- diaphoresis
59
what is isosorbide dinitrate?
similar drug with slower onset of action that is administered orally for prevention of angina and for HF with reduced ejection fraction
60
MOA, Effects, and clinical applications of Hydralazine?
MOA: endothelium dependant
- hypepolarizes
- requires activation of COX
- mediated by prostacyclun (PGI2) receptor
effects: direct vasodilation of arterioles
Clinical applications:
-management of hypertension (not for initial treatment)
off label:
- HF with reduced ejection fraction if not tolerable for ACEI or ARB
- HF (african american)
- Hypertensive emergency in pregnancy
61
Pharmokinetics and toxicities of Hydralazing?
Pharmokinetics: oral or IV
- eliminated in urine
- half life 2-8 hrs
Toxicities: ots!
- angina, flushing
- peripheral edema
- tachycardia
- pruritus
- drug induced lupus like syndrome
62
what order is Digitalis (dioxin) used
second line agent
63
MOA, Effects and Clinical applications of digoxin
MOA: inhibition of the Na+-K+ ATPase
-leads to more Ca stuck in the cell
Effects:
- leads to increased contractility
- suppression of the AV node conduction
-Positive inotropic effect, enhanced vagal tone and decreased ventricular rate to fast atrial arrhythmias
Clinical applications:
- Control of ventricular response rate for patients with atrial fibrillation
- treatment of patients with increase myocardial contractility
64
What are the Pharmacokinetics and toxicities of Digoxin
Pharm: administered orally, IV and IM
- half life is 36-48 hours so needs a loading dose
- can cross the placenta but is safe in pregnant women with supraventricular tachycardia
Toxicites
- accelerated rhythm
- diziness mental disturbances
- rash
- nausea
- weakness
- blurred or yellow vision
- laryngeal edema
65
what happens if there is low potassium with a patient taking digoxin?
it competes with K+ for binding to the Na+/K+ ATPase
need normal K+ levels if there is too little then there is too much block
66
what are the Hemodynamic benefits and electrical effects of digoxin?
Hemodynamic benefits:
-increased cardiac output that causes decreased sympathetic tone, increased urine production, and decreased renin release
Electrical effects:
- Increases the firing rate of vagal fibers
- increases the responsiveness of the SA node to acetylcholine
67
effects of Digoxin on the electrocardiogram
typical changes:
-depression of the ST segment and longer PR interval
Toxic effects on AV conduction: AV dissociation
-lack of relationship between the P and QRS complexes
Toxic effect of digitalis on purkinje automaticity and ventricular refractory period
-ectopic ventricular beats canned bigeminy (ectopic beat alternating with normal beat
68
how does digotoxin affect the AV node
increase duration of refractory period
decrease the conduction velocity
69
how does digitalis effect the purkinje fibers
increased the automaticity
70
how does digitalis effect the ventricular myocardium
decrease the duration of refractory period
71
what are noncardiac adverse effects of digoxin?
```
–
anorexia, nausea, vomiting, salivation
–
excessive urination
–
fatigue, visual disturbances (blurred vision, halos, yellowish or greenish tinge to objects)
```
72
what are the drug interactions of digoxin?
–
diuretics… the “biggie”; diuretics cause hypokalemia, which leads to increased digoxin binding, which leads to increased digoxin toxicity
–
ACE inhibitors and ARBs –can increase plasma K+levels, decreasing digoxin effects
–
sympathomimetics–beneficial interaction on contractility, detrimental effects on arrhythmias
–
quinidine, spironolactone, verapamil, propafenoneand alprazolam are among a range of drugs that interfere with clearance of digoxin
–
cholesterol-binding resins block digoxin absorption from GI tract
73
what is the treatment of too much digoxin?
KCl
lidocaine to block Na+ channels
Phenytoin to block Na channels
Anti-digitalis antibodies
74
what are the guidelines for treatment for HFrEF?
ACEI, ARB, and ARNI
all in conjunction with beta blockers and aldosterone antagonist
75
What are the drug of choice treatments for HFpEF
direct therapy at symptoms
-hypertension, lung disease, coronary artery disease, atrial fibrillation, obesity anemia, diabetes mellitus, kidney disease, sleep disordered breathing
exercise is beneficial/recommended, but avoid: tachycardia, abrupt ↑blood pressure, ischemia, atrial fibrillation
loop diuretics against edema
Aldosterone receptor antagonists
if justified by symptoms:
-β-blockers, ACEI/ARBs, CCB
76
what drugs have shown to have no evidence of benefit against HFpEF
no evidence of benefit: nitrates, PDE5 inhibitors, digoxin
77
what to give to a patient who has Acute decompensated Heart failure?
must get rid of excess volume to relieve the congestion and return ventricular fiber length to more optimal range
place in seated position
- pulse ox
- asses blood pressure
- place 2 IV lines
- Monitor urine output
78
how can patients present with acute decompensated heart failure and how are they treated
Hypertensive: treat with loop diuretic and vasodilator
Normotensive: treat with loop diuretic and vasodilator
Hypotensive: typically treat with loop diuretic
79
what is the difference between Nitroprusside and Nitroglycerin?
Nitroprusside will target both arterial and venous sides
| Nitroglycerin will preferentially dilate the venous side
decrease preload
80
when to give inotropic agents?
indicated if symptomatic hypotension with end organ dysfunction despite adequate filling pressure
dobutamine
dopamine
milrinone
81
when giving an inotropic agent what must you make sure of?
make sure you discontinued carvedilol
-beta blocker
only time keep giving is if the patient is mild decompensation without hypotension or evidence of hypoperfusion
82
MOA, effects and clinical applications of dobutamine
MOA: stimulates both beta1 and Beta 2 adrenergic receptors
-some alpha 1 agonism as well
Effects:
- increased contractility and HR
- lowers central venous pressure and wedge pressure
- no effect on pulmonary vascular resistance
Clinical applications:
- management of patients with cardiac decompensation
- bridge therapy
- pallative therapy
- severe systolic dysfunction
83
what are the pharmacokinetics and toxicities of dobutamie?
Pharm: administer IV
half life 2 min
metabolized by tissues and liver
```
toxicities:
-tachycardia
angina
-fever
-headache
-hypertension
-local pain
```
84
what are the MOA, effects, clinical applications of dopamine
MOA: Catecholamine that activates B1 adrenergic receptors at low doses and stimulates a adrenergic receptors at higher doses
effects: increases HR and contractillity
low does: dilate renal vessels but does no selectively preserve renal function
Clinical applications:
- adjunct in the treatment of shock that persists after adequate fluid volume replacement in cases of:
- MI
- Open heart surgery
- renal failure
- cardiac decompensation
85
Pharmacokinetics and TOxicities of dopamine
Pharm:
- given IV
- half life 2 min
- COMT (MAO) breakdown
- excreted in urine
Toxicities:
•angina pectoris, atrial fibrillation, bradycardia, ectopic beats, hypertension, hypotension, palpitations, tachycardia, vasoconstriction, ventricular arrhythmia, widened QRS complex on ECG
•anxiety, headache
•local tissue necrosis, gangrene (high dose), piloerection
•nausea, vomiting
•increased intraocular pressure, mydriasis
•dyspnea
86
MOA, effects, and clinical application of milrinone?
MOA: selective phosphodiesterase type 3 inhibitor
Effects: Inhibitor in cardiac and vascular tissue resulting in vasodilation and inotropic effects
Clinical applications:
-Inotropic therapy for patients unresponsive to other acute heart failure
87
Pharmacokinetics and toxicities of milrinone
administered IV
- half life 2.5 hrs
- excreted in urine
Toxicities
- ventricular arrhythmia
- supraventricular arrhythmia, hypotension angina
- headache
88
what is the use of inamrinone
a similar drug to milrinone but is less safe and has been removed from the market in 2011
89
Drugs to avoid in Acute decompensated heart failure
•
class I antiarrhythmics… some are negative inotropesand all can cause arrhythmias in heart failure patients
–
consider amiodarone…
•
calcium channel blockers… directly suppress myocardial contractility, especially non-dihydropyridines
•
nonsteroidalanti-inflammatory drugs…impair renal salt and water excretion which can exacerbate heart failure
