Drugs Used for Heart Failure (Wolff) Flashcards
1
Q
Left-sided systolic heart failure is due to failure of what?
A
Failure of the pump function of the heart (EF <45%) due to dysf. or destruction of cardiac myocytes or their molecular components
2
Q
Left-sided diastolic heart failure occurs due to what?
A
Ventricular capacitance is diminished and/or when ventricle becomes “stiff” and cannot fully relax during diastole
3
Q
What are 2 common causes of left-sided diastolic heart failure?
A
- Ventricular hypertrophy due to chronic HTN
- CT disease such as amyloidosis
4
Q
What occurs to both afterload and preload in systolic heart failure?
A
- Increased afterload
- Increased preload
5
Q
What is the LVEF like in systolic HF and there is usually progressive what?
A
- LVEF <50% = HFrEF
- Usually progressive chamber dilation w/ eccentric remodeling
6
Q
Diastolic heart failure is now especially common in whom?
A
Elderly women
7
Q
What occurs to the ejection fraction in diastolic heart failure?
A
Usually normal = HFpEF
8
Q
What occurs to preload in diastolic heart failure?
A
Decreased preload
9
Q
Diastolic heart failure has a poor tolerance of what 2 things and is worsened by an increase in what?
A
- DHF –> poor tolerance of atrial fibrillation
- DHF –> poor tolerance of tachycardia
- DHF is worsened by ↑ MAP
10
Q
Worsening of diastolic HF by ischemia raises left atrial pressure which can lead to which life threatening condition?
A
“Flash” pulmonary edema
11
Q
With a drop in cardiac output, what are the adpative mechanisms (i.e., what gets increased) contributing to HF?
A
- ↑ renin + ↑ aldosterone + ↑ natriuretic peptides
- ↑ sympathetic discharge
- ↑ preload and afterload
- ↑ remodeling of heart
12
Q
ACE-I and ARB’s lead to less angiotensin II which has what 3 positive effects in pt’s with HF?
A
- Less vasoconstriction (↓ afterload)
- Less aldosterone and less Na+/H2O retention (↓ preload)
- ↓ cell proliferation and remodeling
13
Q
Define the terms inotropic agent and chronotropic agent.
A
- Ionotropic agents alter the force/strength of muscle contractions
- Chronotropic agents may change the heart rate and rhythm
14
Q
ACE-I (-prils) are used clinically for what heart conditions?
A
- Heart failure w/ reduced EF (HFrEF) = systolic HF
- LV dysfunction following MI
15
Q
What are 2 major AE’s associated with ACE-I’s?
A
- Cough
- Angioedema
16
Q
Which 2 ACE-I are now widely used due their longer half-life permitting 1x/day dosing?
A
- Benazepril
- Lisonopril
17
Q
Which drugs can be used for HF if patient is intolerant to ACE-I’s?
A
ARBs (-sartans)
18
Q
Which ARB is noteworthy in that it is not a prodrug requiring activation?
A
Valsartan
19
Q
Which ARB is noteworthy in that it displays relatively irreversible binding?
A
Candesartan
20
Q
What is the MOA of sacubitril and what is it co-crystalized with as a combo drug for HF?
A
- Prodrug that inhibits neprilysin (neutral endopeptidase [NEP])
- Co-crystalized with the ARB, Valsartan
- Valsartan/sacubitril
21
Q
What does the neutral endopeptidase blockade by sacubitril lead to?
A
Increased levels of natriuretic peptides
22
Q
What are3 common AE’s of valsartan/sacubitril?
A
- HYPOtension
- HYPERkalemia
- ↑ serum creatinine
23
Q
What is the effect of ↑ ANP on GFR, renin/aldosterone secretion, Na+/H2O reabsorption, and ADH secretion?
A
- ↑ GFR
- ↓ renin + ↓ aldosterone secretion
- ↓ Na+/H2O reabsorption
- ↓ ADH secretion and ADH effects in collecting duct
24
Q
ACE-I’s/ARBs should be administered to all pt’s with LV systolic failure or LV dysfunction w/o HF except in what 5 situations?
A
- Not tolerated (cough, angioedema; try ARB)
- Pregnant
- HYPOtensive
- Serum creatinine >3 mg/dL
- HYPERkalemia
25
Which beta-blocker has been shown to work best in HF?
Carvedilol
26
Which other beta-blocker is a non-selective alpha/beta blocker, used primarily for severe HTN and tx of hypertensive emergencies?
Labetalol
27
What condition should patient be in for use of carvedilol in HF and what are it's recommended uses?
- **IF** **clinically stable**
- **Recent** or **remote hx** of **MI** or **ACS** and ↓ **EF (rEF; \<40%)**
- **rEF** to **prevent SYMPTOMATIC HF** (even if no hx of MI)
28
Carvedilol is used to prevent what in the heart as a result of excessive sympathetic stimulation during HF?
**Prevent down-regulation** of the **β1-receptors**
29
List 5 benefits of carvedilol in HF by **preventing the down-regulation of β1-receptors**?
- **Keeps heart responsive** to **sympathetic** drive
- **Protects** against **dysrhythmias**
- ↓ **renin secretion**
- ↓ **myocardial O2 consumption**
- **Limits heart muscle remodeling**
30
Carvedilol should only be administered to which patients?
**Clinically stable**
31
Which type of HF's is carvedilol useful in and should be given along with ACE-I to which pt's?
- Pts with **diastolic HF** will benefit from a **lower HR**
- Should be given to **all** pt's w/ **symptomatic CHF** and **LVEF \<40%** unless contraindications exist
- Given along **w/ ACE-I** to **all** pt's w/ **LV systolic dysfunction** caused by **MI** to **reduce mortality**
32
What is the MOA of ivabradine and effects on heart?
- **Selective** and **specific** i**nhibition** of the **HCN channels (f-channels**) within **SA node**
- Disrupts **If ("funny" current)** to **prolong** **diastole** and **slow HR**
33
What is the clinical application of ivabradine; specifically in which pt's?
- Tx of **resting HR** ≥70 bpm in pt's w/ **stable**, **symptomatic chronic HF** w/ **LVEF ≤35%** who are in sinus rhythm with:
- **Maximally tolerated doses of β-blockers**
OR
- **Contraindications** to **β-blocker** use
34
What is the MOA of spironolactone and its effects on ion and volume levels?
- Competitive **antagonist** of **aldosterone** receptors
- **K+-sparing diuretic** due to ↓ ability of aldosterone to promote Na+-K+ exchange in **collecting ducts**
- **↓ plasma Na+ and volume**
35
Which K+-sparing diuretic is a **more selective** aldosterone antagonist, approved for use in post-MI heart failure or in combo for tx of HTN?
Eplerenone
36
What are the pharmacokinetics of spironolactone like and why is a single dose effective for 2-3 days?
Steroid effects are **slow on** and **slow off**
37
What are some possible AE's associated with Spironolactone?
- **HYPERkalemia** (duh.)
- **Amenorrhea**, **hirsutism**, **gynecomastia**, and **impotence**
- **Tumorigen** in chronic animal toxicity studies (**boxed warning**)
38
What are 3 beneficial effects of spironolactone on the heart?
- ↓ **myocardial fibrosis**
- **Reduces** early morning rise in HR
- **Reduces** **mortality** and **morbidity** in pt's with **severe HF**
39
Explain the purpose of aldosterone inhibition when treating post-myocardial infarction heart failure?
**- Damaged** heart vasculature synthesizes **aldosterone** after MI
**- Locally** produced **aldosterone** contributes to **cardiac fibrosis**
40
What are some of the effects blocked by spironolactone that occur as a result of aldosterone release following an MI?
- Na+/H2O retention; K+ and Mg2+ loss
- ↓ baroreceptor reflex
- Sympathetic activation
- Cardiac fibrosis + ischemia
41
Spironolactone is approved for what application in HF?
Tx of **symptomatic HF** w/ **reduced systolic function**
42
Why is spironolactone (and eplerenone) the most **underutilized** of all classes of meds for HF?
Primarily due to **fear of HYPEkalemia**
43
Which loop diuretic has a **longer t1/2**, better **oral** absorption and som evidence that it **works better in HF?**
Tors**emide**
44
Furosemide and other loop diuretics are useful in the management of acute pulmonary edema by decreasing what?
Preload
45
Which class of diuretics is useful in patients with low GFR?
Loop diuretics
46
When using diuretics to control the congestive heart failure state, which class is used first and then followed by what 2 classes if needed?
- Use **loop diuretic** first
- Add **K+-sparing** next if needed
- If still need more diuresis, finally add **thiazide**
47
What is the purpose of using diuretics to relieve congestion in HF?
Return ventricular fiber length to more **optimal range**
48
Which vasodilator combo is especially useful in tx of chronic HF in African Americans?
**Isosorbide dinitrate** plus **hydralazine**
49
Where are the vasodilatory effects of isosorbide dinitrate and hydralazine seen and what is the effect on preload/afterload?
- **Isosorbide dinitrate** dilates **veins** and ↓ **preload**
- **Hydralazine** dilates **arteries** and **↓ afterload**
50
Nitroglycerin has a more prominent effect on what vasculature?
Veins
51
What is the clinical application of nitroglycerin in HF?
Acute decompensated HF (especially when assoc. w/ MI)
52
Hydralazine's MOA is dependent on what, requires activation by, and is mediated by what receptor?
- **Endothelium** dependent
- Requires **activation** of **COX**
- Mediated by **PGI2 receptor**
53
What are the clinical applications of hydralazine in HF and use in pregnancy?
- HF w/ **reduced EF** if **intolerance** to ACEI or ARB
- HF w/ reduced EF in **self-identified African Americans**
- **Hypertensive emergency** in **pregnancy**
54
What are some of the major AE's associated with Hydralazine?
- **Angina pectoris**
- Flushing
- **Peripheral edema**
- Tachycardia
- **Pruritus**
- **Drug-induced lupus-like syndrome**
55
What is the MOA of digoxin?
**Inhibition** of **Na+-K+ ATPase** pump in myocardial cells
56
What are the effects of digoxin on myocardial cells via inhibition of the Na+-K+ ATPase?
- Transient ↑ of intracellular Na+ which promotes Ca2+ influx leading to **increased contractility** (**+** **inotropic effect**)
- Direct **suppression** of **AV node conduction** --\> ↑ effective refractory period and ↓ conduction velocity
57
What is the effect of digoxin on inotropy, vagal tone, and ventricular rate?
- **Positive inotropic effect**
- **Enhanced vagal tone**
- ↓ **ventricular rate** to **fast atrial arrhythmias**
58
Increased myocardial contractility produced by digoxin has what effect on cardiac output, sympathetic, and vagal tone?
↑ cardiac output --\> ↓ sympathetic tone + ↑ vagal tone
59
What are the clinical applications of digoxin?
- Control of **ventricular response rate** in adults w/ **chronic atrial fibrillation**
- Tx for mild-to-moderate HF in adults/kids to **increase myocardial contractility**
60
What is the route of administration for digoxin and it's half-life?
What is required to get beneficial effects immediately?
- **Oral** w/ t1/2 = **36-48 hrs**
- **Needs a loading dose**
61
What are the major AE's associated with Digoxin?
Severe dysrhythmias
62
Digoxin cardiac toxicity occurs in part because myocytes becomes overloaded with what?
How does this contribute to arrhythmias?
- Overloaded w/ **Ca2+** and **spontaneous oscillatory uptake** and **release** from **SR** causes delayed afterdepolarizations and aftercontractions
- Excess **free radicals** also contribute
63
What are 3 hemodynamic benefits of Digoxin due to increased cardiac output?
- ↓ sympathetic tone
- ↑ urine production
- ↓ renin release
64
Digoxin increases the responsiveness of the SA node to what?
ACh
65
What are the 2 most important effects of Digoxin on the AV node in regard to duration of refracory period and conduction velocity?
- ↑ **duration** of **refractory period**
- ↓ **conduction velocity**
66
The most important effect of digoxin on purkinje fibers is an increase in what?
Automaticity
67
What is the major effect of digoxin on the duration of the refractory period in ventricular myocardium?
↓ duration of refractory period
68
What are typical changes seen on an EKG with therapeutic levels of digoxin?
- **Depression** of **S-T segment**
- **Longer P-R interval**
69
Toxic effects of digoxin on A-V conduction will be seen how on an EKG?
- A-V dissociation
- Lack of relationship between P and QRS complexes
70
Toxic effects of digoxin on purkinje automaticity and ventricular refractory period will appear how on EKG?
Ectopic ventricular beats
71
What are some of the non-cardiac AE's associated with Digoxin?
- Anorexia, N/V, salivation
- **Excessive** urination
- Fatigue
- **Visual disturbances** (blurred vision, **halos**, and **yellowish or greenish tinge to objects**)
72
What are 4 tx's for digoxin toxicity?
- KCl
- Lidocaine
- Phenytoin
- Antidigitalis Abs
73
Why are digoxin drug interactions with diuretics a big deal?
Diuretics cause **hypo**kalemia, which leads to ↑ digoxin binding ---\> digoxin toxicity
74
Digoxin competes with what ion for binding to Na+-K+-ATPase?
K+
75
What is the effect of ACE-I and ARBs on levels of digoxin?
ACE-I and ARBs can ↑ plasma K+ levels ---\> ↓ digoxin effects
76
Digoxin is used in combo w/ diuretics, β-blockers, and ACE inhibitors in what type of HF?
LV **systolic** HF
77
Why is digoxin especially useful in pt's with atrial fibrillation?
Due to **prolongation** of **effective refractory period** at **AV node**
78
Which drugs should be **used judiciously** in pt's with **diastolic** **HF**, but can also lead to what?
Which drug shows mixed evidence of benefit?
- **Loop diuretics** to tx edema
- **BUT** can ↓ preload too much --\> ↓CO, hypotension, and death
- Mixed evidence with **spironolactone**
79
Which 3 drug classes show **no** evidence of benefit in **diastolic HF?**
- Nitrates
- PDE5 inhibitors
- Digoxin
80
What therapy needs to be initiated in pt's with acute decompensated HF and why?
- **Diuretic therapy**
- **All** pt's with ADHF are **volume overloaded**, must get rid of **excess volume** to **relieve congestion** and **return ventricular fiber length** to more **optimal range**
81
How do the dilatory effects of nitroprusside differ from nitroglycerin?
- **Nitroprusside** = mixed effects, dilates **both** arterial and venous sides
- **Nitroglycerin** = preferentially venous side, **decreases preload**
82
Pt's with ADHF can be hypertensive, normotensive, or hypotensive; how is each treated with vasodilators/diuretics?
- **Hyper**tensive = tx with **diuretic** + **vasodilator** (i.e., nitropursside or nitroglycerin)
- **Normo**tensive = tx with **diuretic** + **vasodilator** (i.e., nitroglycerin)
- **Hypo**tensive = tx with **diuretic**
83
What is the MOA of nitroprusside?
**Forms** free radical **nitric oxide**, which in smooth m. **activates** **soluble guanylate cyclase** to ↑ cGMP
84
What are the systemic and cardiac effects of nitroprusside?
- Peripheral vaso**dilation** w/ action on **venous** and **arteriolar smooth m.**
- Reduces peripheral resistance
- Will ↑ cardiac output by **decreasing afterload**
85
What are 3 clinical applications of Nitroprusside?
1. Management of **hypertensive crisis**
2. **Acute decompensated HF**
3. Used for **controlled hypotension** to **reduce bleeding** during **surgery**
86
One AE of nitroprusside is metabolic acidosis secondary to what?
Cyanide toxicity
87
When are inotropic agents (i.e., sympathomimetics, PDE inhibitors) indicated for HF pt's?
If **symptomatic HYPOtension** w/ end-organ dysfunction despite **adequte filling pressure**
88
Before administering inotropic agents to pt with HF what should be discontinued?
Carvedilol
89
Dobutamine primarily affects what receptors and what is the effect on the heart?
- Stimulates myocardial **β1** and **β2** AR's, also so α1 receptors
- ↑ **contractility** and **HR**
- Some **vasodilation** due to β2 receptor stimuation
90
Which adrenergic receptors are activated by Dopamine in a dose dependent manner and effects on heart?
- **Activates** β1-AR's at **LOW** doses = **↑ HR and contractility**
- **Stimulates** α-AR's at **HIGH** doses
91
Dopamine is used as an adjunct in the tx of what?
**Shock** that persists after adequate fluid replacement in cases of: MI, open heart surgery, renal failure, and **cardiac decompensation**
92
What is the prototypical PDE type III inhibitor used as an inotropic agent in short-term/rescue therapy?
Milrinone
93
The PDE inhibitor, Milrinone results in increasd levels of what?
What is the effect on the heart and systemic circulation?
Must be given via which route?
- **↑ cAMP** ---\> **↑ contractility** in heart + vaso**dilation**
- **Decrease preload** and **afterload**
- Must be given via **IV**
94
What are the clinical applications for Milrinone?
**Inotropic therapy** for **pt's unresponsive** to **other acute HF therapies** (i.e., dobutamine)
95
What are 3 drugs classes to avoid in HF?
- Class I antiarrhythmics
- CCB's
- NSAIDs
96
Which drug may improve cardiac responsiveness during ADHF in a patient who was taking carvedilol/is overdosed on carvedilol?
Milrinone
97
What are some of the concerns with using the PDE inhibitor, Milrinone?
Some studies show it **decreases** survival time
98
Which drug classes can be used in **diastolic HF** if justified by sx's?
- β-blockers
- ACEI/ARBs
- CCB's
