Drugs for HF Flashcards
ACE Inhibitor suffix and prototype
-prils
Captopril and Lisonopril
Angiotensin Receptor Blocker (ARB) suffix
-sartans
Losartan and Valsartan
Briefly describe the symptoms of Left-sided HF
Pulmonary edema Right-sided HF Ascites Edema Orthopnea and PND
Systolic vs. Diastolic Dysfunction
Systolic (HFref): dilated chambers and weak musculature
Diastolic (HFpef): hypertrophied chambers with decreased filling ability
Ischemia in the presence of Diastolic HF that raises LA pressure can lead to what?
“Flash” pulmonary edema
LaPlace’s Law in a nutshell
- Increased wall Thickness decreases wall stress (seen in HFpef)
- Increased radius of the chamber (HFref) decreases pressure but increases wall stress.
What happens when an MI causes fibrosis?
Spherical ventricular dilation and increased interstitial collagen deposition between myocytes.
Why does remodeling of the heart in response to low CO not solve the issue?
It can never keep up, so the cycle repeats which causes more damage than good
3 pharmacological ways to prevent deterioration of Cardiac function
- ACEi/ARBs
- BB
- Aldosterone Antagonist (Spironolactone)
Summary of the RAAS
- JG cells sense drop in BP and secrete Renin (or Macula Densa sense drop in salt content)
- Renin activates Angiotensin I
- Angio I converted to Angio II by ACE in lungs
- Angio II promotes Aldosterone release, vasoconstriction, and cardiac remodeling
- Aldosterone causes resorption of Na+ and secretion of K+
Name the drug classes that block each sequential step of the RAAS
- Aliskiren blocks Renin
- ACEi block Angio I to Angio II
- ARBs block Angio II at AT1 receptors
Why is a side effect of ACEi a cough?
ACE is used to deactivate bradykinin.
Bradykinin causes Vasodilation, Decreased GFR, and Cough
Main results from ACEi
- Decreased after load (vasodilation)
- Decreased preload secondary to decreased Aldosterone (decreased volume)
- Decreased Mitogen activity in the heart
What would you find on blood test of a person taking Captopril (renin, angiotensin, aldosterone)
- Increased Renin (feedback)
- Decreased Aldosterone (downstream)
- Increased Angio I
Captopril profile
ACEi
Lowers BP in HFref
Also used in Diabetic Nephropathy
Side effects: Cough and angioedema
2 additional ACEi that are widely used because of a long half life
- Benazepril
2. Lisonopril
Losartan Profile
ARB (AT1 1000x greater affinity)
NO increased bradykinin (no cough)
Treats HTN alone or in combo with AntiHypertensives
Treats CKD as well
Why use Valsartan over Losartan?
Valsartan is not a prodrug, so does not need to be activated.
Excreted in the poo so no need for good liver or kidney function
Patient presents with LV systolic failure (aka HFref) what do you prescribe?
ACEi or ARB
Beta blocker
5 contraindications for ACEi or ARB
- Intolerant
- Pregnancy
- Hypotension
- Increased Creatinine
- Hyperkalemia
Action of ANP and BNP
Increase GFR
decrease renin, aldosterone, and ADH.
Promotes diuresis and natriuresis
Sacubitril
Endopeptidase Inhibitor
prevents the breakdown of BNP and ANP
3 Beta blockers that are beneficial in HF
Metoprolol
Bisoprolol
Carvedilol
Carvedilol profile
Nonselective a/B blocker (B>a)
Treats previous MI or ACS and HFref
Side effects: SOB, weight gain, pain, swelling
Prevents down-regulation of B1 receptors due to increased sympathetic tone. Keeps heart responsive
When is labetalol used?
Hypertensive emergencies
What is the number one black box warning with Beta blockers?
Do NOT abruptly withdraw because the body will be sensitized to SNS stimulation
Ivabradine
Inhibits funny Na+ channels in nodal tissue to prolong diastole and slow HR (increase filling time)
Treat HFref with a HR>70bpm who are:
- maximally dosed beta blockers
- contraindicated for beta blockers
Spironolactone profile
Competitive Aldosterone Antagonist
HFref
K+ sparing diuretic that acts at the collecting duct (counteracts K+ losing diuretics)
Reduces aldosterone-mediated fibrosis
Common reasons for diuretics
- Primary HTN
2. Edema: CHF, Liver failure, Kidney Failure
2 classes of Diuretics
- K+ sparing: Collecting duct
- Triamterene
- Amiloride
- Spironolactone - K+ losing: Proximal to CD
- Thiazides
- Loop Diuretics
- CAi
- Osmotic diuretics
Cardiac abnormalities caused by Hyperkalemia
- Increased membrane potential closer to threshold
- Arrhythmias (tall T’s, prolonged PR, Widened QRS)
- In nodal tissue, hyperkalemia increases activity of K+ channels and actually causes HYPERpolarization leading to Bradycardia
Just remember: wanna stop the heart? Give K+!
Cardiac abnormalities caused by hypokalemia
- Hyperpolarization
- prolonged QT
- Tall U waves
- VT and VF
Which diuretic is the cannon and causes the most diuresis?
Loop Diuretics- Furosemide (Lasix)
Furosemide profile
Blocks Na/K/2Cl cotransporter in the thick ascending loop.
Used to manage volume overload in HF (decreases preload)
Side effects: Ototoxicity, hypocalcemia, hypomagnesemia, hypochloremic alkalosis
What loop diuretic can be given in place of Furosemide in a person with a sulfa allergy?
Ethacrynic Acid
What other ions does Furosemide also cause to be lost in the urine?
Ca2+ and Mg2+
Without a negative potential across the membrane caused by K+ resorption, there is no drive for Ca or Mg absorption
Order of diuretic usage in HF
- Loop Diuretic
- K+ sparing if needed
- Thiazide last
HCTZ profile
K+ losing diuretic that inhibits the NaCl cotransporter in the distal convoluted tubule.
Treats HTN
Vasodilators used in chronic HF
- Isosorbide Dinitrate (venous)
2. Hydralazine (arterial)
Hydralazine profile
Directly vasodilators arterioles (decreased TPR)
Treats HTN, hypertensive emergency in pregnancy
Off-label use: HFref
Side effects: Pruritus, rash, urticaria
Nitroglycerin profile
NO producer that increases cGMP and dephosphorylates MLC to cause vasodilation (mainly venous)
Uses: Angina Pectoris, acute decompensated HF
Digoxin
Inhibits Na-K ATPase in myocardium
Increases contractility by promoting Ca2+ influx
Suppresses nodal tissue to prolong AP
Uses: Controls Ventricular rate in Afib and treats HF
Hemodynamic effects of Digoxin
Decreased SNS tone
Increased Urine
Decreased Renin
Electrophysiologic effects of Digoxin
- Increased automaticity of Purkinje’s
- Increased AV refractory period (decreased conduction velocity)
- Decreased Ventricular refractory
Can cause a form of 3rd degreee HB where atria are uncoupled from Ventricles
Noncardiac side effects of Digoxin
Visual disturbances (halos, yellow/green tinge)
Main drug interaction with Digoxin
K+ losing diuretics can cause hypokalemia and enhance effects of Digoxin to a toxic amount
ACC/AHA Stages of HF
A- At risk without structural disease or symptoms
B- Structural disease without symptoms
C- Structural Dz with symptoms
D- Advanced structural Dz with marked symptoms
Stage A HF Therapy
Lifestyle mods
ACEi or ARB +/- Statins
Stage B HF Therapy
ACEi/ARB
Beta Blockers
Guidelines for treatment of HFref Stage C
ACEi/ARB or ARNI (Sacubitril + Valsartan)
Beta Blockers
Aldosterone Antagonist
Guidelines for treatment of HFpef
Direct therapy at symptoms and associated conditions
Edema- Loop diuretics
B blockers, ACEi/ARBs, CCB’s as needed
NO evidence for: Nitrates, PDE5i, digoxin
Studies to obtain in Acute Decompensated HF
ECG
CXR
CBC with Troponins
ECHO
ADHF patients are all volume overloaded. What is the correct therapy to initiate?
Diuretics. Get out the urine cannons
Can also give Nitrates to decrease preload if not hypotensive
Patient presents to ED with decompensated HF and hypotension with evidence of end-organ damage. In addition to diuretics, what else could be warranted?
Sympathomimetics- Dobutamine and Dopamine
Make sure you discontinue any Beta blockers slowly
Also PDEIII inhibitor (Milrinone) which increases cAMP
