Cardiac Pt 1 HF, ACS Flashcards
Heart Failure
- Complex clinical ______ that can result from s______ or f______ cardiac disorder that impaires the ability of the ventricle to f____ or e_____ blood
- HFrEF
- LVEF =
- Impaired:
- HFpEF
- LVEF =
- Impaired:
- syndrome, structural, functional, fill, eject
- HFrEF
- < 40%
- wall motion, dilated ventricle
- HFpEF
- >40%
- ventricular relaxation and filling
Inability of heart to meet body’s need of oxygen
Heart Failure: Insult to Injury
- I_______ -> I_______ -> Loss of _______ -> Reduced organ ______ -> Neurohormonal ______ -> Cardiac ______
- Insult to myocardium ->
- Reduced organ perfusion especially v important is the?
- HF is a ______ disease -> eventually pts expire from most commonly depleted cardiac function of LV arrhythmias
- Insult -> Injury -> function -> perfusion -> activation -> remodeling
- most likelty MI, could be longstanding HTN, viral disease, genetics, arrhythmias, drugs, infections, CANCER AGENTS
- kidneys -> RAAS/Sympathetic nervous system (upregulation of aldosterone = v cardiotoxic - binding of aldosterone to cardiac cells -> apoptosis) Short term does increase BP but chronically promotes remodeling
- progressive
Heart Failure: A Vicious Cycle
- Often times damage to monocytes aren’t caught until pt comes into hospital with SYMPTOMS*
- Cardiac remodeling is a vicious cycle*
Dx of Heart Failure
- Subjective Symptoms
- D_____, O______
- C____, H______
- N_____
- Bl______
- F_____
- ______ intolerance
- Poor _______
- Objective Signs
- Ra____
- ___/___ heart sounds
- Pleural e____
- Pulmonary e____
- Ch___ S____ respiration
- Peripheral e_____
- Hepato_____
- As_____
- J _ _
- Weight ____
- Subjective
- Dyspnea, Orthopnea
- Cough, Hemoptysis
- Nausea
- Bloating
- Fatigue -v nonspecific- we don’t really jump to HF
- Exercise
- appetite
- Objective
- Rales
- S3/S4
- effusion
- edema
- Cheyne Stokes
- edema
- megaly
- Ascited
- JVD
- gain
There’s no positive or negative test for HF, is a syndrome - BNP is another test you can use
+Heart Failure Management
Initial Tx =
- Short Term Benefits (____) -> decreased (3)
- Intermediate-term Benefits (____-____) -> decreased (3)
- Long-term Benefits (_____-_____) -> (1)*
Loop Diuretics
- days -> JVD, pulmonary congestion, peripheral edema
- weeks-months -> daily sx, improved cardiac function, increased exercise tolerance
- months-years -> No benefit on mortality
No relationship with mortality -> long term benefits ppl usually need increase in frequency and dose
Heart Failure Management
- Diuretic caveats
- Never use as the ____ therapy bc diuretics have __ effect on disease p____ or m_____
- If a pt has fluid overload, initiate and adjust therapy to result in _-_lb of weight loss per day
- ______ therapy should be adjusted to maintian a _____ state
- May _____ loop diuretic with another class (eg thiazide diuretic) for s_____ if needed
- Caveats
- only, no effect, progression, mortality
- 1-2
- Chronic, euvolemic
- combine, synergy
- With tx of HF think Polypharmacy - never a one and done*
- Diuretics are where we start for decongestion and symptom relief but def not where we stop*
Heart Failure: Pathophysiology and Pharmacology
- Mineralcorticoid (aldosterone) - receptor antagonist*
- Need COMBOS of these drugs*
+Vasodilators in HFrEF
Recommendations
The Clinical strategy of inhibition of the ______ _______ system with (1) or (1) or (1) in conjunction with evidence based (1) and (1) in selected patients, is recommended for pts with chronic HFrEF to reduce morbidity and mortality.
In patients with chronic symptomatic HFrEF NYHA class ___ or ___ who ______ an ACEI or ARB, replacement bt an ____ is recommended to further reduce morbidity and mortality.
Renin-Angiotensin, ACEI, ARB, ARNI, BB, Aldosterone antagonists
II, III, tolerate, switch to ARNI*
ARNI: Dual Neuroendocrine Inhibition
What does ARNI stand for?
What’s the Combo?
What does Neprilysin do? (3)
Why do we need an ARB?
Angiotensin Neprilysin Receptor Inhibitor (has dual endocrine system modultion bc its a combo)
Sacubitril + Valsartan
- Neprilysin usually breaks down NP, so inhibiting increases its favorable effects
- Neprilysin usually breaks down cardiotoxic ang II, so inhibiting leads to accumulation
- Neprilysin usually breaks down bradykinin, so inhibiting leads to accumulation of bradykinin -> angioedema
We need an ARB to combat accumulation of ang II
+Sacubitril/Valsartan: ARNI
- Indication
- Replaces:
- Greater reduction in?
- Starting dose is __/__ mg ____ daily
- _____ AE
- AVOID use with?* (separate by ___ hrs), why?
-
New standard of care for HFrEF “Entresto is Besto”
- ACEI or ARB
- mortality and hospitalization
- 49/51 mg twice daily
- Similar
- ACEI (36) bc combo of ARNI + ACEI = life threatening bradykinin accumulation -> angioedema
ACEI/ARB/ARNI: Monitoring
- C____ (up to 20% of pts)
- A______ (do not _____)
- _____ function (caution with unstable kidney function)
- P______ (weekly during initiation/titration)
- H______ (monitor closely during initiation/titration)
- Caution in:
- Aortic ______
- Bilateral r____ artery s______
- Advanced _____ disease
- H____kalemia ( K > ___ mEq)
- Cough
- Angioedema (x re-challenge)
- Renal ACEI are nephroprotective in LONG RUN not acute -> temporary rise in Serum Cr when initially dosed
- Potassium
- Hypotension
- Aortic Stenosis
- Renal, stenosis
- kidney
- Hyperkalemia (K >5mEq)
+Beta Blockers
Class I
- Use of __ of __ beta blockers is recommended for all patients with current or prior symptoms of HFrEF to reduce morbidity and mortality
- Long term tx with BB can:
- BB can prevent overall ____, the combined ___ of death or h_____, and s____ ____ death
- A clinical trial - proven beta blocker should be _____ as ____ as HFrEF is _____.
- 1 of 3
- lessen symptoms of HF and enhance pts overall sense of well being
- death, risk, hospitalization, sudden cardiac death
- initiated asap when diagnosed
- Use to be contraindicated bc its a negative inotrope so short term reduces contractility and makes them fatigued -> long term reduces mortality*
- Only 3 types of BB allowed in HF, unlike ACEI or ARB where you can use anything.*
+Which 3 Beta Blockers do we use in HF?
Carvedilol
Metoprolol Succinate (XL)
Bisoprolol
+Carvedilol Dosing
- Initial Dialy Dose
- Maximum Doses
- Mean Dose Achieved
- 3.125 mg BID
- 50 mg BID
- 37 mg/day
+Metoprolol Succinate (XL) Dosing
- Initial Daily Dose
- Maximum Doses
- Mean Dose Achieved
- 12.5-25mg daily
- 200mg daily
- 159mg/day
+Bisoprolol Dosing
- Initial Daily Dose
- Maximum Doses
- Mean Dose Achieved
- 1.25 mg daily
- 10 mg daily
- 8.6 mg daily
+Beta Blockers
- ___ ____ assume class effect!
- Start at very ___ doses and titrate ______ (every __ weeks)
- Monitor closely for:
- Aim for?
- Do not?
- DO NOT
- low, slowly, 2
- ADE
- Target doses although not many ppl can tolerate it
- X Abruptly discontinue
+Aldosterone Blockade
(2)
Spironolactone
Eplerenone
+Aldosterone Blockade
- Benefits of Spironolactone in class ___ and ___ HF include decreased _______, hospitalizations, and improved symptoms
- Benefits of Eplerenone (_____ aldosterone blocker) in class __ HF include decreased ______ and hospitalization.
- Used in ______ with other therapies
- Example _____ + ______ + ______
- III, IV, mortality
- (selective) II, mortality
- combination
- ARNI + Carvedilol + Spironolactone
Eplerenone -> doesn’t have SE of gynecomastia but both stll potassium sparing -> SO HYPERKALEMIA*! - must monitor, watch out for potassium rich foods, salt substitutes
Class III = sx during ADLs, Class IV = sx at rest
+Digoxin
- Benefits of digoxin include improved _____ and _____ tolerance, decreased h______
- No effect on?***
- Place in therapy: Should be considered in pts with symptomatic ___ _______, ______ optimal ACE inhibitor or ARB, B Blocker, spironolactone (if appropriate), and diuretic therapy
- May also be used tx of? (2)
- symptoms, exercise, hospitalizations
- MORTALITY X**
- LV dysfunction, despite all other meds
- Supraventricular Tachyarrhythmias (rate control), Afib
Digoxin Notes
- Dig toxicity Story =
- V _____ therapeutic index =
- Is now used as an?
- Van Gogh’s starry night from dig toxicity = blue green halo visual toxicity
- NARROW - so you can very easily get into trouble with dig, also lots of DI and SE
- ADJUNCT - when they run of out med options, they use dig, but dig is slowly getting pushed further away with new med discoveries
“If you can’t tell i hate dig - but old school cardiologists love this drug”
+Digoxin
MOA
- Na+ K+ ATPase inhibitor -> enhances Ca++ entry into the cell
- Slows HR (chronotropic effect) -> good for Afib
- Decreases central sympathetic outflow -> good for HF
+Digoxin PK
Elimination
Half Life
Renally eliminated -> NOT DIALYZABLE
Normal renal function = 36-40 hrs
Anuric patients = 5 days
We don’t like long half lives (hard to control)
+Digoxin
AE
Recently tied to worsened?
- N/V, Diarrhea, Abdominal Pain
- HA, visual disturbances (green/yellow “halos”)
- Cardiac arhythmias
- Increased Mortality (recent studies (not RCTs which is why we only say association)
+Digoxin
Treatment of life threatening digitalis toxicity?
Digibind
Digoxin
Significant Drug Interactions
- _____ of CYP 3A4
- _-_____ inhibitors
3 Medications
- Substrate
- P glycoprotein inhibitors
- Amiodarone (Inhibits P-glycoprotein, reduces dig by 50%) - def big problem bc amio is important
- Antacids (Decreases dig bioavail. by 20-35%, space doses 3 hrs apart)
- Verapamil (Inhibits P glycoprotein, reduces dig by 50%)
+Hydralazine-Isosorbide Dinitrate
- ______ mortality and hospitalizations
- Indication?
- decreases
- Alternative in pts unable to take ACEIs or ARBs bc of severe renal insufficiency, hyperkalemia, or angioedema
Old school combo
+Angiotensin II Receptor Blockers
- Have never been proved ____ to ACEIs
- An alternative for pts unable to take ACEIs bc of?
- X superior
- cough
+Ivabradine (Corlanor)
MOA
Indication
Does it reduce hospitalization and mortality?
SE (2)
Inhibits the “funny” current to slow HR
Used in HFrEF pts with elevated resting HR
Reduces hospitalization rates but NOT mortality
Bradycardia, Visual disturbances
IF current in SA node for depolarization, not rly used anymore
+Dapagliflozin
Indication
FDA approves new treatment for a type of Heart Failure
- (STL2 Inhibitor - good for DM and NOW cardiac risk)* Very recently approved and is the first time we’re giving a diabetes med not for diabetes
- Problem is its branded like ernesto -> copays are high for branded meds (pharmacoeconomics)*
+HFpEF
- Control _______
- Control _______
- Using (2)
- What medication has proved to reduce mortality or lower hospitalization?
- Hypertension
- Tachycardia
- BB
- Non-dihydropyridine CCB
- NO MED* - Is a highly prevalent orphan disease =(
ACS
Patho
Starts with deposition of Athersclerotic Plaques
- Fibrous cap -> ruptures -> clots -> NSTEMI -> infarction
- We’ve found that it begins early in life - but screening doesn’t really start till your 40
Platelet Activation
Agonist (3) -> Activates platelets
Activated Platlet is ____/___ ligand competent
Aggregating Platelets: _______ occupies GPIIIb/IIIa, forming ____ between adjacent platelets
GPIIb/IIIa _______ -> ______ Platelet aggregation
ADP, Thrombin, Epinephrine etc
GPIIb/IIIa
Fibrinogen, bridges
Antagonist -> Inhibits aggregation
- Platelets are usually good! But in setting of ACS, they start to stick together and become platelet clots (diff from red clots) -> so arterial clots -> seen in MI/Stroke*
- Platelets activated by many things - which is why we have to use lots of diff drugs (aspirin only blocks 1 pathway)*
+Antiplatelet Agents
(4)
COX inhibitors
Adenosine Diphosphate (ADP) - Receptor Antagonists
Adenosine reuptake inhibitors
Glycoprotein IIb/IIIa inhibitors
COX Inhibitors
(1)
MOA
Aspirin
Irreversible inhibition of platelet COX-1
Inhibits thromboxane A2 mediated platelet activation and aggregation
each platelet is born with some COX1
COX Inhibitors Pharmacokinetics
- Rapidly absorbed in s_____ and upper _____
- Platelet inhibition ___ hour(s) after ingestion
- Onset: ___ min
- Reversible platelet binding?
- Percent of platelet inhibition: ~ ____%
- stomach, upper intestine
- 1h
- 30min
- NO
- 20%
Glycoprotein IIb/IIIa Inhibitors
MOA
Inhibits formation of platelet thrombi by inhibiting activated receptors from binding with fibrinogen and forming bridges between activated platelets
Coagulation Cascade Patho
- Theres a common pathway factor __ - which many drugs work on*
- Anticoags work on different stages of the cascade*
- _____ has to be generated -> has to happen to stop hemorrhaging*
- 10*
- Thrombin*
+Heparin and LMWH
- One of the disadvantages of LMWH is less so reversable with protamine*
- Do have to renally dose adjust*
- Advantage causes less HIT*
+Factor Xa Inhibitors PK
disadvantage of the Xa inhibitors - CAN”T MONITOR efficacy or toxicity - on the other hand its an advantage bc their so predicable that we don’t need to know? (so more advantage)
Direct Thrombin Inhibitors PK
+Thrombolytic Agents
- “____ _____”
- Indications (3)
- Many contraindications
- Risk for _____
- ________ is historical standard
- _______ is new - _____ specific
- “clot busters”
- Acute MI, Stroke, Severe PE
- Bleeding
- Alteplase
- Tenecteplase, fibrin specific
- Only class that treats an active clot! (all others only prevent from growing)*
- Streptokinase came from bacteria,* Urokinase came from urine
- (all end in plase)*
Antithrombotic Therapy During PCI
- putting it all together*
- In PCI we need to block bleeding and clots*
