UAMS P2 - Therapeutics Exam 3 SG

Oxygen Supply and Demand relation to Athersclerotic CVD

An increase in Demand with a fixed decrease in supply (Demand >> Supply)

Modifiable Risk Factors of CAD

Tobacco, HTN, Dyslipidemia, DM, Obesity

______________ hallmark symptom of Ischemia

Chest pain

Diagnostic Testing Tools for CAD

ECG, Exercise Stress Test, Pharm Stress Test, Coronary Angiogram (gold standard but invasive operation)

Diet Modifactions to reduce CAD risk

Decrease intake of trans and saturated fats, Decrease Na+ In take to no more than 2300mg/day (lower is better, 1g/day = BP lowering effects), DASH diet

Components of a Successful weight management program

Reduced-Calorie Diet, Behavior Therapy, Increased Physical Activity

For Patients with CAD, How should the Following be Managed:

Diabetes:

Dyslipidemia:

HTN:

Diabetes: A1c Goal <7%, Metformin and SGLT-2 or GLP-1

Dyslipidemia: High Intensity Statin

HTN: Goal < 130/80 mmHg

___________ should not be used in Chronic Coronary Disease due to increased CV risk and potential interaction with ACEi and ARBs and restricts blood flow via the afferent arteriole.

NSAIDs

ACEi and ARBs Place in Therapy (not used at the same time though)

SIHD,

HTN,

Diabetes,

HFrEF,

CKD

Dosing range for Aspirin for patients with stable ischemic heart disease

75-162mg (indefinitely)

If a patient with Stable Ischemic Heart disease can't take Aspirin, what's an alternative?

Clopidogrel 75mg

When would Dual Antiplatelet therapy be used in CAD?

After Stent placement or acute coronary syndrome

Clopidogrel has Package Labeled CI with which PPIs?

Omeprazole and Esomeprazole

(Pantoprazole and Dexlansoprazole might be less risky)

What enzyme primarily converts Clopidogrel?

CYP2C19

T/F: For patients 60+, low dose aspirin use is recommended for patients with CVD risk for primary prevention

False - AGAINST low dose aspirin use for primary risk

Stent activates....

cytokines and growth factors that stimulate proliferation of smooth muscle cells, platelets, and macrophages

(Types: Bare metal and Drug-eluting)

Recommended Duration of Antiplatelet Therapy: Without Oral Anticoagulant, No PCI or >12months from Acute Coronary Syndrome

Aspirin indefinitely

Recommended Duration of Antiplatelet Therapy: Without Oral Anticoagulant, Prior Acute Coronary Syndrome with or without PCI

Dual Antiplatelet Therapy for 12 months then reassess

Recommended Duration of Antiplatelet Therapy: Without Oral Anticoagulant, With PCI and Low/Moderate bleeding/Ischemic risk

Drug Eluting Stent and Dual antiplatelet Therapy for 6 months, Single Antiplatelet Therapy indefinitely

Recommended Duration of Antiplatelet Therapy: Without Oral Anticoagulant, With PCI and High Bleeding Risk

Drug-Eluting Stent and Dual Antiplatelet Therapy for 1-3 Months,

P2Y12 for 6 months,

Single Antiplatelet Therapy indefinitely

Recommended Duration of Antiplatelet Therapy: With Oral Anticoagulant, With PCI and Low/Moderate bleeding/Ischemic risk

Direct Oral Anticoagulant/Clopidogrel/Asprin for <= 1 month,

Direct Oral Anticoagulant and Clopidogrel for 6 months,

Direct Oral Anticoagulant only indefinitely

Recommended Duration of Antiplatelet Therapy: With Oral Anticoagulant, With PCI and High Ischemic Risk

Direct oral Anticoagulant/Clopidogrel/Aspirin for 1 month,

Direct oral Anticoagulant and Clopidogrel for 1-6 months,

Direct oral Anticoagulant only indefinitely

Recommended Duration of Antiplatelet Therapy: With Oral Anticoagulant, No PCI

Direct oral Anticoagulant Indefinitely

Clinical Presentation of Coronary Heart Disease

Ischemia may present without signs or symptoms of angina,

Chest pain (main one) and reproducible with activity

Chronic Stable Angina Presentation

angina that involves a reproducible pattern of chest or other symptoms that appear after a specific level of exertion

A patient with CHD and an episode of chest pain <1 time per day would benefit best from

Short acting Nitrates

A patient with CHD and an episode of chest pain >=1 time per day would benefit best from

Maintenance: Beta Blocker, CCB, Long-acting Nitrate and a Short-acting Nitrate

In Antianginal Therapies, which classes/meds decreases myocardial oxygen demand?

Beta Blockers, Non-Dihydropyridine CCBs, Ivabradine

In Antianginal Therapies, which classes/meds increases arterial blood supply?

Nitrates and Dihydropyridine CCBs

Non-dihydropyridines should not be used:

pts wtih HF with reduced ejection fraction (HFrEF), with Beta Blockers (can cause bradycardia)

When to add Dihydropyridines in patients with Chronic Stable Angina?

Patients who are hypertensive and on a beta blocker already

When to add Ranolazine for patients with Chronic Stable Angina?

patients who are symptomatic after already being treated with Beta Blocker or CCB (or previous treatment)

Beta Blockers decreases

Myocardial Contractility and HR leading to Decreased Oxygen demand

Goals of Therapy with Beta Blockers for Chronic Stable Angina

Resting HR 50-60

Limit exercise

HR to 100 BPM

Beta Blockers should be tapered over

2-3 weeks to prevent withdrawal

Beta Blockers Cautions and Contraindications

Bradycardia,

Asthma/COPD (better to use Beta1 selective agents if the case),

Second and Third degree Heart block

Diltiazem and Verapamil are _________ CCBs

Non-dihydropyridine

________________________ CCBs are appropriate in patients with concurrent hypertension when HR lowering is not desired (beta blocker already in use).

Dihydropyridine

Beta Blockers ADEs

Mask the signs and symptoms of hypoglycemia,

Hypotension,

worsen HF,

bradycardia,

Heart block,

Bronchospasms,

Fatigue,

Sexual dysfunction

CCBs ADEs

Hypotension,

Headaches (dihydro),

Peripheral Edema (dihydro),

Flushing (dihydro),

Precipitate HF (non-dihydro),

SA or AV blocks or bradycardia (non-dihydro),

Constipation (verapamil)

Nitrates MOA

generates NO and stimulates guanylyl cyclase leading to venodilation and dilation of large arteries (high doses)

Nitrates Short-Acting Agents

Nitroglycerin SL or Spray

Who should be on Short-Acting Nitrates

All patients with CSA, for acute attacks

Long-Acting Nitrates

isosorbide dinitrate,

isosorbide mononitrate,

nitroglycerin ER,

transdermal patch or ointment

How to take Nitroglycerin SL

1 tab under tongue Q5mins PRN for chest pain (max doses of 3 in 15mins)

Nitroglycerin SL tab Storage

Keep in original dark glass container,

do not dispense or store with a safety cap,

do not store in the bathroom,

keep bottle with you at all times

Nitroglycerin Ointment and Patch interval duration:

12hrs (12 on, 12 off)

Which isosorbide can be taken up to TID if needed?

isosorbide dinitrate IR

Nitrates ADEs

Postural Hypotension, Headaches, Flushing (vasodilation), Nausea, Reflex Tachycardia, Rash, Potential Withdrawal

Nitrates is Contraindicated in patients on _____________ inhibitors

PDE5 (severe hypotension)

Timing interval of sildenafil or vardenafil with Nitrates

24 hours

Timing interval of tadalafil with Nitrates

48 hours

ranolazine (Ranexa) MOA

inhibit late inward Na+ current reducing Na+-depended Ca current during ischemic conditions

Ranolazine effects

No impact to HR, inotropic/hemodynamic states, or increase in coronary blood flow

Ranolazine place in therapy

For patients with receiving standard care (Nitrates, beta blocker, CCBs) and not having adequate benefit

ADEs of Ranolazine

Dizziness, Headache, Constipation, Nausea, Increase in QT interval

Monitoring parameters of Chronic Stable Angina

Every 1-2 Months,

HR and BP,

Frequency of SL nitro use and episode,

Exercise tolerance,

Risk factors,

adherence,

Normal Ejection Fraction

55-70%

HFrEF Factors

EF <= 40%,

Systolic HF,

problem pumping

HFpEF Factors

Diastolic dysfunction,

EF >= 50%,

Filling problem

Common Causes of HF

CAD,

HTN,

Diabetes,

Drug-Induced

Medications that Worsen HF - Negative Inotropic Effects

Antiarrhythmics,

Non-dihydropyridine CCBs,

Beta-Blockers,

Medications that Worsen HF - Cardiotoxic

Chemotherapy, Ethanol, Amphetamines

Medications that Worsen HF - Na+ and Water Retention

NSAIDs,

COX-2 Inhibitors,

Thiazolidinediones (ex: pioglitazone),

Glucocorticoids,

Androgens and Estrogens

Medications that Worsen HF - DPP4 Inhibitors

saxagliptin, alogliptin

BP is a product of

CO and SVR

Explain Frank-Starling Mechanism

ability of the heart to alter force of contraction depends on changes in preload

(Normal Heart: Increase preload = Increase CO but with HF,

Increase preload = little to no increase in CO)

Hallmark Symptoms of HF

Dyspnea, Fatigue, Fluid retention

Clinical Signs of HF

Elevated BNP (increase = increase HF severity),

Tachycardia,

Tachypnea,

Abnormal Heart sounds (extra sounds: S3 and S4),

Pulmonary Edema

Treatment Goals for HF

improve QOL,

relieve symptoms,

prevent/minimize hospitalizations from HF,

Slow/Reverse disease progression,

Prolong survival and reduce mortality

Non-Pharm Therapy

Diet:

- Na+ < 2g/day

- Water 1.5-2L/day

- Weight reduction if obese

Weight monitoring for volume status

Exercise:

- Increases exercise tolerance

Drug Therapy Targets for HF

Tachycardia and Increased Contractility,

Fluid retention and Increased Preload,

Vasoconstriction and Increased Afterload,

Ventricular hypertrophy and remodeling

(Target for Drug therapy to decrease them)

HFrEF Drug Therapy and Mortality Benefit

ACEi,

ARBs,

ARNI,

Beta Blocker,

Aldosterone Antagonists,

SGLT2 Inhibitors,

Hydralazine-isosorbide dinitrate

HFrEF Drug Therapy with Morbidity benefit Only

Digoxin and Ivabradine

HFrEF Drug Therapy with Improve Symptoms

Loop diuretics

Entresto (sacubitril/valsartan) class

ARNI

MOA of Entresto

Neprilysis Inhibitor (sacubitril) and ARB (valsartan),

sacubitril prevents breakdown of natriuretic peptides and other vasoactive peptides

Entresto recommended for patients with NYHA Class _______________

II - IV HFrEF (Chronic HF)

Entresto Monitoring parameters

Vital Signs (BP and HR),

Electrolytes (Potassium),

Renal Function (Serum Creatinine)

Patients with affordable ins coverage and HFrEF would benefit best from starting a(n):

ARNI (Entresto)

(it has better mortality benefit than ACEi)

Entresto Starting dose for patients on High-Dose ACEi/ARB

49/51mg BID

Entresto Starting dose for patients on Low-Medium dose ACEi/ARB

24/26 mg BID

Entresto Starting dose for patients not previously started on ACEi/ARB

24/26 mg BID

T/F: Patients with a history of Angioedema on an ACEi can be put on an ARNI instead

False - Contraindicated in patients with a history of Angioedema

Washout period for patients switching from ACEi -> ARNI (and vice versa)

36hrs

(not needed if patient was on an ARB)

ACEi Contraindications

Pregnancy,

Bilateral Renal Artery stenosis,

Hyperkalemia,

History of Angioedema

Monitoring parameters of Paitnets on ACEi

Renal function and K+ within 2 weeks of starting and when changing dose

Treating HF, Target dose: captopril

50mg TID

Treating HF, Target dose: enalapril

10-20mg BID

Treating HF, Target dose: fosinopril

40mg QD

Treating HF, Target dose: lisinopril

20-40mg QD

Treating HF, Target dose: perindopril

8-16mg QD

Treating HF, Target dose: quinapril

20mg BID

Treating HF, Target dose: ramipril

10mg QD

Treating HF, Target dose: trandolapril

4mg QD

Treating HF, Target dose: candesartan

32mg QD

Treating HF, Target dose: valsartan

160mg BID

Treating HF, Target dose: losartan

150mg QD

Place in therapy for patients on Beta Blocker and HF

For all stable patients withHF and reduced EF

3 Beta Blockers that have been shown to have beneficial effects in patients with HF

bisoprolol, carvedilol, metoprolol succinate