Exam 1

Question 1

How can you choose whether to use beta blockers, organic nitrates/nitrites, or Ca2+ channel blockers when someone presents with angina?

Answer 1

Chronic stable angina & vasospasm angina:
- want to dilate coronary arteries, decrease oxygen demand, and decrease preload/afterload
- use organic nitrates, CCBs, b-blockers, and ivabradine

Question 2

How do beta blockers, organic nitrates/nitrites, and Ca2+ channel blockers impact pre-load, after-load, heart rate, and/or blood pressure in the treatment of angina?

Answer 2

beta blockers - decrease heart rate to decrease O2 demand (increase perfusion). Beta blockers also increase preload (which is bad).

organic nitrates/nitrites - dilates veins (decreases preload), dilates coronary arteries (small affect on afterload), small inhibition of platelet aggregation: decrease O2 demand

Ca2+ channel blockers - decrease heart rate/contractility and dilate vasculature, thus decreasing preload and afterload.

Question 3

Why do organic nitrates/nitrites have limited utility long-term?

Answer 3

• Tolerance develops with all organic nitrates. ALDH2 is inactivated in the mitochondria as nitroglycerin is broken down into NO, and it takes hours for this to be reversed.
• Due to this tolerance, patients must have a 10 hour nitrate free period.
• Nitrates do not impact disease progression, they are just used for symptom relief.

Question 4

What are the key molecular/cellular events that lead to ranolazine’s ability to control angina symptoms?

Answer 4

Ranolazine blocks late sodium channels that allow sodium to enter the myocyte. If too much sodium enters the myocyte, then the cell will want to exchange Na+ with Ca2+, resulting in too much Ca2+ in the myocyte. This causes contraction, increasing pressure and preload.

Question 5

What is pre-load and what does a decrease in pre-load do for O2 consumption and myocardial perfusion? What is after-load and how does dilation of arteries impact after-load? What does a decrease in after-load do to O2 consumption?

Answer 5

Pre-load: The amount of blood coming back to the heart.
- As preload decreases, O2 consumption decreases, which is good.
- As preload decreases, myocardial perfusion goes up.

After-load: The force of the ventricular wall when pumping the blood to the body.
- Dilation of arteries decreases after-load, which is good.
- Decrease in after-load decreases O2 consumption.

Question 6

What is the pathophysiology, clinical presentation, and clinical findings of the major syndromes of chronic coronary artery disease (stable angina, variant angina, etc.) How are the acute coronary syndromes different from stable ischemic heart disease?

Answer 6

Silent ischemia - shows no symptoms

Stable angina - associated with large single to multivessel ASCAD. The chest pain is caused by a fixed obstruction in an epicardial artery. (>70-75% occlusion is considered significant CAD)
- Due to an imbalance between supply and demand. Changes in myocardial function, but no necrosis.
- Seen from exertion. Can be resolved by rest and/or SL NTG. Feels like a substernal squeezing, heaviness, or tightening. Usually lasts less than 20 mins.
- ST-segment depression during ischemic event

ACS:
Unstable angina -

Non-ST Segment Elevation MI -

ST segment elevation MI -

Question 7

How do the drugs used in the management of coronary artery disease affect myocardial oxygen supply and demand?

Answer 7

Increase myocardial oxygen supply -
- somewhat nitrates do this, but nothing else

Decrease myocardial oxygen demand -
- Decrease heart rate: beta-blockers and nonDHPs
- Decrease myocardial contractility - beta-blockers and non-DHPs
- decrease intramyocardial wall tension by decreasing systolic BP (afterload) - DHPs (dilate arteries)
- decrease intramyocardial wall tension by decreasing preload - nitrates (dilate veins)

Question 8

What diagnostic tests are used when evaluating patients with CAD? (stable angina, SMI, variant angina)

Answer 8

Electrocardiogram - See ST segment depression during ischemia, see ST segment elevation in variant angina

Exercise Tolerance Testing - Used to diagnose ischemic heart disease

Cardiac catheterization and coronary angiography - invasive, but definitive, assessment of what’s going on in the coronary arteries.

Question 9

What are the differences in clinical presentation and clinical findings of stable angina, unstable angina, NSTEMI, and STEMI? (ex. history, symptoms, ECG changes, lab changes, etc.)

Answer 9

stable angina - angina upon exertion. Substernal discomfort. ST depression upon ischemic event. Predictable, relieved by rest, lasts a short time.

unstable angina - chest pain that may radiate, most often at rest. N/V, sweating, shortness of breath, etc. Pain doesn’t just go away. Normal ECG. There’s less ischemia here and it doesn’t lead to a detectable level of troponin.

NSTEMI - very similar to unstable angina, but troponin is elevated. May see ST depression.

STEMI - ST elevation, potentially Q wave changes; Expecting high troponin level (over 14ng/L or 0.05ng/mL)

Question 10

How do the drugs in the nitrate class differ from one another?

Answer 10

short term nitroglycerin is used for acute attacks
- SL tabs, spray, powder, buccal tabs

isosobide DN chewable/sublingual used for acute attacks

NTG SR tabs, ointment, patch used for long term

ISDN & ISMN tabs for long term

Question 11

How do the drugs in the beta blocker class differ from one another? (b1, mixed, nonselective, ISA, renally vs. hepatically eliminated)

Answer 11

acebutolol, atenolol, betaxolol, bisoprolol, metoprolol - b1 selective (cardioselective)

carvedilol, labetalol - mixed selectivity, including alpha receptors

nadolol, pindolol, propranolol, timolol - nonselective

pindolol & acebutolol - ISA (partial agonists)

atenolol, bisoprolol, nadolol, pindolol - renally eliminated (water soluble)

carvedilol, labetalol, metoprolol, propranolol, pindolol - hepatically eliminated (lipid soluble)

Question 12

How do the drugs in the calcium channel blocker class differ from one another?

Answer 12

DHPs - see reflex tachycardia, strong peripheral vasodilation and decent coronary vasodilation
- Never give short acting nifedipine or nicardipine to CAD pts due to reflex tachycardia

Verapamil - decrease HR, contractility, decent peripheral vasodilation, and slight coronary vasodilation

Diltiazem - decent reduction in HR, contractility, and peripheral/coronary vasodilation

Question 13

What are the benefits of anti-platelet therapy in the prevention of coronary artery disease events?

Answer 13

ASA - at a low dose, it blocks the formation of TXA, which is a platelet aggregant and vasoconstrictor.

P2Y12 inhibitors - inhibit ADP induced platelet aggregation (no effect on TXA)

Question 14

What is the mechanism, clinical significance, and treatment options for nitrate tolerance?

Answer 14

There’s a decrease in response to nitrates pretty quickly due to inhibition of ALDH2.

We want a 10-12hour nitrate free period to prevent nitrate tolerance.

Question 15

What are reasons why we would choose one therapy over another in terms of MOA, adverse effects, and drug interactions?

Answer 15

Nitrate - use to relieve angina symptoms. Promotes relaxation of veins. Causes headaches, dizziness, and reflex tachycardia. Short-term NTG used for acute attacks, not for long term use. Drug interaction with PDE5i. Use long-term nitrates in combo with BBs/CCBs

Beta blockers - To prevent recurrent ischemia/angina. Reduces HR, contractility, and arterial BP (afterload). Don’t use if HR is lower than 60. Use these first, unless vasospastic angina or conduction disturbances.

nonDHP CCBs - To prevent recurrent ischemia/angina. Have similar effect as beta-blockers. Use these if no beta-blockers!

DHP CCBs -To prevent recurrent ischemia/angina. Main effect is on peripheral and coronary vasodilation.

ranolazine - last line. Only use in combination if there’s been an inadequate response to monotherapy. Has lots of drug interactions (3A4 inhibitors). Shown to increase QT interval.

Question 16

Why or why not would we use certain risk reduction therapies in patients?

Answer 16

• ASA 75-162mg - indefinitely reduces chance of clot without too high of bleeding risk
• ACEi/ARBs - Decrease CV events in high-risk patients. Should especially be considered if pt has LVEF <40%, HTN, DM, or CKD
• Statin - high intensity statin needed in all pts with CAD
• beta blockers - no data to suggest this helps, except if the pt is post-ACS and HFrEF

Question 17

What would be the general treatment plan for chronic ischemic heart disease and variant angina?

Answer 17

Stable angina (chronic IHD):
- Modify risk factors (lifestyle, immunizations, comorbidities, antiplatelet therapy, ACE inhibitor)
- SL NTG for acute attacks
- If vasospastic (variant) angina -> add LA nitrate if BP is <130/80; add CCB is BP >130/80
- If not vasospastic -> add beta blocker (2. non-DHP CCB) if HR >60 bpm
- If not controlled, add ranolazine or LA nitrate if BP is <130/80; add DHP CCP if BP >130/80
- Consider PCI (+ BMS or DES) or CABG if still not controlled

Question 18

What are our treatment goals for these cardiovascular risk factors: dyslipidemia, hypertension, diabetes, smoking, weight management, physical activity

Answer 18

dyslipidemia - ≥50% reduction in LDL

hypertension - <130/80 mmHg

A1c - <7%

smoking - complete cessation

weight management - BMI 18.5-24.9; weight loss of 5-10% initially

physical activity - 30-60 mins of moderate intensity exercise 5-7 days/week

Question 19

How can you differentiate between unstable angina, non ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction?

Answer 19

Unstable angina - less ischemia, doesn’t lead to detectable quantities of troponin, can sometimes be relieved by SL NTG

NSTEMI - troponin is elevated, but no ST elevation on ECG

STEMI - troponin is elevated and ST elevation on ECG

Question 20

What pharmacologic classes are used to treat ACS? When do we use them?

Answer 20

Fibrinolytics - Use this during reperfusion, but not usually preferred. Only preferred if more than 120mins from PCI hospital. If done, needs to be done w/in 30 mins.

Antiplatelets - Loading dose of aspirin (162-325mg) used immediately. Then ASA 81mg daily to be continued daily. Use P2Y12i for 12 months with ASA 81mg for DAPT if STEMI/NSTEMI/UA

GP IIb/IIIa inhibitors - use in addition to ASA and P2Y12i during PCI if the pt is reforming a clot really fast

Anticoagulants - Use in addition to antiplatelet therapy to improve vessel patency and prevent re-occlusion

Beta blockers - Start within 24 hours of ACS unless contraindicated. Use metoprolol succinate, carvedilol, or bisoprolol in pts with HFrEF. Want to use cardioselective for most ACS pts (BAMAN)

nonDHP CCBs - Use for patients with recurrent ischemia and contraindication to beta blockers, but not standard for ACS

ACEi/ARBs - Use for all patients, but especially those with DM, HFrEF, or CKD.

Statins - Need every patient on high intensity statin

Nitrates - Immediate release/IV used to treat acute chest pain. Do this right away. Also PRN nitroglycerin life-long.

Question 21

What are precautions/indications for the pharmacologic agents we use for ACS, and what should we monitor?

Answer 21

Fibrinolytics - Has strict rules on when to use.

Antiplatelets - Watch for bleeding. Prasugrel cannot be used with hx of stroke.

Anticoagulants - Heparin has risk of HIT. LMWH has lower risk of HIT. LMWH is renally eliminated, so look at CrCL. Fondaparinux is contraindicated if CrCL is < 30mL/min.

Beta blockers - Don’t want to start/increase during HF exacerbation. We like cardioselective beta blockers (HFrEF likes metoprolol succinate, carvedilol, or bisoprolol)

ACEi/ARBs - Watch for hypotension or renal dysfunction w/in the first 24 hours. Need to monitor SCr (expect to rise 20-30%, but not more than that), potassium (raise), BP (lower), angioedema

Statins - Watch for muscle pain. Get a lipid panel.

Nitrates - Side effects include headache and hypotension. Monitor BP

Question 22

What are the similarities and differences among the antiplatelet and thrombolytic agents? What are the pros and cons of these?

Answer 22

Thrombolytic agents are very expensive. Some absolute contraindications include intracranial hemorrhage, hx of ischemic stroke w/in 3 months, active bleeding, cerebral vascular malformation/malignancy, head/facial trauma w/in 3 months
- Pros: best option when PCI hospital is more than 2 hours away

Antiplatelets - These don’t break up clots, but they prevent clots from forming. Clopidogrel is a prodrug, but it’s the cheapest P2Y12 inhibitor. Ticagrelor is more potent, but has a higher risk of bleeding (max dose of aspirin w ticagrelor is 81mg daily)

Question 23

What is the general therapeutic plan for a patient with UA, NSTEMI, or STEMI?

Answer 23

1. ECG & troponin within 10 mins of arrival (then troponin again after 3-6 hours)

For STEMI & UA/NSTEMI:
1. MONA (w/in 30 mins)

STEMI:
1. Reperfusion - PCI (preferred, do w/in 90 mins) or fibrinolytic
2. Antiplatelets - 12 months DAPT = ASA + P2Y12i (if PCI, ticagrelor or prasugrel preferred; if fibrinolytic, clopidogrel preferred) +/- GPIIb/IIIa inhibitor
3. Anticoagulation - UFH or bivalirudin

UA/STEMI:
1. Reperfusion - ischemic guided strategy (if to old/frail/etc. for heart cath) or early invasive strategy (no fibrinolytic)
2. Antiplatelets - 12 months DAPT = ASA + P2Y12i (ticagrelor or prasugrel preferred) +/- GPIIb/IIIa inhibitor
3. Anticoagulation - LMWH or UFH

Both post-acute: beta-blocker, ACEi/ARB, statin, nitroglycerin PRN

Question 24

What is the recommended pharmacotherapy regimen for secondary prevention of MI and why?

Answer 24

• Beta blocker within 24 hours (nonDHP CCB if contraindicated)
• High intensity statin
• ACEi/ARB (especially if DM, CKD, or HFrEF)
• DAPT (maybe triple if at every high risk of clot)
• Nitroglycerin PRN

Question 25

What is troponin and what values are normal?

Answer 25

Troponin is released from injured heart cells into the bloodstream, so when they are detected, that means myocytes are not receiving adequate blood flow.

High sensitivity troponin - ng/L
- Normal is < 14ng/L

Conventional troponin - ng/mL
- Normal is <0.05ng/mL

Question 26

What does a TIMI score represent?

Answer 26

TIMI - Thrombolysis in Myocardial Infarction Risk Score
- Represents risk of experiencing either death, myocardial infarction, or urgent need for revascularization within 14 days

Question 27

How do we use MONA to treat patients with ACS?

Answer 27

Morphine - for chest pain. (**avoid NSAIDs besides ASA)
- Initial dose 4-8mg IV, then 2-8mg IV q5-15min
- Side effects include sedation, respiratory depression, N/V

Oxygen - Make sure oxygen is above 90%

Nitrates - Give SL NTG 0.3-0.4mg q5 mins x3 for continuing ischemic pain. Use IV NTG for persistent ischemia, HF or HTN
- Initial IV dose is 10mcg/min, titrate PRN for chest pain
- Side effects include headache and hypotension

Aspirin -
- 162-325mg loading dose once

Question 28

What are the correct loading doses & maintenance doses for antiplatelets? When should you not use certain P2Y12 inhibitors?

Answer 28

aspirin - 325mg loading dose once, then 81-325mg per day indefinitely

clopidogrel - 300-600mg loading dose (if using fibrinolytic: 300mg loading dose if under 75yo, no loading dose if over 75yo), then 75mg daily; Should be used if fibrinolytic is used, but not if PCI

ticagrelor - 180mg loading dose, then 90mg BID

prasugrel - 60mg loading dose, then 10mg daily; Not used for ischemia guided strategy, CI with hx of TIA/stroke, or pts over 75, under 60kg, or high bleeding risk

**hold all P2Y12 before elective CABG (ticagrelor 3 days, clopidogrel 5 days, prasugrel 7 days); hold for 24h before urgent CABG if possible

Question 29

What anticoagulants do we use to treat ACS and when? (NSTEMI - ischemia guided strategy, early invasive strategy; STEMI - fibrinolytic, PCI)

Answer 29

Heparin - Anti-Xa and anti-IIa activity; Can use for ischemia guided strategy for 48 hours, early invasive strategy until PCI, when using a fibrinolytic for 48 hours, and up until giving PCI.
- If HIT is suspected, calculate 4T score (timing, <50% platelets, thrombosis, other causes)

LMWH - Anti-Xa and anti-IIa activity; Can use for ischemia guided strategy for up to 8 days, until PCI for early invasive strategy, and for up to 8 days if using a fibrinolytic.
- Cannot use for PCI if patient has a STEMI

Bivalirudin - Direct thrombin inhibitor; Can use until PCI for early invasive strategy and until PCI for STEMI patients. Not used with GPIIb/IIIa inhibitors, unless to bail out. May be less effective than heparin but lower bleeding risk
- Not used for ischemia guided strategy or thrombolytic-STEMI (may consider using for HIT if using fibrinolytic (STEMI))

Fondaparinux - Factor Xa inhibitor; Can use for up to 8 days for ischemia guided strategy and if using a fibrinolytic (STEMI) for up to 8 days. Not commonly used, but can use if pt has a history of HIT. Never use this alone (needs heparin or bivalirudin of pt is getting PCI). Contraindicated if CrCL <30mL/min