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2020 CPR II Cardio Exam 1 > Drugs for ACS and Stable Angina (Konorev) > Flashcards

Drugs for ACS and Stable Angina (Konorev) Flashcards

1
Q

What are the 3 nitrates (nitrovasodilators) used in chronic IHD?

A
  1. Nitroglycerin
  2. Isosorbide dinitrate
  3. Isosorbide mononitrate
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2
Q

Increasing coronary blood flow using vasodilators is useful in treating what kind of angina?

A

Vasospastic (Prinzmetal) angina

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3
Q

Why is Dipyridamole not useful in atherosclerotic (classic) angina?

A
  • “Coronary steal” phenomenon = redistribution of blood to non-ischemic areas
  • No substantial increase in coronary blood flow into the ischemic area
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4
Q

Which nitrate is a poor substrate of nitrate reductase in the liver and therefore has higher bioavailability?

A

Isosorbide mononitrate

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5
Q

Describe the rationale behind using sublingual, buccal, and transdermal routes of administration of nitrates, as opposed to oral administration of these drugs

A

Undergo significant first-pass metabolism - high nitrate reductase activity in liver = oral bioavailability is LOW

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6
Q

What is the crucial for the activation of nitrates to release nitric oxide?

A

Reduced thiols (ADH2) –> release NO from nitrates

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7
Q

Describe the role of nitric oxide in maintaining vascular tone?

A
  • Open K+ channel = hyperpolarization and reduced Ca2+ entry
  • NO activates guanylate cyclase –> ↑ cGMP –> ↑PKG –> Myosin-LC dephosphorylation –> smooth m. relaxation
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8
Q

Describe sensitivity of different types of vessels towards vasodilatory activity of nitrates, from greatest effect to least

A

Veins > Large arteries > Small arteries and arterioles

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9
Q

Nitrates used in the treatment of angina have a major effect of causing dilation of veins, which leads to what 2 therapeutic effects?

A
  • Increased venous capacitance
  • Reduced ventricular preload –> ↓O2 demand
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10
Q

`Higher concentratins of nitrates are needed to dilate arteries, which will have what 2 effects?

A

``- May reduce afterload

  • May dilate large epicardial coronary arteries
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11
Q

Nitrous oxide has effects beyond just vasodilation, describe some of the inhibitory effects.

A
  • Inhibits platelet aggregation
  • Inhibits monocyte adhesion
  • Inhibits smooth m. proliferation
  • Inhibits free radical formation
  • Inhibits LDL oxidation
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12
Q

Variant (Prinzmetal) angina is characterized by episodes of what (i.e., leading mechanism of injury)?

A

Episodes of vasoconstriction of coronary ateries

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13
Q

Major overall effect of nitrates is a decrease in?

A

Myocardial O2 demand

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14
Q

The development of tolerance to Nitrates is associated with what 4 events?

A
  1. Depletion of thiol compounds
  2. ↑ generation of superoxide radicals
  3. Reflex activation of sympathetic NS –> Tachycardia, ↓ coronary blood supply
  4. Retention of Na+ and H2O
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15
Q

Increased generation of superoxide radical depletes tissues of what?

A

NO

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16
Q

What are short-acting formulations of nitrates used for clinically?

Via which route of administration?

A
  • Used to relieve the angina attacks
  • Sublingual spray
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17
Q

What are long-acting formulations of nitrates used for clinically?

Via which route of administration?

A
  • Used to prevent attacks
  • Oral, ointment, or patch
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18
Q

Nitroglycerin comes in 3 long-acting formulations, which can be administered via which routes?

A
  • Oral
  • Ointment
  • Patch
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19
Q

What are 4 adverse effects associated with Nitrates?

A
  • Headache
  • Orthostatic hypotension
  • Increased sympathetic discharge –> Tachycardia + ↑ contractility
  • Increased renal Na+ and H2O reabsorption
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20
Q

Why are nitrates contraindicated if ICP is elevated?

A

Due to meningeal vasodilation

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21
Q

Which drug should nitrates not be used in combination with due to drug-drug interactions?

A

ED drugs –> Sildenafil, Vardenafil, Tadalafil

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22
Q

Combination of nitrates with drugs for ED (i.e., Sildenafil, Vardenafil, Tadalafil) cause what AE?

What serious AE has been reported?

A
  • Severe ↑ in cGMP and a dramatic ↓ in BP
  • Acute MI have been reported
23
Q

What are the 3 non-cardioactive (dihydropyridines) calcium channel blockers used in angina?

A

1) Amlodipine
2) Nifedipine
3) Nicardipine

24
Q

What are the 2 cardioactive calcium channel blockers used in angina?

A
  1. Diltiazem
  2. Verapamil
25
What are the anti-anginal mechanism of CCB's in atherosclerotic ("classic") angina?
- **Dilation** of **peripheral arterioles** - **↓ PVR** and **afterload** + **↓ BP (heart doesn't have to work as hard)**
26
Which non-cardioactive (dihydropyridine) is the **longest**-acting?
Amlodipine
27
Which group of CCB's are more potent **vasodilators**?
Non-cardioactive (dihydropyridines)
28
Why is there less orthostatic hypotension as an AE when using CCB's for angina?
**Arterioles are affected more** than veins
29
Which CCB's lead to ↓ cardiac contractility and HR?
**Cardioactive** CCB's (diltiazem and verapamil)
30
Which CCB causes the greatest ↓ cardiac contractility, ↓ SA and AV node conduction?
Verapamil
31
What is the therapeutic action of CCB's in **variant** angina?
**Dilation** of **coronary** arteries **relieves** local spasm
32
What are the major AE's associated with cardioactive CCB's?
- Cardiac depression, arrest, and acute heart failure - Bradyarrhythmias, AV block
33
Adverse effects associated with the short-acting dihydropyridine CCB's?
Vasodilation triggers **relfex** sympathetic activation
34
What is an AE of Nifedipine (immediate release) in pts w/ HTN? Should use what type of dihydropyridine instead?
- ↑ risk of MI in pts w/ HTN - Slow-release and long-acting (amlodipine) are better tolerated
35
What are some of the minor AE's associated w/ CCB's?
- Flushing, HA, anorexia, dizziness - Peripheal edema - Constipation
36
What are the 4 beta-blockers indicated in tx of angina?
- Propranolol - Nadolol - Metoprolol - Atenolol
37
What is the major MOA of beta-blockers in tx of angina (i.e., HR, contractility, BP, O2 demand)?
- **↓ HR** ---\> improved myocardial perfusion and **↓ O2 demand at rest and during exercise** - **↓ contractility** - **↓ BP** leads to **↓ afterload**
38
Withdrawl syndrome from beta-blockers is associated with what?
Sympathetic **hyper**responsiveness
39
What are 5 AE's associated with beta-blockers?
- ↓ cardiac output - Broncho**constriction** - Impaired liver glucose mobilization - Produce **unfavorable blood lipoprotein profile** (↓ HDL and ↑ VLDL) - Sedation, depression
40
Beta-blockers are contraindicated in pts with what 5 conditions?
- **Asthma** - Peripheral vascular disease - Type 1 diabetics **on insulin** - Bradyarrhythmias and AV conduction abnormalities - Severe depression of cardiac function
41
What are 2 potential undersirable effects of using nitrates alone for angina?
- Reflex ↑ in HR - Reflex ↑ in contractility
42
What are 2 potential undesirable effects of using beta-blockers or CCB's alone for treatment of angina?
- ↑ end-diastolic volume - ↑ ejection time
43
What is the rational for using a combo of nitrates w/ beta-blockers or CCB's for angina?
- **↓ HR** (avoids reflex ↑ seen in nitrates) - **No effect or ↓ EDV** (avoid ↑ associated w/ beta-blockers or CCB's) - **No effect** on **contractility** (avoid reflex ↑ seen in nitrates) - **No effect** on **ejection time** (avoid ↑ seen w/ beta-blockers or CCB's)
44
What is the MOA of Ranolazine?
Inhibits **late** Na+ current in cardiomyocytes
45
Ischemic myocardium is often partially in what state of polarization? How do late Na+ channels contribute to this?
- **Partially** depolarized - **Late Na+ current** is **enhanced** ---\> **Ca2+ overload** and repolarizaton abnormalities
46
What is the rationale for using Ranolazine for tx of angina based on its MOA?
**Normalizes repolarization** of cardiac myocytes and ↓ mechanical dysfunction
47
Ranolazine may reduce what 2 complications in the heart which contribute to angina?
- Reduce **diastolic tension** and **compression** of coronary vessels in diastole - Reduce **cardiac contractility** and **O2 demand**
48
What is the effect of ranolazine on HR, coronary blood flow, and peripheral hemodynamics?
No effect
49
What are 2 indications for using Ranolazine for angina? Especially in pts taking what medications?
- **Stable** angina which is **refractory** to standard meds - ↓ angina episodes and improves exercise tolerance in pts taking **nitrates** or **amlodipine**, or **atenolol**
50
Which class of drugs are the first line for **variant** angina?
CCB's
51
If CCBs are contraindicated (low BP, bradycardia, AV block) for tx of **variant** angina, what is used?
**Long-acting (LA) nitrates**
52
What are 4 approaches for tx of stable (atherosclerotic) angina?
1. Lipid-lowering therapy 2. Lifestyle modifications 3. **Immediate release nitrates** (SL or spray) 4. **Antiplatelet therapy** (aspirin)
53
If more than immediate release nitrates are needed for stable (atherosclerotic) angina what is the next in line? Describe the progression of treatment if more drug is needed.
- Beta blocker or alternative (CCB or LA nitrate) - **Add** CCB or BB (if not 1st drug) - Consider **triple therapy** (BB + CCB + LA nitrate or ranolazine)
54
If pt with angina has low BP what 2 drugs can be used?
- LA nitrate (oral, ointment or patch) or - Ranolazine

2020 CPR II Cardio Exam 1 (31 decks)

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