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CPR II Exam 1 > Drugs for Angina/ACS > Flashcards

Drugs for Angina/ACS 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
Q

What are the anti-anginal mechanism of CCB’s in atherosclerotic (“classic”) angina?

A
  • Dilation of peripheral arterioles
  • ↓ PVR and afterload + ↓ BP (heart doesn’t have to work as hard)
26
Q

Which non-cardioactive (dihydropyridine) is the longest-acting?

A

Amlodipine

27
Q

Which group of CCB’s are more potent vasodilators?

A

Non-cardioactive (dihydropyridines)

28
Q

Why is there less orthostatic hypotension as an AE when using CCB’s for angina?

A

Arterioles are affected more than veins

29
Q

Which CCB’s lead to ↓ cardiac contractility and HR?

A

Cardioactive CCB’s (diltiazem and verapamil)

30
Q

Which CCB causes the greatest ↓ cardiac contractility, ↓ SA and AV node conduction?

A

Verapamil

31
Q

What is the therapeutic action of CCB’s in variant angina?

A

Dilation of coronary arteries relieves local spasm

32
Q

What are the major AE’s associated with cardioactive CCB’s?

A
  • Cardiac depression, arrest, and acute heart failure
  • Bradyarrhythmias, AV block
33
Q

Adverse effects associated with the short-acting dihydropyridine CCB’s?

A

Vasodilation triggers relfex sympathetic activation

34
Q

What is an AE of Nifedipine (immediate release) in pts w/ HTN?

Should use what type of dihydropyridine instead?

A
  • ↑ risk of MI in pts w/ HTN
  • Slow-release and long-acting (amlodipine) are better tolerated
35
Q

What are some of the minor AE’s associated w/ CCB’s?

A
  • Flushing, HA, anorexia, dizziness
  • Peripheal edema
  • Constipation
36
Q

What are the 4 beta-blockers indicated in tx of angina?

A
  • Propranolol
  • Nadolol
  • Metoprolol
  • Atenolol
37
Q

What is the major MOA of beta-blockers in tx of angina (i.e., HR, contractility, BP, O2 demand)?

A
  • ↓ HR —> improved myocardial perfusion and ↓ O2 demand at rest and during exercise
  • ↓ contractility
  • ↓ BP leads to ↓ afterload
38
Q

Withdrawl syndrome from beta-blockers is associated with what?

A

Sympathetic hyperresponsiveness

39
Q

What are 5 AE’s associated with beta-blockers?

A
  • ↓ cardiac output
  • Bronchoconstriction
  • Impaired liver glucose mobilization
  • Produce unfavorable blood lipoprotein profile (↓ HDL and ↑ VLDL)
  • Sedation, depression
40
Q

Beta-blockers are contraindicated in pts with what 5 conditions?

A
  • Asthma
  • Peripheral vascular disease
  • Type 1 diabetics on insulin
  • Bradyarrhythmias and AV conduction abnormalities
  • Severe depression of cardiac function
41
Q

What are 2 potential undersirable effects of using nitrates alone for angina?

A
  • Reflex ↑ in HR
  • Reflex ↑ in contractility
42
Q

What are 2 potential undesirable effects of using beta-blockers or CCB’s alone for treatment of angina?

A
  • ↑ end-diastolic volume
  • ↑ ejection time
43
Q

What is the rational for using a combo of nitrates w/ beta-blockers or CCB’s for angina?

A
  • ↓ 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
Q

What is the MOA of Ranolazine?

A

Inhibits late Na+ current in cardiomyocytes

45
Q

Ischemic myocardium is often partially in what state of polarization?

How do late Na+ channels contribute to this?

A
  • Partially depolarized
  • Late Na+ current is enhanced —> Ca2+ overload and repolarizaton abnormalities
46
Q

What is the rationale for using Ranolazine for tx of angina based on its MOA?

A

Normalizes repolarization of cardiac myocytes and ↓ mechanical dysfunction

47
Q

Ranolazine may reduce what 2 complications in the heart which contribute to angina?

A
  • Reduce diastolic tension and compression of coronary vessels in diastole
  • Reduce cardiac contractility and O2 demand
48
Q

What is the effect of ranolazine on HR, coronary blood flow, and peripheral hemodynamics?

A

No effect

49
Q

What are 2 indications for using Ranolazine for angina?

Especially in pts taking what medications?

A
  • Stable angina which is refractory to standard meds
  • ↓ angina episodes and improves exercise tolerance in pts taking nitrates or amlodipine, or atenolol
50
Q

Which class of drugs are the first line for variant angina?

A

CCB’s

51
Q

If CCBs are contraindicated (low BP, bradycardia, AV block) for tx of variant angina, what is used?

A

Long-acting (LA) nitrates

52
Q

What are 4 approaches for tx of stable (atherosclerotic) angina?

A
  1. Lipid-lowering therapy
  2. Lifestyle modifications
  3. Immediate release nitrates (SL or spray)
  4. Antiplatelet therapy (aspirin)
53
Q

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.

A
  • 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
Q

If pt with angina has low BP what 2 drugs can be used?

A
  • LA nitrate (oral, ointment or patch)

or

  • Ranolazine

CPR II Exam 1 (25 decks)

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