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Cardiovascular 2 > Drugs for Ischemic Heart Disease - Konorev > Flashcards

Drugs for Ischemic Heart Disease - Konorev Flashcards

1
Q

2 ways to treat angina pectoris

A
  • Decreased cardiac work (i.e. oxygen demand)

- Increase blood flow through coronary arteries

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2
Q

When are vasodilators most useful in treating angina?

A

Prinzmetal (vasospastic) angina

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3
Q

Coronary steal phenomenon

A

Why NOT to use vasodilators in atherosclerotic angina…

- Dilate un-blocked arterioles –> LESS collateral flow around block to blocked arterioles

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4
Q

4 determinants of myocardial oxygen demand (to be altered in angina)

A
  • HR
  • Contractility
  • Preload
  • Afterload
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5
Q

3 drug classes used in chronic ischemic heart disease

A
  • Nitrates (vasodilate)
  • CCBs (vasodilate, slow HR)
  • Beta-blockers (slow HR)
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6
Q

3 nitrovasodilator drugs

A
  • Nitroglycerin
  • Isosorbide dinitrate
  • Isosorbide mononitrate
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7
Q

Function of endothelium on vascular relaxation

A
  • Nitric oxide release w/ ACh or bradykinin stimulation
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8
Q

Describe N.O. release following stimulation of endothelium

A

Receptor –> calcium release –> calmodulin –> NOS active –> arginine converted to NO –> released onto SM

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9
Q

Molecular pathway of N.O. on muscle cell

A

Activates guanylyl cyclase –> cGMP –> K+ channel opens and myosin LC dephosphorylation –> hyperpolarization and SM relaxation

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10
Q

2 functions of nitrates at low concentration

A

Dilate VEINS and LARGE arteries, inhibit platelet aggregation

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11
Q

Benefit of nitrates vs. other vasodilators in atherosclerotic angina

A

No coronary steal phenomenon since arterioles not affected

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12
Q

MOA of nitrates in treating atherosclerotic angina

A
  • Dilate veins –> reduced preload
  • Dilate arteries –> reduced pressure
    EFFECT = DECREASED O2 DEMAND OF HEART
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13
Q

MOA of nitrates in treating vasospastic angina

A

Coronary artery relaxation

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14
Q

Most short acting formulation of nitrates

Used for?

A

Sublingual or spray nitroglycerin (10-30 min)

Relieving current attack

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15
Q

Most long acting formulation of nitrates

Used for?

A

Oral nitroglycerin or isosorbide (4-10 hours)

Prevent future attacks

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16
Q

3 ways to generate tolerance to nitrates

A
  • Increased oxygen free radical formation (combines to make H2O2 + O2)
  • Reflex sympathetics (tachy, vasoconstriction)
  • Na/H2O retention
17
Q

Adverse effects of nitrates

A
  • Headache (vasodilation)
  • Hypotension (orthostatic)
  • Sympathetic symptoms (tachy, HTN)
18
Q

Dangerous combination when treating elderly man with nitrates

A

Do NOT combine w/ E.D. drugs…

  • Nitrates + alpha-1 inhibitors (-afil) = BP DROP
  • Nitrates + alprostadil = cGMP increase –> BP DROP
19
Q

Non-cardioactive (DHP) CCBs

A
  • Amlodipine
  • Nifedipine
  • Nicardipine
20
Q

Cardioactive (non-DHP) CCBs

A
  • Diltiazem

- Verapamil

21
Q

Long-acting CCB

A

Amlodipine (30-50 hr half life)

22
Q

CCB MOA

A

Block L-type calcium flow into SM and cardiac muscle –> decreased myosin LC kinase activation –> decreased LC phosphorylation –> decreased contraction

23
Q

Non-DHP CCB MOAs in treating angina

A
  • Dilate ARTERIOLES + decreased contractility/HR –> decreased O2 demand of myocardium
  • Dilate coronary arteries –> vasospastic angina relief
24
Q

Immediate release CCB

A

Nifedipine

25
Q

4 beta blockers used for angina

A
  • Propranolol
  • Nadolol
  • Metoprolol
  • Atenolol
26
Q

MOA of beta blockers in angina

A

Decreased oxygen demand via decreased HR, contractility, and afterload

27
Q

Bad side effects of nitrates (2)

Correction?

A

Reflex tachycardia, reflex contractility increase

Combine w/ beta-blocker or CCB

28
Q

Ranolazine - MOA

A

Inhibits late Na+ influx in cardiomyocytes

29
Q

Describe how Ranolazine works against ischemic myocardium

A
  • Ischemic myocardium = enhanced late Na+ current = Ca++ overload = repolarization abnormalities
  • Ranolazine = normalizes repolarization, reducing dysfunction
30
Q

Benefits of Ranolazine

A

Doesn’t affect HR, contractility, coronary flow, or peripheral hemodynamics

31
Q

When is Ranolazine used?

A
  • Stable angina not controlled w/ normal meds

- Together w/ nitrates, amlodipine, or atenolol

32
Q

Adverse effects of Ranolazine

A
  • QT prolongation –> ventricular arrhythmias
  • Constipation
  • Nausea, dizziness, headache
33
Q

Drugs that alter Ranolazine metabolism

A

CYP3A4 inhibitors: Antifungal azoles, verapamil

34
Q

Drugs who’s metabolism is altered by Ranolazine

A

CYP2D6 substrates: Amitriptyline, Fluoxetine, Metoprolol, opioids

35
Q

Other drugs that prolong QT interval

A

Quinidine (anti-arrhythmic), Thioridazine (anti-psychotic)

Cardiovascular 2 (20 decks)

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