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Pharm: Pre Midterm 1 > Antianginal Drugs > Flashcards

Antianginal Drugs Flashcards

1
Q

What is the primary cause of angina?

A

Imbalance between the oxygen demand of the heart and the oxygen supplied to it via the coronary vessels

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2
Q

What is the cause of chest pain and discomfort in angina?

A

Coronary blood flow cannot deliver sufficient oxygen to support cardiac oxidative metabolism — myocardium becomes hypoxic
–triggers pain receptors in the heart

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3
Q

There are three types of Angina. The first is chronic stable angina. What is this caused by?

A

Chronic narrowing of coronary arteries due to atherosclerosis

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4
Q

What is the classification system for chronic stable angina?

A

Class:

0: asymptomatic
1: angina with strenuous exercise
2: Angina with moderate exercise
3: Angina with mild exertion: walking1-2 level blocks at a normal pace or climbing 1 flight of stairs at a normal pace
4. Angina at any level of physical exertion

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5
Q

The second type of angina is unstable angina. What is this caused by?

A

Transient formation and dissolution of a blood clot within a coronary artery

  • -in response to a plaque rupture in the coronary arteries
  • -coronary flow is reduced, leading to a reduction in oxygen supply
  • -if the clot completely occludes the coronary artery for a long period of time, the myocardium supplied by the vessel may become infarcted.
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6
Q

The third type of angina is Variant (Prinzmetal’s) Angina. What is this caused by?

A

Coronary vasospasm

–reduces coronary blood flow

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7
Q

What are the principles of antianginal therapy?

A

Short term goals: reduce symptoms that impair quality of life and exercise
Long term goals: prevent cardiovascular events and extension of life

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8
Q

In order to alleviate anginal pain oxygen supply/demand ratio has to be raised. How can this be achieved?

A

Increase blood flow (increase oxygen delivery or supply)
Decrease oxygen demand (decrease myocardial oxygen consumption)
–coronary vasodilators or anti-thrombotic drugs (increase oxygen delivery)
–vasodilators or cardiac depressant drugs (decrease oxygen demand)

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9
Q

Now going through the drugs to treat angina. The first are the vasodilators, calcium channel blockers (CCB). What are the clinical applications of these drugs?

A

Tx: HTN, angina, arrhythmias, chronic stable, unstable and Prinzmetal’s angina
–need to use beta blockers with CCB due to the reflex tachycardia

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10
Q

What is the MOA for CCB?

A

Block calcium channels on vascular smooth muscle, cardiac myocytes and cardiac nodal tissue
–reducing entry into the cells of Ca2+
Result:
vascular smooth muscle relaxation, decreased myocardial force and decreased heart rate

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11
Q

How do CCB drugs work for angina?

A

Vasodilator and Cardiodepressant Actions

  • -increase in oxygen supply
  • –reduction in oxygen demand
  • -dilate coronary arteries
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12
Q

The dihydropyridines are CCB. What is their role in angina control?

A

Little effect on cardiac conduction or heart rate
–used for their vasodilator effects
Used for variant angina

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13
Q

The non-dihydropyridines are Verapamil and Diltiazem. What is their role in angina control?

A

Verapamil:
–weak vasodilator but strong negative inotropic action therefore reduces oxygen demand by decreasing heart rate and contractility
–used for chronic stable, unstable and variant angina
Diltiazem:
–relieve coronary vasospasm by dilating coronary arteries
–used for variant angina

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14
Q

What are the adverse effects of the dihydropyridines CCB?

A 
Reflex tachycardia (nifedipine being the strongest) 
Dizziness, flushing, headache, hypotension, constipation, and peripheral edema
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15
Q

What are the adverse effects of Verapamil and Diltiazem CCB?

A

Cardiac conduction abnormalities: bradycardia, AV block
Anorexia, nausea, edema, hypotension
Constipation

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16
Q

What are contraindications when using a CCB?

A

Bradycardia
Conduction Defects
Heart failure

17
Q

Continuing with the vasodilating drugs are the nitrates (isosorbide dinitrate, isosorbide mononitrate, nitroglycerin and sodium nitroprusside). What are the clinical applications?

A

Variant Angina
Stable and Unstable Angina
–nitroglycerin: first line therapy for tx of acute anginal symptoms
—isosorbide mononitrate: orally for prophylaxis of angina
–sodium nitroprusside: used in ICU and emergency settings

18
Q

What is the MOA for the nitrates?

A

NO produced by the vascular endothelial cells — activates cGMP — inhibits Ca2+ entry into the cell — decreases intracellular Ca2+ concentrations — smooth muscle relaxation

19
Q

What are the important functions of NO?

A
  1. Relaxing vascular smooth muscle (Vasodilation)
  2. Inhibiting platelet aggregation (anti-thrombotic)
  3. Inhibiting leukocyte-endothelial interactions (anti-inflammatory)
20
Q

Do nitrates have more effect on veins or arteries?

A

Veins

–decrease venous pressure and ventricular preload this results in a decrease in oxygen demand by the heart

21
Q

Tolerance to nitrates develops rapidly, what is a way to help with tolerance?

A

Daily nitrate free interval of 10-12H

–removing the drug at night

22
Q

What are the adverse effects of the nitrates?

A

Hypotension: most serious toxicity
Reflex tachycardia: worsens angina by increasing oxygen demand
Headache: cerebral vasodilation
Facial flushing
Sodium nitroprusside: cyanide toxicity due to parent compound releases both NO and cyanide (tx with sodium thiosulfate infusion)

23
Q

What are the contraindications in nitrates?

A

Should not be taken alongside sildenafil
–inhibits breakdown of cGMP leading to an increase in cGMP levels leading to hypotension and impaired coronary perfusion.

24
Q

Moving on to the cardioinhibitory drugs are the beta blockers. Particularly in regards to angina, Propanolol, Metoprolol and Atenolol. What are the clinical applications?

A

Beta Blockers:
tx: HTN, angina, myocardial infarction, arrhythmias and heart failure
Angina: beta blockers are recommended in all patients with stable angina who have had an ACS or who have left ventricular dysfunction.

25
Q

What is the MOA of beta blockers?

A

1) decrease myocardial contractility, heart rate and cardiac output
2) Reduce renin secretion thus decrease circulating angiotensin II levels
–no reflex tachycardia
Antianginal effects:
-due to the negative inotropic and antihypertensive actions
–reduce work load thus reduce oxygen demand

26
Q

What are the adverse effects of beta blockers?

A 
Drug withdrawal: 
--abrupt cessation of beta blocker therapy may produce unstable angina, MI or even death in patients with coronary disease. 
--without coronary disease: tachycardia, sweating and generalized malaise due to increased blood pressure 
Cardiovascular Effects 
Disturb lipid metabolism 
Hypoglycemia 
Bronchoconstriction 
CNS effects
27
Q

What are the contraindications of a beta blockers?

A

Variant Angina:
–due to an oxygen supply problem
Beta blockers work by reducing oxygen demand
Reactive Airway Disease
Patients with sinus bradycardia and partial AV block
Heart Failure

28
Q

The next cardioinhibitory drug is Ranolazine, an Na channel blocker. What is the clinical application?

A

Alternative option for patients with chronic angina that have failed all other therapies

29
Q

What is the MOA for Ranolazine?

A

Blocks late inward Na channels
–prevents Ca2+ overload within the cell leading to improved coronary blood flow
NO effect on heart rate or arterial pressure

30
Q

What are the pharmacokinetics, adverse effects and contraindications for Ranolazine?

A 
Pharmaco:
--metabolized by CYP 3A4 
Adverse effects: 
--QT prolongation
Cointraindications: 
QT prolongation: risk of torsades de pointes and  ventricular tachyarrhythmias
31
Q

The last few cards will just be an overview of angina treatment. What is the acute and maintenance therapy for stable angina?

A

Acute:
Nitroglycerin or rest
Maintenance:
Long acting nitrates plus beta blockers
–Ca2+ blockers are used when beta blockers are unsuccessful
–Ranolazine is used when all above fails

32
Q

What is the treatment for unstable angina?

A

Relieve symptoms with rest or nitroglycerin

–long term therapy with nitroglycerin and beta blockers

33
Q

What is the treatment for Variant (Prinzmetal’s) Angina?

A

Symptoms respond to nitroglycerin and Ca2+ channel blockers

Pharm: Pre Midterm 1 (30 decks)

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