Pharmacology Test 2: Antianginal Drugs

Front 1

What is Stable Angina (effort/exertional angina)?

Back 1

- precipitated by physical activity
- chronic stable angina pectoris--exertional
- most common form of ischemic heart disease
Cause: coronary artery occlusion (atherosclerosis or stenosis)

Front 2

What is Variant Angina (prinzmetal angina)?

Back 2

- oxygen supply is decreased even if demand has not changed
- can occur at rest
Cause: coronary artery vasospasm

Front 3

What is Unstable Angina?

Back 3

- myocardial oxygen supply decreases or oxygen demand may increase if patient exercises
- occurs at rest and during exertion
- most serious and dangerous form of angina
Cause: atherosclerotic plaque rupture within the coronary artery

Front 4

Risk Factors for Ischemic Heart Disease

Back 4

- hypertension
- smoking
- hyperlipidemia
- hyperglycemia
- male
- post-menopausal females (b/c of estrogen decrease)

Front 5

Organic Nitrates: Mechanism of Action

Back 5

Main Effect: non-specific relaxation of smooth muscle, especially venous smooth muscle

Action: produced by nitrite (NO2) anion, liberated within cells when organic nitrates react with tissue sulfhydryl (-SH) groups

Within the cell, nitrite anions are converted to nitric oxide (NO) which activates the cytosolic form of the enzyme guanylate cyclase causing an increase in cGMP formation

cGMP activates protein kinase G and leads to a cascade of effects in the smooth muscle culminating in dephosphorylation of myosin light chains and sequestration of intracellular Ca2+, leading to relaxation

Front 6

Nitroglycerin

Back 6

Class: Organic Nitrate

Side Effects: headache hypotension with risk of fainting

-tolerance can develop if doses are given within 10-12 hours
-several formulations exist, including: extended release oral tablets, sublingual tablets, ointments, transdermal delivery system, intravenous
Contraindications: known hypersensitivity, hypotension or uncorrected hypovolemia, increased intracranial pressure (head trauma), inadequate cerebral circulation, constrictive pericarditis or pericardial tamponade severe anemia

*Should not be taken together with Phosphodiesterase 5 inhibitors (Sildenafil, Viagra)

Front 7

The Organic Nitrates

Back 7

Nitroglycerin
Isosorbide dinitrate (ISORDIL, SORBITRATE, DILATRATE-SR)
Isosorbide-5-mononitrate (IMDUR, ISMO)

Front 8

Isosorbide dinitrates

Back 8

Isordil
Sorbitrate
Dilatrate-SR

Front 9

Isosorbide-5-mononitrates

Back 9

Imdur
Ismo

Front 10

Isosorbide dinitrate and Isosorbide-5-monoitrate: Side Effects

Back 10

flushing methaemoglobinaemia (oxidation of Fe2+ to Fe3+, forming brown pigment that does not take up oxygen). Rarely serious and occurs only with a large dosage

*Should not be taken together with Phosphodiesterase 5 inhibitors (Sildenafil, Viagra)

Front 11

alpha-1 adrenergic receptors

Back 11

- Vasoconstriction
- Increase blood pressure
- Mydriasis-pupil constriction

Front 12

alpha-2 adrenergic receptors

Back 12

- Inhibit NE release
- Inhibit insulin release

Front 13

beta adrenergic receptors

Back 13

- Increase cardiac activity
- Vasodilation
- Bronchodilation
- Increases lipolysis
- Increases glucagon release

Front 14

Beta Adrenergic Blockers: Mechanism of Action

Back 14

- Blockade of sympathetic stimulation and of circulating adrenaline on myocardium, thus limiting in cardiac work during exercise or stress
- Reduce heart rate and increase time spent in diastole prolonging perfusion of the coronary arteries but increased filling
- Reduce the frequency of anginal attacks
- Decrease the incidence of myocardial infarctions in patients with coronary artery disease (CAD)
- So, they have a prophylactic and a therapeutic use
- May be administered orally or intravenously

Front 15

The Beta Adrenergic Receptor Blockers

Back 15

Metoprolol- specific beta-1

Atenolol- specific beta-1

Propranolol- nonspecific beta-1 and 2

Nadolol- nonspecific beta- 1 and 2

Front 16

Beta Blocker: Side Effects

Back 16

- Bradycardia and cardiac depression
- In pts. with peripheral vascular disease (PVD) and diabetes mellitus, a selective beta-1 antagonist is preferred
**Non-selective antagonists should be avoided in pts. with ASTHMA and other obstructive pulmonary diseases

Front 17

Calcium Channel Blockers: Mechanism of Action

Back 17

- Close the voltage-dependent-Ca2+ channels
- Depression of conduction and decreasing heart rate
- Depression of force of contraction, by limiting Ca2+ entry during plateau
- Reduced Ca2+ entry and inhibits ectopic beats
- Increased resistance to ischemic damage, due to reduction of cardiac work and possibly to inhibition of depolarization-induced Ca2+ entry, which is thought to initiate ischemic cell damage

Front 18

The Calcium Channel Blockers

Back 18

Nifedipine

Verapamil

Diltiazem

Front 19

Nifedipine

Back 19

Class: Calcium Channel Blocker (most common)

Side Effects: dizziness, flushing, headache, transient hypotension, peripheral edema

Major Drug Interactions: cimetidine (80% increase in nifedipine plasma levels)

Front 20

Verapamil

Back 20

Class: Calcium Channel Blocker

Side Effects: hypertension, constipation, bradycardia, AV conduction block, asystole

Major Drug Interactions: produce additive effects with other antihypertensive drugs and may potentiate cardiac effects of beta blockers

Front 21

Diltiazem

Back 21

Class: Calcium Channel Blocker

Side Effects: hypotension, AV conduction block, bradycardia

Major Drug Interactions: produce additive effects with other antihypertensive drugs and may potentiate cardiac effects of beta blockers

Front 22

Antiplatelet, Anti-Integrin, and Antithrombotic Agents

Back 22

- Aspirin reduces the incidence of MI and death in pts. with unstable angina (reduces mortality)
- In addition, low doses of aspirin appear to reduce the incidence of MI in pts. with chronic stable angina
- The addition of clopidogrel (Plavix, platelet inhibitor) to aspirin therapy reduces mortality in pts. with acute coronary syndromes (unstable angina)
- Heparins- inhibit coagulation by activating antithrombin III
- Glycoprotein IIb/IIIa inhibitors (ex: abciximab, tirofiban)--inhibit all pathways of platelet activation by inhibiting the glycoprotein IIb/IIIa receptor

Front 23

Combination Therapy: Nitrates + Beta Adrenergic Antagonists

Back 23

Nitrates attenuate adverse cardiovascular effects of the beta blockers, whereas beta blockers inhibit the tachycardia and positive inotropic effects of nitrates

Front 24

Combination Therapy: Nitrates + Calcium Channel Blockers

Back 24

Indicated in severe exertional or vasospastic angina; however, severe hypotension and vasodilation can occur

Front 25

Combination Therapy: Beta Adrenergic Blockers + Calcium Channel Blockers

Back 25

- Recommended in pts. with heart disease, but only when dihydropyridines (nifedipine, amlodipine) are used
- Diltiazem and Verapamil should not be considered with a beta adrenergic antagonist because of increasing risk of conduction blocks

Front 26

Other Pharmacological Approaches for the Treatment of Angina

Back 26

Dypiridamole

Nicorandil

Statins

Front 27

Dypiridamole

Back 27

Adenosine uptake inhibitor, not very effective

Front 28

Nicorandil

Back 28

Potassium Channel Activator

Front 29

Angina pectoris

Back 29

Chest pain due to inadequate delivery of oxygen to the cardiac muscle

Precipitating Factors: EXERCISE, EMOTIONAL STRESS, cold, meals, posture, smoking, or drugs

Results from ischemia of the myocardium

Front 30

Ischemia

Back 30

Deficient supply of blood to a body part (such as the heart or brain) that is due to obstruction of the inflow of arterial blood (b/c of the narrowing of arteries by spasm or disease

Front 31

Factors Controlling Coronary Circulation

Back 31

Arterial Pressure

Cardiac Cycle

Direct sensitivity of arterioles to anaerobic metabolites (adenosine and ADP)

Front 32

Angina is caused by the REDUCED CORONARY FLOW due to...

Back 32

Atherosclerotic occlusion (most common cause)

Coronary artery spasm (variant angina)