Antianginal Drugs

Question 1

Angina

Answer 1

symptom, not a disease!

• chest pain caused by accumulation of metabolites due to ischemia
• squeezing, pressure, heaviness or tightness
• most common cause = CAD

Question 2

Primary Cause

Answer 2

imbalance between O2 requirement and O2 supplied

Question 3

Classic Angina

Answer 3

“effort angina” - inadequate flow in presence of CAD

Question 4

Prinzmetal Angina

Answer 4

“vasospastic” - transient spasm of localized portions of coronary vessels (underlying atheromas)
- can have nocturnal episodes –> increase in VR triggers alpha-adrenergic vasospasm

Question 5

Unstable Angina

Answer 5

“Acute Coronary Syndrome”

• episodes occur at rest
• increased severity, frequency, duration of pain (progressive worsening)
• imbalance occurs when there is reduced blood flow due to partially occlusive thrombi
• increased risk of MI and sudden death

Question 6

Theory behind treating angina???

Answer 6

REVERSE THE IMBALANCE!!

• classic angina = decrease cardiac work and shift demands
• prinzmetal angina = reverse spasms, treat atherosclerosis
• unstable angina = BOTH (more aggressive approach)

Question 7

Determinants of Myocardial O2 demand

Answer 7

1. Ventricular Wall Stress
2. Heart Rate
3. Contractility
4. Basal Metabolism

Question 8

Ventricular Wall Stress

Answer 8

• tangible force acting on myocardial fibers (stretching)
• energy is expended to resist that force!
  VWS = (P x r) / 2h
  increase VWS = increase O2 consumption (stenosis, hypertension)
  augment LV filling = raise VWS and O2 consumption
  inversely proportional to wall thickness

Question 9

Heart Rate and O2 consumption

Answer 9

Increased HR = increased contractions per minute = increased ATP consumed per minute = increased O2 consumption

Question 10

Contractility and O2 consumption

Answer 10

greater force of contraction = greater O2 consumption

Question 11

Systolic Wall Stress

Answer 11

arteriolar tone directly controls peripheral resistance and arterial BP

Question 12

Diastolic Wall Stress

Answer 12

venous tone determines capacity of venous circulation and location of blood sequestration

Question 13

All anti-anginal drugs

Answer 13

ALL HELP DECREASE MYOCARDIAL O2 DEMAND

Question 14

Nitrates

Answer 14

can develop tolerance with chronic use
MOA: release NO in smooth muscle –> activates guanylyl cyclase –> increase cAMP
Effects: smooth muscle relaxation (preference to veins)
- decrease preload, decreased pulmonary vascular resistance, decreased LV end-diastolic pressure
- high first pass metabolism (use sublingual - smaller dose)
- Drug interaction with PDE inhibitors (type 5)

Question 15

Isosorbide dinitrate

Answer 15

same as nitro

- slightly longer duration of action

Question 16

Isosorbide mononitrate

Answer 16

same as nitro

- used for oral prophylaxis

Question 17

Ca2+ channel blockers

Answer 17

blockade of Ca2+ channels causes muscle relaxation

• orally active agents
• high first pass effect
• high plasma protein binding
• extensive metabolism

Question 18

Verapamil and Diltiazem

Answer 18

MOA: nonselective L-type blockers in vessels and heart
Effects: reduced vascular resistance, HR, contractility –> decreased O2 demand
Use: prophylaxis of angina, hypertension
Tox: AV block, heart failure, additive with other cardiac depressants

Question 19

Nifedipine

Answer 19

MOA: blocks vascular L-type channels
Effects: like Verapamil and diltiaze, but less cardiac effects
Use: prophylaxis of angina, hypertension

Question 20

beta-blockers

Answer 20

Extremely useful for managment of classic angina

• decreased HR, blood pressure, contractility –> decreased O2 demand
• improved survival and prevention of stroke in patients with HTN
• contraindicated with asthma, bradycardia, AV block

Question 21

Propranolol

Answer 21

• beta-blocker (nonselective)
• decreases HR, BP, CO –> decreased O2 demand
• asthma, AV block, and acute heart failure are toxicities

Question 22

Atenolol and Metoprolol

Answer 22

• beta-1 selective blockers, less risk of bronchospasm