Coronary artery disease (CAD)

CAD

O2 supply vs. demand

supply = Flow x CaO2

• Q = P/R
• R - autoregulation; neural, local (adenosine)
• P - diastolic aortic pressure

demand = rate, inotropy, pressure, wall tension

• VO2 proportional to HR x Systolic BP (double product)

CAD

Fixed

• •Congenital anomalies
• •Vasculitides (collagen diseases)
• •Aortic dissection
• •Tumors
• •Scarring from trauma, radiation

Transient

• •Vasospasm
• •Embolus
• •Trombus in situ

Angina = Greek word ankhon (ἄγχω) meaning to strangle, throttle, or choke

• Classic (effort)
• Vasospastic or variant (Prinzmetal)
• Localized spasms associated with atheroma
• Unstable (medical emergency)
• Angina at rest or when it becomes longer or more frequent

Factors that Can Aggravate Myocardial Ischemia

Increased myocardial oxygen demand

• Tachycardia
• Hypertension 
• Thyrotoxicosis
• Heart failure
• Valvular heart disease
• Catecholamine analogues (eg, bronchodilators, tricyclic antidepressants)

Reduced myocardial oxygen supply 

• Tachycardia - reduces diastolic (flow) time
• Anemia
• Hypoxia
• Hypotension
• Smoking - produces HbCO

Treatment of CAD

1. Nitrates

Nitrates relax veins >>> arteries

• Increase venous capacitance
• Decrease preload
• Decrease pulmonary vascular pressure
• Heart size is decreased
• Decrease cardiac output
• Net:  decrease O2 demand, NOT increase O2 supply

•Dilate coronaries (normal individuals):

• Epicardial are sensitive (but not with concentric atheromas)
• Arterioles and precapillary spinchters are dilated least

Nitroglycerine is an arterial and venous dilator = reduces afterload and preload.

http://cvpharmacology.com/vasodilator/nitro.htm

Nitrates should not be used for right heart MI because reduced preload will worsen condition.

Adverse effects of nitrates

• Reflex tachycardia
• Increased myocardial O2 demand
• Decrease coronary perfusion (↓ diastole)
• Reflex increase in contractility
• Increased myocardial O2 demand
• formation of methemoglobin
• hypotension
• increase intracranial pressure
• tachyphylaxis (tolerance)

Other uses of nitrovasodilators

1.Hypertensive Emergencies: Na+ Nitroprusside

2.Congestive heart failure: isosorbide dinitrate + 

hydralazine

Congestive heart failure: isosorbide dinitrate + hydralazine (BiDil. Bi = two; Dil = dilators)

Na+ Nitroprusside

• Complex of cyanide, iron and nitrosomoiety

• Powerful, parentheral vasodilator. Rapid onset and dissapearance of action.

• Used for hypertensive emergencies and severe heart failure

• Dilates both veins and arteries

• Decreases peripheral resistance; ↔ or ↓cardiac output

• Rapidly metabolized in red blood cells; cyanide is metabolized by rhodanase, combined to less toxic thiocyanate in presence of a sulfur donor (thiosulfate). Thiocyanate is slowly eliminated by kidneys

• Side Effects:

1. Excessive decrease in blood pressure

2. Cyanide toxicity-to decrease risk co-administer thiocyanate or hydroxocobalamin

3. Thiocyanide toxicity in patients with renal failure (psychosis, seizures)

2. Beta blockers

-- ↓

Heart rate and 

contractility 

-- ↓

Cardiac Output

-- ↓

renin secretion

β1 selective blockers - name starts with letter A - M; e.g., metopralol = β1 blocker

Complications

1. bronchconstriction
2. decrease cardiac output
3. hypoglycemia
4. intermittent claudication
5. increase LDL decrease HDL
6. impotence
7. depression, sedation, nightmares
1. atenolol does not cross BBB - others do

The 70 year-old male patient being treated with dinitrate isosorbide returns to the 

family practice clinic because his angina pectoris symptoms have returned. He 

complains of palpitations. A decision is made to add metoprolol to his treatment 

regimen. The patient feels better a few days after the addition of this medication. 

What is the most likely mechanism responsible for the improvement in this 

patient’s condition:

A. Afterload reduction - no vasoconstricters

B. Coronary dilation - no beta receptors

C. Decreased heart rate

D. Increased renin levels  - decrease

E. Increased diastolic volume - not best choice

3. Ca channel blockers

Amlodipine (Norvasc (Pfizer) and generics) (as besylate, mesylate or maleate) is a long-acting calcium channel blocker dihydropyridine (DHP) class

• Slow, smooth onset of action
• •Long half life (once a day administration)
• •Antiatherogenic action (hyperlipidemia increases Ca2+
• influx to smooth muscle?). Decreased progression of 
• carotid atherosclerosis (but not coronary).
• •Reduced risk of major cardiovascular events
• •Minimum negative ionotropic effects (useful in patients 
• with LV dysfunction)

summary - angina drugs

4. Coronary revascularization

Compensatory Responses to Vasodilators - prevented by "polypharmacy"