Title: Pharmacology CVS Final / Ischemic Heart Disease

Q: Categories of ischemic heart disease: (4)
A: 1. Fixed "Stable“, Effort  Angina
2. Variant Angina “Primary Angina”
3. Unstable Angina
4. Myocardial Infarction

Q: What is myocardial stunning?
A: Myocardial stunning is the reversible reduction of function of heart contraction after reperfusion not accounted for by tissue damage or reduced blood flow.

Q: The difference between secondary and primary angina: (7)
A: 1. In secondary angina it is classical while in primary angina it is variant (Prinzmetal's)
2. In secondary angina it is an angina of effort while in primary angina it is an angina of rest
3. In secondary angina it is typical while in primary angina it is atypical or variant
4. In secondary angina it usually occurs in small vessels while in primary angina it occurs in large vessels.
5. In secondary angina it can occur in a single or multiple vessels while in primary angina it occurs in a single vessel.
6. In secondary angina it is caused by atheroscelrosis while in primary angina it is caused by vasospasm
7. In secondary angina it is shown on the ECG as a ST depression while in primary angina it is shown on the ECG as a ST elevation.

Q: Explain control of smooth muscle contraction: (4)
A: ►Contraction is triggered by influx of calcium through L-type transmembrane calcium channels.
►Calcium combines with calmodulin to form a complex that converts the enzyme myosin light-chain kinase to its active form (MLCK*).
►MLCK* phosphorylates myosin light chains, thereby initiating the interaction of myosin with actin leading to contraction.
►Beta2 agonists (and other substances that increase cAMP) may cause relaxation by accelerating the inactivation of MLCK and by facilitating the expulsion of calcium from the cell.

Q: Major determinants of myocardial oxygen supply: (8)
A: 1. Percentage of oxygen extraction
2. Coronary blood flow
3. Aortic diastolic pressure
4. Coronary arteriolar resistance
5. metabolic autoregulation
6. Endocardial- epicardial flow
7. Coronary collateral blood flow
8. Large coronary artery diameter

Q: Major determinants of myocardial oxygen demand: (8)
A: 1. Wall tension
2. Ventricular volume
3. Radius or heart size
4. Ventricular pressure
5. Systolic pressure (afterload)
6. Diastoliic pressure (preload)
7. Heart rate
8. Contractility

Q: What is the collateral circulation:
A: It develops in later age, arteries grow to make a natural bypass towards the area of reduced blood flow

Q: Nitroglycerine (GTN): (4)
A: ►Prototype, used for more than 150 years.
►Nonspecific smooth muscle relaxant.
►Action is due to release of NO, leading to activation of guanylyl cyclase.
►Action not antagonized by any known antagonist.

Q: Administration of Nitroglycerine: (5)
A: ►Usually administered sublingually.
►Can be administered by various routes.
►Fast onset of action(1-3minutes, peaks at 10 minutes).
►Short duration (15-30minutes).
►Reductase enzyme, in liver, breaks down the drug.

Q: Nitroglycerine causes general vasodilation, explain its effect on arteriolar dilation: (3)
A: ► Short lived (5-10 min)
► Decreases systemic blood pressure (afterload).
► This can elicit the baroreceptor reflex to cause reflex tachycardia and increased contractility, and might increase MVO2.

Q: Nitroglycerine causes general vasodilation, explain its effect on venous dilation: (2)
A: ► More intense, even with low doses, lasts for 30 minutes.
►Decreases venous return (preload) and decreases MVO2.

Q: Potential beneficial effects of nitrates in the treatment of angina: (6)
A: 1. Decreased ventricular volume
2. Decreased arterial pressure
3. Decreased ejection time
4. Vasodilation of epicardial coronary arteries
5. Increased collateral flow
6. Decreased left ventricular diastolic pressure

Q: Potential deleterious effects of nitrates in the treatment of angina: (3)
A: 1. Reflex tachycardia
2. Reflex increase in contractility
3. Decreased diastolic perfusion time due to tachycardia

Q: Side effects of nitroglycerine: (6)
A: ► Headache.
► Hypotension  and tachycardia.
► Increased intraocular and intracranial   pressures.
► Methemoglobinemia.
► Tolerance: only for the arteriolar effects.
► Withdrawal: in workers in ammunition   industry.

Q: Actions of beta adrenergic blockers: (4)
A: ► Prevent actions of catecholamines, so more effective during exertion.
► Do not dilate coronary arteries, might constrict them.
► Do not increase collateral blood flow.
► Cause subjective and objective improvement

Q: The subjective and objective improvement beta blockers cause in ischemic heart disease: (4)
A: 1. Decreased number of anginal episodes
2. Nitroglycerine consumption
3. Enhanced exercise tolerance
4. Improved ECG.

Q: Actions of calcium channel blockers: (3)
A: 1. Particularly beneficial in vasospasm.
2. Can also affect platelets aggregation.
3. May be dangerous in the presence of heart failure and in patients susceptible to hypotension.

Q: Side effects of calcium channel blockers: (4)
A: ►Hypotension.
►Headache, dizziness.
►Flushing.
►Peripheral edema.

Q: MOA of Dipyridamole: (3)
A: ►Inhibits the uptake of adenosine and inhibits adenosine deaminase enzyme.
►Thought to be a good coronary dilator.
►Increases the blood flow to the normal area i.e.  “Coronary Steal Phenomenon”.
-->Still used as an antiplatelet drug (in TIAs), but not better than aspirin.

Q: Other treatments for ischemic heart disease: (5)
A: ►ACEI.
►Anticoagulants and/or Thrombolytic Therapy.
►Cholesterol Lowering Agents.
►Angioplasty
►Surgery.