M3 L3: antianginals

Question 1

Coronary artery disease (CAD)

Answer 1

• narrowing or blocking of coronary arteries -> decreased blood flow -> decreased O2 supply to the heart

Question 2

manifestations of CAD

Answer 2

• asympt
• angina pectoris
• myocardial infarction (MI)
• complications: HF, dysrhythmias, etc
• sudden death

Question 3

angina pectoris

Answer 3

sudden onset chest pain due to myocardial ischemia

Question 4

types of angina

Answer 4

1. typical (exertional)
   - chest pain w exertion
   - due to coronary obstruction
   - 2 patterns: stable, unstable (more dangerous -> MI)
2. variant (prinzmetal’s)
   - chest pain at rest
   - due to coronary vasospasm

Question 5

factors affecting anginal pain

Answer 5

• precipitating factors: exertion, stress, heavy meals. cold weather
• relieving factors: rest, nitrates

Question 6

treatment of angina

Answer 6

rest
antianginal drugs

rationale:
- maintain the balance btwn O2 supply and demand

Question 7

antianginal drugs

Answer 7

• organic nitrates
• β blockers
• calcium channel blockers

vasodilators: nitrates, calcium blockers
cardiac depressants: calcium blockers, beta-blockers

Question 8

organic nitrates

Answer 8

• esters of nitric oxide (NO)
• short acting: glyceryl trinitrate (= nitroglycerin - GTN)
• long acting: isosorbide dinitrate, isosorbide mononitrate

Question 9

mechanism of action of treatments for angina

Answer 9

• nitrates ->reduction-> nitric oxide (NO) -> increased GC -> converts GTP -> cGMP -> increased PKG -> decreased intracellular Ca2+ ->
• relaxation of smooth muscles of BV ->
• vasodilation - venous, coronary, arteriolar

Question 10

venous dilation

Answer 10

decreased
- venous return (preload)
- cardiac output (CO)
- myocardial work
- myocardial O2 demand

Question 11

coronary dilation

Answer 11

increased
- blood supply to heart
- perfusion
- O2 supply to ischemic myocardium

Question 12

arteriolar dilatation

Answer 12

decreased
- peripheral resistance (afterload)
- bp

Question 13

adverse effects of angina treatments

Answer 13

• headache
• flushing
• hypotension
• tachycardia
• dizziness
• methemoglobinemia
• tolerance!

Question 14

angina drug tolerance

Answer 14

due to continuous exposure
prevention: nitrate-free periods (overnight)
monday disease!

Question 15

what happens when nitrates are mixed w PDE5 (ex: sildenafil) decrease

Answer 15

severe hypotension

Question 16

rapid onset routes of administration

Answer 16

sublingual tablets
oral spray
IV

Question 17

slow onset routes of administration

Answer 17

oral tablets
ointment
transdermal patch

Question 18

what route of administration for GTN

Answer 18

any route except oral

Question 19

how do you prepare isosorbide dintrate

Answer 19

sublingual or oral tablets

Question 20

isosorbide monontrate

Answer 20

oral tablets

Question 21

mechanism of action for calcium channel blockers

Answer 21

• block L-type voltage-gated Ca2+ channels
• prevent Ca2+ flow into:
  1. vascular smooth muscles -> vasodilation
• arteries rather than veins
• coronaries are particularly sensitive
  2. cardiomyocytes
• decreased cardiac contractility
• (-‘ve inotropic) -> decreased CO

Question 22

classes of CCB

Answer 22

1. dihydropyridine
   - more vascular selective (ex: nifedipine)
2. phenylalkylamine
   - more myocardial selective (ex: verapamil)
3. benzothiazepine
   - balanced (ex: diltiazem)

Question 23

adverse effects of CCB

Answer 23

• myocardial depression (verapamil, diltiazem)
• hypotension (nifedipine)
• changes in heart rate (increased HR [nifedipine], decreased HR [verapamil, diltiazem])
• flushing
• ankle edema
• headache

Question 24

therapeutic indication for angina

Answer 24

diltiazem, verapamil

Question 25

therapeutic indication for hypertension

Answer 25

nifedipine, diltiazem

Question 26

therapeutic indication for supraventricular tachycardia

Answer 26

verapamil

Question 27

how do you choose the antianginal drug

Answer 27

1. prevention or termination of attacks
   (short acting nitrates ex: GTN)
2. long term prophylaxis
   - slowly acting nitrates
   - plus/minus β blocker (avoid in variant angina) NOT GREAT
   - plus/minus CCB (of choice in variant angina) BEST
   - + antiplatelet agents (ex: asprin)