Antianginals

Question 1

What are three examples of drugs that are metabolized into nitric oxide?

Answer 1

Amyl nitrite
Nitroglycerin
Isosorbide dinitrate

Question 2

What is sildenafil?

Answer 2

A type 5 phosphodiesterase inhibitor

Question 3

What are nifedipine, amlodipine and felodipine?

Answer 3

Dihydropyridine calcium channel blockers

Question 4

What are verapamil and diltiazem?

Answer 4

Non-dihydropyridine calcium channel blockers

Question 5

What is propranolol?

Answer 5

Beta adrenergic receptor antagonist

Question 6

What is metoproplol?

Answer 6

Beta1 adrenergic receptor antagonist

Question 7

What causes angina (when does angina occur)?

Answer 7

When oxygen demand exceeds oxygen supply

Question 8

What are the three types of angina?

Answer 8

Stable (angina of effort)
Unstable
Vasospastic (Variant; Prinzmetal’s)

Question 9

Describe stable angina

Answer 9

It is the most common (atherosclerosis with cap)
A fixed narrowing of the coronary artery (partial occlusion to flow)
Onset is associated with a given level of activity (it’s predictable)

Question 10

Describe unstable angina

Answer 10

Onset is at rest or increased physical activity (not predictable)
Related to coronary arteriosclerotic plaque rupture (emboli) - dislodged clots lodge in the coronary blood vessels
Could also be due to platelet accumulation and breaking off of a thrombus

Question 11

Describe vasospastic angina

Answer 11

Occurs at anytime

Spasms of the coronary artery

Question 12

How is angina treated?

Answer 12

Increase the oxygen supply
and/or
Decrease the oxygen demand
Modify/treat risk factors
Pharmacological treatment
Surgical intervention

Question 13

What can increase oxygen supply?

Answer 13

pO2 and hemoglobin concentration (can't really change)
Oxygen extraction (can't really change)
Coronary blood flow (site for pharmacological intervention)
Micro-circulation (site for pharmacological intervention)

Question 14

What can decrease oxygen demand?

Answer 14

Heart rate (site for pharmacological intervention)
Ventricular wall stress (intraventricular pressure, ventricular wall radius, wall thickness; site for pharmacological intervention)
Contractile state (site for pharmacological intervention)

Question 15

What risk factors should we modify/treat to treat angina?

Answer 15

Smoking, dyslipidemias, diabetes, hypertension, sedentary, obesity, stress
Family history is important (but unable to modify)

Question 16

What are pharmacological treatment options for angina?

Answer 16

Nitrates/nitrites
Beta adrenergic receptor blockers
Calcium channel blockers
Aspirin

Question 17

What are surgical intervention options for angina?

Answer 17

Angioplasty

Revascularization

Question 18

How is nitroglycerin used in angina?

Answer 18

Acutely (when there is pain) - sublingual, lingual spray (rapid onset 2-5 minutes, duration 15-30 minutes)
Prophylactically (to prevent pain with exercise). There is a patch (onset 30 min, duration 8-14 hours) or oral (long acting, duration 6-8 hours)

Question 19

How is isosorbide dinitrate used in angina?

Answer 19

Prophylactically (prevent pain with exercise)
Sublingual - onset 2-5 minutes, duration 1.5-2 hours
Oral - onset 15-30 minutes, duration 3-6 hours

Question 20

Describe the mechanism of nitrates

Answer 20

They are metabolized into nitric oxide (mainly in the veins)
Nitric oxide increases cGMP which mediates dilation (important to avoid giving drugs that block cGMP breakdown, such as sildenafil aka Viagra)
Nitrates can relax veins (at low doses) and larger arteries (at higher doses). They decrease preload (venous return) which decrease heart rate (which decreases wall stress) and may redistribute blood to ischemic areas. They decrease pulmonary artery resistance which is useful in pulmonary hypertension seen in COPD

Question 21

How do nitrates affect the endocardium?

Answer 21

When the heart constricts, the pressure inside is going to squeeze on the endocardium and that tissue is not getting much blood flow. If the heart isn’t constricting as hard, it helps blood flow not drop for as long of time

Question 22

How do nitrates prevent coronary steal?

Answer 22

Smaller arterioles and pre capillary sphincters are less affected by nitrates (good thing). This prevents blood flow to ‘healthy’ regions. The arterial vessels that are effected then to be larger and this increases blood flow to healthy and ischemic regions

Question 23

How does hydralazine affect angina?

Answer 23

Some vasodilators may worsen angina (including hydralazine)

Question 24

Why do nitrates need to be taken in 12 hour treatment intervals?

Answer 24

Because tolerance develops

Question 25

What are the adverse effects of nitrates?

Answer 25

``` Orthostasis Throbbing headache Reflex activation of SNS Salt and water retention High doses may decrease BP and increase sympathetic nerve activity (results in increased oxygen demand and decrease perfusion pressure may be problematic) ```

Question 26

How should nitrates be used?

Answer 26

Sublingual nitrates should be use for acute episodes of angina Contact a physician if the pain persists or worsens 5 minutes after one tablet

Question 27

How do Asians responsd to nitrates?

Answer 27

30 -50% of Asians may be poor responders due to decreased mitochondrial aldehyde dehydrogenase (ALDH2) which is needed to convert nitrate to nitric oxide ALDH2 is also needed to breakdown aldehyde associated with alcohol metabolism (a flush response to alcohol suggests a lack of ALDH2)

Question 28

What are propranolol and metoprolol? What are they used for?

Answer 28

Beta adrenergic receptor blockers First line treatment in chronic stable angina (not for acute angina attacks) They are recommended as initial treatment in relief of angina symptoms in stable ischemic heart disease

Question 29

Describe the mechanism of beta blockers

Answer 29

They decrease oxygen demand (decreased heart rate, blood pressure and contractility) May produce reverse steal (increase flow to ischemic regions)

Question 30

What are the benefits of beta blockers?

Answer 30

Improved survival (important) Following an MI, it's the only antianginal proven to decrease incidence of reinfarction and improve patient survival (if there is no previous MI, they are as good as CCBs and nitrates but prophylactic use to prevent the first MI appears to be ineffective) They are also a benefit in systolic heart failure

Question 31

What are the adverse effects of beta blockers?

Answer 31

Slowing of the heart, increased EDV, increased oxygen demand (may use with nitrates to decrease preload and EDV) Not for vasospastic angina because you want to relax the vessels (may worsen if beta2 is blocked)

Question 32

What do dihydropyridines do?

Answer 32

They decrease afterload (peripheral resistance) and may also decrease coronary vascular tone (arterial vessels are more sensitive than veins) They may cause reflex SNS in cardiac beta receptor activity They decrease coronary artery spasm (good for Primzmetal angina) They do not change "double product" value where angina is felt They work by decreasing oxygen demand The arterial vessels are more sensitive than vein; little cardiac suppression

Question 33

What are verapamil and diltiazem?

Answer 33

Non-dihydropyridines

Question 34

What does verapamil do?

Answer 34

Decreases oxygen demand (negative inotrope, chronotrope and lowers blood pressure) Poor vascular dilator

Question 35

What does diltiazem do?

Answer 35

Decreases oxygen demand (negative inotrope, negative chronotrope and lowers blood pressure) Effective coronary arterial dilator (less peripheral)

Question 36

What are the benefits of calcium channel blockers?

Answer 36

They decrease symptoms, increase exercise tolerance/time If beta blocker is ineffective or contraindicated, we can substitute a CCB or combine with a CCB They are effective for vasospastic angina (dihydropyridines are preferred)

Question 37

What are the adverse effects of CCBs?

Answer 37

Serious cardiac suppression (verapamil and beta blocker can cause possible heart block) Constipation, ankle oedema Sympathetic reflexes (nifedipine vs verapamil) Dizziness, hypotension, headache, flushing

Question 38

What is angina of effort? What should be done about it?

Answer 38

Stable angina Patients should be on aspirin or clopidogrel Nitrates and beta-adrenergic receptor blockers are initial treatment (or CCB is there is problems with these two)

Question 39

How should unstable angina be treated?

Answer 39

With anti platelet therapy (aspirin, clopidogrel, IV heparin) Oxygen Nitroglycerin sublingual, or give IV if pain persists after three tablets Morphine, IV for pain and anxiety Oral beta-adrenergic receptor blockers IV Statins Beta-adrenergic receptor blockers decrease ischemic episodes but not mortality

Question 40

What should be taken for vasospastic angina?

Answer 40

CCBs (vascular) and/or nitrates

Question 41

What should be avoided with vasospastic angina?

Answer 41

Beta-adrenergic receptors blockers may worsen the condition (beta1 selective blockers may be okay) Aspirin decreases prostacyclin which is a vasodilator Sumatriptan is used in migraines and may constrict coronary arteries

Question 42

If someone has concomitant asthma, what is the preferred drug and what is the least preferred?

Answer 42

Preferred: CCBs, nitrates | Least preferred: beta blockers

Question 43

If someone has concomitant diabetes mellitus, what is the preferred drug and what is the least preferred?

Answer 43

Preferred: CCBs, nitrates | Least preferred: beta blockers

Question 44

If someone has concomitant heart failure, what is the preferred drug and what is the least preferred?

Answer 44

Preferred: nitrates, beta blocker | Least preferred: Non-dihydropyridines

Question 45

If someone has concomitant hypertension, what is the preferred drug and what is the least preferred?

Answer 45

Preferred: beta blockers, CCBs | Least preferred: nitrates

Question 46

If someone has concomitant peptic ulcer, what is the preferred drug and what is the least preferred?

Answer 46

Preferred: beta blockers, nitrates | Least preferred: CCBs