Anti-angina Dr. Roane

Question 1

Classic or exertion angina

Answer 1

atheromatous obstruction of the large coronary vessels (CAD)

-hurts when effort is exerted

Question 2

Prinzmetal or Variant Angina

Answer 2

transient spasm of portions of the vessel after blockage
-with myocardial ischemia and pain: vasospastic or variant angina

-diagnosed by a test that provokes temporary spasm

Question 3

Unstable angina

Answer 3

-unpredictable and occurs at rest or becomes worse and occurs with less physical effort

-typically severe and last longer (20m) than classical angina

Question 4

O2 demand and supply

Answer 4

O2 demand = O2 supply -> Balance
O2 demand > O2 supply -> Imbalance

-in classical angina: imbalance due to increased O2 demand (physical exercise)

-in variant angina: imbalance due to decreased O2 supply (caused by vasospasm)

Question 5

What causes pain in angina?

Answer 5

-imbalance O2 demand and supply
->ischemia with accumulation of acidic metabolites

Question 6

Correction of imbalance in classical exertion angina?

Answer 6

-reducing O2 demand by using substrates requiring less oxygen per unit of ATP: glucose uses less oxygen than FA

Question 7

Correction of imbalance in variant angina?

Answer 7

-stops vasospasm with nitrates or calcium channel-blocking vasodilators

Question 8

Correction of imbalance in unstable angina?

Answer 8

-increase oxygen delivery (Stents)
-decrease oxygen demand

-lipid-lowering drugs

Question 9

What determines the left ventricular wall stress?

Answer 9

arterial blood pressure, state of constriction in the arteries
-harder for the heart to eject blood if the arteries are constricted

Question 10

What determines the right ventricular wall stress?

Answer 10

venous tone, state of constriction of the vein
-determines the amount of blood that is returned to the heart

-thereby determining the right diastolic right wall stress

Question 11

Equation wall stress

Answer 11

Wall stress = pressure X radius

Question 12

MOA of nitrates

Answer 12

-nitrates are metabolized to nitric oxide (NO) via Aldehyde dehydrogenase (not fully clear)

-NO stimulates soluble guanylate cyclase (sGC) -> in smooth muscle cells -> causes VASODILATION

Question 13

Effects of nitrates on low-dose

Answer 13

more in the veins than in the arteries
-blood pools in the veins
-venous return is reduced
-less stretch to the ventricles, lower wall tension
-less work for the heart, less O2 demand

Question 14

Effects of nitrates on high-dose

Answer 14

-arteriole dilates
-BP falls
-Tachycardia -> O2 demand goes up

Question 15

Nitrate drugs

Answer 15

-Nitroglycerin (Nitrostat)
-Isosorbide 5 mononitrate (Imdur, ISMN)
-Isosorbide dinitrate (ISDN) - seen in Bidil hydralazine + isosorbide dinitrate

Question 16

When may Nitroglycerin be beneficial?

Answer 16

-vasospastic variant angina
-cause some arteriole vasodilation mostly in larger vessel
-flushing, headache

-main effects are still due to decreased preload (venous dilation)

Question 17

Short-acting nitrates

Answer 17

Nitroglycerin

Question 18

Long-acting nitrates

Answer 18

-Isosorbide 5 mononitrate (Imdur, ISMN)
-Isosorbide dinitrate (ISDN)

Question 19

How to combat tolerance in nitrate therapy

Answer 19

-can cause increased sensitivity to vasoconstriction via angiotensin II

-irregular dosing schedule with 8-14h breaks

Question 20

Which drugs interact with nitrates

Answer 20

PDE5 inhibitor: Sildenafil (Viagra), Tadalafil (Cialis)
->Contraindication!

-cause more vasodilation: postural hypotension, tachycardia

Question 21

Rare side effect of nitrates

Answer 21

-Methemoglobinemia
-pts become cyanotic blue
-O2 saturation drops bc Fe2+ in the Hg is oxidized to F3+
-F3+ doesn’t bind O2 well

-treated with injectable methylene blue

Question 22

MOA Methylene blue

Answer 22

methylene blue gets reduced by NADPH to leukomethylene blue now carrying electrons that can be used to reduce HbFe3+ back to Fe2+

-NADPH comes from G6PDH (converting glucose to 6-phosphogluconate)
-pts with G6PDH needs a blood transfusion

Question 23

Which drug to use in variant angina?

Answer 23

-CCB more effective than nitrates in long-term use
-can be used together

Question 24

Side effects of CCBs

Answer 24

-inhibiting other smooth muscles

-inhibition of the lower esophageal sphincter -> worsens gerd reflux

-constipation: inhibiting smooth muscles in the GI

Question 25

Other drugs for angina

Answer 25

-Beta-blockers
-Ivabradine: blocks funny Na channels
-Ranolazine (Ranexa) - MOA uncertain, maybe by shifting metabolism to glucose using less O2

Question 26

Extra effect of some beta-blockers

Answer 26

-Carvedilol blocks some Ca channels
Carvedilol as antioxidant

-Nebivolol and carteolol agonize ß2 causing vasodilation (usually in the lungs)

Nebivolol stimulates NO oxide production -> Vasodilation (via sGC)