Anti-angina Dr. Roane Flashcards
Dr. Roane EXAM III
Classic or exertion angina
atheromatous obstruction of the large coronary vessels (CAD)
-hurts when effort is exerted
Prinzmetal or Variant Angina
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
Unstable angina
-unpredictable and occurs at rest or becomes worse and occurs with less physical effort
-typically severe and last longer (20m) than classical angina
O2 demand and supply
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)
What causes pain in angina?
-imbalance O2 demand and supply
->ischemia with accumulation of acidic metabolites
Correction of imbalance in classical exertion angina?
-reducing O2 demand by using substrates requiring less oxygen per unit of ATP: glucose uses less oxygen than FA
Correction of imbalance in variant angina?
-stops vasospasm with nitrates or calcium channel-blocking vasodilators
Correction of imbalance in unstable angina?
-increase oxygen delivery (Stents)
-decrease oxygen demand
-lipid-lowering drugs
What determines the left ventricular wall stress?
arterial blood pressure, state of constriction in the arteries
-harder for the heart to eject blood if the arteries are constricted
What determines the right ventricular wall stress?
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
Equation wall stress
Wall stress = pressure X radius
MOA of nitrates
-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
Effects of nitrates on low-dose
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
Effects of nitrates on high-dose
-arteriole dilates
-BP falls
-Tachycardia -> O2 demand goes up
Nitrate drugs
-Nitroglycerin (Nitrostat)
-Isosorbide 5 mononitrate (Imdur, ISMN)
-Isosorbide dinitrate (ISDN) - seen in Bidil hydralazine + isosorbide dinitrate
When may Nitroglycerin be beneficial?
-vasospastic variant angina
-cause some arteriole vasodilation mostly in larger vessel
-flushing, headache
-main effects are still due to decreased preload (venous dilation)
Short-acting nitrates
Nitroglycerin
Long-acting nitrates
-Isosorbide 5 mononitrate (Imdur, ISMN)
-Isosorbide dinitrate (ISDN)
How to combat tolerance in nitrate therapy
-can cause increased sensitivity to vasoconstriction via angiotensin II
-irregular dosing schedule with 8-14h breaks
Which drugs interact with nitrates
PDE5 inhibitor: Sildenafil (Viagra), Tadalafil (Cialis)
->Contraindication!
-cause more vasodilation: postural hypotension, tachycardia
Rare side effect of nitrates
-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
MOA Methylene blue
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
Which drug to use in variant angina?
-CCB more effective than nitrates in long-term use
-can be used together
Side effects of CCBs
-inhibiting other smooth muscles
-inhibition of the lower esophageal sphincter -> worsens gerd reflux
-constipation: inhibiting smooth muscles in the GI
Other drugs for angina
-Beta-blockers
-Ivabradine: blocks funny Na channels
-Ranolazine (Ranexa) - MOA uncertain, maybe by shifting metabolism to glucose using less O2
Extra effect of some beta-blockers
-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)
