ACS/Stable Angina Flashcards
What are your approaches to treating stable angina?
- Increase or restore coronary blood flow through
- Surgery: CABG, PCI, Stent
Typically pharmacology is not helpful in increasing blood flow through the stenotic coronary artery into ischemic area
Talk about the bioavailability of nitrates
Significant first pass metabolism means that bioavailability through oral route is low
Isosorbide mononitrate is a poor substrate of nitrate reductase that is characterized by high bioavailability
What is the mechanism of action of nitrates?
Organic nitrates get metabolically active -> forms NO -> cGMP -> PKG
PKG -> opens potassium channels to hyperpolarize and reduce calcium entry
PKG -> myosin-LC-dephosphorylation and relax smooth muscle
What is the LEADING mechanism in stable angina?
Drop O2 demand
How does tolerance develop in nitrates?
Through depletion of thiol compounds that normally release NO, now NO is stuck and helps form superoxide radicals. This means no vasodilation, and SNS activation now.
Drug free for 8 hours to be okay
What are the adverse effects of nitrates?
- Headache (b/c meningeal vasodilation)
- Orthostatic hypotension
- Increase sympathetic discharge
- Increased renal Na+ and H2O reabsorption
Explain the interaction between nitrates and PDE5 inhibitors?
cGMP increased with nitrates
“Fils” prevent breakdown of cGMP
BP drops hella
What is the MOA of CCBs in stable angina?
- Decrease O2 demand
- Decrease PVR and afterload to drop BP - aftfects arterioles more than veins so less orthostatic hypotension
- Dihydropyridines work better
Drop contractility and HR
What is the major risk associated with nifedipine?
MI in pts with HTN, slow release and long acting are better tolerated
When does vasodilation trigger reflex sympathetic activation?
Short acting Dihydropyridine CCBs
What are the cardioactive CCBs and what does this mean?
Diltiazem and Verapamil - slows HR because drops HR
What is the MOA of Beta blockers?
Drop O2 demand
incidentally drops contractility and BP due to reduced afterload
What are some contraindications for beta blockers?
Asthma, PVD, Type 1 D, Bradyarrythmias, depressed function
What is the MOA of ranolazine?
Inhibit late Na+ current in cardiomyocytes targeting the LATE current by fast sodium channel responsible for phase 0 rapid depolarization
Pathologically NCX for Na/Ca remains open which brings in more calcium so we block this
What does ranolazine NOT affect?
HR and peripheral hemodynamics
What does ranolazine do?
- Reduce diastolic tension (usually caused by increased calcium) and coronary vessel compression
- Reduce cardiac contracitlity and O2 demand
This drug is used for stable angina refractory to standard meds and to drop anginal episodes and improve exercise tolerance in patients taking nitrates, amlodipine, or atenolol
Ranolazine
How do we treat stable angina?
- We try lipid lowering, lifestyle mods, nitrates, aspirin
- BB or CCB/nitrate next
- Add BB or CCB we didn’t add before, if we have low BP try the LA nitrate or ranolazine
- Consider triple therapy of BB, CCB, LA nitrate or ranolazine
- Consider CABG
What are the bad effects of nitrates alone?
HR reflex increases
Contractility reflex increases
What are the bad effects of BB and CCB? What happens when we add nitrates?
Increase EDV
Increase Ejection time
None of these bad effects!
What do we do to treat vasospastic angina?
- CCBs (Diltiazem or Amlodipine)
2. If CCB contraindicated, we use long acting nitrates
Local ischemia due to arterial occlusion and ACS leads to the formation of
White thrombus (platelet rich)
Pain/swelliing, embolic strokes lead to the formation of
Red thrombus (fibrin-rich with trapped RBCs)
Anticoagulants are used to prevent clots in the
Venous system (red thrombi)
Antiplatelet drugs are used to prevent clots from forming in
Arteries (white thrombi)
When do we treat with aspirin?
In acute coronary events as part of dual antiplatelet therapy with P2Y12 blocker OR secondary prevention of conary events with low dose aspirin
What are the adverse effects associated with aspirin?
GI bleed, aspirin hypersensitivty
What is the MOA of P2Y12 (ADP) receptor blockers?
ADP activates P2Y12 receptor, GPCR, inhibits adenyl cyclase to reduce cAMP levels - blocking will increase these levels and cAMP levels
CYP2C19 is associated with what drug resistance
Clopidogrel - half of Chinese people have this resistance, then AAs, whites, mexicans
When do we start someone on P2Y12 receptor blocker?
ASAP in acute coronary events with dual therapy
Used alone if aspirin hypersensitivity
Secondary prevention in patients with ACS hx
What are the adverse effects of P2Y12 blockers?
Minor and major bleeding complications
MOA of GP IIb/IIIa inhibitors?
Prevents binding of ligands to GP IIb/IIIa receptor to inhibit platelet aggregation
This drug is indicated during PCI in high risk patients
Glycoprotein IIB/IIIA inhibitors
What are the adverse effects of GP IIB/IIIA inhibitors?
Bleeding (CKD)
Thrombocytopenia (seen with abciximab)
MOA of streptokinase
Binds plasminogen to activate it
MOA of “plase”
Cleave plasminogen to convert to plasmin
Use these drugs if PCI cannot be performed timely manner
Thrombolytics
Used in STEMI or NSTEMI within 12 hours after onset of symptoms
Thrombolytics
What are adverse effects associated with fibrinolytic drugs?
Bleeding and allergic reactions (streptokinase)
