Lecture 8: Drugs to Treat ACS and Stable Angina Flashcards
What are the 4 drug classes used to treat Stable Angina? (N/C/B/R)
nitrates, calcium channel blockers, beta blockers, ranolazine
Nitrates
What is their MOA, how are they given and where is their effect localized to?
MOA: metabolically activate Nitric Oxide; activates Guanylyl Cyclase creating cGMP –> turns on PKG that opens potassium channels and dephosphorylates myosin light-chains = SMOOTH MUSCLE RELAXATION
- given through IV do to first-pass metabolism (isosorbide mononitrate has higher bioavailability)
- cause VENOUS dilation that reduced PRELOAD and decreased oxygen demand by the heart
Nitrates
What are the 3 drugs of this family (N/ID/IM) and what are their adverse effects?
What are these drugs contraindicated in?
Drugs: nitroglycerin, isosorbide dinitrate, isosorbide mononitrate
AE: inc. generation of superoxide radicals depletes tissue NO, reflexive tachycardia, inc. salt/water renal retention
CI: if intracranial pressure is elevated (HEADACHES due to meningeal vasodilation)
What are 3 drugs (S/V/T) used for erectile dysfunction and why are Nitrates contraindicated in patients taking them?
Drugs: sildenafil, vardenafil, tadalafil (“-afil”)
- they inhibit cGMP-phosphodiesterase-5, which inc. levels of cGMP
- when given with nitrates - cause SEVERE increase in cGMP and dramatic BP drop (acute MIs)
Calcium Channel Blockers
What are the 3 non-cardioactive drugs (A/N/N) and 2 cardioactive drugs (D/V) used to treat Stable Angina?
NCA: Amlodipine, Nifedipine, Nicardipine
- dihydropyridines
CA: Diltiazem, Verapamil
Calcium Channel Blockers
What is their MOA and what are their adverse effects?
MOA: decrease myocardial oxygen demand
- dilate peripheral arterioles (dec. PVR/afterload)
- dec. cardiac contractility (CA CCB only)
- reduce HR (CA CCB only)
AE: short acting dihydropyridines can trigger reflex sympathetic activation; cardiac depression, AV block
Beta Blockers
What are 4 drugs of this family used to treat Stable Angina? (P/N/M/A)
What is their MOA?
propranolol, nadolol, metoprolol, atenolol
MOA: dec. myocardial oxygen demand
- reduce HR
- dec. cardiac contractility
- dec. blood pressure = reduced afterload
Ranolazine
What is its MOA and how does it affect the heart?
When is it used?
MOA: normalizes repolarization of cardiac myocytes and reduces mechanical dysfunction (inhibits late Na current in ischemic myocardium, preventing Ca overload)
- may reduce diastolic tension and compression of coronary vessels; may reduce cardiac contractility and oxygen demand
Use: for stable angina that is refractory to standard medications
How is Vasospastic Angina treated?
- CCBs are the FIRST CHOICE drug (either diltiazem or amlodipine)
- if CCBs are contraindicated (low BP/bradycardia/AV block) use LONG-ACTING NITRATES
- effective but less desirable due to tolerance
- can be used with CCBs to improve efficacy
What are the 3 families of Antiplatelet drugs and what thrombus are they normally used to treat?
- thromboxane A2 synthesis inhibitors
- P2Y12 (ADP) receptor blockers
- Platelet Glycoprotein (IIb/IIIa) receptor blockers
- used to treat white thrombi that form in arteries (like acute coronary syndromes)
Thromboxane A2 Synthesis Inhibitor
What drug is in this family, what is its MOA, and what is it used for?
ASPIRIN
MOA: irreversible inhibition of cyclooxygenase to block TxA2 production (potent inducer of platelet agg.)
Use: started ASAP for acute coronary events and secondary prevention of coronary events (low dose)
P2Y12 (ADP) Receptor Blockers
What are the 3 drugs of this family (C/P/T), what is their MOA, what causes resistance, and what are they used for?
Clopidogrel, Prasugrel, Ticagrelor
MOA: bind to P2Y12 receptor and prevent adenylyl cyclase inactivation = inc. cAMP that prevents platelet agg.
R: 85% of clopidogrel is eliminated, so if pt. has nonfunctional CYP2C19 allele, the 15% that remains will not be turned on (Prodrug)
Use: ASAP for acute coronary syndrome or alone in pts. with aspirin hypersensitivity
Glycoprotein IIb/IIIa Inhibitors
What are the 3 drugs of this family (A/E/T), what is their MOA, and what are they used for?
Abciximab (not in US), Eptifibatide, Tirofiban
MOA: prevent binding of ligands to GP receptor to inhibit platelet aggregation
Use: clinical use has declined but can be used during PCI in high-risk patients
- Abciximab caused thrombocytopenia
Thrombolytic Drugs
What are the 3 TpD drugs (A/R/T) and streptokinase preparation (S) that are used?
TpD = Alteplase, Reteplase, Tenecteplase
- all end in suffix “-teplase”
- activate plasminogen in thrombus ONLY
Streptokinase prep = Streptokinase
-causes systemic plasminogen activation
Thrombolytic Drugs
What is their MOA and what are they clinically used for?
MOA: bind to plasminogen to activate it (becomes plasmin) –> degrades fibrin to break up clot
Use: used it PCI cannot be performed in a timely manner; also for STEMI and less often NSTEMI within 12 hours following onset of symptoms
