Drug
Nitrates
MOA
NO release  increases cGMP 
mediates vasorelaxation by
reducing Ca
Anti-Ischemic Drugs
Pharmacodynamics
Adverse Effects / Contraindications
1. Vasodilators (minimal effect on coronary resistance
vessels): increases myocardial blood supply
2. Venodilators  venous capacitance  decreases
ventricular volume  decreases preload  decreases wall
tension  decreases myocardial oxygen demand
- Headache, hypotension, syncope, dizziness
- Tolerance: occurs rapidly over a 24 hr period.
- So, create a nitrate free interval at some point in the
day
CI: PDE-5 Inhibitors  causes severe hypotension
Decreases smooth muscle tone  peripheral and coronary
vasodilation  decrease in angina
Indications: vasodilates smaller resistance vessels,
arterioles, vasospasm, systemic hypertension,
supraventricular tachycardias (NDHP) by inhibiting AV
node.
NDHP class: Negative Chronotropic and Dromotropic effects
on SA/AV Tissue. NOTICE DIFF BELOW:
- NDHP has negative inotrope effect and inhibit SA/AV
conduction compared to DHP.
- Headache, flushing, EDEMA, hypotension, bradycardia, and
constipation
- CI: Sick sinus syndrome, AV node dz, heart block,
bradycardia, acute heart failure, WPW w/ atrial fibrillation
- BLOCK CYP3A!
Calcium Channel Blockers
Verapamil
(NDHP)
Diltiazem
(NDHP)
-Interfere w/ entry of Ca into
cells through T and L type
channels.
-Look at PPT for specific
pathways.
-Sites of Action: vascular smooth
muscle, cardiac myocytes, SA/AV
cells
- Better tolerated than verapamil – still headache, edema,
hypoT, and bradycardia
- CI: Similar to verapamil
- BLOCK CYP3A!
- Hypotension, EDEMA.
- No SA/AV effects, minimal negative inotropic effect so less
concern w/ heart block and heart failure, thus safer to use
w/ beta blockers than NDHP!
- BLOCK CYP3A!
Amlodipine
(DHP)
(long half life!)
BETA-BLOCKERS
-B1 Receptors  cause
increase in HR  increase
in contractile force 
increase in velocity of
muscle fiber shortening.
Leads to increased
myocardial oxygen
consumption  >O2 supply
 angina!!!
-B2 receptors 
vasodilation and bronchial
dilation
B-BLOCKERS INHIBIT THIS!
-Indications: angina, arrhythmias, HTN, HCM, CHF,
MVP, aortic dissection, silent ischemia, migraine,
essential tremor, thyrotoxicosis
1. decreased HR  increased O2 supply!
2. decreased force of contraction and decreased
velocity of contraction  decreased oxygen
demand!
- ISA are partial agonists – partially stimulates B
receptor while preventing catecholamines from
stimulating
- A and B blockers: adds vasodilator component of
alpha blockers
- Bradycardia, AV Nodal Block, Decreased Inotropy (beware
of acute heart failure), Bronchospasm, Impotence
- CI: interact w/ other nodal blocking and negative inotropic
agents (CCB)
- May increase risk of Type II DM and alter lipids: decrease
HDL and increase TGs.
- Fatigue and depression sometimes require lower dose.
- Withdrawal is an issue – may have excessive B stimulation
effects if immediately taken off.
Ranolazine
- Inhibits late phase of myocyte
Na current (late INa)
- If you’re ischemic, Na is
increased, leading to the
exchanger allowing more Ca
inside which causes contraction.
Impaired relaxation  angina.
Anti-Platelet
Aspirin
P2Y12 Antagonists
Clopidogrel
Prasugrel
- Increases Total Exercise Time and Time to Ischemia
- Decreases Freq. of Anginal attacks, # of SL NTG taken and
recurrent ischemia.
- No mortality benefit.
- No hemodynamic effects on HR or BP
Indications: ACS where Ischemia is rapid and caused by platelet mediated thrombus.
Plaque rupture allows platelet adhesion, activation, and aggregation. Thrombus can be either partially or completely occlusive.
- Inhibits COX1
- Blocks formation of TXA2, a
platelet stimulator.
- High doses inhibit COX2 which
has anti-inflammatory effects
- Irreversible P2Y12 Inhibition
- P2Y12 receptor activated by ADP
 G protein coupled  platelet
activation and aggregation
MOA
- Absorbed in GI tract
- Enteric Coated Delays Absorption
- Irreversible Inhibition
- Indication: secondary prevention for stable CAD, Post-ACS,
Post-PCI, Post-CABG; reductions in death, MI, recurrent
ischemia
- Synergistic effect when given w/ aspirin.
Indications:
Clopidogrel – secondary prevention of recurrent ischemia in
pts allergic to ASA post MI, post CVA or w/ PAD
Added to Aspirin: Post-ACS, Post-PCI, where dual antiplatelet therapy for 12 mo is recommended
Prasugrel – reduce rate of thrombotic events post-PCI in
ACS
- Bleeding!
- CI: NSAIDs- may exacerbate bleeding and compete for
COX1
- True aspirin allergy can be life threatening – use clopidogrel
as alternative, can desensitize
- Prasugrel had much higher rates of major bleeding