Nitrate/Antiplatelets Pharmacology

Question 1

Angina

Answer 1

-Results from myocardial oxygen demand higher than coronary artery oxygen supply

Question 2

Organic Nitrates

Answer 2

• Enzymatically reduced to NO
• Stimulates soluble guanylyl cyclase (sGC) to increase the concersion of GTP to cGMP, causing asodilation
• Site of action: arteriole and venous smooth muscle
• Increase coronary oxygen delivery by dilating coronary arteries and decreasing oxygen demand by dilating peripheral veins and arteries
• Decreases preload and afterload

Question 3

Organic Nitrates Examples

Answer 3

• Nitroglycerin
• Isosorbide dinitrate
• Isosorbide mononitrate

Question 4

Organic Nitrates + Metabolism

Answer 4

• Undergo first-pass metabolism
• Low bioavailability
• Isosorbide mononitrate does NOT undergo this first-pass
• Nitroglycerin has a very fast onset making it an ideal rescue medication

Question 5

Nitrate SE

Answer 5

• Tolerance
• Flushing
• Headache
• Dizziness
• C/I with PDE5 inhibitors

Question 6

Prophylatic Treatments for Angina

Answer 6

• CCB: dilate arteries (DHP) or slow HR/reduce contractiltiy (Non-DHP)
• Beta Blocker: reduce HR and contractility from blocking receptors on SA node
• Ranolazine: inhibits late phase sodium current and reduces intracellular sodium, reduces ventriculartension

Question 7

Antiplatelet Drugs

Answer 7

• Target platelets
• Platelets are immediate responders, adhering to the site of tissue damage
• Activated platelets then initiate the coagulation cascade

Question 8

Platelets + Arterial Clots

Answer 8

• Larger component in arterial clots than venous
• Antiplatelet drugs primarily prevent arterial clots
• Anticoagulants prevent both

Question 9

Platelet Activation

Answer 9

• Activated by sub-endothelial ECM
• Leads to a feed-forward amplification of platelet activation and aggregation
• Four targets: COX-I, P2Y12 receptors, GP IIb/IIIa receptors, and PAR-1

Question 10

Aspirin MoA

Answer 10

• Target: platelet
• Mechanism: Irreversibly inhibits COX-1 and prevents TXA2
• Benefit: reduces platelet activation and aggregation

Question 11

P2Y12 antagonist Examples

Answer 11

• Thienopyridine (irreversible)
• Clopidogrel
• Prasugrel
• Ticagrelor (reversible) - don’t use with >100 mg of Aspirin a day

Question 12

P2Y12 Antagonist MoA

Answer 12

• Target: Platelets
• Mechanism: Block ADP binding to P2Y12 receptor
• Benefit: reduce platelet activation and aggregation

Question 13

GP IIb/IIIa Antagonist Examples

Answer 13

• Abciximab
• Tirofiban
• Eptifabtide

Question 14

GP Antagonist MoA

Answer 14

• Target: platelets
• Mechanism: Block fibrinogen binding to GP IIb/IIIa receptor
• Benefit: Prevent platelet aggregation

Question 15

Vorapaxar MoA

Answer 15

• Target: platelet
• Mechanism: Blocks thrombin binding to PAR-1
• Benefit: reduces platelet activation and aggregation

Question 16

Antiplatelet Drugs SE

Answer 16

• Results in bruising or bleeding more easily

- Other SE are rare/drug specific

Question 17

Clopidogrel/Prasugrel SE

Answer 17

• TTP - Thrombotic thrombocytopenic purpura
• Rare
• Blood clots in small vessels
• Thrombocytopenia

Question 18

Ticagrelor SE

Answer 18

• Dyspnea
• Possibly adenosine mediated
• Blocks adenosine cellular reuptake transporter
• Increases serum adenosine levels

Question 19

Clopidogrel

Answer 19

• Prodrug that requires P450 metabolism to generate active metabolites
• Allelic variants in CYP2C19 reduce its efficacy
• Intermediate/poor metabolizers have reduced or significantly reduced response