Pharmacology

Question 1

Aspirin: MOA

Answer 1

Nonselective COX inhibitor

In platelets, aspirin irreversibly acetylates COX-1, inhibiting COX-1 –> prevents TxA2 synthesis and associated platelet aggregation

Question 2

Aspirin: differential effect in platelets vs endothelial cells

Answer 2

Platelets express COX-1 –> TxA2 synthesis (PROMOTES platelet aggregation)

• Endothelial cells express COX-1 and COX-2 –> prostacyclin synthesis (INHIBITS platelet aggregation)

However, effect of aspirin in platelets lasts longer because platelets do not have a nucleus and cannot regenerate COX-1, thus tipping balance in favor of inhibited platelet aggregation

Question 3

Aspirin: dose dependent effect

Answer 3

Low doses: anti-thrombotic

Higher doses: anti-inflammatory (3-5g/day)

Question 4

Aspirin: adverse effects

Answer 4

• Bleeding
• GI upset and ulcers (COX-1 involved in production of stomach mucus)
• Renal toxicity (prostaglandins involved in vasodilation of afferent arteriole and regulation of GFR)

Question 5

Aspirin in kids after viral illness: consequence

Answer 5

Reye Syndrome: hepatic injury and encephalopathy in kids –> AVOID!!

Question 6

Aspirin: indications

Answer 6

Arterial thrombosis: MI, stroke, peripheral artery disease, angina, atrial fibrillation, during and post PCI (percutaneous coronary intervention, aka stent)

Question 7

Clopidogrel: MOA

Answer 7

Irreversible ADP receptor antagonist

Prodrug requiring CYP activation

Question 8

Clopidogrel: indications

Answer 8

Pre-PCI: bolus given

After-PCI: clopidogrel + aspirin for one year

Question 9

ADP receptor antagonists: name 3

Answer 9

“GREL’s”

1) Clopidogrel (irreversible, prodrug)
2) Prasugrel (irreversible, prodrug, faster kinetics)
3) Ticagrelor (reversible, NOT a prodrug)

Question 10

GpIIb/IIIa inhibitors: name 3

Answer 10

Abciximab
Tirofiban
Eptifibitide

Question 11

GpIIb/IIIa inhibitors: indications

Answer 11

During PCI (only IV), and after for 12-24 hours

Question 12

Anticoagulants: indications

Answer 12

Both venous and arterial: PE, DVT, MI, acute coronary syndromes

Question 13

Heparin: MOA

Answer 13

Catalyzes antithrombin-3 (AT3) inactivation of thrombin and factor Xa

Question 14

Low molecular weight (LMW) heparin (enoxaparin): MOA

Answer 14

Catalyzes antithrombin-3 (AT3) inactivation of factor Xa (like fondaparinux)

Question 15

Fondaparinux: MOA

Answer 15

Catalyzes antithrombin-3 (AT3) inactivation of factor Xa (like enoxaparin)

Question 16

LMWH and fondaparinux: monitoring

Answer 16

None needed. Can use anti-Xa testing

Thrombin: rate limiting step, which comes AFTER Factor Xa

Question 17

What reverses heparin activity?

Answer 17

Protamine

Question 18

Heparin: adverse effects

Answer 18

Heparin-induced thrombocytopenia: IgG antibody to heparin and platelet factor 4 activates platelets, leading to widespread platelet coagulation and thrombocytopenia

Question 19

Heparin: route

Answer 19

IV or SC

Question 20

LMW heparin: route

Answer 20

SC

Question 21

Thrombin inhibitors: name 3

Answer 21

Dabigatran (reversible)

“Rudins”: bivalirudin, desirudin

Question 22

Dabigatran: MOA

Answer 22

Thrombin inhibitor (antidote exists)

“DABigatran” –> II [arms]

Question 23

“Rudins”: MOA

Answer 23

Thrombin inhibitors

“RU” rhymes with TWO

Question 24

Rivaroxaban: MOA

Answer 24

Factor X inhibitor (no antidote)

RivaroXaBAN
“Ban” = X

Question 25

Unfractionated heparin: indications

Answer 25

Bypass surgeries | Dialysis

Question 26

Warfarin: MOA

Answer 26

Inhibition of epoxide reductase (normally activates Vit K in liver) --> inhibits vitamin K dependent gamma-carboxylation of Factors 10, 9, 7, 2, and Proteins C and S "1972"

Question 27

Why is heparin bridge needed when administering warfarin?

Answer 27

Proteins C and S ("clot stoppers") are first to be depleted after warfarin is administered --> there's actually an increased risk of clotting and skin necrosis immediately after

Question 28

Reversal for warfarin

Answer 28

Vit K | Fresh frozen plasma (faster)

Question 29

Warfarin: route

Answer 29

Oral

Question 30

Oral anticoagulants

Answer 30

Warfarin Dabigatran Rivaroxaban

Question 31

PTT or PT for monitoring unfractionated heparin?

Answer 31

PTT Heparin catalyzes AT3-mediated inactivation of thrombin and Factor Xa

Question 32

PTT or PT for monitoring warfarin?

Answer 32

PT Factor 7 is Vit-K dependent

Question 33

PTT test: what does it measure?

Answer 33

Intrinsic pathway, common pathway Rate-limiting step: Factor IIa (thrombin) Two T's: "IN" a relationship

Question 34

PT test: what does it measure?

Answer 34

Extrinsic pathway Common pathway Rate-limiting step: Factor VII (short half life) Need to add tissue factor to sample to activate extrinsic pathway

Question 35

What is PT/INR?

Answer 35

PT times are standardized b/c of variability in added TF INR = (PTtest/PTnl)^ISI

Question 36

Warfarin: adverse events

Answer 36

Bleeding Teratogen Skin and tissue necrosis Early transient hypercoagulability

Question 37

Direct Factor Xa inhibitors

Answer 37

Rivaroxaban (Xarelto) | Apixaban (Eliquis)

Question 38

Thrombolytics: name 4

Answer 38

Streptokinase | Alteplase, reteplase, tenecteplase

Question 39

Thrombolytics: MOA

Answer 39

Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots "Clot busters"

Question 40

Thrombolytics: indications

Answer 40

STEMI Stroke PE

Question 41

Thrombolytics: contraindications

Answer 41

Active bleeding, Hx intracranial bleeding, recent surgery, stroke <6 mo