Pharmacology Flashcards
Aspirin: MOA
Nonselective COX inhibitor
In platelets, aspirin irreversibly acetylates COX-1, inhibiting COX-1 –> prevents TxA2 synthesis and associated platelet aggregation
Aspirin: differential effect in platelets vs endothelial cells
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
Aspirin: dose dependent effect
Low doses: anti-thrombotic
Higher doses: anti-inflammatory (3-5g/day)
Aspirin: adverse effects
- 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)
Aspirin in kids after viral illness: consequence
Reye Syndrome: hepatic injury and encephalopathy in kids –> AVOID!!
Aspirin: indications
Arterial thrombosis: MI, stroke, peripheral artery disease, angina, atrial fibrillation, during and post PCI (percutaneous coronary intervention, aka stent)
Clopidogrel: MOA
Irreversible ADP receptor antagonist
Prodrug requiring CYP activation
Clopidogrel: indications
Pre-PCI: bolus given
After-PCI: clopidogrel + aspirin for one year
ADP receptor antagonists: name 3
“GREL’s”
1) Clopidogrel (irreversible, prodrug)
2) Prasugrel (irreversible, prodrug, faster kinetics)
3) Ticagrelor (reversible, NOT a prodrug)
GpIIb/IIIa inhibitors: name 3
Abciximab
Tirofiban
Eptifibitide
GpIIb/IIIa inhibitors: indications
During PCI (only IV), and after for 12-24 hours
Anticoagulants: indications
Both venous and arterial: PE, DVT, MI, acute coronary syndromes
Heparin: MOA
Catalyzes antithrombin-3 (AT3) inactivation of thrombin and factor Xa
Low molecular weight (LMW) heparin (enoxaparin): MOA
Catalyzes antithrombin-3 (AT3) inactivation of factor Xa (like fondaparinux)
Fondaparinux: MOA
Catalyzes antithrombin-3 (AT3) inactivation of factor Xa (like enoxaparin)
LMWH and fondaparinux: monitoring
None needed. Can use anti-Xa testing
Thrombin: rate limiting step, which comes AFTER Factor Xa
What reverses heparin activity?
Protamine
Heparin: adverse effects
Heparin-induced thrombocytopenia: IgG antibody to heparin and platelet factor 4 activates platelets, leading to widespread platelet coagulation and thrombocytopenia
Heparin: route
IV or SC
LMW heparin: route
SC
Thrombin inhibitors: name 3
Dabigatran (reversible)
“Rudins”: bivalirudin, desirudin
Dabigatran: MOA
Thrombin inhibitor (antidote exists)
“DABigatran” –> II [arms]
“Rudins”: MOA
Thrombin inhibitors
“RU” rhymes with TWO
Rivaroxaban: MOA
Factor X inhibitor (no antidote)
RivaroXaBAN
“Ban” = X
Unfractionated heparin: indications
Bypass surgeries
Dialysis
Warfarin: MOA
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”
Why is heparin bridge needed when administering warfarin?
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
Reversal for warfarin
Vit K
Fresh frozen plasma (faster)
Warfarin: route
Oral
Oral anticoagulants
Warfarin
Dabigatran
Rivaroxaban
PTT or PT for monitoring unfractionated heparin?
PTT
Heparin catalyzes AT3-mediated inactivation of thrombin and Factor Xa
PTT or PT for monitoring warfarin?
PT
Factor 7 is Vit-K dependent
PTT test: what does it measure?
Intrinsic pathway, common pathway
Rate-limiting step: Factor IIa (thrombin)
Two T’s: “IN” a relationship
PT test: what does it measure?
Extrinsic pathway
Common pathway
Rate-limiting step: Factor VII (short half life)
Need to add tissue factor to sample to activate extrinsic pathway
What is PT/INR?
PT times are standardized b/c of variability in added TF
INR = (PTtest/PTnl)^ISI
Warfarin: adverse events
Bleeding
Teratogen
Skin and tissue necrosis
Early transient hypercoagulability
Direct Factor Xa inhibitors
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Thrombolytics: name 4
Streptokinase
Alteplase, reteplase, tenecteplase
Thrombolytics: MOA
Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin
clots
“Clot busters”
Thrombolytics: indications
STEMI
Stroke
PE
Thrombolytics: contraindications
Active bleeding, Hx intracranial bleeding, recent surgery, stroke <6 mo
