Sketchy Pharma 2 Flashcards
-Gi and Endo drugs -Antimetabolites -Neuropsych drugs
Mechanism of
(a) Fondaparinox
(b) Bivalirudin
(c) Rivaraoxaban
(d) Enoxaparin
Mechanism
(a) Fondaparinox = indirect thrombin inhibitor, acts like LMWH to bind ATIIII (which inactivates Xa)
(b) Bivalirudin = direct thrombin inhibitor
(c) Rivaraoxaban = direct Xa inhibitor (‘Xaban’)
(d) Enoxaparin = LMWH = Lovenox, binds ATIII
Mechanism of
(a) LMWH
(b) Dabigatran
(c) Apixaban
Mechanism
(a) LMWH = Enoxaparin = binds ATIIII (which inactivates Xa)
(b) Dabigatran = direct thrombin inhibitor
(c) Apixaban = direct Xa inhibitor ‘Xaban’
Mechanism of
(a) Argatroban
(b) Rivaroxaban
(c) Heparin
(d) Fondaparinox
Mechanism
(a) Argatroban = direct thrombin inhibitor
(b) Rivaroxaban = direct Xa inhibitor ‘Xaban’
(c) Heparin = binds ATIII to irreversibly inhibit thrombin and Xa
(d) Fondaparinox = indirect thrombin inhibitor that binds and inactivates ATIII
Name the 3 indirect thrombin inhibitors
3 indirect thrombin inhibitors: bind ATIII
Heparin (unfractionated)
LMWH (Enoxaparin)
Fondaparinux
Unfractionated heparin vs. LMWH
(a) Activity
(b) Monitoring
(c) When need to use unfractionated
(a) Unfractionated heparin binds ATIII w/ higher affinity so inhibits both thrombin and Xa, while LMHW binds ATIII to inhibit Xa w/ less effect on thrombin
(b) LMWH doesn’t require monitoring, much more predictable response => just give a weight-based dose
(c) LMWH renally excreted, so need to use unfractionated in renal insufficiency
AC in pregnancy
Heparin (and esp. LMWH) are very safe in pregnancy
“keep the baby heppy w/ heparin”
While coumadin is teratogenic: can cause hemorrhage and abnormal bone formation in utero
Name 3 main clinical indications for indirect thrombin inhibitors
Indirect thrombin inhibitors (heparin, LMWH, fondaparinux)
- Acute tx of DVT and PE
- Ppx of DVT and PE
- Acute tx of MI
Name an electrolyte abnormality seen as an AE to long term heparin therapy
Long term heparin therapy can result in hyperkalemia 2/2 hypoaldosteronism (reduced aldo release from adrenal cortex)
Differentiate the effect of protamine sulfate on indirect thrombin inhibitors
Protamine sulfate = heparin reversal agent
-less effective against LMWH and does not at all reverse fondaparinux
Why does warfarin have so many drug interactions?
B/c it’s metabolized by cyt p450
=> any drug that activates p450 (ex: rifampin, isoniazid) can decrease circulating levels
=> any drug that inhibits p450 can increase risk of warfarin toxicity
Differentiate the risk of HIT w/ the different indirect thrombin inhibitors
HIT risk highest w/ unfractionated heparin
- intermediate risk w/ LMWH (enoxaparin)
- low to no risk w/ fondaparinux
Fondaparinox vs. Enoxaparin
(a) Mechanism of action
(b) Risk of AE
Fondaparinox (binds ATIII so indirect thrombin inhibitor) vs. Enoxaparin (LMWH also binds ATIII)
(a) Both are indirect thrombin inhibitors, but fondaparinox binds ATIII w/ different affinity so inhibits Xa stronger w/ less effect on thrombin
(b) Fondaparinox has lowest risk (almost no risk) of HIT
Main shared indication of Bivalirudin and Argatroban
Bilvalirudin and Argatroban (and Dabigatran) are direct thrombin inhibitors that are used for anticoagulation in HIT
Name the 2 direct Xa inhibitors
Direct Xa inhibitors have ban Xa in their name!!!
Apixaban
Rivaroxaban ‘Xa-ban’
Mechanism of warfarin
Warfarin inhibits VKOR (vitamin K epoxide reductase) enzyme in the liver that activates vit K
-so vit K is inactive and can’t gamma carboxylate protein C/S, factors 1972
What test is best for monitoring warfarin therapy and why?
Warfarin therapy best monitored by PT/INR (INR is just an internationally standardized PT) b/c PT measured extrinsic pathway and common pathway
Extrinsic pathway involves just factor VII and X, and factor VII has the shortest half life of the vitamin-K dependent clotting factors so best to monitor for warfarin effect
What to do when you get symptomatic bleeding on warfarin therapy
- Stop warfarin therapy
- Give factors
- need to immediately replace factors, b/c stopping warfarin and giving vitamin K only allows for synthesis of new factors, still takes time for these factors to be made, so need to treat immediately by giving factors - Give vitamin K
Why does warfarin have so many drug interactions?
B/c it’s metabolized by cyt p450
=> any drug that activates p450 (ex: rifampin, isoniazid) can decrease circulating levels
=> any drug that inhibits p450 can increase risk of warfarin toxicity
Mechanism of
(a) Fondaparinox
(b) Clopidogrel
(c) Rivaraoxaban
(d) Abcximab
Mechanism of
(a) Fondaparinux = indirect thrombin inhibitor by binding ATIII (antithrombin III)
(b) Clopidogrel = ADP-receptor antagonist
- ADP receptor (P2-Y12) on plts is what allows ADP to bind and activate plts to aggregate
(c) Rivaraoxaban = direct Xa inhibitor
(d) Abcximab = monoclonal ab against plt receptor Gp2b3a
TXA2 released by plt degranulation
(a) Where and how produced
(b) Function
TXA2 (thromboxane A2)
(a) Produced by COX enzyme in plts- so this is inhibited by plts (mechanism by which plts inhibit plts)
(b) Function to activate plts to degranulate and aggregate
Mechanism by which aspirin inhibits platelets
ASA inhibits COX1 and COX2 (irreversibly via covalent acetylation) => decreased production of TXA2 which stimulates plt degranulation and aggregation
What is dual plt therapy?
Dual therapy = both
- Aspirin (inhibits TXA2 production by inhibiting COX)
- ADP receptor (P2-Y12) inhibitor that prevents ADP’s activation of plts to cause aggregation
Describe aspirin pseudo-allergy
(a) Clinical symptoms
(b) Why ‘pseudo’
(c) Seen in what pts?
ASA pseudo allergy
(a) Hives, itching, SOB shortly after ASA administration
(b) Pseudo b/c not due to IgE cross-linking, instead is due to increased leukotriene synthesis (AA shunted down LOX since COX is inhibited)
(c) More common in pts w/ h/o asthma, atopy
Why is aspirin held for a few days and not just one dose before surgery?
Aspirin irreversibly inhibits COX enzyme by covalently acetylating COX
-so can’t make any more TXA (no more active COX) until gene transcription upregulated and new COX enzyme is produced
Key is that aspirin irreversibly covalently acetylates COX