Pharm II - Hefnawy Flashcards
1
Q
what do you need to do with thrombin inhibition?
A
-do a aPTT for monitoring***
2
Q
what do you need to do with factor 10 inhibition?
A
-no need for monitoring with aPTT or PT**
3
Q
INDIRECT thrombin (factor 2a) inhibitors
A
- unfractionated heparin
- LMW heparin –>Dalteparin, Enoxaparin
- fondaparinux
4
Q
unfractionated heparin
A
- effectiveness of drug is variable (extractions can lead to variable lengths and allergic rxns)
- binds as cofactor to antithrombin 3** –> allows it to bind to factor 10a and thrombin (inhibits thrombin 10x more)**
- also inhibits factor 5,8,9a,11a,13a
- spares factor 7a –> does not effect extrinsic pathway**
5
Q
difference b/w unfrationated and LMW heparin**
A
- unfractionated - inhibits thrombin 10x more than factor 10a because it has a longer tail
- LMW - inhibits factor 10a more than thrombin bc it has a shorter tail
6
Q
unfractionated heparin indications
A
- short term anticoagulant
- does not dissolve clots, but prevents spreading*
- prevent and treat venous thromboembolism, clotting during surgery (heart, blood vessels), DIC patients*
- drug of choice for acute arterial occlusion due to fast action*
- bridge therapy with warfarin to prevent hyper coagulation** (used before warfarin*)
- green top tubes
7
Q
pharmokinetics of UF heparin
A
- very neg. charged
- given subcutaneous or infusion (IV)** - not given IM (can lead to hematoma)
- does not cross placenta
- high affinity to proteins, Macs, endothelial cells –> poor renal excretion*
- cleared by liver heparinase**
- heparin resistance if too many proteins bind heparin
8
Q
side effects of UF heparin
A
- heparin induced thrombocytopenia (HIT)** –> higher in UF heparin than LMW heparin
- low aldosterone synthesis and angiotensin II receptors –> Hyperkalemia**
- long term administration –> osteoporosis and fractures*
9
Q
protamine sulfate**
A
- a heavily + charged molecule that combats the effects of heparin (a heavily neg charged molecule)
- antidote for UF heparin (not as good for LMW heparin)
10
Q
heparin induced thrombocytopenia (HIT)
A
- heparin binds to PF4 –> IgG antibody attaches with Fc region –> activates platelets causing them to release more factors causing them to aggregate and form thrombi –> thrombocytopenia*
- worry about platelet count the 1st few days someone is on heparin
11
Q
what’s leads to heparin resistance
A
- excessive heparin binding proteins –> cannot have effects when bound
- deficient antithrombin 3 –> heparin used as cofactor and can’t function without
12
Q
heparin contraindications
A
- history of allergy or HIT*
- hypersensitivity patients with risk of bleeding
- hypertension* –> cerebral hemorrhage
- liver impairment** –> heparinase in liver clears it; no excretion in renal bc it is protein bound
- other NSAIDs
-can give to pregnant women (strictly)* –> does not cross placenta
13
Q
LMW heparin (Dalteparin, enoxaparin and danaparoid)
A
- binds to antithrombin 3 –> stronger inhibition of 10a than thrombin due to shorter tail**
- less inhibition of thrombin than UFH –> don’t need aPTT monitoring*
- less frequent cause of HIT*
- better bioavailability than UFH when injected subcu
- less binding of protein, Macs, endothelial –> renal clearance** (not used in renal failure)
- less risk of osteoporosis
- protamine sulfate not as good of reversal*
14
Q
Fondaparinux
A
- binds to antithrombin 3 with higher affinity that LMW heparin*
- long half-life (15hr)* –> only inject subcu 1x daily
- lower risk of HIT than UFH and does not cross react**
- less reversible with protamine sulfate**
- not bound to protein –> renal clearance** (not given in renal insufficiency)
- higher risk of bleeding than LMW heparin*
15
Q
oral direct 10a inhibitors
A
- Rivaroxaban (Xarelto)
- Betrixaban
- Apixaban
- Edoxaban
“xa” - direct factor 10a inhibitors
don’t interfere with antithrombin/thrombin –> don’t affect aPTT*
