hemostasis disorder drugs Flashcards
1
Q
platelet inhibitors
A
Aspirin
ticlopidine
clopidogrel
abciximab
small mol receptor inhibitors (tirofiban, eptifibatide)
phosphodiesterase inhibitors (dipyridamole, cilostazol)
anagrelide
2
Q
aspirin (acetylsalicylic acid)
A
Inhibits the synthesis of thromboxan A2 (TxA2) by irreversible acetylation of COX-1 in platelets
- Use: reduce risk of MI and recurring transient ishcemic attacks (TIAs)
- Antithrombotic effects on platelts are seen 1-2 days after administration and lasts for the duration of the platelets life span (7-10 days)
- COX is irreversibly inhibited and the platelet has no way to make more
3
Q
ticlopidine
A
ADP antagonist
- Inhibits ADP receptors on platelets which prevents activation of GPIIb-IIIa (GPIIb-IIIa promotes platelet aggregation (binds to fibrinogen))
- Inhibits platelet adhesion (I would think it would inhibit aggregation) and platelet - platelet interactions
- Use: alternative to aspirin to prevent an initial or recurrent thromboembolic stroke
- Oral
- AE: nausea, dyspnea, diarrhe (20%), hemorrhage (5%)
- Rare: severe bone marrow toxicity
4
Q
clopidogrel
A
- Similar mech to ticlopidine but has a lower incidence of adverse effects
- Use: in patients with history of recent stroke/MI or established peripheral vascular disease, and in patients with stents
- Requires activation by CYP2C19 resulting in drug-drug interactions with other drugs metabolized by 2C-19 (its is better than ticlopidine if the patient is not taking other drugs)
- Proton pump inhibitors
- Anti-epileptics (diazepam, phenytoin, mephenytoin)
- Amitryptiline, imiprimine
- Propranolol
- R-warfarin
5
Q
abciximab
A
- Inhibits platelet aggregation by preventing binding of fibrinogen to glycoprotein receptor IIb-IIIa on activated platelets
- Given IV to high risk patients undergoing coronary angioplasty and patients undergoing angioplasty, atherectomy and stent placement - often with clopidogrel
- Expensive
- Bleeding is most common side effect
6
Q
tirofiban and eptifibatide
A
small molecule
tiro - peptidomimetic
epti - cyclic peptide
both have short half lifes
7
Q
dipyridamole
A
phosphodiesterase inhibitors - act inside the cell
- Coronary vasodilator that also inhibits platelet aggregation
- Use: In combination with warfarin - inhibits embolism from prosthetic heart valves
- In combo with aspirin, reduces thrombosis in patients with thrombotic disease
8
Q
cilostazol
A
phosphodiesterase inhibitor - acts inside the cells
- Antithrombotic, antiplastlets and vasodilatory action
- Use: intermittent claudication and PVD
9
Q
anagrelide
A
- Reduces platelet numbers directly
- Inhibits megakaryocyte development in the late postmitotic stage
- Use: treatment of thrombocytosis secondary to myeloproliferative disorders such as polycythemia vera and chronic myelogenous leukemia to reduce the risk of stroke and MI
10
Q
anticoagulants
A
calcium chelators
heparins
11
Q
calcium chelators
A
- Inhibit blood coagulation in vitro - our bodies need Ca so we can’t use it on blood that is in the body
- Examples: oxalic acid, sodium citrate, disodium edetate (EDTA)
12
Q
heparins
A
- Accelerates the action of antithrombin 3 to neutralize thrombin and other coagulation factors
- Standard heparin (UFH)
- Sources: porcine intesintal mucosa and bovine lung
- Structure: sulfated mucopolysaccharide (acidic molecule)
- Formulations: standard, unfractionated heparin (UFH) polymer (3000-30000)
- There are lots of heparins - with different weights - this is a mixture of all of them
- Onset of action: immediate
- Mech of action
- Activates AT3 -> AT3 inactivates factor 2a and 10a
13
Q
AE of heparins
A
- Bleeding/hemorhage - minimized with carful monitoring of PTT and platelet counts
- Allergic reaction (it is an animal prodouct)
- Osteoporosis (long term therapy)
- Transient and occasionally severe heparin induced thrombocytopenia (HIT)
- Type 1 = transient and rapidly reversible
- Antibodies are generated against platelets
- Results in a decrease in platelet count
- Type 2 = severe
- Antibodies decrease platelet count
- These antibodies also activate platelets
- This may produce a thromboembolism, which may be life threatening
- Type 1 = transient and rapidly reversible
14
Q
antidote for OD on standard heparin
A
- Protamine sulfate
- Protamine is a basic protein that binds to heparin (anion/cation interaciton)
- Excessive antidote must be avoided because protamine itself is an anticoagulant
- Need to titrate it - just need enough so that all the heparin is bound but no more
- Protamine is much less capable of reversing the effects of LMWH
15
Q
LMWH
A
- Advantages over UFH
- Dose dependent kinetics
- Conviencnec - can be admin subcutanous, don’t need PTT monitoring
- Safety
- Contrainication: HIT
- Not readily reversed with protamine sulfate (no antidote)
- Monitored by anti-Xa activity assay when needed (not a good eval)
