Heme drugs Flashcards
1
Q
herparin mech and clinical use
A
- cofactor for the activation of antithrombin
- decreases thrombin and factor Xa
- short half-life
- used for immediate anticoagulation for PE, ACS, MI and DVT
- used during pregnancy
2
Q
heparin tox
A
- bleeding, HIT, osteoporosis, drug-drug interactions
- protamine is rapid reversal agent (+vely charged molecule that binds negatively charged heparin)
3
Q
HIT
A
- development of IgG Abs to hep-PF4
- leads to thrombosis and thrombocytopenia
4
Q
argatroban, bivalirudin
A
- derivatives of hirudin, the antcoagulant used by leeches, inhibit thrombin directly (binds thrombin active site)
- used instead of heparin for anticoagulating pts with HIT
5
Q
warfarin
A
- interferest with normal synthesis and gamma-carboxylation of vit K dependent clotting factors, protein C and S
- p450 metabolism
- has effect on extrinsic pathway (PT)
- tox: bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions
- give FFP for faster reversal than Vit K
6
Q
direct factor Xa inhibitors
A
- apixaban, rivaroxaban
- binds Xa directly and inhibits its activity
- used for treatment and prophylaxis for DVT and PE, stroke prophylaxis in pts with atrial fibrillation
- oral agents that do not require coag monitoring
- tox: bleeding, no specific reversal agent available
7
Q
thrombolytics
- alteplase (tPA), reteplase (rPA) and tenecteplase (TNK-tPA)
A
- directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots
- increases PT, PTT, no change in platelet count
- used in early MI, stroke, direct thrombolysis of severe PE
- tox: bleeding
- treat tox with aminocaproic acid
8
Q
aspirin
A
- irreversibly inhibits COX enzyme by covalent acetylation
- platelets cannot make new enzyme
- increased bleeding time, dec TXA and prostaglandins
- no effect on PT and PTT
- tox: GI ulceration, tinnitus, renal failure, interstitial nephritis, upper GI bleeding
9
Q
ADP receptor inhibitors
- clopidogrel, ticlopidine, prasugrel, ticagrelor
A
- inhibit platelet aggregation by blocking ADP receptors
- inhibits fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
- used in ACS, coronary stenting, decreased incidence or recurrence of thrombotic stroke
- tox: neutropenia (ticlopidine), TTP/HUS may be seen
- can be substituted for aspirin in aspirin-induced asthma
10
Q
cilostazol, dipyridamole
A
- PDE III inhibitors, inc cAMP in platelets, inhibiting aggregation, vasodilators
- used in claudication, coronary vasodilation, prevention of stroke, TIAs and angina ppx
- tox: nausea, headache, flushing, hypotension, abdominal pain
11
Q
GP IIb/IIIa inhibitors
- abciximab, eptifibatide, tirofiban
A
- bind to GP IIb/IIIa receptors on activated platelets, preventing aggregation
- used for unstable angina, PCI
- tox: bleeding, thrombocytopenia
12
Q
MTX
A
- folic acid analog that inhibits DHF reductase –> dTMP –> decreased DNA and protein synthesis
- used in leukemias, lymphomas and chronic sarcomas as well as abortion, ectopic preg, RA, psoriasis, IBD
- tox: myelosuppression (pancytopenia), macrovesicular fatty change in liver, mucositis, teratogenic
- can prevent myelosuppression with folinic acid rescue
13
Q
5-FU
A
- pyrimidine analog bioactivated to 5F-dUMP which covalently complexes folic acid
- this complex inhibits thymidylate synthase –> dec dTMP –> dec DNA and protein synthesis
- used in colon cancer, pancreatic cancer and basal cell carcinoma
- tox: myelosuppression (NOT reversible with leucovorin), photosensitivity, if overdose, “rescue” with uridine
14
Q
cytarabine (arabinofuranosyl cytidine)
A
- pyrimidine analog –> inhibits DNA polymerase
- used in leukemias and lymphomas
- tox: leukopenia, thrombocytopenia, megaloblastic anemia
- CYTarabine causes panCYTopenia
15
Q
azathioprine, 6-MP and 6-TG
A
- purine (thiol) analogs –> decreased de novo purine synthesis
- activated by HGPRT
- used in preventing organ rejection, RA and SLE, leukemia, IBD
- affects bone marrow, GI and liver
- azathioprine and 6-MP are metabolized by xanthine oxidase, so increased tox with allopurinol
