Thrombosis and Dermatopath Flashcards
Unfractionated heparin
Class: Indirect thrombin inhibitors
Mech: Bind antithrombin, potentiating formation of antithrombin-coagulation factor complex (Xa, IIa; some IXa, XIa, XIIa)
Thera: Prevention and treatment of venous thromboembolism; maintain patency in dialysis, bypass surgery, venous lines; unsable angina, MI, angioplasty, stent
Important SE’s: HIT (platelets can be removed by splenic macrophages, leading to thrombocytopenia; IgG is binding heparin and PF4 on platelets), bleeding
Other SE’s: Osteoporosis
Misc: Given parenterally (iv or sc); monitored via PTT (want 2-2.5X normal value); reversed by protamine: rapid to turn-on and turn-off
Dalteparin (Fragmin)
Class: Indirect thrombin inhibitors
Mech: LMWH that inhibits thrombin less effectively than Xa
Thera: Prevent thrombosis and embolism from clots
Important SE’s: Bleeding; LOWER RISK OF INDUCING HIT, ALONG WITH THE OTHER LMWH’S!!!
Misc: Monitored by heparin assay (anti-factor Xa) but no need for monitoring; fixed or weight-adjusted dosing; longer half-life than heparin (1-2/day); reversed by protamine (less effective than with unfrac heparin)
Enoxaparin (Lovenox)
Class: Indirect thrombin inhibitors
Mech: LMWH that inhibits thrombin less effectively than Xa
Thera: Drug of choice in pregnancy; prevention and treatment of venous thromboembolism
Important SE’s: HIT; bleeding; osteoporosis and thrombocytopenia uncommon
Misc: Can be monitored by heparin assay (anti-factor Xa); longer half-life than heparin (1-2/day); reversed by protamine
Tinzaparin (Innohep)
Class: Indirect thrombin inhibitors
Mech: LMWH that inhibits thrombin less effectively than Xa
Important SE’s: HIT; osteoporosis and thrombocytopenia uncommon
Other SE’s: Bleeding
Misc: Monitored by heparin assay (anti-factor Xa); longer half-life than heparin (1-2/day); reversed by protamine
Fondaparinux (Arixtra)
Class: Indirect thrombin inhibitors
Mech: Synthetic polysaccharide (pentasaccharide) that binds active site of antithrombin; inhibits Xa
Thera: Given for HIT; moderate VTE risk in hospitalized patients as an alternative to LMWH
Other SE’s: Bleeding
Misc: No antidote
Warfarin (Coumadin)
Class: Vitamin K antagonist
Mech: Blocks vitamin K-dependent gamma-carboxylation of factors II, VII, IX, X, Protein C and S (does not affect already synthesized factors)
Thera: Long-term anticoagulation
Important SE’s: Thrombosis (Protein C depression, with skin and fat necrosis)
Other SE’s: Bleeding
Misc: Metabolism enhanced by drugs that induce P450 activity (e.g., barbiturates); monitored by PT/INR; reversed by vitamin K and factor concentrates or if you just stop the warfarin; contraindicated in pregnancy (teratogen); oral with long half-life and slow onset; preceded by another anticoagulant; NO ORGAN TOXICITY!! 99% bound to albumin so easy to be displaced
Bivalirudin (Angiomax)
Class: Direct thrombin inhibitor
Mech: Inactivate fibrinogen-bound AND unbound thrombin; irreversible; directly binds to thrombin catalytic site
Thera: Percutaneous coronary intervention (PCI); inhibit platelet aggregation
Important SE’s: Bleeding
Misc: Administered parenterally; monitored by PTT; no antidote; immediate onset of action
Argatroban (Acova): how is it different from bivalirudin?
Thera: includes HIT
Dabigatran (Pradaxa)
Class: Direct thrombin inhibitor
Mech: Inactivate fibrinogen-bound AND unbound thrombin; competitive (reversible); serine protease inhibitor
Thera: DVT / PE; AFib
Important SE’s: Bleeding
Misc: Oral; no antidote; renal fixed dose clearance
Rivaroxaban (Xarelto)
Class: Direct Xa inhibitor
Mech: Reversible bind active site of Xa
Thera: DVT / PE prophylaxis, Afib, postop DVT prophylaxis
Important SE’s: Bleeding
Misc: Oral; no antidote; renal fixed dose clearance; no methods to assess levels
How is Apixaban different from rivaroxaban?
IT’S NOT!!!
Alteplase
Class: Fibrinolytic
Mech: Lyse already formed clots by activating circulating plasminogen (converted to plasmin)
Thera: Acute MI, acute stroke, central DVT, multiple PE;
Misc: effective when started within 3-12 hours of thrombosis, given for 1-2 days; not entirely clot specific
Reteplase (Retavase): how different from alteplase?
Mech: Lyse already formed clots; more clot specific, less systemic activation
How is tenecteplase different from reteplase?
IT’S NOT!!
Aspirin
Class: Antiplatelet
Mech: Irreversibly inhibits platelets and irreversibly binds to COX-1, preventing thromboxane A2 formation and platelet aggregation; prevents prostacyclin PGI2 formation, which inhibits platelet aggregation; relatively weak but effective antiplatelet drug
Thera: Often as “baby aspirin” to prevent and treat MI and stroke/TIA
Dipyridamole (Persantine)
Class: Antiplatelet
Mech: PDE inhibitor –> increase in platelet cAMP
Thera: Weak antiplatelet effect; secondary stroke prevention
Misc: Given parenterally; used alone or with aspirin
Clopidogrel (Plavix)
Class: Antiplatelet
Mech: Inhibits platelet ADP receptors; activated by P450 enzymes in liver and has irreversible binding leading to slow offset
Thera: Prevent & treat ACS, stroke, peripheral vascular disease, angina, stent
Important SE’s: Bleeding; TTP (rare)
Misc: Reversed by platelet transfusion; USE PRASUGREL IF THERE IS RESISTANCE TO CLAPIDOGREL!!
Abciximab (Reopro)
Class: Antiplatelet
Mech: Monoclonal antibody against GP IIb/IIIa
Important SE’s: May elicit immune response
Misc: Given parenterally
Eptifibatide (Integrilin)
Class: Antiplatelet Mech: Fibrinogen analog which competes with endogenous fibrinogen for IIb/IIIa Important SE's: Bleeding; ACS; PCI Other SE's: Thrombocytopenia Misc: Given parenterally
Tirofiban (Aggrastat)
Class: Antiplatelet
Mech: Fibrinogen analog which competes with endogenous fibrinogen and vWF for IIb/IIIa
Important SE’s: Bleeding; NSTE-ACS
Misc: Given parenterally; immediate effect
Hydrocortisone
Class: Steroid
Thera: Dermatitis, psoriasis
Important SE’s: Atrophy/thinning of skin (collagen), stretch marks, talangiectasias, acne, cataract or glaucoma if applied near eye
Other SE’s: Systemically, affects hypothalamic-pituitary-adrenal axis –> growth retardation
Misc: Seven classes, w/class I being the strongest and class VII being the weakest; side effects may be permanent
Cyclosporine
Class: Immunosuppressant
Thera: Inflammatory conditions (psoriasis)
Important SE’s: Raise blood pressure, damage kidneys if used long-term
Methotrexate
Class: Folate analog
Mech: Inhibits DHFR
Thera: Inflammatory conditions (psoriasis), conditions needing immunosuppression
Important SE’s: Hepatotoxicity (develops slowly, can give up to 4.5 g over life); pulmonary toxicity (develops quickly); leukopenia; rarely, renal toxicity
Other SE’s: Nausea, vomiting
Misc: PO, IM (1/week); any drug increasing unbound protein may cause methotrexate toxicity (sulfa, salicylates, TCN, phenytoin)
Biologics
Mech: Block TNF-a
Thera: Inflammatory conditions, arthritis
Important SE’s: Few (may unmask neurologic disease, latent infections (must do PPDs), malignancies)
Misc: Costly
UV light therapy
Class: UVA, UVB, UVC
Mech: Immunosuppression of T-cells via type I or type II reactions –> mono- or bifunctional adducts in DNA
Thera: Inflammatory conditions: atopic dermatitis, CTCL, lichen planus, psoriasis (not useful for non-inflammatory conditions)
Important SE’s: Skin cancer, thinning/leathering of skin
Misc: Usually used with psoralens (photosensitizing agents that increase efficacy); phenothiazines, thiazides, sulfonamides, NSAIDs, tetracycline, benzodiazapenes also sensitize skin to light therapy
Isotretinoin (Accutane)
Class: Retinoid
Mech: Stimulate epithelial cell turnover; also anti-inflammatory
Thera: Acne
Important SE’s: Teratogenic effects (washes out in three weeks)
Misc: Good as adjunct to other therapies
Acitretin (Soriatane)
Class: Retinoid
Mech: Stimulate epithelial cell turnover; also anti-inflammatory
Thera: Psoriasis
Important SE’s: Teratogenic effects (stays in fat stores for three years)
Misc: Good as adjunct to other therapies
