Hematology Pharmacology

Front 1

Heparin
(Mechanism)

Back 1

1. Binds to antithrombin III inducing a conformational change that allows antithrobmin III to inactivate other clotting factors (IIa, IXa, and Xa; also XIa and XIIa);
Antiplatelet properties by blocking action of vWF

Front 2

Heparin
(Side effects, pharmacokinetics, drug interactions)

Back 2

1. Bleeding
Osteoporosis
Thrombocytopenia
Reversible hair loss
2. A: parenterally
D: Extensively bound to LDL, globulins, and fibrinogen
M: Cleared from circulation by reticuloendothelial system;
Partially metabolized by liver
E: Small fraction excreted in the urine unchanged
Half life: 1-2 hours (decreased in patients with liver impairment; prolonged in patients with cirrhosis or severe renal impairment)
3. Other anticoagulants (antihistamines, digitalis, tetracycline)

Front 3

Heparin (LMWH)
(Mechanism)

Back 3

1. Preferential effect on factor X; fewer effect on thrombin than heparin. LMWHs increase activity of anti-thrombin III by 1000 fold

Front 4

Heparing (LMWH)
(Side effects, pharmacokinetics, drug interactions)

Back 4

1. Bleeding
Osteoporosis (much less than with unfractionated heparin)
Thrombocytopenia (rare)
Skin reactions near site of injection
2. A: Subcutaneous injection
D: Less non-specific binding to plasma proteins than heparin
M: Long half life
E: Renal elimination; adjustments necessary for those with renal insufficiency
3. Other anticoagulants

Front 5

Warfarin
(Mechanism)

Back 5

1. inhibits hepatic synthesis of vitamin K-dependent clotting factors (II, VII, IX, X) by interfering with the reduction of vitamin K by inhibiting vitamin K epoxide reductase

Front 6

Warfarin
(Side effects, pharmacokinetics, drug interactions)

Back 6

1. Bleeding
Skin necrosis and Purple Toe Syndrome
Teratogenic if used during pregnancy
2. A: Oral
D: Bound to plasma proteins (97-99.9%)
M: Cytochrome P450's; sensitive to inhibitors and inducers
E:Principally in urine as metobolites and to a lesser extent in bile
Long half life ~36 hours
3. Salicylates/NSAIDs (increased risk of bleeding)

Front 7

Aspirin
(Mechanism)

Back 7

1. Irreversibly inhibits (by acetylation) and inactivates COX1 in platelets. Reversibly inhibits COX2

Front 8

Aspirin
(Side effects, pharmacokinetics, drug interactions)

Back 8

1. increased risk of bleeding (esp with alcoholism, inherited, or acquired bleeding disorders. GI toxicity (ulcers), hypersensitivity reactions
2. (A) Oral, (D) wide distribution, cross placenta, synovial fluid, 95% bind to plasma proteins at high concentrations (M) hydrolized to salicylate in GI mucosa, further hydrolized by esterases in liver (mainly) and plasma. (E) Excreted by the kidney, t1/2 of aspirin - 15 to 20 mins, t1/2 salicylate - 2-3 hours (15-30 hrs in high doses)
3. Alcohol, Protein bound drugs (anticoagulants, anticonvulsants, alkalinizing/acidifying agents

Front 9

Ticlopidine
(Mechanism)

Back 9

1. Inhibits platelet aggregation and release of granule constituents (inhibits ADP induced fibrinogen binding for platelet-platelet interactions.
**platelet effects are irreversible for the life of the platlet (5-9 days)

Front 10

Ticlopidine
(Side effects, pharmacokinetics, drug interactions)

Back 10

1. Severe hematologic effects (neutropenia, granulocytosis, TTP, aplastic anemia)
2. (A) Oral, food increases bioavailability. (D) Plasma bound. (M) Liver (E) 60% urine, 23% feces
3. Drugs metabolized by hepatic microsomal enzymes (causes increased plasma t1/2)

Front 11

Clopidogrel (Plavix)
(Mechanism)

Back 11

1. Similar MOA to Ticlopidine. Prodrug that inhibits platelet agregation (dependent on liver for activation of prodrug) by irreversably binding ADP receptor thus preventing activation. Inhibits dense granule (ADP, calcium, serotonin) and alpha granule (fibrinogen, thrombospondin).

Front 12

Clopidogrel (Plavix)
(Side effects, pharmacokinetics, drug interactions)

Back 12

1. Drugs metabolized by hepatic microsomal enzymes (aspirin, heparin, warfarin, tamoxifen)
2. (A) 50% Orally absorbed. (D) Plasma bound. (M) Hydrolyzed by liver to inactive metabolite. (E) Excreted in urine, t1/2 - 8 hrs (11 days for the drug bound to the platelets)