Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Indirect Thrombin Inhibitors (act through antithrombin)
Binds to & enhances anti-thrombin, which then inhibits clotting factors (IIa, IXa, Xa). Heparin is then released for renewed binding to more anti-thrombin.
|
bleeding, loss of hair (reversible alopecia), osteoporosis, mineralocorticoid deficiency,
heparin-induced thrombocytopenia (systemic hypercoagulable state), allergic reactions
|
CI: bleeding issues (hemophilia, hypertension), infective endocarditis, active TB, visceral carcinoma, advanced hepatic/renal disease
|
|
|
|
Term
Enoxaparin
and other low molecular weight "parin"s |
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Indirect Thrombin Inhibitors (act through antithrombin)
Inhibit activated factor X but have less effect on thrombin than HMW
Equal efficacy but increased bioavailability = less frequent dosing requirements
|
“
Osteoporosis, thrombocytopenia
|
thromboembolism
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Indirect Thrombin Inhibitors (act through antithrombin)
Binds antithrombin with high specific affinity resulting in efficient inactivation of factor Xa
|
Does not cross-react with heparin-induced thrombocytopenia (HIT) antibodies in most people
|
Thromboembolism
Long half-life (1/day dosage)
|
|
|
|
Term
Epirudin
and other "rudin"s |
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Direct Thrombin Inhibitors (Bind directly to thrombin)
Bivalent DTIs that bind at both the catalytic or active site of thrombin as well as at a substrate recognition site
Excreted by kidney
|
Up to 40% of patients who receive long-term infusions develop antibody against thrombin-lepirudin complex
|
Rx: HIT, coronary angioplasty
in patients w. HIT
CI: renal insufficiency
Preferred for patients with hepatic insufficiency
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Direct Thrombin Inhibitors (Bind directly to thrombin)
Small molecules that bind only at the thrombin active site
Clearance by liver
|
|
Rx: HIT, coronary angioplasty
in patients w. HIT
CI: hepatic insufficiency
Preferred for patients with renal insufficiency
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Coumarin Anticoagulants
Blocks the γ-carboxylation of glutamate residues in prothrombin and factors VII, IX, and X as well as anticoagulant proteins C and S. => incomplete coagulation factor molecules that are biologically inactive. Protein carboxylation is coupled to oxidation of vitamin K. Warfarin prevents reductive metabolism of the inactive vitamin K back to its active form.
|
CI: pregnancy (crosses placenta
and can cause hemorrhage or
abnormal bone formation in fetus)
Drug Interactions:
Synergistic effects with aspirin pyrazolones, metronidazole & trimethoprim
Competitive antagonism with
barbiturates & rifampin
|
By interfering with the
synthesis of clotting factors,
coumarin anticoagulants take
longer until the onset of effects.
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Fibrinolytic Drugs (Catalyze plasminogen → plasmin )
Protein synthesized by streptococci that combines with the proactivator plasminogen forming an enzymatic complex that catalyzes conversion of plasminogen to plasmin
|
Patients with antistreptococcal antibodies can develop fever, allergic reactions, and resistance ↑ bleeding risk in ischemic stroke
|
Pulmonary embolism
Deep venous thrombosis
Ascending thrombophlebitis Peripheral vascular disease
Acute MI
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Fibrinolytic Drugs (Catalyze plasminogen → plasmin )
Enzyme synthesized by the kidney that directly converts plasminogen to active plasmin
|
|
“
|
|
|
|
Term
Tissue Plasminogen Activator |
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
Fibrinolytic Drugs (Catalyze plasminogen → plasmin )
Activates plasminogen that is bound to fibrin, which (theoretically) confines fibrinolysis to formed thrombi and avoids systemic activation
|
|
“ + acute ischemic stroke
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Anticoagulant Drugs
recombinant form of activated protein C, which inhibits factors Va and VIIIa; anti-thrombotic, anti-inflammatory, and profibrinolytic properties
|
bleeding
|
Sever sepsis or septic shock
(but efficacy is now questionable)
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Irreversibly block the ADP receptor on platelets, inhibiting ADP induced platelet aggregation
|
hemorrhage, leukopenia, purpura
Agranulocytosis,
blood dyscrasias
Clopidogrel has ↓ neutropenia
|
Prevention of vascular events among patients with transient ischemic attacks, strokes, and angina pectoris
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Irreversibly block the ADP receptor on platelets, inhibiting ADP induced platelet aggregation
|
hemorrhage, leukopenia, purpura
Agranulocytosis,
blood dyscrasias
Clopidogrel has ↓ neutropenia
|
Prevention of vascular events among patients with transient ischemic attacks, strokes, and angina pectoris
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Inhibits glycoprotein IIb/IIIa receptor. This glycoprotein acts as the final common pathway for platelet aggregation. It is normally activated by fibronectin,
vitronectin, fibrinogen & vWF
|
Thrombocytopenia
|
Percutaneous coronary
interventions, acute coronary
syndrome
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Inhibits glycoprotein IIb/IIIa receptor
|
Thrombocytopenia
|
Percutaneous coronary interventions, acute coronary
syndrome
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Inhibits glycoprotein IIb/IIIa receptor
|
Thrombocytopenia
|
Percutaneous coronary interventions, acute coronary
syndrome
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Vasodilator; ↓ platelet function by inhibiting adenosine uptake and cGMP phosphodiesterase activity
|
Little or no beneficial effect on its own
|
prevent cerebrovascular ischemia (w/aspirin), thromboembolis with prosthetic heart valves (w/ warfarin)
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
Phosphodiesterase inhibitor that promotes vasodilation and inhibition of platelet aggregation
|
|
Rx: intermittent claudication
(leg cramp w/ exercise d/t
arterial obstruction)
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Antiplatelet Agents
cAMP-PDE-III inhibitor that inhibits megakaryocyte maturation into platelets
|
Hepatic toxicity, CVA, hemorrhage
|
Essential thrombocytosis (overproduction of platelets); chronic myeloid leukemia
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Fibrinolytic Inhibitors
Inhibits fibrinolysis by inhibiting
plasminogen activation
|
|
Rx: adjunctive therapy in
hemophilia, or as a prophylaxis
for re-bleeding from
intracranial aneurysms
|
|
|
|
Term
|
Definition
CH 34 Drugs Used in Disorders of Coagulation
Fibrinolytic Inhibitors
Serine protease inhibitor that inhibits fibrinolysis by free plasmin. Inhibits the
plasmin-streptokinase complex
|
↑ risk of renal failure, heart attack, and stroke
|
Reduce bleeding from surgery
|
|
|
|