Primary CNS Vasculitis of Childhood Medication

Updated: Dec 14, 2018
  • Author: Jefferson R Roberts, MD; Chief Editor: Lawrence K Jung, MD  more...
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Medication

Immunosuppressants

Class Summary

Induction immunosuppression occurs over a 6-month period with cyclophosphamide, followed by 18 months of maintenance therapy with azathioprine or mycophenolate mofetil. An oral corticosteroid is administered with cyclophosphamide before a slow, controlled taper during maintenance therapy.

Cyclophosphamide (Cytoxan)

Cyclic polypeptide that suppresses some humoral activity. Chemically related to nitrogen mustards. Activated in the liver to its active metabolite, 4-hydroxycyclophosphamide, which alkylates the target sites in susceptible cells in an all-or-none type reaction. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Biotransformed by cytochrome P-450 system to hydroxylated intermediates that break down to active phosphoramide mustard and acrolein. Interaction of phosphoramide mustard with DNA considered cytotoxic.

When used in autoimmune diseases, mechanism of action is thought to involve immunosuppression due to destruction of immune cells via DNA cross-linking.

In high doses, affects B cells by inhibiting clonal expansion and suppression of production of immunoglobulins. With long-term low-dose therapy, affects T-cell functions.

Azathioprine (Imuran)

Imidazolyl derivative of 6-mercaptopurine. Many of biological effects are similar to those of parent compound. Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver. No azathioprine or mercaptopurine is detectable in urine 8 h after taken.

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Mechanism whereby azathioprine affects autoimmune diseases is unknown. Works primarily on T cells. Suppresses hypersensitivities of cell-mediated type and causes variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity tests are suppressed to a greater degree than antibody responses. Works very slowly; may require 6-12 mo of trial prior to effect. As many as 10% of patients may have idiosyncratic reaction disallowing use. Do not allow WBC count to drop below 3000/mL or lymphocyte count to drop below 1000/mL.

Available in tablet form for PO administration or in 100-mg vials for IV injection.

Mycophenolate mofetil (CellCept)

Inhibits inosine monophosphate dehydrogenase and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

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Anti-inflammatory Agent

Class Summary

An oral corticosteroid is administered with cyclophosphamide. Attempt a slow, controlled downward dosage taper during maintenance therapy.

Prednisone (Deltasone, Prednisone Intensol Concentrate)

Used to control acute symptoms and laboratory evidence of inflammation. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocytes and antibody production.

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Antiplatelet and anticoagulant agents

Class Summary

Low molecular weight heparin is administered for a brief period at presentation and is followed by an antiplatelet agent; this is frequently administered in progressive large-medium vessel disease.

Enoxaparin (Lovenox)

Produced by partial chemical or enzymatic depolymerization of UFH. Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared to UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.

No use in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Titrate dosing based on enoxaparin levels. Average duration of treatment is 7-14 d.

Aspirin (Bayer)

Odorless white powdery substance available in 81 mg, 325 mg, and 500 mg for PO administration. When exposed to moisture, aspirin hydrolyzes into salicylic acid and acetic acids.

Stronger inhibitor of both prostaglandin synthesis and platelet aggregation than other salicylic acid derivatives. Acetyl group is responsible for inactivation of cyclooxygenase via acetylation. Aspirin is hydrolyzed rapidly in plasma, and elimination follows zero order pharmacokinetics.

Irreversibly inhibits platelet aggregation by inhibiting platelet cyclooxygenase. This, in turn, inhibits conversion of arachidonic acid to PGI2 (potent vasodilator and inhibitor of platelet activation) and thromboxane A2 (potent vasoconstrictor and platelet aggregate). Platelet-inhibition lasts for life of cell (approximately 10 d).

May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis. Reduces likelihood of myocardial infarction. Also very effective in reducing risk of stroke. Early administration of aspirin in patients with AMI may reduce cardiac mortality in first mo.

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