RECOMBINANT PROTEINS AND OTHER BIOLOGICALS
Becaplermin (Regranex) is a recombinant human platelet–derived growth factor (rhPDGF-BB) which is thought to enhance wound healing by stimulating gran-ulation tissue. It is approved for the treatment of lower extremity neuropathic ulcers extending to the subcuta-neous tissue in diabetic patients with an adequate blood supply. Local irritant reactions (erythema, burning, pain) occur in a minority of patients.
Etanercept (Enbrel) is a recombinant fusion protein de-signed to block the action of TNF-α . The drug is composed of the extracellular ligand-bind-ing portion of the 75-kilodalton human TNF receptor linked to the Fc portion of human IgG1. TNF-α is a cy-tokine thought to play a major role in the pathogenesis of a number of inflammatory skin diseases, including psoriasis. Etanercept binds soluble TNF-α , preventing it from binding to and activating receptors for TNF that are present on cell membranes.
Etanercept is administered by subcutaneous injec-tion. The maximum serum concentration is reached af-ter approximately 72 hours. The half-life is approxi-mately 115 hours.
Etanercept is approved in the United States for the treatment of psoriatic arthritis and rheumatoid arthritis. Although etanercept has not been specifically approved for the treatment of the cutaneous manifestations of psoriasis, it significantly improves the skin lesions of pa-tients with moderate to severe cutaneous psoriasis who have used it for psoriatic joint disease.
Injection site reactions characterized by mild to moderate erythema, itching, burning, and/or pain occur in approximately one-third of patients but rarely neces-sitate drug discontinuation. The impact of etanercept on the host’s response to new or chronic infections is not fully understood. Serious infections and sepsis, includ-ing fatalities, have been reported in patients treated with etanercept. Increased levels of autoantibodies, including antinuclear antibodies and anti-double-stranded DNA antibodies, have also been reported, but the clinical significance of this observation is unknown.
Denileukin diftitox (DAB389 IL-2, Ontak) is indicated for treatment of patients with cutaneous T-cell lym-phoma whose malignant cells express the CD25 compo-nent of the IL-2 receptor. Denileukin diftitox is a re-combinant fusion protein composed of IL-2 amino acid sequences joined to sequences of diphtheria toxin. The drug targets and destroys cells expressing the high-affinity (CD25/CD122/CD132) IL-2 receptor, including the malignant cells of cutaneous T-cell lymphoma.
The half-life of the drug is approximately 75 minutes after intravenous infusion. Antibodies directed against the diphtheria domain decrease mean systemic expo-sure by approximately 75%. Approximately 85% of pa-tients develop such antibodies after a single course of treatment, and nearly all do after 3 cycles.
Most patients using denileukin diftitox have flulike symptoms (fever, chills, myalgias, nausea, diarrhea) within a few hours to days of treatment. Another com-mon adverse effect is an immediate hypersensitivity syndrome in which hypotension, back pain, dyspnea, chest pain or tightness, and rash may occur. Other no-table side effects include a vascular leak syndrome (edema, hypoalbuminemia, hypotension), infections, and elevations of transaminases.
Botulinum toxin purified neurotoxin complex (Botox) is a purified form of botulinum toxin type A, produced from a culture of Clostridium botulinum. Injection of botulinum toxin into muscle induces paralysis by inhibiting the re-lease of acetylcholine from motor neurons, thereby block-ing neuromuscular conduction. It is approved for the treatment of blepharospasm, strabismus, and excessive sweating. Botox is also approved for use in dermatology to induce paralysis of the muscles of facial expression to reverse deep wrinkles. The effect of an individual treat-ment usually becomes apparent within 3 days and lasts approximately 3 months. The effect may persist for a longer period after a series of treatments because the muscles atrophy. The major adverse effect is temporary loss of function of a muscle required for normal social functioning, as may occur after inadvertent injection of muscles required for smiling or raising the upper eyelids.
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