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Proliferative Verrucous Leukoplakia Medication

  • Author: Rahat S Azfar, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jul 05, 2016
 
 

Antineoplastic Agent, Antibiotic

Bleomycin (Blenoxane)

 

This agent consists of a group of glycopeptides extracted from Streptomyces species. Each molecule has a planar end and an amine end; different glycopeptides of the group differ in their terminal amine moieties. The planar end intercalates with DNA, while the amine end facilitates oxidation of bound ferrous ions to ferric ions, thereby generating free radicals, which subsequently cleave DNA, acting specifically at purine-G-C-pyrimidine sequences.

It is not absorbed when given orally; peak levels are reached in approximately 30-60 min when given intramuscularly and are only one third of the levels obtained after intravenous administration; approximately 50% of the drug is absorbed systemically after intrapleural or intraperitoneal administration; systemic absorption after intracavitary administration for craniopharyngioma not negligible.

The volume of distribution is 20-30 L, both in intracellular and extracellular fluid. Less than 10% is bound to plasma proteins.

Bleomycin has plasma half-life of more than 1 hour and a terminal half-life of 2-4 hours, but it could be as long as 22 hours in patients with renal dysfunction or those previously treated with cisplatin.

Approximately 50% is eliminated in the urine within 24 hours. Most tissues (known exceptions—skin and lungs) contain an enzyme, bleomycin hydrolase (most active tissues are liver and kidney), which readily inactivates the drug; therefore, toxicity is tissue specific, occurring in tissues lacking this enzyme. Bleomycin is mostly used systemically in combination with other drugs (mostly with cisplatin and vincristine).

The principal mechanisms of resistance include high levels of bleomycin hydrolase, cell mutations altering DNA sequences to prevent intercalation, poor cell accumulation of the drug, and rapid plasma removal. None of these factors plays an important role when bleomycin is administered locally in a residual cyst.

Toxicity is age dependent and cumulative-dose related; systemic administration mostly causes pulmonary toxicity. This consists of pneumonitis, which can progress to fatal pulmonary fibrosis.

The maximum recommended total cumulative dose for systemic use is 400 U. Unit measurement is based on toxicity to bacteria; 1 U equals approximately 1.7 mg.

Administered systemically, bleomycin does not produce significant bone marrow toxicity. Toxicity with local administration is due to both systemic contamination (when anaphylactoid reactions, transient fever, nausea, and vomiting could occur) and leakage into surrounding neural tissue. Fatal outcomes have been reported with leakage, owing to subsequent diffuse diencephalon and brainstem edema.

Contrast CT cystography is required prior to intracavitary administration to ensure cyst wall integrity; when inconclusive, MR cystography with gadopentetate dimeglumine has been advocated.

 
Contributor Information and Disclosures
Author

Rahat S Azfar, MD Clinical Instructor, Department of Dermatology, University of Pennsylvania Health System

Rahat S Azfar, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

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A leukokeratotic plaque is seen in on the upper lip, along with an erythematous plaque on the left hard palate. The patient has a large right-palate defect from a prior surgical excision of a squamous cell carcinoma.
 
 
 
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