DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

active derivative, inhibits the enzyme inosine monophosphatase
dehydrogenase (IMPDH), thereby depleting
guanosine nucleotides essential for DNA and RNA synthesis
(Carter et al., 2004). Moreover, mycophenolic acid
is a 5-fold more potent inhibitor of the type II isoform of
IMPDH found in activated B and T lymphocytes and thus
functions as a specific inhibitor of T- and B-lymphocyte
activation and proliferation. The drug also may enhance
apoptosis.
Mycophenolate mofetil is used increasingly to treat inflammatory
and auto-immune diseases in dermatology in dosages ranging from
1-2 g/day orally (Carter et al., 2004). Mycophenolate mofetil is particularly
useful as a corticosteroid-sparing agent in the treatment of autoimmune
blistering disorders, including pemphigus vulgaris, bullous
pemphigoid, cicatricial pemphigoid, and pemphigus foliaceus. It also
has been used effectively in the treatment of inflammatory diseases
such as psoriasis, atopic dermatitis, and pyoderma gangrenosum.
Isolated cases of progressive multifocal leukoencephalopathy
(PML) and pure red cell aplasia have been reported in solid organ
transplant patients receiving mycophenolate mofetil. PML is a progressive,
demyelinating disease of the CNS that usually leads to
death or severe disability. PML is caused by the reactivation of the
JC virus, a polyomavirus that resides in latent form in 70-90% of the
adult population worldwide.
Imiquimod. Imiquimod (ALDARA) is a synthetic imidazoquinoline
amine believed to exert immunomodulatory
effects by acting as a ligand at toll-like receptors
in the innate immune system and inducing the
cytokines interferon- (IFN-), tumor necrosis factor-
(TNF-), and IL-1, IL-6, IL-8, IL-10, and IL-12.
Approved for the treatment of genital warts, imiquimod is
applied to genital or perianal lesions two times a week usually for a
16-week period that may be repeated as necessary. Imiquimod also
has been approved for the treatment of actinic keratoses. In this capacity,
imiquimod is applied three times a week for 16 weeks to the face,
scalp, and arms. No more than 36 single-use packets per 16-week
course of therapy should be prescribed for actinic keratoses. Phase II
trials evaluating imiquimod for the treatment of nodular and superficial
basal cell carcinomas suggest that imiquimod may prove useful
(Salasche and Shumack, 2003). The drug is FDA approved for this
indication at a dosage of five applications per week for 6 weeks. Offlabel
applications include the treatment of nongenital warts, molluscum
contagiosum, extramammary Paget’s disease, and Bowen’s disease.
Irritant reactions occur in virtually all patients, and some develop
edema, vesicles, erosions, or ulcers. It appears that the degree of
inflammation parallels therapeutic efficacy. Other than minor flu-like
symptoms, no severe systemic effects have been reported.
Vinblastine. Systemic vinblastine (VELBAN, others) is
approved for use in Kaposi sarcoma and advanced cutaneous
T-cell lymphoma. Intralesional vinblastine also is
used to treat Kaposi sarcoma (Hengge et al., 2002).
Intralesional bleomycin (BLENOXANE, others) is used for
recalcitrant warts and has cytotoxic and pro-inflammatory
effects. Intralesional injection of bleomycin into the
digits has been associated with a vasospastic response that
mimics Raynaud’s phenomenon, local skin necrosis, and
flagellate hyperpigmentation (Abess et al., 2003).
Intralesional bleomycin has been used for palliative treatment
of squamous cell carcinoma. Systemic bleomycin
has been used for Kaposi sarcoma (see Chapter 61 for a
more complete discussion of these agents). Liposomal
anthracyclines (specifically doxorubicin [DOXIL, CAELYX])
may provide first-line monotherapy for advanced Kaposi
sarcoma (Hengge et al., 2002).
Dapsone. Dapsone (4,4-diaminodiphenylsulfone) has
been in clinical use for ~50 years.
Dapsone is used in dermatology for its anti-inflammatory
properties, particularly in sterile (non-infectious)
pustular diseases of the skin. Dapsone prevents the
respiratory burst from myeloperoxidase, suppresses
neutrophil migration by blocking integrin-mediated
adherence, inhibits adherence of antibodies to neutrophils,
and decreases the release of eicosanoids and
blocks their inflammatory effects; all of these actions are
likely to be important in auto-immune skin diseases (Zhu
and Stiller, 2001).
Dapsone is approved for use in dermatitis herpetiformis and
leprosy. It is particularly useful in the treatment of linear
immunoglobulin A (IgA) dermatosis, bullous systemic lupus erythematosus,
erythema elevatum diutinum, and subcorneal pustular dermatosis.
In addition, reports indicate efficacy in patients with acne
fulminans, pustular psoriasis, lichen planus, Hailey–Hailey disease,
pemphigus vulgaris, bullous pemphigoid, cicatricial pemphigoid,
leukocytoclastic vasculitis, Sweet’s syndrome, granuloma faciale,
relapsing polychondritis, Behçet’s disease, urticarial vasculitis,
pyoderma gangrenosum, and granuloma annulare (Paniker and
Levine, 2001).
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CHAPTER 65
DERMATOLOGICAL PHARMACOLOGY