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

sepsis, tuberculosis), including leading to hospitalization
or death. Patients should be screened for latent tuberculosis
infection before beginning treatment and closely
monitored during and after drug therapy.
Infliximab. Infliximab (REMICADE) is a mouse-human
chimeric IgG 1
monoclonal antibody that binds to soluble
and membrane-bound TNF- (Krueger and Callis,
2004). Infliximab is a complement-fixing antibody that
induces complement-dependent and cell-mediated lysis
when bound to cell-surface-bound TNF-. Neutralizing
antibodies to infliximab may develop against its chimeric
structure. Concomitant administration of methotrexate
or glucocorticoids may suppress this antibody formation.
Adalimumab. Adalimumab (HUMIRA) is a human IgG 1
monoclonal antibody that binds soluble and membranebound
TNF-. Like infliximab, it can mediate complement-induced
cytolysis on cells expressing TNF. Unlike
infliximab, however, it is fully human, which reduces the
risk for development of neutralizing antibodies.
Cutaneous T-cell Lymphoma
Denileukin diftitox. Denileukin diftitox or DAB 389
–IL-2
(ONTAK) is a fusion protein composed of diphtheria toxin
fragments A and B and the receptor-binding portion of
IL-2. DAB 389
–IL-2 is indicated for advanced cutaneous
T-cell lymphoma in patients with >20% of T cells
expressing the surface marker CD25. Specificity is
derived from the presence of IL-2 receptor (IL-2R) on
malignant and activated T cells but not resting B and T
cells. Following binding to the IL-2R, DAB 389
–IL-2 is
internalized by endocytosis. The active fragment of diphtheria
toxin then is released into the cytosol, where it
inhibits protein synthesis through ADP ribosylation,
leading to cell death. Clinical trials have shown an overall
response rate of 30% and a complete response rate of
10% in cutaneous T-cell lymphoma. Adverse effects
include pain, fevers, chills, nausea, vomiting, and diarrhea;
immediate hypersensitivity reaction (hypotension,
back pain, dyspnea, and chest pain) in 60% of patients;
and capillary leak syndrome (edema, hypoalbuminemia,
and/or hypotension) in 20-30% of patients (Duvic and
Talpur, 2008).
INTRAVENOUS IMMUNOGLOBULIN
IN DERMATOLOGY
Intravenous immunoglobulin (IVIG) is prepared from
fractionated pooled human sera derived from thousands
of donors with various antigenic exposures (see Chapter
35). There are several commercial preparations of IVIG,
all of which are composed of >90% IgG, with minimal
amounts of IgA, soluble CD4, CD8, HLA molecules,
and cytokines. Although the mechanism of action of
IVIG is not understood fully, proposed mechanisms
include suppression of IgG production, accelerated
catabolism of IgG, neutralization of complementmediated
reactions, neutralization of pathogenic antibodies,
downregulation of inflammatory cytokines, inhibition
of autoreactive T lymphocytes, inhibition of
immune cell trafficking, and blockage of Fas-ligand/
Fas-receptor interactions (Smith et al., 2007).
In dermatology, IVIG is used off label as an adjuvant or rescue
therapy for multiple diseases. These include auto-immune bullous
diseases, toxic epidermal necrolysis, connective tissue diseases,
vasculitis, urticaria, atopic dermatitis, and graft-versus-host disease.
Prospective controlled studies are lacking for the efficacy in these
diseases and likely vary based on the IVIG product used.
IVIG is relatively contraindicated in patients with severe
selective IgA deficiency (IgA <0.05 g/L). These patients may possess
anti-IgA antibodies that place them at risk for severe anaphylactic
reactions. Other relative contraindications include congestive
heart failure and renal failure due to the risk of fluid overload.
Patients with rheumatoid arthritis or cryoglobulinemia are at an
increased risk of renal failure (Thomas et al., 2007).
SUNSCREENS
Photoprotection from the acute and chronic effects of sun
exposure is readily available with sunscreens. The major
active ingredients of available sunscreens include chemical
agents that absorb incident solar radiation in the
UVB and/or UVA ranges and physical agents that
contain particulate materials that can block or reflect
incident energy and reduce its transmission to the skin.
Many of the sunscreens available are mixtures of organic
chemical absorbers and particulate physical substances.
Ideal sunscreens provide a broad spectrum of protection
and are formulations that are photostable and remain
intact for sustained periods on the skin. They also should
be non-irritating, invisible, and nonstaining to clothing.
No single sunscreen ingredient possesses all these desirable
properties, but many are quite effective nonetheless.
UVA Sunscreen Agents. Currently available UVA filters in the U.S.
include 1) avobenzone, also known as Parsol 1789; 2) oxybenzone;
3) titanium dioxide; 4) zinc oxide; and 5) ecamsule (MEXORYL SX).
Additional UVA sunscreens, including bemotrizinol (TINOSORB S)
and bisoctrizole (TINSORB M), are available in Europe and elsewhere,
but not in the U.S.
UVB Sunscreen Agents. There are numerous UVB filters, including 1)
p-aminobenzoic acid (PABA) esters (e.g., padimate O), 2) cinnamates
(e.g., octinoxate), 3) octocrylene, and 4) salicylates (e.g., octisalate).
The major measurement of sunscreen photoprotection is the
sun protection factor (SPF), which defines a ratio of the minimal dose
of incident sunlight that will produce erythema or redness (sunburn)
on skin with the sunscreen in place (protected) and the dose that
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CHAPTER 65
DERMATOLOGICAL PHARMACOLOGY