Dermatological Toxicology
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Transcript of Dermatological Toxicology
8/3/2019 Dermatological Toxicology
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Seminar onSeminar on
Dermatological ToxicitiesDermatological Toxicities
Presented By:Presented By:
SurbhiSurbhi sharmasharma
M.PharmM.Pharm IIII semsem
Pharmacy PracticePharmacy Practice
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Dermatological ToxicologyDermatological Toxicology
y
Skin is the largest organ of the body. It protects the bodyfrom Environmental Insults, and maintains Body Homeostasis.
y Dermatological toxicity includes toxicities to skin, nails.
y Dermatotoxicological Investigations of Toxicities including Irritation,
Skin Corrosion and Allergy necessitate Toxicological Skin Testing prior
to Manufacture, Transport, or Marketing of Drugs, Cosmetics, and many
other Products.
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CONTACT DER MATITISCONTACT DER MATITIS
y Contact dermatitis falls into the two major categories of irritant andallergic forms. Both involve inflammatory processes and have
indistinguishable clinical characteristics of erythema (redness),
induration (thickening and firmness), scaling (flaking), and vesiculation
(blistering) in areas of direct contact with the chemical.
y H
igh and long time exposure.y Individuals vary greatly in sensitivity to irritant dermatitis.
y Lipid-rich moisturizers and barrier creams containing dimethicone or
perfluoropolyethers may be useful in protecting skin from offending
agents.
y Allergic contact dermatitis is a delayed (T-cell mediated) hypersensitive
reaction.
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Contact irritant dermatitisContact irritant dermatitis
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y Diagnosis and Testing When a patient exhibits allergic contact dermatitis,
finding the responsible chemical is important to avoid continued exposure.
Patch testing is commonly employed for this.
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GRANULOMATOUS DISEASEGRANULOMATOUS DISEASE
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PHOTOTOXICITYPHOTOTOXICITYy Phototoxic reactions from exogenous chemicals may be produced by
systemic or topical administration or exposure.
y Adequate doses of artificially produced UVC (<290 nm) or X-rays can
produce profound physical and toxicological skin changes..
y The protective skin pigment melanin, synthesized in melanocytes, absorbs
a broad range of radiation from UVB (290±320 nm) through the visible
spectrum.
y Other chromophores in the skin include amino acids, primarily tryptophan
and to a lesser extent tyrosine, and their breakdown products(e.g., urocanic
acid), which absorb light in the UVB range.
y Biologically, the most significant chromophore is DNA, because damage
from radiation can have lasting effects on the genetic information in target
cells.y The most evident acute feature of ultraviolet radiation exposure is erythema
(redness or sunburn).
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y exposing the skin to coal tar and sunlight can quickly produce a stinging
sensation and elicit damage resembling a bad sunburn with
hyperpigmentation.
y Pigmentary changes such as freckling and hypomelanotic areas, wrinkling,
telangiectasias (fine superficial blood vessels), actinic keratoses
(precancerous lesions), and malignant skin lesions such as basal and
squamous cell carcinomas and malignant melanomas are all consequences
of chronic exposure to ultraviolet light exposure.
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PhototoxicityPhototoxicity from lime juicefrom lime juice
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PHOTOSENSITIVITYPHOTOSENSITIVITY
y Abnormal sensitivity to ultraviolet and visible light.
y Results from a variety of genetic diseases, such as xeroderma
pigmentosum, impair the cell¶s ability to repair ultraviolet light
induced damage.
y A ³constitutional´ sensitivity to light (porphyria cutanea tarda)
can be precipitated by alcohol, estrogens, or certain antibioticsin individuals with hereditary abnormalities in porphyrin
synthesis, and an ³acquired´ sensitivity in general by
hexachlorobenzene and mixtures of polyhalogenated aromatic
hydrocarbons.
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UR TICAR IAUR TICAR IA
y
an immediate type I hypersensitivity reaction.y subsequent contact can lead to development of hives.
y Food allergies and pharmaceuticals are major causes of acute urticaria.
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PIGMENTAR Y DISTUR BANCESPIGMENTAR Y DISTUR BANCES
y Melanocytes protect the skin from harmful effects of ultraviolet light by
producing the insoluble polymeric pigment melanin.
y hyperpigmentation is well knownto result from exposure to phototoxic
agents including coal tar, coumarin derivatives found in perfumes and
certain food such as limes (shown in Fig. 19-2G) and food plants (parsely,
celery), dyes in cosmetics, and elements such as lead, bismuth, and arsenic
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leukodermaleukoderma from rubberfrom rubberantioxidantsantioxidants
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hyperpigmentationhyperpigmentation fromfrommercaptobenzothiazolemercaptobenzothiazole
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DER MATOLOGIC TOXICITY OF CHEMOTHER APEUTICDER MATOLOGIC TOXICITY OF CHEMOTHER APEUTIC
AGENTSAGENTS
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y There are anecdotal reports on the efficacy of pyridoxine at a dose of 50
mg three times daily for treatment of palmar-plantar erythrodysesthesia
due to taxane therapy and one case of successful treatment with localhypothermia.
y Recently, a trial using a glycerin-containing Elasto-Gel thermal glove
(APT, Akromed, France), which was cooled to 25°C and worn on the
hands just before, during, and after docetaxel infusion, was shown to
significantly decrease the incidence of onycholysis, pigmentation, and
acral erythrodysesthesia.
y There are anecdotal reports of successful treatment measures for liposomal
doxorubicinassociated acral erythrodysesthesia, including topical 99%
dimethylsulfoxide four times daily, regional cooling, and oral pyridoxine
with methylprednisolone.
y Thalidomide was approved in 1998 for the cutaneous treatment of moderate to severe erythema nodosum leprosum. Hall et al summarized
four historical and two new cases of exfoliative erythroderma and/or toxic
epidermal necrolysis (TE N) associated with thalidomide therapy.
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y Tattoos in a dermatological perspective:
Tattoos are very popular
used standard industrial pigments lacks basic knowledge concerning pigments, epidemiology and
complications such as allergy, granulomas, skin cancer and foreignbody reactions.
risks associated with laser treatment are unknown.
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R eferencesR eferencesy Curtis D. Klaassen, Casarett and Doull¶s Toxicology, Seventh Edition
2008, 741-761.
y Aimee S. Payne, William D. James, Raymond B. Weissb. Dermatologic
toxicity of chemotherapeutic agents. Elsevier Inc. 2006; 86-97.
y Høgsberg T, O'Goshi K , Serup J. Tattoos in a dermatological perspective.
Ugeskr Laeger. 2011 Jan 3;173(1):34-39.