Dermatological Toxicology

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 Seminar on Seminar on Derma tological T oxi cities Derma tological T oxi cities Presented By: Presented By: Surbhi Surbhi sharma sharma M.Pharm M.Pharm II II sem sem Pharmacy Practice Pharmacy Practice

Transcript of 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.