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PUVA therapy Dr Shubhangi Paunikar

PUVA therapy Dr Shubhangi Paunikar. Light therapy (phototherapy) . nonionizing electro-magnetic radiation . UVC-GERMICIDAL UVB-SUNBURN UVA-BLACK LIGHT. PUVA THERAPY (PHOTOCHEMOTHERAPY). Non-ionizing radiation +photosensitizing chemical ( psoralen ) Chromophore -photoproduct

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PUVA therapy Dr Shubhangi Paunikar

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  1. PUVA therapy • Dr ShubhangiPaunikar

  2. Light therapy (phototherapy) • nonionizing electro-magnetic radiation

  3. UVC-GERMICIDAL UVB-SUNBURN UVA-BLACK LIGHT

  4. PUVA THERAPY (PHOTOCHEMOTHERAPY) • Non-ionizing radiation +photosensitizing chemical (psoralen) • Chromophore-photoproduct • Triggers a photochemical reaction

  5. Psoralens • Phototoxic compounds ,inactive • Enters cells and then absorb photons (of UVA) • Produce photochemical reactions • Alter the function of cellular constituents • The therapeutic effect results after repeated controlled phototoxic reactions • Invented in 1947 • First used in vitiligo.

  6. Three psoralens are used • 8-methoxypsoralen / 8-MOP / methoxsalen – derived from seeds of Ammimajus – most widely used • 5-methoxypsoralen / 5-MOP /Bergapten (used in Europe; lower potential for phototoxicity than 8-MOP) • 4,5’,8-trimethylpsoralen / TMP / trioxsalen (used mainly in Bath PUVA)

  7. Franco-Indian Pharmaceuticals 

  8. MELANOCYL® Tablets Each uncoated tablet contains : Methoxsalen U.S.P 10 mg.(Ammoidine) MELANOCYL® Topical Solution Methoxsalen U.S.P 1% w/vPropylene Glycol base q.s. MELANOCYL® Ointment Methoxsalen U.S.P 0.75% w/w. (Ammoidine) Aminobenzoic Acid B.P. 2% w/w.

  9. 8-MOP hard gelatin capsule

  10. ABSORPTION • Lipophilic , nonionized, insoluble in water • Solubility –methoxsalen:bergapten:trioxsalen-36:6:1 • Physical formulations influences absorption • Elongated crystals • Micronized crystals • Dissolved psoralen(oxsoralen ultra)-soft gelatin capsules

  11. Cont; • Food decreases absorption • Ideally empty stomach-but nausea • Food intake –alleviate nausea • Strong first pass metabolism • Dose <20mg not clinically effective

  12. BIOAVAILABILITY • Methoxsalen -75-80% protien bound -90% epidermal tissue bound • 5-methoxypsoralen -98-99% serum bound -99%epidermal tissue bound • Short lived ,reversible • No significant activity after 24 hr • MPD

  13. METABOLISM- rapid-in liver • EXCRETION-rapid -74.2%urine -14.4% fecal

  14. PUVA units - full body cabinets containing 6' 100W fluorescent low-pressure mercury bulbs • UVA lamps (TL100/209R) have black markings (e.g. FS72T12BLHO) • Most units have 36 or 48 bulbs, and may be the same cabinet as BB-UVB and rarely NB-UVB bulbs • Hand & foot units contain 2' bulbs • Modern units have integrated dosimetry , the time to deliver the correct dose is automatically calculated • For older units, irradiance is checked manually prior to treatment

  15. Mechanism of action • Phototype 1 reaction- do not require O2 ,site of damage DNA/nuclei-mainly in hyperproliferative disease-psoriasis

  16. Phototype 2 reaction-needs o2

  17. Phototype 2 reaction

  18. Immunologic /immunomodulatory effect

  19. Immunologic effect

  20. Side effects

  21. Side effects

  22. Side effects

  23. Contra-indications • Pregnancy (category C) , Lactation • Age below 12 years • Genetic disorders with increased skin cancer risk • Photosensitizing medication like thiazides ,coal tar • Photosensitivity disorders such as lupus erythematosus, porphyria, etc • Previous skin tumors including past history of melanoma

  24. Cont; • Dysplastic nevi • Severe liver or kidney or cardiovascular disease • Previous treatment with X-rays or arsenic. • Furocoumarin-containing foods, such as limes, figs, parsley, parsnips, mustard, carrots, and celery • Concurrent use -trioxsalen +phenothiazines - potentiate intraocular photochemical damage to the choroid, retina, and lens

  25. Cont; Relative contra-indications – • Pemphigus and bullouspemphigoidas they may get exacerbated • Aphakia ( Adequate eye protection ) • Both UV radiation and psoralens activate the HIV promoter which could boost viral gene transcription • Nevertheless PUVA is not contraindicated for HIV positive patients with PUVA-responsive diseases

  26. PUVA monitoring guidelines

  27. Precautions

  28. Grading of erythema • E0 -no erythema • E1 -minimal perceptible erythema • E2 -marked erythema-red • E3 - fiery red erythema with edema • E4 -fiery red erythema with edema ,blistering

  29. MPD • Minimal dose of UVA that produce barely perceptible but well defined erythema ,when template areas of skin are exposed to geometrically increasing dose of UVA • Perform on previously non exposed skin • It is calculated after 72 hr of testing –peak action • Time consuming than skin phototyping ,it allows more accurate and higher UVA doses during initial treatment

  30. Treatment protocols of PUVA • Oral PUVA(protocols in psoriasis and vitiligo in details) • Topical PUVA • Bath PUVA • Soak PUVA • PUVAsol • Combination treatment

  31. Uses of PUVA therapy

  32. uses FDA approved • vitiligo • Psoriasis • CTCL

  33. Vitiligo REGIMEN- • 0.4-0.6mg/kg 8-MOP • UVA exposure after 2 hr • Starting dose-2.5-3.5 J/cm2 • Increments of 0.5 J/cm2 every third sitting • 2-3 treatments /wk for 12-24 months • Stop if no response after 6months or 50 treatments • Max sittings-not standardized for Indians,150-200 in westerns

  34. Cont; DEFAULTER • One regularly scheduled t/t missed-use last dose only • >1 t/t missed-dose should be reduced by 0.5J/cm2 /session missed

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