All about psoralens in dermatology. This ppt has postgraduate.

1. PSORALENS
A.AARTI BERNETT
1ST YR PG DVL

2. It is a naturally occurring linear furocumourin found in certain plants like hog
Weed, common fig, celery , parsley and all citrus fruits
Contact with such plants and subsequent exposure to sunlight results in
PHYTOPHOTODERMATITIS ( Erythema , blistering and pigmentation )
What is Psoralen?

3. Photochemotherapy with Psoralen
Combination of long wave UVA (320 to 400) with Psoralen.
Therapeutically beneficial photo toxic effect – not produced by
either of the Compounds alone.
Psoralens can be administered orally, or applied topically in the
form of solutions , creams or baths with subsequent UVA
Exposure after 1 to 2 hours

4. PUVASOL
Here psoralen ingestion or application is followed by exposure to natural
Sunlight.
Ideal time for PUVASOL is 9.30 am to 11 am / 2 pm to 3.30 pm
(Incidental UVB is less)

5. Historical background
Topical exposure to plant parts containing natural psoralens (Ammi Majus,
Psoralea corylifolia)- followed by exposure to sunlight – Vitiligo remedy – Egypt

6. Historical background
In 1974 oral ingestion of 8-Methoxypsoralen (found in seeds of Amma majus)
followed by exposure to artificial UVA radiation – highly effective for psoriasis

7. PSORALEN
PHOTOCHEMISTRY

8. STEP : 1
Psoralen reacts with DNA in three steps
In the absence of UV radiation Psoralen intercalates
into the DNA double Strand between Adenine and
Thymine base pairs

9. STEP : 2
Now , in the presence of UVA radiation ,
Psoralen absorbs the first photon
Psoralen along with the photon photochemically
reacts with Pyramidine bases Of DNA and forms
4,5 cyclobutane monoadduct & 3,4 cyclobutane
monoadduct

10. STEP : 3
The monoadduct formed, absorbs a second
photon
Leads to formation of Interstrand cross linking
between the two strands of the DNA double
helix

11. MOA AT CELLULAR LEVEL
1. This cross linking inhibits DNA replication and causes cell cycle arrest
2. Also inhibit RNA and protein synthesis
3. UVA activated psoralens causes alteration of cytokines and Cytokines Receptors
4.UVA activated psoralens produce reactive oxygen species which damages cell
membrane by lipid peroxidation and indirectly modify proteins and lipids.

12. EFFECTS OF PHOTOACTIVATED PSORALEN
1. Inhibits epidermal DNA replication and on reverting back proliferation rate
comes back to normal – Therapeutic mechanism in Psoriasis
2. Can reverse the pathologically altered keratinocytes differentiation markers -
Hence reduce the number of epidermal proliferating cells
3. Infiltrating lymphocytes are suppressed and causes apoptosis of lymphocytes
Diminishes Langerhans cell number in epidermis , Downregulates APCs -
Therapeutic mechanism in cutaneous T cell lymphoma

13. EFFECTS OF PHOTOACTIVATED PSORALEN
4. Stimulation of melanogenesis – therapeutic for vitiligo
Hair follicle melanocytes proliferate and repopulate the epidermis
Photoactivated psoralens attach to Melanocyte DNA and result in
1. Increased mitosis and proliferation of melanocytes
2. Increased formation and melanization of melanosomes
3. Enhanced transfer of melanosomes to keratinocytes
4. Increased synthesis of tyrosinase via cAMP

14. ROUTES OF PSORALEN ADMINISTRATION
I. Oral route
II. Topical
1. Solutions
2. Creams
3. Baths

15. PHARMACOKINETICS
OF ORAL PSORALEN
Steps between ingestion of a psoralen and its
arrival in skin include
1. Disintegration and dissolution of drug
2. Absorption
3. First pass effect
4. Blood transport
5. Tissue distribution
6. Excretion

16. PHARMACOKINETICS OF ORAL PSORALEN
1. Available in liquid and crystalline formulations
2. Liquid preparations give higher and earlier serum peak levels
3. Metabolised in liver and excreted via kidney 74.2% and feces 14.4%
4. After being metabolised in liver , they reach blood stream , peak levels in blood
Is 1 to 8 hours with mean of 2 hours
5. From blood they reach skin , and peak photo sensitivity is 1 to 2 hours after
Psoralen ingestion ( So we give UVA generally 2 hours after oral psoralen)

17. PHARMACOKINETICS OF ORAL PSORALEN
6. Though psoralen is widely distributed throughout the body only after
UVA / sunlight exposure it gets activated
7. Near completely excreted within 24 hours, so no activity after that
8. Hence action is short lived and reversible
9. Food decreases absorption , ideally empty stomach is preferred - NAUSEA
10. Dose < 20mg is not effective usually

18. PHARMACOKINETICS OF TOPICAL PSORALEN
When applied topically , they rapidly penetrate the skin and are detected in
urine 4 hours
Peak plasma levels are comparable to oral psoralens
They are promptly eliminated without cutaneous accumulation

19. PSORALENS IN CLINICAL USE
1. Methoxsalen or 8- Methoxypsoralen (8-MOP)
Derived from seeds of Ammi majus. Most widely used
More phototoxic when given orally
2.Bergapten or 5- Methoxypsoralen (5-MOP)
Lower phototoxicity than 8-MOP. Less erythema . Less intolerance
3.Trioxsalen or Trimethylpsoralen
Usually used in bath PUVA.
More toxic when used topically. Less toxic when used orally

20. METHOXSALEN (8 MOP)
Generic name Photoactivity Bioavailability Formulations Dose
8-Methoxy
psoralen
++++++
Maximum
75 to 80
percent serum
albumin bound.
90 percent
epidermal
tissue bound.
So good
bioavailability
10 mg capsule
/10 mg tablet
for oral use
Methoxsalen
aminobenzoic
acid ointment
10mg/ml
topical solution
0.6 to 0.8
mg/kg 1 to 3
hour prior to
PUVA
Topical
application

22. BERGAPTEN (5 MOP)
Generic name Photoactivity Bioavailability Formulations Dose
8-Methoxy
psoralen
+++
Moderate
98 to 99
percent serum
albumin bound
99 percent
epidermal
tissue bound.
Highest
bioavailability
20 mg capsule
/20 mg tablet
for oral use
Was used in
European
countries but
now not
commercially
available
1.2 to 1.8
mg/kg - 3 hour
prior to PUVA

23. TRIOXSALEN
Generic name Photoactivity Bioavailability Formulations Dose
4,5,8 Trimethyl
psoralen
+
Least
Poor oral
bioavailability.
Hence topically
used
5 mg tablet for
oral use
0.01 percent
ointment
0.6 mg/kg -2
hour prior to
PUVA
Topical
application

25. PRESENT DAY USE OF PSORALEN WITH UVA
1. Vitiligo
2. Psoriasis
3. Cutaneous T cell lymphoma - Mycosis fungoides
4. Pitryasis lichenoides chronica
5. Pitryasis rosea
6. Lichen planus
7. Graft versus host disease

26. PRESENT DAY USE OF PSORALEN WITH UVA
8. Atopic dermatitis
9. Urticaria pigmentosa
10. Polymorphic light eruption
11. Solar urticaria
12. Photoallergic dermatitis

27. SIDE EFFECTS
OF
PSORALEN
PHOTOCHEMOTHERAPY

28. ACUTE EFFECTS
1. Nausea and vomiting
More common with liquid preparations due to high serum levels
8 MOP - 10 % people get nausea
5 MOP - Nausea is rare
Can be alleviated by taking with food like milk , ginger or food.
Divide dose into two and take with a gap of 30 minutes

29. ACUTE EFFECTS
2. Pruritis
10 % of people undergoing PUVA develop pruritis
Usually emollients are enough
If severe systemic antihistamines can be given
A stinging pain may occur rarely which stops only on discontinuing treatment

30. ACUTE EFFECTS
3. Transient local erythema after PUVA therapy occurs frequently
- Such areas should be shielded in subsequent PUVA sessions
- Erythema occurring within 24 hours of treatment has propensity to
Aggregate further . Patient should be protected from further UV exposures

31. ACUTE EFFECTS
4. Hepatotoxicity
5.CNS side effects ( headache , vertigo, tinnitus)
6. Maculopapular rash

32. ACUTE EFFECTS
7. Tanning (Most common side effect)
8. Acniform eruptions

33. ACUTE EFFECTS
9.PMLE like eruptions
10. Photo onycholysis

34. ACUTE EFFECTS
11. Exacerbation of
Photosensitive dermatosis
Plaque psoriasis
Precipitation of pustular psoriasis in psoriasis patients
12. Hypertrichiosis of the face

35. CHRONIC EFFECTS
1. Photoaging of skin (worsening on sun exposure)
2. PUVA lentigenes (Brown Macules , proliferation of large melanocytes)
Associated with BRAF mutation
Less lentigens lesser risk of malignancy

36. CHRONIC EFFECTS
3. Increased risk of melanoma and non melanoma skin cancers
Dose dependent relationship with Psoralen dose and UVA dose
4. Increases risk of genital malignancies
Hence genital shielding is a must

37. CHRONIC EFFECTS
5. Anterior cortical cataract
6. Corneal opacities
7. Conjunctival hyperaemia and decreases lacrimation

38. CONTRAINDICATIONS FOR
PSORALEN UVA THERAPY
1. Previous idiosyncratic reactions to Psoralen compounds.
2. In case of liver disease or renal diseases
3. Patients possessing a history of light sensitive diseases should
not initiate psoralen therapy like
- Lupus erythematosus
- Porphyria cutanea tarda
- Eryhropoietic porphyria
- varigate porphyria
- Xeroderma pigmentosum
- Albinism

39. CONTRAINDICATIONS FOR PSORALEN
UVA THERAPY
4. Patients exhibiting Melanoma or possessing a
history of melanoma
5. Patients exhibiting squamous cell carcinomas
6. Patients with aphakia because of the
significantly increased risk of retinal damage
damage due to the absence of lenses.

40. SPECIAL SITUATION and PSORALENS
1. Category C drug in pregnancy . Hence should be given only if
Benefits outweighs risk.Usually not recommended
2. Less studies regarding secretion in breast milk. Better to avoid in lactating
Mothers.
3. Usually not preferred in paediatric aged group because of lack of data and
High risk of side effects due to immature liver