Photochemotherapy π₯ Flashcards
Difference between Phototherapy vs. Photochemotherapy
Photorherapy = natural chemophores as light absorber
> endogenous chemical absorbs light eg. Bilirubin
Photochemotheraphy = added photosensitiser
> exogenous chemical also required eg. PUVA, PDT
Process of Elimianting Bilirubin??
- Bilirubin gets oxidated (B-Ox in blood) 2. Excreted in urine
Or
- Bilirubin forms with albumin in blood
- Exceeted by liver
What is PUVA therapy?
Formation of adducts in DNA resulting in inhibition of DNA synthesis = cell death and slower cell growth
Used in treatment of psoriasis, vitiligo and cutaneous lymphoma
Whats the problem with (Z,Z) isomer of bilirubin?
Has intramuscular binding (H bonds), making it more lipophilic, and unable to bind with O2
Furocoumarin derivative
What is the UVQ absorbence due to?
The pyrone ring
8MOP molecule
MOA
- 8-MOP: purine ring + pyrone ring
Once taken it can will intracalate with DNA. - Once light enters (photon), the furniture ring is excited and reacts forming a bind with Thymine (monofunctional adduct is 4β5β with pyramidine base.
- The 2nd photon of light comes in ans excites the carbon on the furan ring.
- You then get a bifunctionam cross linked adduct (3,4 and 4,5 with pyrimidine base)
8-MOP molecule:
Where does the photon have to enter from first to get the bifunctional adduct formation?
Pyrone or purine?
Must FIRST enter via PURINE, then pyrone.
(If entered from pyrone first will only get a bifunctional adduct)
Effects of PUVA
- Phototoxic effect on skin
- Anitproliferative effect
- Mutagenic effect
- Photocarcinogenic activity
What is Photodynamic therapy
PDT
Involves administration of a photosensitiser followed by irradiation with visible light
Photosensitiser is often a derivative of what?
Porphyrin derivative
Mechanism of PDT
Photosensitising agents 2
ALA (5-aminolevulinic acid)
And
Verteporfin (Visudyne)
Photosensitiser:
How does ALA work
Stimulates synthesis protoporphyrin IX (PpIX) = the immediate precursor to haem and an endogenous photosensitiser
Potential uses of PDT
- actinic keratins
- superficial basal cell carcinoma
- superficial squamous cell carcinoma
- Psoriasis, acne
- warts
- hair removal
- brain tumours
Radiotherapy has 2 critical cell targets for radiation.
Name them
- DNA = directly causes double strand breakage
- Water = causing formation of free radics in the cells Aqueous environment, leading to radical attack on DNA