- Calcineurin is a phosphatase responsible fro dephosphorylating Nuclear Factor of Activated T cells - cytoplasm (NFAT-c) - This allows for the translocation of NFAT-c to the nucleus, where it interacts with NFAT-n to increase the transcription of cytokines

Dermatological Agents Flashcards by Ciara O'Mahony

What are the 2 types of melanin?

Eumelanin (black)
Pheomelanin (red)

How well did you know this?

Not at all

Perfectly

How is Eumelanin produced?

Production is regulated by melanocyte stimulating hormone (MSH) which acts via melanocortin Type 1 receptor (MC1R) on melanocytes

How well did you know this?

Not at all

Perfectly

Briefly explain the 3 types of UVR including their wavelengths

UVC has the shortest wavelength and is filtered out by the ozone layer (100-290 nm)
UVA is responsible for skin aging (320-400nm)
UVB has shorter wavelength than UVA, and is responsible for sunburn (290-320nm)

How well did you know this?

Not at all

Perfectly

How does UV radiation exert an effect on the skin?

the energy present in radiation must be absorbed by a chromophore in the skin

How well did you know this?

Not at all

Perfectly

Give examples of chromophores

nucleic acids
aromatic amino acids
melanin

cellular DNA is recognised as a chromophore - why sun exposure can lead to skin cancer

How well did you know this?

Not at all

Perfectly

How does UVB directly damage DNA?

pyrimidine dimer formation

How well did you know this?

Not at all

Perfectly

List ways in which sun exposure can be beneficial

Essential for stimulating the production of Vitamin D
Mental health
Treatment of cutaneous T-cell lymphoma
Psoriasis
Viltigo carcinomas using photo dynamic therapy
PUVA (psoralen and UV radiation)

How well did you know this?

Not at all

Perfectly

Name the 2 types of sunscreens

Inorganic/ mineral UV filters (n=2) (reflectant)
Chemical/ organic UV filters (n=25) (absorbant)

How well did you know this?

Not at all

Perfectly

How do inorganic/ mineral sunscreens work?

Scatter UV light (‘mirror’)
TiO2 (nano) - UVB + short UVA filter

How well did you know this?

Not at all

Perfectly

How do chemical/ organic sunscreens work?

Aromatic, lipophilic molecules
Absorb UV radiation and emit IR radiation
Ethylhexyl salicylate - UVB filter

How well did you know this?

Not at all

Perfectly

Name 2 topical and 1 systemic calcineurin inhibitors

topical - pimecrolimus, tacrolimus
systemic - ciclosporin

How well did you know this?

Not at all

Perfectly

4 side effects of calcineuin inhibitors

alcohol intolerance
increased risk of infections
skin discolouration
skin papilloma

How well did you know this?

Not at all

Perfectly

why are calcineurin inhibitors contraindicated in pregnancy?

they cross the placenta and risk a premature deliver
intra-uterine growth restriction
hyperkalaemia

How well did you know this?

Not at all

Perfectly

What is calcineurin?

Calcineurin is a phosphatase responsible fro dephosphorylating Nuclear Factor of Activated T cells - cytoplasm (NFAT-c)
This allows for the translocation of NFAT-c to the nucleus, where it interacts with NFAT-n to increase the transcription of cytokines

How well did you know this?

Not at all

Perfectly

How is calcineuin activated?

T cell activation leads to increased calcium
Calcium interacts with calmodulin
Calmodulin activates calcineurin

How well did you know this?

Not at all

Perfectly

MOA of topical calcineurin inhibitors?

Form complexes with peptidyl-propyl isomerases FKBP12

inhibit calcineurin - prevent translocation of NFAT-c to the nucleus - inhibit cytokine/ inflammatory mediator production - inhibits T cell activation

How well did you know this?

Not at all

Perfectly

MOA of systemic calcineurin inhibitors?

Form complexes with cyclophilin

inhibit calcineurin - prevent translocation of NFAT-c to the nucleus - inhibit cytokine/ inflammatory mediator production - inhibits T cell activation

How well did you know this?

Not at all

Perfectly

List 2 indications of mycophenolate mofetil

prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants
dermatological conditions including severe atopic dermatitis, blistering conditions, lupus erythematosus

2 prodrugs of mycophenolic acid

CELLCEPT - mycophenolate mofetil
MYFORTIC - mycophenolate sodium

MOA of mycophenolic acid

Inhibits the enzyme IMPDH - inosine monophosphate dehydrogenase - thereby depleting guanosine residues which are essential for DNA and RNA synthesis
5 fold more potent inhibitor of the type II isoform of IMPDH found in activated B and T lymphocytes
Therefore acts as a specific inhibitor of T and B lymphocyte activation and proliferation

what is the brand name of Dupilumab

Dupixent

List 2 indications of Dupilumab

asthma
treatment of moderate -severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy

MOA of Dupilumab

Human mAb
Binds to the alpha subunit of the IL-4 receptor
Inhibition of both IL-4 and IL-13 complexes
- these are both important for Th2 response

Side effects of Dupilumab

Eosinophilia
Eye inflammation
Eye pruritis
Headache
Oral herpes
Hypersensitivity
Pneumonia eosinophilic
Vasculitis

List the 3 ways that psoriasis works

- epidermal hyperproliferation (increased DNA synthesis and a markedly decreased turnover rate for the epidermis) - abnormal differentiation of epidermal keratinocytes (involves increased expression of certain keratinocytes (6 and 16) and delay in expression of others (1 and 10) that are expressed in a normally differentiating skin - inflammation with immunological alterations in the skin (results from an infiltrate of neutrophils in the epidermis and superficial dermis and an infiltrate of T lymphocytes in teh dermis with a predominance of CD8+ cells)

What kind of receptor is the Vitamin D receptor

nuclear

MOA of vitamin D analogues

- reduce keratinocyte proliferation - induce keratinocyte differentiation - immunomodulator functions

How does the calcipotriol/ corticosteroid combination work?

- Calcipotriol acts on keratinocytes to repress the expression of IL-36alpha/gamma - Corticosteroid acts on immune cells to suppress the IL-23/1L-17 axis superior than either alone

What does PUVA stand for

psoralen and ultraviolet a radiation

what does PUVA do

highly effective at clearing psoriasis and viltigo

Name 2 psoralens

methoxsalen trioxsalen

When is the psoralen given?

po 90-120 minutes before UVA exposrues

explain the 2 types of reactions with phototherapy

Reaction 1: addition of psoralens to pyrimidine bases of DNA (oxygen independent) Reaction 2: involves the transfer of energy to O2, creating a ROS both reactions stimulate melanocytes and induce anti-proliferative, immune- suppressive and anti-inflammatory effects

List the 3 indications of Acitretin

- Severe extensive psoriasis resistant to other forms of therapy - Palmoplantar pustular psoriasis - Severe congenital ichthyosis

MOA of Acitretin

- synthetic aromatic derivative of retinoic acid - reverses hyperkeratotic and metaplastic skin changes - the usual therapeutic response consists of desquamation (skin peeling/shedding), followed by a more normal re-epithelialisation

What is the brand name of Ustekinumab

STELARA

List 4 indications for Ustekinumab

- Plaque psoriasis - Psoriatic arthritis - Crohn's disease - Ulcerative colitis

MOA of Ustekinumab

Human IgG1 mAb which is directed against the p40 subunit or IL-12 and IL-23 Prevents p40 from binding to the IL-12RB1 receptor expressed on the surface of immune cells

What does IL-12 do?

stimulates NK cells and drives the differentiation of CD4+ T cells towards the TH1 phenotype (inhibited along with IL-23 by Ustekinumab (STELARA))

What does IL-23 do?

Induces the T helper 17 (Th17) pathway Inhibited along with IL-23 by Ustekinumab (STELARA)

What is the brand name of Secukinumab

COSENTYX

Clinical indication of Secukinumab (COSENTYX)

Psoriatic arthritis with concomitant moderate to severe plaque psoriasis Ankylosing spondylitis

MOA of Secukinumab

- recombinant human mAb that selectively binds to cytokine IL-17A - targets IL-17A and inhibits its interaction with the IL-17 receptor, which is expressed on various cells including keratinocytes - inhibits the release of pro-inflammatory cytokines, chemokines and mediators of tissue damage - reduces erytheme, induration and desquamation present in plaque psoriasis plaques