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PF3012 > Dermatological Agents > Flashcards

Dermatological Agents Flashcards

1
Q

What are the 2 types of melanin?

A
  • Eumelanin (black)
  • Pheomelanin (red)
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2
Q

How is Eumelanin produced?

A

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

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3
Q

Briefly explain the 3 types of UVR including their wavelengths

A

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)

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4
Q

How does UV radiation exert an effect on the skin?

A

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

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5
Q

Give examples of chromophores

A
  • nucleic acids
  • aromatic amino acids
  • melanin

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

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6
Q

How does UVB directly damage DNA?

A

pyrimidine dimer formation

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7
Q

List ways in which sun exposure can be beneficial

A
  • 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)
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8
Q

Name the 2 types of sunscreens

A
  • Inorganic/ mineral UV filters (n=2) (reflectant)
  • Chemical/ organic UV filters (n=25) (absorbant)
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9
Q

How do inorganic/ mineral sunscreens work?

A

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

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10
Q

How do chemical/ organic sunscreens work?

A

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

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11
Q

Name 2 topical and 1 systemic calcineurin inhibitors

A

topical - pimecrolimus, tacrolimus
systemic - ciclosporin

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12
Q

4 side effects of calcineuin inhibitors

A
  • alcohol intolerance
  • increased risk of infections
  • skin discolouration
  • skin papilloma
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13
Q

why are calcineurin inhibitors contraindicated in pregnancy?

A

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

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14
Q

What is calcineurin?

A
  • 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
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15
Q

How is calcineuin activated?

A

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

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16
Q

MOA of topical calcineurin inhibitors?

A

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

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17
Q

MOA of systemic calcineurin inhibitors?

A

Form complexes with cyclophilin

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

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18
Q

List 2 indications of mycophenolate mofetil

A
  • prophylaxis of acute transplant rejection in patients receiving allogeneic renal, cardiac or hepatic transplants
  • dermatological conditions including severe atopic dermatitis, blistering conditions, lupus erythematosus
19
Q

2 prodrugs of mycophenolic acid

A

CELLCEPT - mycophenolate mofetil
MYFORTIC - mycophenolate sodium

20
Q

MOA of mycophenolic acid

A

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

21
Q

what is the brand name of Dupilumab

A

Dupixent

22
Q

List 2 indications of Dupilumab

A
  • asthma
  • treatment of moderate -severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy
23
Q

MOA of Dupilumab

A

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

24
Q

Side effects of Dupilumab

A

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

25
Q

List the 3 ways that psoriasis works

A
  • 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)
26
Q

What kind of receptor is the Vitamin D receptor

A

nuclear

27
Q

MOA of vitamin D analogues

A
  • reduce keratinocyte proliferation
  • induce keratinocyte differentiation
  • immunomodulator functions
28
Q

How does the calcipotriol/ corticosteroid combination work?

A
  • 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
29
Q

What does PUVA stand for

A

psoralen and ultraviolet a radiation

30
Q

what does PUVA do

A

highly effective at clearing psoriasis and viltigo

31
Q

Name 2 psoralens

A

methoxsalen
trioxsalen

32
Q

When is the psoralen given?

A

po 90-120 minutes before UVA exposrues

33
Q

explain the 2 types of reactions with phototherapy

A

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

34
Q

List the 3 indications of Acitretin

A
  • Severe extensive psoriasis resistant to other forms of therapy
  • Palmoplantar pustular psoriasis
  • Severe congenital ichthyosis
35
Q

MOA of Acitretin

A
  • 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
36
Q

What is the brand name of Ustekinumab

A

STELARA

37
Q

List 4 indications for Ustekinumab

A
  • Plaque psoriasis
  • Psoriatic arthritis
  • Crohn’s disease
  • Ulcerative colitis
38
Q

MOA of Ustekinumab

A

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

39
Q

What does IL-12 do?

A

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

40
Q

What does IL-23 do?

A

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

41
Q

What is the brand name of Secukinumab

A

COSENTYX

42
Q

Clinical indication of Secukinumab (COSENTYX)

A

Psoriatic arthritis with concomitant moderate to severe plaque psoriasis
Ankylosing spondylitis

43
Q

MOA of Secukinumab

A
  • 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

PF3012 (10 decks)

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