Dermatologic Pharmacology (Part 5)

Question 1

what is the initial choice for mild to moderate psoriasis?

Answer 1

emoliients + corticosteroids

Question 2

how does topical vitamin D analogs help treat psoriasis?

Answer 2

the mechanism is unclear, but it reduces keratinocyte proliferation

Question 3

what is a good initial choice for moderate- severe psoriasis?

Answer 3

UV light therapies

Question 4

what are the clinical modalities of UV light therapies?

Answer 4

UVB radiation to point of erythema 3x per week +/- topical tar; photochemotehrapy (PUVA)

Question 5

UVB radiation to treat psoriasis is thought to work via what?

Answer 5

immunomodulation

Question 6

how does photochemotherapy (PUVA) work?

Answer 6

uses UVA radiation, which penetrates deeper into the skin without causing sunburn

Question 7

what is the process of PUVA?

Answer 7

patients usually ingest the plant photosensitizer psoralen 2 hours before treatment; 3 times a week until remission

Question 8

what are patients undergoing PUVA at increased risk of?

Answer 8

melanoma

Question 9

what is the MOA of apremilast?

Answer 9

it inhibits phosphodiesterase 4 (PDE4) which is specific for cyclic adenosine monophosphate (cAMP)–> leads to an increased level of cAMP levels in cells

Question 10

what are the effects of apremilast?

Answer 10

decreases nitric oxide synthase, TNF-alpha and IL-23; increases IL-10

Question 11

what are the clinical applications of apremilast?

Answer 11

moderate to severe plaque psoriasis; active psoriatic arthritis

Question 12

what are the pharmacokinetics of apremilast?

Answer 12

administered orally

Question 13

what is the MOA of ustekinumab?

Answer 13

it is a human monoclonal antibody that targets proinflammatory cytokines IL-12 and IL-23

Question 14

what are the effects of ustekinumab?

Answer 14

it blunts IL-12 and IL-23 so: there is a decrease in NK cell activation, a decrease in CD4 T cell differentiation and activation, a decrease in MCP-1, TNF-alpha, CXCL-10, IL-8 expression

Question 15

what are the clinical applications of ustekinumab?

Answer 15

plaque psoriasis, psoriatic arthritis, crohn disease

Question 16

what is the MOA of secukinumab?

Answer 16

it is a human monoclonal antibody that target proinflammatory cytokine IL-17A

Question 17

what are the effects of secukinumab?

Answer 17

it blunts IL-17A effects thereby decreasing its ability to induce the production of many other proinflammatory signaling molecules

Question 18

what are the clinical applications of secukinumab?

Answer 18

ankylosing spondylitis, plaque psoriasis, psoriatic arthritis

Question 19

what is actinic keratosis?

Answer 19

cutaneous neoplasms that develop on sun-damaged skin, thought to be on a continuum with cutaneous squamous cell carcinoma

Question 20

what are 6 treatment options for actinic keratosis?

Answer 20

liquid nitrogen cryotherapy; surgical therapy; pharmacotherapy; red light therapy; dermabrasion; and chemical peels

Question 21

what are the 3 pharmacotherapy options for actinic keratosis we talked about?

Answer 21

topical 5-fluorouracil, Imiquimod, and ingenol mebutate

Question 22

what is the MOA of imiquimod?

Answer 22

stimulates local cytokine induction leading to an inflammatory cell infiltration

Question 23

what is the MOA of ingenol mebutate?

Answer 23

1. chemoablation (cell necrosis) 2. neutrophil-mediated antibody dependent cellular cytotoxicity

Question 24

what is the MOA of topical 5 flurouracil?

Answer 24

it inhibits thymidylate synthase, which is a critical enzyme in the synthesis of DNA; a lack of DNA synthesis in the fast-growing dysplastic cell prevents cell proliferation and causes cell death

Question 25

what are the effects of topical 5 flurouracil?

Answer 25

causes inflammation and destruction of the lesions; after 4-6 weeks skin will have progressed from erythema through blistering, necrosis with erosion, and then re-epithelialization

Question 26

for advanced basal cell carcinoma, what is the treatment option?

Answer 26

vismodegib

Question 27

how do vismodegib work?

Answer 27

both are oral "hedgehog" signaling pathway inhibitors

Question 28

what is the surgical treatment of melanoma?

Answer 28

surgical excision with 1-2 cm margins often combined with sentinel node biopsy

Question 29

what is the conventional chemotherapy for melanoma?

Answer 29

dacarbazine

Question 30

what is vemurafenib?

Answer 30

it is a MAP kinase pathway inhibitor leading to apoptosis

Question 31

what are 2 treatment options for male pattern baldness?

Answer 31

minoxidil and finasteride

Question 32

how does minoxidil work?

Answer 32

it vasodilates due to K+ channel opening; promotes hair growth by increasing the duration of anagen, shortening telogen, and enlarging miniaturized follicles

Question 33

how does finasteride work?

Answer 33

it is an oral inhibitor of DHT production; increases hair count

Question 34

what is the second line of treatment for female pattern baldness?

Answer 34

anti-androgens

Question 35

what are the 3 different anti-androgens used for female pattern baldness?

Answer 35

spironolactone, finasteride, and flutamide

Question 36

how does spironolactone work?

Answer 36

it is an androgen partial agonist

Question 37

how does flutamide work?

Answer 37

it is an androgen antagonist

Question 38

what is alopecia areata?

Answer 38

it is a chronic relapsing immune-mediated inflammatory disorder affecting hair follicles resulting in non-scarring hair loss

Question 39

how does alopecia areata present?

Answer 39

ranges from small patches of alopecia on any hair-bearing area to the complete loss of scalp, eyebrow, eyelash, and body hair

Question 40

what are two treatment options for alopecia areata?

Answer 40

intralesional or topical corticosteroids; topical immunotherapy

Question 41

what is an example of a topical immunotherapy option?

Answer 41

DPCP (it causes contact dermatitis, which causes hair growth for an unknown reason)