Other Topical Medications

Question 1

What is the mechanism of action of topical calcipotriene and calcitriol?

Answer 1

Product binds to vitamin D receptors –> drug-receptor complex + RXR-alpha binding to DNA at vitamin D response elements. This leads to decreased keratinocyte proliferation/epidermal differentiation, decreases IL-2/6/IFN-gamma/GM-CSE, decreases NK-cell and cytotoxic t-cell activity, and increases involucrin/transglutaminase which leads to enhanced cornified envelope formation

Question 2

What are the uses of vitamin D analogs?

Answer 2

psoriasis, morphea, vitiligo, and prurigo nodularis

Question 3

Side-effects of topical calcipotriene and calcitriol

Answer 3

irritation (most common), mild photosensitivity and hypercalcemia (rare)

Question 4

What is the mechanism of action and the use of eflornithine?

Answer 4

Binds and inhibits ornithine decarboxylase

• For female facial hirsutism; acne most common side effect

Question 5

How does topical hydroquinone lighten the skin?

Answer 5

active reduction of pigment production (auto-oxidation of melanin, tyrosinase, and phenol oxidases into various reactive substances). Also competes for w/ tyrosine as a state for tyrosinase; leads to the production of ROS and monocyte damage.

Question 6

What are the side effects of hydroquinone?

Answer 6

Dermatitis is the most common SE, most concerning are paradoxical hyperpigmentation and exogenous ochronosis (high concentrations for too much time).

Question 7

What is the mechanism of action for topical pimecrolimus and tacrolimus?

Answer 7

Binds to FK506-binding protein which makes a complex and binds to enzyme calcineurin preventing calcineurin from dephosphorylating transcription factor NFAT-1. This leads to decrease transcription of cytokine IL-2 leading to decreased t-cell activation/proliferation

Question 8

In what condition must systemic absorption of pimecrolimus/tacrolimus be considered in?

Answer 8

Netherton syndrome

Question 9

Side effects for pimecrolimus/tacrolimus?

Answer 9

Burning sensation with initial use, especially in inflamed skin, black box warning for malignancy (super low, but patients should be counseled regarding it).

Question 10

What is the mechanism of action for topical 5-FU?

Answer 10

Inhibits thymidylate synthase (converts deoxyuridine to thymidine)= decreased DNA synthesis

Question 11

Side effects of topical 5-FU?

Answer 11

Local reactions (erythema, blistering, necrosis, erosions, and burning

• Pregnancy category X

Question 12

What is the mechanism of action for imiquimod?

Answer 12

Activator of TLR 7 and 8 –> activates NF-kappa B transcriptions factor –> increased cytokines/chemokines (TNF-alpha and interferon-gamma –> innate/acquired immune pathway stimulation –> antitumor and antiviral activity

• Also antiangiogenic, proapoptotic, and increased lymphatic transport of immune cells/factors

Together leads to tumor destruction

Question 13

FDA approved indications for imiquimod?

Answer 13

AK’s, superficial BCC’s (5% only), genital perianal warts

Question 14

Most common side effects with imiquimod?

Answer 14

Local reactions similar to 5-FU, sometimes flu-like or GI sx’s (increased risk with large areas), and psoriasis exacerbation

Pregnancy Class C

Question 15

What is the mechanism of topical diclofenac for AK treatment?

Answer 15

Decrease cyclooxygenase (COX) which leads to increased apoptosis

Question 16

Side effects of topical diclofenac?

Answer 16

Mild irritation, rare photosensitivity/photocontact dermatitis; avoid in patients with NSAID hypersensitivity and known bleeding diatheses

Question 17

What is the mechanism of ingenol mebutate?

Answer 17

Has 2 phases
1. Induces rapid cellular death (within hours) via mitochondrial swelling/plasma membrane disruption then
2. Intense inflammatory response (within days) via protein kinase C activation