Pharmacology of Psoriasis and Acne - Sweatman

Question 1

What does the T cell surface antigen, CD-2, interact with on antigen presenting cells?

Answer 1

LFA-3

pre-requisite for T cell activation

Question 2

What is the structure and MOA of Adalimumab?

Answer 2

TNF-a monoclonal Ab

Binds TNF-a, blocks its interaction with p55 and p75 cell surface receptors

Question 3

what is the structure and MOA of Alefacept?

Answer 3

Recombinant human LFA-3/IgG1 fusion protein

Binds to CD2 on effector T cells prevents T cell activation

Question 4

What is the structure and MOA of Apremilast?

Answer 4

Phosphodiesterase 4 inhibitor (PDE4)

Increases cellular cAMP, consequences poorly understood

Question 5

What is the structure and MOA of Etanercept

Answer 5

fusion protein of ligand binding portion of p75 TNF receptor and human IgG Fc
binds to and inactivates TNF
acts as “false” receptor for circulating TNF

Question 6

use of biological agents in the context of psoriasis have what two general side effects? what are pts more susceptible to?

Answer 6

Immunosuppression - increased susceptibility to bacterial, fungal, and parasitic infection
may increase likelihood of a malignancy

Question 7

what biological agents used in the treatment of psoriasis show CHF or hypotension/angina/dysrhythmia as side effects?

Answer 7

Adalimumab, infliximab, Rituximab

CHF is a contraindicaiton in the use of infliximab

Question 8

What biological agents used in tx of psoriasis cause a lupus-like syndrome? (arthralgias, myalgias, fatigue, skin rashes?)

Answer 8

Adalimumab, Etanercept, Infliximab

Question 9

What biological agent used in the treatment of psoriasis must you do LFTs for?

Answer 9

Infliximab

Question 10

What is the structure and MOA of Infliximab?

Answer 10

Chimeric (mouse-human) IgG1k monoclonal Ab against TNF-a

binds to and neutralizes both soluble and transmembrane TNF-a

Question 11

What is the structure and MOA of Uztekinamab?

Answer 11

Human IgG1k monoclonal Ab

binds to the p40 subunits of IL-12 and IL-23 cytokines

Question 12

In general, what are the effects of retinoids?

Answer 12

critical signaling molecules, related to Vit A - produce myriad of effects in cell - antitumoral, immunomodulatory, and anti-inflamm (by inhibiting inflammatory cytokines)

Question 13

with regards to the effects of retinoids on the skin, it is somewhat unclear what their effect is on keratinocyte proliferation. What are retinoids effects on sebum?

Answer 13

retinoids decrease sebum secretion and sebaceous gland size

Question 14

Retionoids target RAR/RXR receptors - which target is more important for dermatologic treatment

Answer 14

RAR - predominantly affects cellular differentiation and proliferation

Question 15

What is the main systemic toxicity we are worried about retinoids?

Answer 15

they are teratogens

Question 16

What is the effects of acute toxicity to retinoids?

Answer 16

similar to effects of too much Vit A - dry skin, nosebleeds, conjunctivitis, reduced night vision

Question 17

when are topical retinoids considered first line? what are they also effective in?

Answer 17

1st line for non inflammatory acne

also effective in reducing fine wrinkles and dyspigmentations assoc with photoaging

Question 18

what are the principal side effects of topical retinoid use?

Answer 18

increased risk of sunburn

Question 19

What is the MOA of Calcipotriene?

Answer 19

topical drug, binds to Vit D receptor; complex associates with RXR-a ad binds DNA Vit D response elements
(basically, it is a calcitriol analog I think)

Question 20

what is the principal adverse effect of topical Calcipotriene use, and how is this fixed?

Answer 20

topical irritant - reduced by concurrent corticosteroids

Question 21

what side effects can be seen with Calcipotriene as you reach the max weekly dosage

Answer 21

hypercalcemia/ hypercalciuria

Question 22

what should you use instead of Calcipotriene in sensitive skin areas?

Answer 22

Calcitriol

Question 23

How do we define the potency of corticosteroids in the setting of psoriasis treatment?

Answer 23

potency is based upon their ability to blanch the skin

Question 24

not all dermatologic conditions respond well to corticosteroid activity - what determines this?

Answer 24

drug responsiveness varies by condition and by anatomical location

Question 25

what is a key point about corticosteroids in the use of dermatologic conditions? do they treat the underlying cause?

Answer 25

they reduce the symptoms of inflammation, but do not address the underlying cause

Question 26

What is the utility of fluorinated steroids? what precaution should be taken?

Answer 26

fluorination increases the potency

fluorinated steroids should NOT be applied to the face

Question 27

in addition to topical application, what is another delivery option for corticosteroids in setting of derm conditions

Answer 27

intralesional injections of relatively insoluble agents whose release over an extended period

Question 28

what parameters affect the topical adverse effects of corticosteroids?

Answer 28

potency, duration of application and surface area to which drug is applied

Question 29

what are the principal adv effects of topical corticosteroid use?

Answer 29

dermal atrophy - “cigarette-paper” appearing skin
corticoid rosacea
other contact toxicities

Question 30

what is the MOA of Benzoyl Peroxide?

Answer 30

liberates a free radical that is lethal to the Propiobacterium acnes bug

Question 31

besides the free radical mediated effect of benzoyl peroxide, what other effect does BP have on the skin

Answer 31

keratinolytic activity that dries the skin and desquamative action

Question 32

what is a side effect of benzoyl peroxide?

Answer 32

the oxidant nature will bleach clothes or hair

Question 33

what is the MOA of salicylic acid?

Answer 33

topical keratolytic - causes desquamation of horny layer of skin

Question 34

what pt population do we need to be cautious in using salicylic acid in?

Answer 34

mothers - neonatal toxicity via breast milk and contact toxicity