Pharmacology of Psoriasis and Acne - Sweatman Flashcards
What does the T cell surface antigen, CD-2, interact with on antigen presenting cells?
LFA-3
pre-requisite for T cell activation
What is the structure and MOA of Adalimumab?
TNF-a monoclonal Ab
Binds TNF-a, blocks its interaction with p55 and p75 cell surface receptors
what is the structure and MOA of Alefacept?
Recombinant human LFA-3/IgG1 fusion protein
Binds to CD2 on effector T cells prevents T cell activation
What is the structure and MOA of Apremilast?
Phosphodiesterase 4 inhibitor (PDE4)
Increases cellular cAMP, consequences poorly understood
What is the structure and MOA of Etanercept
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
use of biological agents in the context of psoriasis have what two general side effects? what are pts more susceptible to?
Immunosuppression - increased susceptibility to bacterial, fungal, and parasitic infection
may increase likelihood of a malignancy
what biological agents used in the treatment of psoriasis show CHF or hypotension/angina/dysrhythmia as side effects?
Adalimumab, infliximab, Rituximab
CHF is a contraindicaiton in the use of infliximab
What biological agents used in tx of psoriasis cause a lupus-like syndrome? (arthralgias, myalgias, fatigue, skin rashes?)
Adalimumab, Etanercept, Infliximab
What biological agent used in the treatment of psoriasis must you do LFTs for?
Infliximab
What is the structure and MOA of Infliximab?
Chimeric (mouse-human) IgG1k monoclonal Ab against TNF-a
binds to and neutralizes both soluble and transmembrane TNF-a
What is the structure and MOA of Uztekinamab?
Human IgG1k monoclonal Ab
binds to the p40 subunits of IL-12 and IL-23 cytokines
In general, what are the effects of retinoids?
critical signaling molecules, related to Vit A - produce myriad of effects in cell - antitumoral, immunomodulatory, and anti-inflamm (by inhibiting inflammatory cytokines)
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?
retinoids decrease sebum secretion and sebaceous gland size
Retionoids target RAR/RXR receptors - which target is more important for dermatologic treatment
RAR - predominantly affects cellular differentiation and proliferation
What is the main systemic toxicity we are worried about retinoids?
they are teratogens
What is the effects of acute toxicity to retinoids?
similar to effects of too much Vit A - dry skin, nosebleeds, conjunctivitis, reduced night vision
when are topical retinoids considered first line? what are they also effective in?
1st line for non inflammatory acne
also effective in reducing fine wrinkles and dyspigmentations assoc with photoaging
what are the principal side effects of topical retinoid use?
increased risk of sunburn
What is the MOA of Calcipotriene?
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)
what is the principal adverse effect of topical Calcipotriene use, and how is this fixed?
topical irritant - reduced by concurrent corticosteroids
what side effects can be seen with Calcipotriene as you reach the max weekly dosage
hypercalcemia/ hypercalciuria
what should you use instead of Calcipotriene in sensitive skin areas?
Calcitriol
How do we define the potency of corticosteroids in the setting of psoriasis treatment?
potency is based upon their ability to blanch the skin
not all dermatologic conditions respond well to corticosteroid activity - what determines this?
drug responsiveness varies by condition and by anatomical location
