Tx of Psoriasis and Acne Flashcards
What causes psoriasis?
A trigger causes recruitment of a number of inflammatory mediators including interferon-alpha, ILs, TNFa, and TGF-b. The net effect of this inflammatory process is recruitment of T cells, neutrophils, dendritic cells, and fibroblasts to the area and ultimately a proliferation of keratinocytes at the affected area
What are some drugs available for psoriasis?
- Adalimumab
- Alefacept
- Etanercept
- Infliximab
- Ustekinumab
- Calcipotriene and Calcitriol
others
How does Adalimumab work?
SC drug that acts as a TNFa monoclonal that binds TNFa and blocks its interactions with the p55 and p75 cell surface receptors
How does Alefacept work?
IM recombinant human LFA-3/IgG1 fusion protein that binds to CD2 on memory effector T-cells, which prevents T-cell activation and promotes apoptosis
How does Apremilast work?
PO drug that is a phosphodiesterase 4 inhibitor which increases cellular cAMP (consequences poorly understood)
How does Etancercept (Enbrel) work?
SC drug that consists of the extracellular ligand-binding portion of human p75 TNF receptor linked to IgG FC that binds to TNF to inactivate it (but does not affect TNF production or serum levels)
How does Infliximab work?
IV drug that is a chimeric (mouse-human) IgG1k monoclonal against TNFa to bind and neutralize both soluble and transmembrane TNFa
How does Uztekinamab work?
Human IgG1-kappa monoclonal Ab that binds to the p40 subunits IL-12 and Il-23 for treatment of psoriasis
How should patients be adviced when taking biologicals like etancercept or infliximab?
These drugs cause immunosuppression (dont initiate in a patient with active infection) and could potentiate infection (partiuclarly URI). Advise patients to report any signs/symptoms of infection and avoid live vaccines during use.
These can also increase the likelihood of malignancy
AEs reported in biologicals like etancercept, infliximab, and adalimumab?
- CHF or hypotension/angina and LFT elevation (especially in Infliximab)
- lupus-like syndrome (myalgias, skin rashes, fatigue)
- injection site rxns in those injected SC or IM (adal, alefacept, etancercept)
Another class of agents used to treat psoriasis (and some for acne) are the retinoids. How do they work?
Retinoids produce anti-inflammatory, anti-tumoral, and immunomodulatory effects and on the skin can stimulation keratinization and decrease sebum secretion and sebaceous gland size (isotretinoin)
What malignancy are retinoids used for?
acute promyelocytic leukemia (act on the nuclear retinoid receptors (RXR/RARa)
How do retinoids cause increased basal keratinocyte proliferation?
Topical application of a retinoid activates RXR/RAR heterodimers in suprabasal heratinocytes, causing activation of yet unidentified transcription factors. These, in turn, activate the synthesis of heparin-binding epidermal growth factor (HB-EGF) and amphiregulin (AR). Throguh activation of EGF-r, HB-EGR and AR cause keratinocte proliferation.
Note about RAR/RXR receptors
Targeting RARs predominantly affects cellular differentiation and proliferation (i.e. tretinoin, adapalene, and tazarotene are primarily used in acne, psoriasis, and photoaging) while targeting RXRs predominantly induces apoptosis are better suited for tumor related use (Bexarotene and alitretinoin used in mycosis fungoides and Kaposi sarcoma)
What are some of the toxicities of retinoids?
Acute toxicity resembles vitamin A toxicity including dry skin, nosebleeds, reduced night vision, and hair loss
ALL oral retinoids are potent teratogens