Immune-mediated dermatoses: drugs Flashcards
(29 cards)
what are broad immune effects of oral GCs
suppress eos, mast, monocytes, lymphocytes
increase neuts (increase bone marrow release, decreased margination and entrance into tissue)
decrease infl mediation prod’n
decrease vascular permeability, Ab syntheses, T-cell activation, T-cell cytokines, T-cell proliferation
what re some side effects of oral GCs (not skin related ones, say the others)
PU/PD/PP
muscle atrophy, pant, lipidemia, hypercoagulability, GI ulceration, vomiting
liver dz, kidney dz, diabetes, iatrogenic Cushings, secondary infection
what are some skin side effects of oral GCs
cutaneous atrophy, comedones, cysts, mili, striae, hypotrichosis, alopecia, dull coat
calcinosis cutis
give a few contraindications/cautions for glucocorticoids
kidney, liver, or heart disease
diabetes, serious infection, GI ulceration, Demodex
concurrent NSAID or immunosuppressive usage
proposed dosing for glucocorticoids: what case would you give lowest dose, and highest dose
physiologic dose (0.2 to 1.0 mg/kg daily)
antipruritic dose 0.5 mg//kg/day
antiinfmalltory dose 1-2
immunosuppressive 2-4
modified cyclosporine is extensively metabolized by ___, so by administering _____ can increase drug levels
p450 enzymes; p450 enzyme inhibitors like ketoconazole
unfortunately you need to know MOA of modified cyclosporine, which is…
modified cyclosporine crosses plasma membrane and binds to cyclophilin
forms a CsA-cyclophilin complex which inhibits calcineurin and NF-AT (nuclear factor of activated T cells)
what is modified cyclopsoirns used for, what minimum age, how fast does it work
tx atopy in dogs at least 6 months old
(autoimmuen/immune-mediated dz, eg. Perianalfistulae,sebaceousadenitis,pemphigusfoliaceus,sterile nodular panniculitis, vasculitis, erythema multiforme, toxic epidermal necrolysis)
can take 4-8 weeks to reach full effect
some side effects of modified cyclosporine
GI upset, gingival hyperplasia, hypertrichosis, UTI, cat toxoplasmosis
how do we monitor cyclosporine
rarely check CsA levels when modified cyclosporine is used at atopy doses
we do check CBC, chem, UA baseline and 2X yearly
and serum levels wither when used with ketoconazole, when not responsive, or persistent adverse effects are present
azathioprine is converted by liver to 6-mercaptopurine (6-mp) and this in turn its degraded by thiopurine methyltransferase (TMPT). why does this matter
cats deficient in TMPT, so azathioprine not recommended in cats
and differences in TMPT levels in dogs, so may be why there is variability of response
why is azathioprine primarily used, in who, and how log to take effect
as potent steroid-sparing agent, in dogs, and takes 1-2 weeks to reach therapeutic concentrations but maybe 3-6 weeks for effects
azathioprine is started at 1.0-2.5 mg/kg daily initially then tapered to EOD, aiming for eventually 0.5-1.0 mg/kg or less q72h.
what is difference between small and big dog starting dose
high range in smaller dogs and lower range in larger dogs
what are some side effects of azathioprine
V/D
pancreatitis, esp. if on steroids too
bone marrow suppression
rarely, fulminant hepatic necrosis
long-term, can get Demodex, pyoderma, ordermatophytosis
this drug once converted by liver to 6-mp acts as a prune analog that inserts itself into DNA causing missense mutations, leading to cell death, and has greatest effect on cell-mediated immunity
azathioprine
this drug is a prodrug to mycophenolic acid, inhibits inside monophosphate dehydrogenase, inhibits purine synthesis (T and B lymphocytes), decreases IL-1, increases IL-1 receptor antagonist
it is dosed BID, but try to taper to SID or less
mycophenolate mofetil
what are documented side effects of mycophenolate mofetil
V/D common
bone marrow suppression
this alkylating agent that cross-links DNA has side effects of myelosuppression, V/D, anorexia, is generally well-tolerated, and need to monitor CBC q2 weeks initially
chlorambucil
what are a few diseases chlorambucil can be used to treat
feline pemphigus foliaceus (dosed at 0.1-0.2 mg/kg q24-48h, and can take weeks to see effects), maybe other autoimmune diseases and in dogs
this methylxanthine derivative has the following effects:
increased RBC deformability and chemotaxis-vasculitis, decreased platelet aggregation, decreased response to IL-1 and TNF-alpha, decreased cytokine production, inhibit lymphocyte activation, is dosed TID or BID, and rarely has side effects
pentoxifylline
what are a few indications for pentoxifylline tx
vasculitis, dermatomyositis, symmetric lupoid onychodystrophy, ischemia dermatopathy, contact dermatitis, other mild autoimmune conditions
this form of vitamin B3 blocks histamine release, blocks degradation of mast cells, acts asn aphotoprotectant and cytoprotectant, inhibits phosphodiesterase, and decreases protease relase
niacinamide
this drug class suppresses leukocytes chemotaxis, Ab prod’n, cytokines; also inhibits complement, prostaglandins, lipases, collagenases
tetracycline (doxycycline and minocycline are used in derm)
what are some side effects of tetracycline/niacinimiade
V/D, anorexia, lethargy, increased liver enzymes
