Oral Immunosuppressants

Question 1

Oral CorticoSteroids

Answer 1

Intermediate and long-acting glucocorticoids → methylprednisolone, triamcinolone, dexamethasone, betamethasone
o Virtually no mineralocorticoid activity; dexamethasone/betamethasone with highest glucocorticoid activity
Dosing
o Single morning dose ↓ risk of HPA suppression
o Divided daily dosing may ↑ anti-inflammatory efficacy but also ↑ systemic toxicity
o Alternate day dosing reduces complications except osteoporosis and cataracts

Question 2

Methotrexate

Answer 2

oral pill 10-20 mg weekly, can do SubQ or IM,
-need folic acid supplementation
-Antimetabolite and antifolate, nec for DNA/RNA synth, ↓ inflam
-Renal excretion
-treat acute toxicity with leucovorin
-caution in patients with ↑ alcohol intake, diabetes, or renal failure
* CBC, CMP, LFTs, HIV, hepatitis panel, UA)
-SE: hepatotoxicity, pancytopenia, teratogenicity (egg and sperm), pulmonary fibrosis, ± lymphoma
* ↑ Pancytopenia risk with concomitant use of: NSAID, dapsone, TMP/SMX, or no folate supplementation; ↑ MTX
levels with concomitant use of TCN, phenytoin, phenothiazine, barbiturate, NSAID, salicylate, sulfonamide
* Pregnancy category C

Question 3

Apremilast (Otezla)

Answer 3

(Otezla)
* (PDE4) inhibitor -> ↑ cyclic adenosine monophosphate (cAMP) in Keratinocytes -> ↓ proinflammatory cytoikines
-can use in pt with chronic infection
-PsO (33% pasi 75) - best in scalp PsO
* SE: nausea, diarrhea, depression, weight loss

Question 4

Cyclosporine (CsA)

Answer 4

• Inhibits T cell activity -> calcineurin inhibition -> ↓ IL-2
• Oral: 2-4 mg/kg by mouth per day (often divided into 2 doses)
• PASI 60-70 within 4 weeks
• Good for patients with chronic conditions and severe flares, use limited to 1 year, longer use
  c/ -> glomerulosclerosis
• Monitor CsA levels, Mg, BP, CMP
• Treatment for psoriasis, pyoderma gangrenosum, severe atopic dermatitis, autoimmune bullous disorders
• SE: nephrotoxicity, reversible HTN, gingival hyperplasia, hyperlipidemia, ↑ K and ↓ Mg, ↑ uric acid, paresthesias,
  hypertrichosis, lymphoma
• mtblzd by p450 3A4: ->
  
  • p450 inhibs ->↑ levels CsA - diltiazem, nicardipine,
    verapamil, ketoconazole, fluconazole, itraconazole, erythromycin);
    -p450 inducers -> ↓ CsA levels - rifampin, phenobarbital, phenytoin, carbamazepine
• Check BP regularly; Cr> 30% of baseline, ↓ dose
• ↑ Risk for renal toxicity: aminoglycosides, NSAIDs, amphotericin B and vancomycin
• Pregnancy category C
• Defer next cyclosporine dose until 2-4 weeks after live vaccine

Question 5

Hydroxyurea

Answer 5

• Inhibits RNA reductase; S-phase specific
• SE: hematologic toxicity, photosensitivity, mucosal ulceration, anemia, hepatitis, renal toxicity, poikiloderma of
  hands/feet, diffuse hyperpigmentation, leg ulcers, radiation recall
• Category D

Question 6

Thalidomide

Answer 6

• Inhibits TNFα - mechanism unknown
• Treats: erythema nodosum leprosum, HIV associated mucosal ulceration, recalcitrant DLE or SCLE
• SE: fetal anomalies (phocomelia), peripheral neuropathy (proximal muscle weakness, painful paresthesias of extremi-
  ties), somnolence, TEN, hypersensitivity reaction, leukopenia