Systemic Drugs

Psoriasis
Cyclosporine A (CsA)
• Derived from Tolypocladium inflatum Gams
• MOA:

Cyclosporine Cyclophilin Cyclos Cycloph

porine ilin

Stop production of IL (IL-2)

= ↓T Cell proliferation
Cyclos Cycloph
NFATc porin ilin
↑TGF-B (IL-2 inhibitor)
Calcineu
rin
Cyclosporine A (CsA)
• Formulation: Oral solutions or capsule
• For cutaneous psoriasis and nail psoriasis
Cyclosporine A (CsA)
• Dosage: 2 to 5 mg/kg/day
• Nephrotoxic: irreversible

• Adverse effects:

• Use at short periods:

neurologic (tremors, headache, paresthesis, and/or hyperesthesia)

• Long-term:
Increased risk of nonmelanoma skin cancers
Cyclosporine A (CsA)
• Contraindications:

• Uncontrolled HTN
• Abnormal renal function
• Hx/current malignancy
Methotrexate (MTX)
• For:
chronic plaque psoriasis
long-term management of severe forms of psoriasis: psoriatic
erythroderma and pustular psoriasis
Methotrexate (MTX) MOA

Methotrexate

Dihydrofolate
reductase
DNA and RNA
Dihydrofolate Tetrahydrofolate
synthesis
Methotrexate (MTX) MOA
• Also blocks AICAR transformylase → accumulation of anti-
inflammatory adenosine
Methotrexate (MTX)
• Dosage:

Test dose of 2.5mg and gradually increase dose until therapeutic

level is reached.
ave. range: 10-15 mg weekly
maximum: 25-30 mg weekly
Methotrexate (MTX)
• If with folic acid, reduces side effects such as nausea and
megaloblastic anemia

• Another side effect: Myelosuppression esp. pancytopenia

• Leucovorin calcium (folinic acid) is the only antidote for the

hematotoxicity of MTX.
Methotrexate (MTX)
• Discontinue tx if there is hepatotoxicity, hematopoietic suppression,
active infections, nausea, and pneumonitis.

• Teratogenic

• NSAIDs and sulphonamides increase toxicity

Acitretin
• 2nd generation systemic retinoid. Metabolite of etretinate.

• Retinoid of 1st choice for oral Tx of psoriasis

• Pustular psoriasis of the palmoplantar or generalized (von

Zumbusch) type and erythrodermic psoriasis

• MOA: not clearly understood, binds to retinoic receptors

Acitretin
• Dose: 25mg/day with maintenance dose of 20-50 mg/day
• Adverse effects: hair loss and paronychia
• Discontinue liver dysfunction, hyperlipidemia, or diffuse idiopathic
hypertosis develops
Fumaric Acid Esters
• Active metabolite: monoethyl fumarate
• MOA: not completely understood
• Change from Th1-dominated T-cell to Th2-like pattern
• Inhibition of keratinocyte proliferation

• Dose: initiate at low dose, and escalate dose weekly. Max is

1.2 g/day
Fumaric Acid Esters
• Contraindications:

• Severe concomitant disease, chronic disease of the GIT,

chronic kidney disease, or with bone marrow disease, (+)
Hx of malignancy

• Pregnant or lactating women

Hydroxyurea
• Dose: 500 mg daily, increased to 1.0-1.5 g daily based on response
and tolerance

• 50% of Px who achieved marked improvement develop bone marrow

toxicity with leukopenia and thrombocytopenia

• Megaloblastic anemia
• Cutaneous reactions (leg ulcers)
Hydroxyurea
• MOA:
Ribonucleotide
diphosphate
reductase

DNA synthesis in
ribonucleotide deoxyribonucleotide
proliferating cells
6-Thioguanine
• Purine analog

• MOA:
• interferes with purine biosynthesis → cell cycle arrest and apoptosis

• Dose:
• start with 80 mg 2x weekly
• with 20-mg increments every 2-4 weeks
• Max: 160 mg 3x weekly
6-Thioguanine
• Bone marrow suppression, GIT complaints (nausea and diarrhea),
elevation of liver function tests.

• Isolated cases of hepatic veno-occlusive disease

• Contraindication:
• Inherited deficiency of thiopurine methyltransferase enzyme due to increased
risk of myelosuppression
• Liver toxicity
• Pregnancy
Mycophenolate Mofetil
• Prodrug of mycophenolic acid
• MOA: Inhibits inosine-5’-monophosphate dehydrogenase → blocks
purine biosynthesis

• Depletes guanosine nucleotides preferentially in T and B lymphocytes

and inhibits their proliferation

• Dose: initated at 500-750 mg bid and then increased to 1.0-1.5 g bid

• Only moderately effective for psoriasis treatment
Sulfasalazine
• Uncommonly used, with moderate effectivity for severe psoriasis

• MOA: Anti-inflammatory agent, inhibits 5-lipoxygenase, molecular

mechanism unclear

• Dose: 500 mg tid. If tolerated after 3 days, increase dose to 1 g tid. If

tolerated after 6 weeks, increase dose to 1 g qid
Sulfasalazine
• Contraindications: hypersensitivity to sulfasalazine, sulfa drugs,
salicylates, intestinal or urinary obstruction, porphyria. Precaution in
Px with G6PD deficiency.
Systemic Steroids
• In general, should not be used in routine care of psoriasis.
• Clearance of psoriasis is rapid, but the disease usually breaks through,
requiring higher doses to control symptoms.
Thank you!