Disease Modifying Antirheumatic Drugs (DMARDs)

Drug Mechanism Use Toxicity Notes

Azathioprine Inhibits de novo acute bon Derivative of mercaptopurine
synthesis of purines glomerulonep e marrow Prodrug
required for lymphocyte hritis depressio Antimetabolite precursor of
proliferation systemic n: 6-mercaptopurine
Prevents clonal lupus leukopeni Metabolized in the liver to
expansion of both B and erythematous a thiouric acid (inactive metabolite)
T lymphocytes rheumat muc by xanthine oxidase
oid arthritis ositis Metabolized in the liver to
inflamm gast another inactive metabolite by
atory bowel rointestin thiopurine methyltransferase
disease al toxicity Produces 6-thioguanine, an
(nausea, active metabolite, via thiopurine
vomiting, methyltransferase or inosine
diarrhea) monophosphate dehydrogenase
hep gets incorporated into the
atotoxicity elongating chain of DNA to prevent
incr lymphocyte proliferation
eased risk If a patient has low activity of TPMT
of then more 6MP will be converted to an
infections active metabolite than the inactive
metabolite, and can cause more
toxicity
1. Lower doses recommended
Excreted primarily in urine
PO or IV
Widely distributed but does
not cross the blood brain
barrier(BBB)
Safe for use in pregnancy
Interactions: Co-
administration of allopurinol with
azathioprine may lead to toxicity
due to inhibition of xanthine
oxidase by allopurinol
Cyclophosphami Phosphoramide Rheumat Alop Prodgrug
de cross links DNA to oid arthritis ecia Activated into
prevent cell replication SLE Hem phosphoramide
Destroys Vasculitis orrhagic IV or PO
proliferating lymphoid cystitis Anticancer and
cells, and suppresses T GI immunosuppressant in
 Disease Modifying Antirheumatic Drugs (DMARDs)
Drug Mechanism Use Toxicity Notes
cell and B cell function symptoms autoimmune disease
steri
lity
 Disease Modifying Antirheumatic Drugs (DMARDs)
Drug Mechanism Use Toxicity Notes
Hydroxychloroq Unclear Rheumat Nau Small molecule DMARDs
uine and mechanism proposed oid arthritis sea Hydroxychloroquine is also
Chloroquine to inhibit immune Malaria Ras antimalarial
responses and inhibition Skin h Toxicity is thought to be
of antigen presentation manifestations Ocul greater with chloroquine
to CD4+ T cells of SLE ar toxicity Safe for use during
Sjogrens Agra pregnancy
syndrome nulocytosi
s
Apla
stic
anemia
Leflunomide Inhibits de novo Rheumat Elev Prodrug
pyrimidine synthesis by oid arthritis ation of Active metabolite(A77-1726)
blocking dihydroorotate liver undergoes enterohepatic
dehydrogenase and enzymes circulation long half life
inhibiting synthesis of Ren Given orally and has long
uridine al duration of action
Cell growth arrest in G1 impairme
phase of cell cycle nt
Mild
alopecia
Wei
ght gain
Incr
eased
blood
pressure
Cont
raindicate
d in
pregnancy
Methotrexate Folic acid Rheumat GI PO, IV, IM
antagonist oid Arthritis symptoms Excreted in urine
Inhibits dihydrofolate Psoriasis Alop Some symptoms of toxicity
reductase required for Crohns ecia can be alleviated with folic acid
formation of tetrahydrofolate disease Bon supplements or leucovorin
Inhibition of DNA, RNA, and Graft vs. e marrow
protein synthesis host disease depressio
Interferes with T cell n
 Disease Modifying Antirheumatic Drugs (DMARDs)
Drug Mechanism Use Toxicity Notes
replication Pul
Inhibits monary
aminoinidazolecarboxam fibrosis
ide ribonucleotide Nep
(AICAR) transformylase hrotoxicity
and thymidylate Hep
synthetase atotoxicity
AICAR accumulates dose-
intracellularly and dependen
competitively inhibits AMP t
deaminase Cont
AMP accumulation and raindicate
conversion to adenosine a d in
potent inhibitor of pregnancy
inflammation
 Disease Modifying Antirheumatic Drugs (DMARDs)
Drug Mechanism Use Toxicity Notes
Mycophenolate Inhibits de novo Solid Gi Prodrug
Mofetil synthesis of purines organ and toxicity Hydrolyzed to
Mycophenolic acid hematopoietic Leuk mycophenolic acid
is a potent inhibitor of stem cell openia, IV, IM, PO
inosine monophosphate patients neutropen Highly protein bound
dehydrogenase (IMP) Combine ia Metabolized in the liver via
Causes suppression d with Lym glucuronidation then excreted in
of B and T cell prednisone as phoma the urine
proliferation alternative to Cont More selective than
Interferes with cyclosporine raindicate azathioprine for IMP
leukocyte adhesion to or tacrolimus d in
endothelial cells through Rheumat pregnancy
inhibition of E-selectin, P- oid arthritis
selectin and intercellular Dermatol
adhesion molecule 1 ogic disorders
Vasculitis
Wegener
s
granulomatosi
s
Renal
disease due to
SLE
Sulfasalazine Unclear Rheumat Hea Small molecule DMARDs
mechanism proposed oid arthritis dache Combined with other
to interfere with T and B Inflamm Vom DMARDs
cell immune responses, atory bowel iting Decreases signs and
potentially by inhibiting disease Ras symptoms of disease and slows
the activity of the NF-kB h radiographic evidence of joint
transcription factor destruction
More toxic than
hydroxychloroquine
Less effective than
methotrexate
Metabolized to 5-
aminosalicylic acid covalently
linked to sulfapyridine
Effect can be seen in 1-3
months
Safe in pregnancy
 Immunophilin Ligands
Drug Mechanism Use Toxicity Notes
Cyclosporine Interferes with calcineurin by Organ Peripheral neuropathy Less potent than tacrolimus
forming complexes with cyclophilin transplantation Tremor Increased episodes of
NFAT is not dephosphorylated Rheumatoid Nephrotoxicity rejection compared with
no gene transcription arthritis Hypertension tacrolimus
inhibits IL-2, IL-3, and IFN- Crohns disease Hyperglycemia IV or PO
production Psoriasis Hyperkalemia Metabolized by CYP 450 3A
Inhibits T cell function and Hyperlipidemia Interaction with: CYP 450
proliferation Hirsutism (excessive hair metabolized drugs:
growth) Clarithromycin -
Gingival hyperplasia Diltiazem
Opportunistic infections Fluconazole -
Rifampin
Ketoconazole
Phenytoin
Verapamil
Sirolimus Binds to FKBP inhibits mTOR Organ Bone marrow suppression Macrolide
(Rapamycin) inhibits translation T cells arrest transplantation Thrombocytopenia PO only
in the G1 phase Mainly used as Liver dysfunction Metabolized by CYP 450 3A
Inhibitor of IL-2 action adjunctive therapy Increase in triglycerides Interactions with: CYP 450
hypertension metabolized drugs:
Cyclosporine -
Rifampin
Diltiazem -
Ketoconazole
Tacrolimus Interferes with calcineurin by 1st choice for organ Peripheral neuropathy Macrolide
forming complexes with FKBP transplantation greater than w/ IV or PO
NFAT is not dephosphorylated no cyclosporine 10-100x more potent than
gene transcription Tremor cyclosporine in inhibiting
inhibits IL-2 production Nephrotoxicity immune responses
Inhibits T cell function and Greater than w/ Has decreased episodes of
proliferation cyclosporine rejection compared with
Hypertension cyclosporine
Hyperglycemia Combined with lower doses of
Hyperkalemia glucocorticoids compared to
Hyperlipidemia cyclosporine
Hirsutism Metabolized by CYP 450
Gingival hyperplasia Interactions with: CYP 450
 Immunophilin Ligands
Drug Mechanism Use Toxicity Notes
Opportunistic infections metabolized drugs:
Clarithromycin
Fluconazole
Ketoconazole
Rifampin