DMARD Flashcards
1
Q
DRUGS FOR RHEUMATOID ARTHRITIS
A
- NSAIDs
- Corticosteroids
- DMARDs
Note: NSAIDs and corticosteroids do not prevent disease progression or joint destruction.
2
Q
DMARD Drug list
A
- miscellaneous group of drugs with the potential to reduce or prevent joint damage.
- have no immediate analgesic effects, but can control symptoms and can delay and possibly stop progression of the disease.
Non-Biologicals
- Methotrexate
- Leflunomide
- Hydroxychloroquine
- Sulfasalazine
- Cyclosporine
- Azathioprine
- Cyclophosphamide
- Gold Compounds
Biologicals
- Anti-TNF Drugs: Adalimumab, Infliximab, Etanercept
- Anti-Interleukin Drugs: Anakinra
- Rituximab
- Abatacept
3
Q
METHOTREXATE
A
DMARD of first choice to treat rheumatoid arthritis.
1o MOA: Inhibits amino imidazole carboxamide ribonucleotide (AICAR) transformylase.
- AICAR Transformylase catalyzes the penultimate and final steps in de novo purine biosynthesis which lead to synthesis of inosine monophosphate (IMP).
- The inhibition of AICAR transformylase results in the accumulation and release of adenosine.
Other MOA:
- Adenosine is a potentanti-inflammatory mediator. Adenosine, acting on A2b receptors, suppresses NF-kappaB activation induced by TNF and other inflammatory stimuli.
- DHF Reductase inhibition: thymidylate synthase pathway also may be involved.
Adverse
- Nausea
- Mucosalulcers
- Hepatotoxicity
- Cirrhosisisrare
- Toxicity can be reduced with leucovorin or folic acid
- Contraindicated in pregnancy.
4
Q
LEFLUNOMIDE
A
- Leflunomide undergoes conversion to an active metabolite which inhibits dihydroorotate dehydrogenase, leading to lower levels of UMP.
- Cells arrest in the G1 phase.
- Thus, leflunomide inhibits autoimmune T cell proliferation and production of autoantibodies by B cells.
- Other cells are not affected because they can use the salvage pathways to maintain their basal requirements for pyrimidines.
- Activated lymphocytes depend on the de novo synthesis of pyrimidine because their need is increased eightfold.
Adverse
- Diarrhea.
- Reversible alopecia, rash, myelosuppression and increases in aminotransferase activity.
- CBC and LFT should be monitored.
- Carcinogenic and teratogenic in animals.
- Contraindicated in pregnancy.
5
Q
HYDROXYCHLOROQUINE
A
- mechanism of anti-inflammatory action is unclear.
- Often used with methotrexate and sulfasalazine.
Adverse
- Hemolysis may occur in patients with G6PD deficiency.
- Retinal damage is a rare complication.
- Ophthalmologic exam is recommended before treatment, and regularly afterwards.
6
Q
SULFASALAZINE
A
Consists of sulfa pyridine and 5-aminosalicylic (5-ASA) connected by a diazo bond.
Metabolized by bacteria in the colon to the constituent moieties.
The 5-ASA moiety is thought not to be very important in rheumatoid arthritis (unlike in ulcerative colitis).
Adverse
- Nausea, anorexia and rash are common.
- Hepatitis,leukopenia and agranulocytos is are rare.
- A lupus-like syndrome has been reported.
- Hemolysis may occur in patients with G6PD deficiency.
- Probably safe in pregnancy.
7
Q
CYCLOSPORINE
A
- inhibits antigen-triggered signal transduction in T lymphocytes.
- Calcineurin is a phosphatase necessary for activation of a T- cell-specific transcription factor: NFAT.
- NFAT is required for the induction of cytokine genes.
- forms a complex with cyclophilin, an immunophilin. This complex inhibits calcineurin.
- Cyclosporine can be helpful in some patients with rheumatoid arthritis.
Adverse
- Nephrotoxicity and many interactions with drugs and foods limit its use.
- Main adverse reactions: Nephrotoxicity, tremor, hypertension, hyperglycemia, hyperlipidemia, osteoporosis, hirsutism, gum hyperplasia.
- Nephrotoxicity is limiting and occurs in the majority of patients treated. It is the major indication for cessation or modification of therapy.
- Very little bone marrow toxicity.
8
Q
AZATHIOPRINE
A
- Purine antimetabolite.
- Azathioprine is converted to 6-mercaptopurine, which, in turn, is converted to additional metabolites, which inhibit de novo purine synthesis.
- This leads to suppression of B and T cell function.
- Indications: used for patients with refractory rheumatoid arthritis.
Adverse
- Bone marrow suppression
- GI disturbances
- Infections and malignancies.
9
Q
CYCLOPHOSPHAMIDE
A
- Cross-links DNA, thereby preventing cell replication.
- Cyclophosphamide is generally limited to the most severe cases of rheumatoid arthritis.
Adverse
- Bone marrow suppression, infertility and hemorrhagic cystitis.
- Long-term use increases risk of infection and malignancy.
10
Q
GOLD COMPOUNDS
A
- Gold sodium thiomalate. Given IM.
- Auranofin. Given orally.
- Gold salts are taken up by macrophages and suppress phagocytosis and lysosomal enzyme activity.
- This mechanism retards progression of bone and articular destruction.
- Because of their toxicity gold compounds are used infrequently today.
11
Q
ADALIMUMAB
A
- ANTI-TNF DRUGS
- Fully human IgG1 anti-TNF monoclonal antibody.
- Binds to soluble TNF-alpha and prevents its interaction with TNF receptors.
- This results in down- regulation of macrophage and T cell function.
12
Q
INFLIXIMAB
A
- ANTI-TNF DRUGS
- Chimeric monoclonal anti-TNF-alpha antibody.
- Binds to human TNF-alpha
13
Q
ETANERCEPT
A
- ANTI-TNF DRUGS
- Recombinant fusion protein: two TNF receptors linked to the Fc portion of human IgG1.
- Binds TNF-alpha molecules
14
Q
ADVERSE EFFECTS OF THE ANTI-TNF-alpha DRUGS
A
- Cytopenias can occur. CBC should be monitored regularly.
- Serious infections are the most important potential adverse effects of TNF inhibition.
- These drugs should not be given to patients with an active infection.
- Patients should be screened for latent TB infection before and during treatment with a TNF inhibitor.
15
Q
ANAKINRA
A
- ANTI-INTERLEUKIN DRUGS
- IL-1 receptor antagonist
