Management of Autoimmune disease

A patient using immunosuppressant should take influenza vaccine and pneumococcal Drug-induced SLE:
vaccine, but should avoid using attenuated vaccine such as influenza nasal spray
1. Sulfasalazine (DMARDs, for
1. Antibody immunosuppressant: rheumatoid arthritis)
a. T-cell inhibitors: 2.Hydralazine (Arteriolodilator)
i. Antithymocytes are useful against initial rejection or steroid resistant
rejection. 3. Isoniazid
ii. Basiliximab and Daclizumab: monoclonal antibodies that bind to 4. Procainamide/ Phenytoin
alpha subunit of IL-2 receptor, preventing IL-2 activation: approved 5. Statins
for prophylaxis of acute rejection in renal transplantation. But increases the risk of viral infections.
b. B-cell inhibitors:
i. Belimumab: antibodies against BLyS (B-lymphocyte stimulator factor), preventing B cell activation
ii. Rituximab: monoclonal antibodies bind to CD20 on B cells and used for NHLs

2. Cytokine suppressors:
a. Calcinurin inhibitors:
i. Cyclosporine, binds to cyclophilin forming a complex that inhibits Calcinurin, so no IL-2 production
1. Used in drug combinations to prevent transplant rejection like Cyclosporine & corticosteroids
+ Mycophenolate mofetil
2. Used also in psoriasis and rheumatoid arthritis
3. Metabolized by CYP3A4 (Similar to tamoxifen, statins, proguanil)
4. Excreted in the bile
ii. Tacrolimus: binds to FKBP inhibiting calcineurin has higher potency than cyclosporines
iii. Adverse effects for both medications:
1. Neurotoxicity
2. Nephrotoxicity
3. Hyperlipidemia
4. Type 2 diabetes in tacrolimus, at the same time it can be used in early stages type 1 diabetes
5. Gingival hyperplasia and hirsutism in Cyclosporine
b. mTOR inhibitors:
i. Sirolimus and everolimus
1. Similar to tacrolimus binds to FKBP but instead they inhibit mTOR (Intracellular effect of IL-
2)
2. Used to prevent kidney transplantation, has synergistic effects with cyclosporine, prevents
restenosis after angioplasty
3. Results in Hyperlipidemia, insulin resistance, pancytopenia and nephrotoxicity
3. Antimetabolites:
a. Azathioprine:
i. Prodrug converted into 6-mercaptopurine, which then converted into purine form by HGPRT,
incorporated into the DNA, or it can be metabolized by xanthine oxidase resulting in inhibition of the
drug (so using allopurinol will increase the activity of the drug)
ii. If used with ACEI: increase pancytopenia

b. Mycophenolate Mofetil:
i. Inhibits Inosine monophosphate dehydrogenase (IMPD inhibitor)
ii. More potent than Azathioprine
iii. Inhibits B & T lymphocytes
iv. ADR: GI upset, myelosuppression & neutropenia, can also results in increase CMV susceptibility

4. Steroids:
a. COX2 inhibitors result in MI due to inhibition of coronary artery PGI2 which acts as a vasodilator and inhibitor
of platelet aggregation.
b. Increases expression of genes for Gluconeogenesis (PEPCK) and reduces Phospholipase A2 formation
c. Adverse reaction:
i. Hyperglycemia: increase in enzymes required for gluconeogenesis,
ii. Osteoporosis by activating RANK-L and suppressing OPG release)
iii. Muscle atrophy
iv. Buffalo hump with lipid redisposition
v. Decrease collagen synthesis with skin thinning
vi. Adrenal suppression,

5. Hydroxychloroquine:
a. Antimalarial agent acts by increasing lysosomal pH, so suppressing intracellular antigen processing and loading
on MHC II, decreasing T cell activation
b. ADR: ocular dysfunction, corneal deposits and retinopathy