Immunosuppressive medication



Treatment of uveitis

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Suggested treatment scheme, one possible stepwise approach to ocular inflammation

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Action

• Anti inflammatory

• Analgesic

• Anti pyretic

• Inhibit platelet aggregation

Indications

• CME

• Prevention of intraoperative miosis

• Post surgical inflammation

• Allergy

• Episcleritis

• Uveitis

o NSAIDs have no role during episode of acute anterior uveitis

o May be useful in long term management of recurrent anterior uveitis

o Adjuvant therapy with systemic NSAIDs was shown to reduce inflammatory activity and allow reduction in dose of steroid in group of children with JRA associated uveitis

o For posterior uveitis with CME, oral NSAIDs showed good results once combined with local steroids injection, once it been used for 6-12 months to prevent recurrence

Dose and Route

• Topical TID-QID

• Oral

o Non-selective

o Selective COX2 inhibitor

• Celebrex 100-200 mg BID

• Vioxx 12.5-25-50 mg qd

Side effect

• Topical

o Irritation

o Keratitis

o Infiltrate

o Thinning

o Perforation

• Systemic

o GI

o CNS

o Hematological

o Renal

o Hepatic

Corticosteroids

Mechanism of action

The anti-inflammatory actions of corticosteroids involve phospholipase A2 inhibitory proteins called lipocortins, which control the biosynthesis of inflammatory mediators, such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid.

Phenotypic effect of steroid includes:

1. Constrict blood vessels, and decrease vascular permeability.

2. Stabilization of intracellular lysosomal membrane and inhibition of expression of various damaging enzymes.

3. Stabilization of mast cells and basophil membrane is important in inhibiting the process of degranulation and subsequent release of histamine, bradykinin, platelet activating-factor, protease, and eosinophil, chemotactic factor.

4. Suppression of lymphocytes proliferation.

5. Reduction of circulating eosinophils and monocytes.

6. Inhibition of macrophage recruitment and migration.

Suggested guidelines for use of prednisone for chronic ocular inflammation

|Initial dose |1mg /kg/day |

|Maximum adult oral dose |60 to 80 mg/day |

|Maintenance dose (adult) |≤ 10mg/day |

|Tapering schedule |over 40mg/day, decrease by 10 mg/day every 1-2 weeks |

| |40-20mg/day decrease by 5 mg/day every 1-2 weeks |

| |20-10 mg/day decrease by 2.5mg/day every 1-2weeks |

| |10-0mg/day decrease by1-2.5 mg/day every |

|Monitor | Blood pressure, weight, and glucose every 3 months |

| |Lipids (cholesterols and triglycerides) annually |

| |Bone density within first 3 months and annually thereafter1-4weeks|

| | |

| | |

| |BMD measurement needed to be done in the first 3 months and if it |

|Supplemental treatment |decreased or we are treating post menopausal women |

| | |

| |supplement treatment needed |

| |But as a role any patient who are on ≥7.5 mg for 6 months, should |

| |receive supplement treatment |

| |Calcium 1500 mg daily and vitamin D 800 IU daily (all patients on |

| |>7.5 mg steroid longer than 6 months) |

| |Estrogens (postmenopausal women) |

| |Antiresorpative (residronate 2.5 to 5mg/day. Etidronate, |

| |Calcitonin) as needed |

• In selected situations, where immediate effect is needed, some would begin with IV methylprednisolone at a dosage of 1 gm/day (over 30 to 60 mins to avoid arrhythmia, cardiovascular shock, myocardial infarction, and severe infection) for 3 days and then start oral prednisone.

• Typically high-dose oral steroid are continued for no longer than 1 month.

• If the patient disease worsens on high-dose prednisone, no response after 2-4 weeks, disease no completely quiet after 4 weeks with high-dose oral steroid, or if chronic suppression of disease requires more than 10mg/day of prednisone an immunosuppressive agents should started.

• Ocular inflammation varies in their responses to steroid, some do response to short duration oral steroid 3-12 weeks, other need longer duration 6-12 months.

• Children’s should not be on steroid longer than 3 months.

Systemic side effect

• Musculoskeletal

▪ Myopathy

▪ Osteoporosis

▪ Aseptic necrosis ( pts on 60 mg/day for 1 months or 20mg/day for 6 months have are associated with 15% 20% risk of aseptic necrosis)

• Gastrointestinal

▪ ?Peptic ulcer ( 2 published studies showed that inc0idence of ulcer doesn’t increase by steroid and the use of H2 blocker is not necessary

▪ Pancreatitis

• CNS

▪ Psychiatric disorders

▪ Pseudotumor cerebri

• Ocular

▪ Glaucoma

▪ Cataract

▪ Secondary infection

▪ Delay wound healing

▪ Mydriasis

▪ Ptosis

▪ Tissue atrophy

• CVS/Renal

▪ HTN

▪ Na and water retention

▪ Hypokalemic alkalosis

• Metabolic

▪ Ketoacidosis

▪ DM

▪ Hyperosmolar coma

▪ Hyperlipidemia

▪ Obesity

• Endocrine

▪ Growth failure

▪ Amenorrhoea

▪ Suppression of hypothalamic-pituitary-adrenal system

• Suppression of immune system

Agents commonly used to treat autoimmune inflammatory conditions

|Class |Type of Agen |Names |

|Antimetabolites |Folic acid analogue |Methotrexate |

| |Purine analogue |Azathioprine |

| | |Mycophenolate mofetil |

| |Pyrimidine analogue |5 Fluorouracil |

| | |Leflunomide (Arava) |

|Alkylating agents |Nitrogen mustards |Cyclophosphamide |

| | |Chlorambucil |

|Natural products |Antibiotics |Cyclosporine |

| | |Dapsone |

| | |Tacrolimus |

| | |Mitomycin |

| | | |

| |Antibodies |Antilymphocytes serum |

| | |Anti-T-cells antibodies |

| | |Gamma globulin |

| | | |

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Indication of immunosuppressive medication

Absolute

• Behcet disease with retinal involvement

• Sympathetic ophthalmia

• VKH

• RA with necrotizing Scleritis or PUK

• Wegener’s granulomatosis

• Relapsing polychondritis with scleritis

• JRA

• OCP

• Bilateral Mooren’s

• Serpiginous choroidopathy

Relative

• Intermediate uveitis

• Retinal vasculitis

• Severs chronic iridocyclitis

Questionable

• Intermediate uveitis in children

• Sarcoid uveitis

• High risk graft

Antimetabolites

I. Methotrexate ( Rheumatrex)

Mechanism of action

1. Antimetabolite

2. Folic acid analogue

3. Reversibly inhibit the enzyme Dihydrofolate reducatse (which convert folic acid to tetrahydrofolic acid which is necessary for DNA replication

4. Tissue with a high cellular turnover such as hair follicles, fetal cells, gastrointestinal lining, bone marrow, and neoplasm are most sensitive

5. MTX is excreted unchanged by the kidney

6. Dosage doesn’t have to be adjusted in liver disease

Indication

1. JRA

2. Scleritis secondary to connective disease

3. Sympathetic ophthalmia

4. systemic SLE, RA, and Psoriatic arthritis

Suggested guidelines for use of MTX

|Initial dose | most clinicians would start with 7.5mg/week in single |

|Oral formulation 2.5 mg tablet | |

| |Undivided dose, then increase the dose gradually to achieve an |

| |effect. It can be given orally, IM, or IV.usual therapeutic dose|

| |is15 mg/week It has slow in onset, it might takes 3 to 4 weeks |

| | |

| |to see anti-inflammatory effect. |

|Maximum adult oral dose |25mg/week |

|Maintenance dose (adult) |≤ 25mg/week |

|Tapering schedule |usually between 2.5-5 mg/week |

|Monitor |CBC and platelet count should be taken every 3-4 weeks |

| |WBC ................
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