Cyclosporin

Cyclosporin


CYCLOSPORIN

  • Type of immunosuppressant drug.
  • Specific T-cell Inhibitor/ calcineurin Inhibitor.
  • Acts on CD4 cells & lymphocytes.

Major pharmacological effects:

Selective inhibition:

  • Antigen-stimulated activation & proliferation of T-cells (CD4 helper cells).
  • Expression IL-2 & other cytokines by T cells.
  • Affects inducer T-cells response to IL-1, without affecting suppressor T-cells.

Mechanism of action:

  • Binding protein – Cyclophilin.
  • Inactivates calcineurin.
  • Failure of antigenic stimulation by helper T-cell.
  • Activates IL-2 inhibitor.
  • Attenuating IL-2 stimulated T-cell proliferation.
  • Block transcription of IL-2.
  • Production of killer lymphocytes.
  • Most active before antigen exposure.
  • Suppress responses of primed helper T-cells.
  • Hence, useful in auto-immune diseases.

Pharmacokinetics:

  • Low oral bioavailability  
  • Bile-dependent
  • Concentrated in WBC’s and RBC’s
  • Metabolised in liver; Excreted in bile
  • Biphasic plasma t1/2 – 4-6 hrs & 12-18 hrs

Advantages:

  • Selectively suppresses cell-mediated immunity.
  • Prevents graft rejection, unaffecting host’s immune system.
  • No toxic effects on bone marrow & RE system (unlike cytotoxic immunosuppressants).
  • Intact humoral immunity.

Adverse effects:

  • Nephrotoxicity.
  • Rise in serum creatinine levels.
  • Reduced GFR.
  • Impaired liver function.
  • Post-transplant hypertension.
  • Sustained rise in BP.
  • Vasoconstriction & activation of RA system.

Other effects:

  • Hyperuricemia.
  • Hyperkalemia.
  • Hypomagnesemia.
  • Hirsutism.
  • Gum hyperplasia.
  • Tremor.
  • Seizures.
  • Precipitation of diabetes.
  • Anorexia.
  • Lethargy.
  • Hyperkalemia.
  • Viral infection. 

Indications:

1. Prevention and treatment of graft rejection reaction  

  • Routinely used in renal, hepatic, cardiac, bone marrow and other transplants.
  • Initial induction – Orally, 12 hrs prior transplant surgery.
  • Maintenance dose – Until needed.

2. Autoimmune diseases – Second line drug.

  • Severe rheumatoid arthritis, uveitis, IBD, psoriasis, & suppress acute exacerbations.
  • Combined with glucocorticoid.

3. Aplastic anemia 

  • Low dose (2-5mg/kg/day).
  • Not curative.
  • Relapse on withdrawal.

Interactions:

1. Enhanced toxicity:

  • Intake of nephrotoxic drugs.
  • Vancomycin, Amphotericin B, & NSAIDS.
  • Erythromycin & Ketoconazole (CYP3A4 inhibitors) inhibits its metabolism causing toxicity.

2. Excretory interference:

  • Excretion of other drugs impaired by decreased renal function.
3. Drugs affecting cyclosporin:
  • Phenytoin, Phenobarbitone & Rifampicin lower drug levels in blood.
  • K+ supplements & K+ sparing diuretics produce marked hyperkalemia.
Exam Question
 

CYCLOSPORIN

  • Specific T-cell Inhibitor/ Calcineurin Inhibitor
  • Inactivates calcineurin.
  • Acts by selective inhibition
  • Suppress responses of primed helper T-cells
  • Hence, useful in auto-immune diseases
  • Bile-independent.
  • Prevents graft rejection, unaffecting host’s immune system.
  • No toxic effects on bone marrow & RE system.

Adverse effects:

  • Nephrotoxicity
  • Post-transplant hypertension
  • Hyperuricemia, hyperkalemia & hypomagnesemia 
  • Hirsutism
  • Gum hyperplasia
  • Tremor
  • Seizures

Indicated in:

  • Prevention and treatment of graft rejection reaction.
  • Routinely used in renal, hepatic, cardiac, bone marrow.
  • Autoimmune diseases – Second line drug.
  • Severe rheumatoid arthritis, uveitis, IBD, psoriasis.
  • Aplastic anaemia.

Drug interactions: 

  • Enhanced toxicity when given along with Vancomycin, Amphotericin B, & NSAIDS.
Don’t Forget to Solve all the previous Year Question asked on Cyclosporin

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
WordPress Security