immunosuppression

Question 1

Indications of immunosupressants:

Answer 1

Indications

1. Autoimmune diseases:
   - Lupus , pemphigus complex
   - IHA ( immune haemolytic anemia
   - KCS
2. Hypersensitivity diseases
   - Atopic dermatitis
   - Asthma
   - IBD ( Inflammatory bowel disease )
3. Transplantation

Question 2

Antimetabolites:

-

Answer 2

Antimetabolites: (inhibition or DNA damage)
= Purine and pyrimidine analogues

• Purine analogues; (azathioprin , mycophenolate mofetil)
• Pyrimidine analogues: (leflunomide)
• Folic acid antagonists: (methotrexate)

Question 3

Alkylating agents:

Answer 3

Alkylating agents:

cyclophosphamide

Question 4

Cytokine gene expression inhibitors:

Answer 4

Cytokine gene expression inhibitors:
Calcineurin inhibitors (cyclosporine , tacrolimus ,
pimecrolimus)

Question 5

immunosupressant drug groups:

Answer 5

• Alkylating agents
• Glucocorticoids
• Cytokine gene expression inhibitors
• Antimetabolites

(often combo of antimetabolites and alkylating agents)

Question 6

Azathioprine

• use
• rate of release?
• how to apply
• side effects

Answer 6

Azathioprine (=Antimetabolite)

• Prodrug
• Application: autoimmune diseases
• Slow release —-> longer effect
• I.v, or oral
• Side effects Fe

Question 7

mycophenolate mofetil:

• use
• how to apply
• effect
• side effects?

Answer 7

mycophenolate mofetil (=Antimetabolite)

• Prodrug
• Inosine monophosphate dehydrogenase inhibitor (GMP levels down)
• Specific to T and B lymphocytes! (de novo GTP synthesis)
• in other cells : salvage pathway
• Much safer , than azathioprine (GI, BM rare)
• Rarely used in veterinary medicine

Question 8

Methotrexate:

• use
• effect

Answer 8

Methotrexate (=Antimetabolite)

• Folic acid antagonist
• Dihydrofolate reductase inhibitors
• Apoptosis of activated T cells

Question 9

Cyclophosphamide

- use

Answer 9

Cyclophosphamide (=Alkylating agent)

• B and T cells equally affected
• GI, BM side effects (<2 G/L!)
• haemorrhagic cystitis acrolein ,( Fe rare ) —> furosemide
• Mostly per os: antineoplastic , autoimmune disorders

Question 10

Cyclosporin and tacrolimus

• effects:
• mechanisms

Answer 10

Cyclosporin and tacrolimus (=Calcineurin inhibitors)
Calcineurin
-  dephosphorylates NFAT activation
    ---->Translocation to the nucleus
    ---->IL 2 expression

• Mechanism: Only in T cells
  *Calcineurin inhibition
  
  • Mastocyte inhibition
    *inhibition of degranulation
    Decreased IL and TNF- alpha expressions

Question 11

Cyclosporin

• application and use
• side effects

Answer 11

Cyclosporin (=Calcineurin inhibitor):
Application: very common
with food and locally
- Autoimmune diseases: pemphigus , lupus , AIHA,
KCS 
- Atopic dermatitis
-IBD

Side effects :
Ho (kidney , liver ) Ca , Fe
GI: vomiting , diarrhea, Alopecia, Gingival hyperplasia

Question 12

Tacrolimus, pimercrolimus:

• use
• contradictions

Answer 12

Tacrolimus, pimecrolimus(= Calcineurin inhibitor)

• 500x more active than cyclosporin
• Toxicity= higher!
• Topical application ! (0,1% ointment)
• against: Atopic dermatitis, lupus , pemphigus
• Pimecrolimus: locally atopic dermatitis , KCS

Question 13

1st and 2nd generation antioxidants:

Answer 13

1st generation
ethylenediamins:
chloropyramin , chlorpheniramine
ethanolamines:
diphenhydramine , dimenhydrinate
phenothiazines: promethazine
piperazines:
hydroxyzine
other: dimetinden,
cyproheptadine

2nd generation
loratadine, cetirizine, levocetirizine