What are the 4 Immunosuppressives?
- azathioprine
- mercaptopurine
- cyclosporine
- methotrexate
What are the 2 Purine Analogs?
(Immunosuppressives)
- Azathioprine
- 6-Mercaptopurine
6-MP (purine analog/immunosuppresive) is transformed by what 2 things?
- xanthine oxidase
- thiopurine
Azathioprine (purine analog/immunosuppressive) is rapidly converted –> to what?
6-MP
Which drug prolongs the half life of purine analogs (Azath & 6-MP) days, to delay of 17 weeks, BEFORE the onset of therapeutic benefit of the oral azath/6-MP?
6-thioguanine nucleotides
Which drug?
- Induction and maintenance of remission of Ulcerative colitis and Crohn’s disease
- helps eliminate/reduce steroid use,
- remission within 3-6 months
Purine Analogs:
Azathioprine & 6-Mercaptopurine
ADE’s of which drug?
- ↓ depress bone marrow à leukopenia, macrocytosis, anemia, thrombocytopenia
- ↑ inc. risk of lymphoma,
- Hepatoxicity (MUST get CBC & LFTs to monitor)
- hypersensitivity rxn = pancreatitis/hepatitis
- Crosses placenta, but pregnancies successful/low risk of teratogenicity
Purine Analogs: (immunosuppressives)
Azathioprine & 6-Mercaptopurine
- What drug has a bad interaction w/ Purine Analogs/Immunosuppressive?
- What are the 3 results?
Allopurinol
- inhibits Xanthine oxidase from breaking down purine analogs
- ↑ increasing active 6-thioguanine nucleotides
- Severe leukopenia
Which drug?
- Inhibits dihydrofolate reductase enzyme (important in production of thymidine & purines)
- May interfere w/ inflammatory actions of interleukin
Methotrexate
(immunosuppressive)
Which drug?
- May stimulate increased release of adenosine (endogenous anti-inflammatory autacoid)
- May stimulate apoptosis & DEATH of activated T-lymphocytes
Methotrexate
(Immunosuppressive)
Which drug is used in maintenance of Crohn’s?
Methotrexate
ADEs of which drug?
- depress bone marrow
- megaloblastic anemia***
- alopecia**
- mucositis
- mouth sores (stomatitis)***
- PERMANANT peripheral neuropathy (if prolonged use)***
- liver damage if +psoriasis, renal insufficiency inc. risk of liver toxicity
Methotrexate
Name the 5 Biologic Anti-TNFs
- Infliximab
- Adalimumab
- Natalizumab
- Golizumab
- Certolizumab
“I CAN Go”
Which drug?
- inhibits inflammatory cytokine release
- impairs T-cells
- PREVENT cytokine from binding to its receptors
- REVERSE signaling à suppress cytokine release
Anti-TNF / Biologics (mab)
Which drug?
- acute/chronic Mod-Severe Crohn’s
- 1/3 lose response bc/ antibodies are made…
- Antibody development is less common if combo tx w/ _____, BUT this increases risk of lymphoma
Anti-TNFs (Biologics, mab)
- purine analogs (metho or 6-MP)
Monoclonal antibodies to human TNF are approved in these conditions.
Which drug?
- Crohn’s, Plaque psoriasis, Psoriatic arthritis, RA, UC
- Infliximab
- Adalimumab
Monoclonal antibodies to human TNF are approved in these conditions.
Which drug?
- MS
Natalizumab
Monoclonal antibodies to human TNF are approved in these conditions.
Which drug?
- Plaque psoriasis, Psoriatic arthritis, RA, UC
- NOT CROHN’s
Golimumab
Which drug?
- Bind to membrane bound TNF
- Fc portion of human IgG region promotes antibody-mediated apoptosis
- Complement activation
- Cellular cytotoxicity of activated T-lymphocytes & macrophages
GIA
- Infliximab
- Adalimumab
- Golimumab
Which drug?
- lacks Fc portion
Certolizumab
(also lacks properties of GIA)
ADE’s of which drug?
- reactivate latent TB
- Listeriosis
- Sinusitis, bronchitis, PNA, cellulitis
- delayed serum sickness like rxn (1-2 wks after starting med)
- myalgia, jaw tight, urticaria, edema
- Lupus-like syndrome (rare/reversible)
- SERIOUS INFECTIONS increased w/ corticosteroid use
- Antibodies to Antibody (ATA)
- New/Worsened CHF
Anti-TNF (biologics) mab
What are the 2 “anti-integrins”
- Natalizumab
- Vedolizumab
Which drug?
- Humanized IgG4 monoclonal antibody targeted against alpha-4 subunit
- Blocks SEVERAL integrins on circulating inflammatory cells
- Prevents binding to adhesion molecules, prevents migration into tissues
Anti-integrin (Nat/Vedo)
ADE’s of which drug?
- Acute infusion rxn
- Small risk of opportunistic infections
Natalizumab
