Lecture 38: Solid Organ Transplant Flashcards
What is important about the Human Leukocyte Antigen [HLA] Typing?
- Found on short chromosome 6; distinguishing from self and non self
- Class I = A, B and Class II = DR
Which organ types are at the Higher Risk of rejection?
- Liver is the Lowest;
- Then Kidney & Pancreas
- Then Heart
- And Bowel and Lungs are the Highest
Higher the risk; the most likely to use Prednisone but probably just use pred in general
What are some of the induction agents for immunosuppression in organ transplant?
- Polyclonal [Tymoglobulin (Rabbit) or ATGAM (Horse)]
- Monoclonal [Alemtuzumab]
- IL-2a [Basiliximab]
What is the MOA for Rabbit Antithymocyte Globulin [tymoglobulin]?
- T-Lymphocytes depletion for induction and/or rejection
What is the Dosing and Adverse Effects for Thymoglobulin>?
- 1 - 1.5mg/kg/day IV
- Leukopenia, Thrombocytopenia, Fever, Chills [Premedicate with APAP or benadryl]
What is the MOA for Alemtuzumab?
- Causes profound t-cell depletion by targeting CD52
- Off label for SOT induction
- 1 dose needed
What are some of the Adverse Effects for Alemtuzumab?
- Chills, Rigor, Fever [Pretreat with APAP and Benadryl]
What is the MOA for Basiliximab?
- Inhibit IL-2a activiation; being a CD25 antibody
- NON-lymphdeleting
What is the way that we choose an induction agent?
- Depleting is more common [especially for those that are high risk]
- Basiliximab: for those that have Hx of Maglignancy, Infection Risk, Immunocompromised, HIV, HCV, Old
what are maintenance agents that are used in SOT?
- Calcineurin Inhibitors
- Antimetabolites
- mTOR Inhibitors
- Corticosteroids
- T-Cell Co-stimulation Blockers
What are the Calcineurin Inhibitors that are used and what is there MOA?
- Cyclosporine, Tacrolimus [Cornerstone]
- MOA: Inhibits signal-1 which inhibits calcineurin within T-cells = NO T-Cell activation
What is important to know about Cyclosporine?
Formulations? Dosing? Monitoring?
- Modified [Neoral & Gengraf] are better than NON-Modified
- Coversion IV:PO = 3:1
- Want a 12h trough of 100-400
What is important to know about Tacrolimus?
Formulation? Monitoring?
- Prograf [BID] is IM & Astagraf and Envarsus [QD] is ER [ER has lower drug doses, improved adherence, less peak = less ADE]
- 50x more potent than Cyclosporine [trough of 5-15]
What is the Metabolism and Elimination of CNIs?
- Cyclo: 3A4 & PGP inhibitor; Half-life is longer [10-40h]
- Tacro: 3A4 inhibitor; Half-life is okish [12-18h]
What are some of the Adverse effects of Cyclosporine?
- Hypertension
- Hypercholesterolemia
- Hypertriglceridemia
- Gingival Hyperplasia
- Hirsutism
