SOT drugs and therapeutics Flashcards
what drugs can be used in the induction period before a SOT
corticosteroids
basiliximab
alemtuzumab
antithymocyte globulin
which drugs are used in SOT maintenance
ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
balatecept
sirolimus
what are the side effects of corticosteroids
adrenal suppression
hypertension
diabetes
osteoporosis
cushings syndrome
GI irritation
weight gain
hyperlipidaemia
what is basiliximab
chimeric MAB against IL2 receptors
how does Basiliximab work
Inhibits differentiation and proliferation but is minimally T cell depleting
what is alemtuzumab
humanised rat IgG MAB against CD52 cell surface antigen
how does alemtuzumab work
causes cell lysis and prolonged depletion (also inhibits most monocytes, macrophages and natural killer cells)
side effects of alemtuzumab
Associated with first dose reaction, neutropenia, anaemia, pancytopenia (rare) and autoimmunity (haemolytic anaemia, thrombocytopenia and hyperthyroidism)
what is ATG - antithrombocyte globulin
IgG from horses or rabbits immunised with human thymocytes
how does ATG - antithrombocyte globulin work
Blocks a large number of T cell membrane proteins (CD2, CD3, CD45) causing altered function, lysis and prolonged T cell depletion
what are the side effects of ATG - antithrombocyte globulin
cytokine release syndrome - fever, chills, hypotension caused by cell lysis
thrombocytopenia, leukopenia, occasional serum sickness and allergic reactions
what pre-meds are required with ATG
paracetamol, chlorphenamine and corticosteroids
which medications can be used for maintenance
ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
Balatecept
sirolimus
what is ciclosporin
calcineurin inhibitor - binds to cyclophilin and inhibits calcineurin phosphatase - inhibits IL2 production and T cell activation
what are the side effects of ciclosporin
§ Nephrotoxicity, hypertension, hyperlipidaemia, gingival hyperplasia, hirsutism, tremor
§ Diabetes!
use of ciclosporin in clinic
BD dosing
prescribed by brand
CYP450 metabolised
what is tacrolimus
Macrolide antibiotic binds to FK506-binding protein 12 (an immunophilin) to inhibit calcineurin and T cell activation (binds a different intracellular protein to ciclosporin but has subsequent same mechanism of action)
side effects of tacrolimus
Similar S/E to ciclosporin (nephrotoxicity and haemolytic uremic syndrome) but lower incidence of hypertension, hyperlipidaemia, hirsutism and gum hyperplasia and higher incidence of diabetes mellitus and neurotoxicity
use of tacrolimus in clinic
OD or BD depending on brand/transplant type
must be prescribed by brand
best taken with food
CYP metabolised
what are the therapeutic monitoring parameters for tacrolimus
trough level
what is azathioprine
antimetabolite that inhibits proliferation of T and B cells
what are the side effects of azathioprine
Haematological (dose dependent myelosuppression can occur with over 50% of patients developing leukopenia – reversed by reducing/stopping the drug), thrombocytopenia (reversed by reducing/stopping the drug); N&V (alleviated when given with food or in divided doses)
use of azathioprine in clinic
OD
FBC monitoring
interacts with allopurinol
what is mycophenolate
active component of mycophenolate mofetil - blocks inosine monophosphate dehydrogenase - required for de novo synthesis of guanosine nucleotides - x b/t cell proliferation (more potent than aza)
what are the side effects of mycophenolate
§ Haematological – neutropenia, leukopenia, mild anaemia
§ Gastrointestinal – diarrhoea can be dose limiting (EC MPA (Myfortic)may improve this)
mycophenolate use in clinic
monitor FBC
BD dosing
decreased by antacids, iron and rifampicin
increased by antivirals
what is Balatecept
Binds CD80 and CD86 receptors on the antigen presenting cell preventing CD28 on the T cell from binding
Balatecept dosing
2 phases
1. IV on days 1 and 5 on weeks 2, 4, 8, 12
2. IV end of week 16 and then every 4 weeks
side effects of Balatecept
○ Risk of post-transplant lymphoproliferative disease
§ B cells infected with EBV rapidly proliferate - immunosuppression means no control of this by T cells
what is sirolimus
Used as an alternative to calcineurin inhibitors and antiproliferatives or in combination with calcineurin inhibitors - binds the immunophilin FKBP12 forming a complex that inhibits mTOR
what is mTOR
serine/threonine protein kinase involved in regulation of cell growth, proliferation and of protein synthesis and ribosome biogenesis
what are the side effects of sirolimus
§ Less nephrotoxic than CNI
§ Less likely to cause diabetes
§ Risk of life threatening pneumonitis (resolves after treatment withdrawal)
§ Impair wound healing (mTOR inhibition of fibroblast response to fibroblast growth factor) – not used immediately post-transplant
§ Hyperlipidaemia
§ Thrombocytopenia
use of sirolimus in clinic
Metabolised by the CYP 450 enzymes = NUMEROUS interactions
Administer consistently (with or without food)
monitoring required
what are the benefits of using combinations in SOT therapeutics
- Combination therapies with different modes of action reduced steroid use and lead to better patient outcomes
what medications are given for an intestinal transplant
○ Alemtuzumab (SC with pre-meds to reduce effects of cytokine allergies)
○ Methylprednisolone IV to oral - reduce to stop
○ Prograf - immediate release tacrolimus
○ Then starting azathioprine or mycophenolate after surgery
what pre meds are given for a renal transplant
§ Mycophenolate
§ Methylprednisolone IV
§ Basiliximab or alemtuzumab (if higher risk)
what drugs are given after a renal transplant
○ Basiliximab 2nd dose (BNF 4 days but local policies differ) - UNLESS given alemtuzumab
○ Prednisolone 20mg OD (per policy)
○ Advagraf - prolonged release tacrolimus - 0.15mg/kg OD
○ Mycophenolate mofetil - 750mg BD
what other infection risks need to be considered in renal transplants
Pneumocystis jiroveci (PCP)
fungal infections
TB
cytomegalovirus
how is Pneumocystis jiroveci (PCP) treated in renal transplants
6 month prophylaxis using co-trimoxazole
how are fungal infections treated in renal transplant
nystatin for prophylaxis for 4 weeks
what is cytomegalovirus
§ Can be asymptomatic or can lead to end organ damage
§ Spread by bodily fluids when virus is active
§ If have ever had it - can become dormant - risk
how is cytomegalovirus treated in renal transplant patients
§ Valganciclovir prophylaxis for all at risk
□ Patients that are CMV IgG seropositive (R+) or receive an organ from a seropositive donor (D+)
Prophylaxis for 3-6 months
what other issues are associated with renal transplant and how are they treated
DVT- LMWH
gastric mucosal protection - PPI
pain - paracetamol, fentanyl PCA
