SOT drugs and therapeutics Flashcards by kayleigh wootten

what drugs can be used in the induction period before a SOT

corticosteroids
basiliximab
alemtuzumab
antithymocyte globulin

How well did you know this?

Not at all

Perfectly

which drugs are used in SOT maintenance

ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
balatecept
sirolimus

How well did you know this?

Not at all

Perfectly

what are the side effects of corticosteroids

adrenal suppression
hypertension
diabetes
osteoporosis
cushings syndrome
GI irritation
weight gain
hyperlipidaemia

How well did you know this?

Not at all

Perfectly

what is basiliximab

chimeric MAB against IL2 receptors

How well did you know this?

Not at all

Perfectly

how does Basiliximab work

Inhibits differentiation and proliferation but is minimally T cell depleting

How well did you know this?

Not at all

Perfectly

what is alemtuzumab

humanised rat IgG MAB against CD52 cell surface antigen

How well did you know this?

Not at all

Perfectly

how does alemtuzumab work

causes cell lysis and prolonged depletion (also inhibits most monocytes, macrophages and natural killer cells)

How well did you know this?

Not at all

Perfectly

side effects of alemtuzumab

Associated with first dose reaction, neutropenia, anaemia, pancytopenia (rare) and autoimmunity (haemolytic anaemia, thrombocytopenia and hyperthyroidism)

How well did you know this?

Not at all

Perfectly

what is ATG - antithrombocyte globulin

IgG from horses or rabbits immunised with human thymocytes

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

what pre-meds are required with ATG

paracetamol, chlorphenamine and corticosteroids

How well did you know this?

Not at all

Perfectly

which medications can be used for maintenance

ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
Balatecept
sirolimus

How well did you know this?

Not at all

Perfectly

what is ciclosporin

calcineurin inhibitor - binds to cyclophilin and inhibits calcineurin phosphatase - inhibits IL2 production and T cell activation

How well did you know this?

Not at all

Perfectly

what are the side effects of ciclosporin

§ Nephrotoxicity, hypertension, hyperlipidaemia, gingival hyperplasia, hirsutism, tremor
§ Diabetes!

How well did you know this?

Not at all

Perfectly

use of ciclosporin in clinic

BD dosing
prescribed by brand
CYP450 metabolised

How well did you know this?

Not at all

Perfectly

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)

How well did you know this?

Not at all

Perfectly

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