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year three exam 2 > SOT drugs and therapeutics > Flashcards

SOT drugs and therapeutics Flashcards

1
Q

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

A

corticosteroids
basiliximab
alemtuzumab
antithymocyte globulin

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2
Q

which drugs are used in SOT maintenance

A

ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
balatecept
sirolimus

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3
Q

what are the side effects of corticosteroids

A

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

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4
Q

what is basiliximab

A

chimeric MAB against IL2 receptors

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5
Q

how does Basiliximab work

A

Inhibits differentiation and proliferation but is minimally T cell depleting

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6
Q

what is alemtuzumab

A

humanised rat IgG MAB against CD52 cell surface antigen

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7
Q

how does alemtuzumab work

A

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

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8
Q

side effects of alemtuzumab

A

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

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9
Q

what is ATG - antithrombocyte globulin

A

IgG from horses or rabbits immunised with human thymocytes

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10
Q

how does ATG - antithrombocyte globulin work

A

Blocks a large number of T cell membrane proteins (CD2, CD3, CD45) causing altered function, lysis and prolonged T cell depletion

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11
Q

what are the side effects of ATG - antithrombocyte globulin

A

cytokine release syndrome - fever, chills, hypotension caused by cell lysis
thrombocytopenia, leukopenia, occasional serum sickness and allergic reactions

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12
Q

what pre-meds are required with ATG

A

paracetamol, chlorphenamine and corticosteroids

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13
Q

which medications can be used for maintenance

A

ciclosporin
tacrolimus
azathioprine
mycophenolate
corticosteroids
Balatecept
sirolimus

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14
Q

what is ciclosporin

A

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

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15
Q

what are the side effects of ciclosporin

A

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

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16
Q

use of ciclosporin in clinic

A

BD dosing
prescribed by brand
CYP450 metabolised

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17
Q

what is tacrolimus

A

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)

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18
Q

side effects of tacrolimus

A

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

19
Q

use of tacrolimus in clinic

A

OD or BD depending on brand/transplant type
must be prescribed by brand
best taken with food
CYP metabolised

20
Q

what are the therapeutic monitoring parameters for tacrolimus

A

trough level

21
Q

what is azathioprine

A

antimetabolite that inhibits proliferation of T and B cells

22
Q

what are the side effects of azathioprine

A

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)

23
Q

use of azathioprine in clinic

A

OD
FBC monitoring
interacts with allopurinol

24
Q

what is mycophenolate

A

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)

25
Q

what are the side effects of mycophenolate

A

§ Haematological – neutropenia, leukopenia, mild anaemia
§ Gastrointestinal – diarrhoea can be dose limiting (EC MPA (Myfortic)may improve this)

26
Q

mycophenolate use in clinic

A

monitor FBC
BD dosing
decreased by antacids, iron and rifampicin
increased by antivirals

27
Q

what is Balatecept

A

Binds CD80 and CD86 receptors on the antigen presenting cell preventing CD28 on the T cell from binding

28
Q

Balatecept dosing

A

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

29
Q

side effects of Balatecept

A

○ Risk of post-transplant lymphoproliferative disease
§ B cells infected with EBV rapidly proliferate - immunosuppression means no control of this by T cells

30
Q

what is sirolimus

A

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

31
Q

what is mTOR

A

serine/threonine protein kinase involved in regulation of cell growth, proliferation and of protein synthesis and ribosome biogenesis

32
Q

what are the side effects of sirolimus

A

§ 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

33
Q

use of sirolimus in clinic

A

Metabolised by the CYP 450 enzymes = NUMEROUS interactions
Administer consistently (with or without food)
monitoring required

34
Q

what are the benefits of using combinations in SOT therapeutics

A
  • Combination therapies with different modes of action reduced steroid use and lead to better patient outcomes
35
Q

what medications are given for an intestinal transplant

A

○ 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

36
Q

what pre meds are given for a renal transplant

A

§ Mycophenolate
§ Methylprednisolone IV
§ Basiliximab or alemtuzumab (if higher risk)

37
Q

what drugs are given after a renal transplant

A

○ 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

38
Q

what other infection risks need to be considered in renal transplants

A

Pneumocystis jiroveci (PCP)
fungal infections
TB
cytomegalovirus

39
Q

how is Pneumocystis jiroveci (PCP) treated in renal transplants

A

6 month prophylaxis using co-trimoxazole

40
Q

how are fungal infections treated in renal transplant

A

nystatin for prophylaxis for 4 weeks

41
Q

what is cytomegalovirus

A

§ 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

42
Q

how is cytomegalovirus treated in renal transplant patients

A

§ 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

43
Q

what other issues are associated with renal transplant and how are they treated

A

DVT- LMWH
gastric mucosal protection - PPI
pain - paracetamol, fentanyl PCA

year three exam 2 (38 decks)

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