Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Solid organ transplants > SOT drugs > Flashcards

SOT drugs Flashcards

1
Q

What are the two phases drugs are given following a transplant?

A

Immunosuppressive drugs are given at both induction, during or immediately following the transplant and then some are continued as maintenance therapy to avoid graft rejection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why are drugs given at a higher dose in the induction phase?

A

As the risk of rejection is highest immediately following the transplant so higher dosed immunosuppressive is required.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

State the drugs used at induction following a transplant.

A

Corticosteroids
Basiliximab
Alemtuzumab
Antithymocyte globulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How is immunosuppression enhanced at induction?

A

By the administration of mono or polyclonal antibodies which are given intraoperatively and shortly afterwards.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

State the drugs used during maintenance therapy following a transplant.

A

Ciclosporin/Tacrolimus
Azathioprine, Mycophenolate
Corticosteroids
Balatacept
Sirolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Are all of the maintenance drugs used?

A

No usually following induction, the number and the doses of immunosuppressive drugs is slowly reduced and the patient will end up on just one which is continued for as long as the graft is functioning.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some of the generalised signs of rejection?

A

Using the example of a renal transplant:
Renal function doesn’t improve within 24-48 hours
Doing an ultrasound or biopsy, histological changes in the cell

In the patient symptoms of rejection may include:
A high temperature of 38C or above
Feeling hot and shivery
Severe headache
Diarrhoea
Vomiting
Shortness of breath
New chest pain
Fatigue or generally feeling ‘rough’
Little or no urine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

When is Basiliximab usually given?

A

At induction and then four days later, however this can vary depending on the trust. At Addenbrooke’s it is given at induction and Day 3.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the mechanism of action of Basiliximab?

A

The chimeric monoclonal antibody acts against CD25 (IL-2) which is expressed on activated T-cells. Inhibits the proliferation and differentiation of T-cells, but not the T-cells already present.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

State the therapeutic and toxic monitoring parameters for Basiliximab.

A

Therapeutic monitoring parameter:
Lack of acute rejection

Toxic monitoring parameters:
Infection
Signs of rejection
Hypersensitivity
Blood pressure
FBC - anaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the advantages and disadvantages of using Basiliximab?

A

Advantages - it has minimal adverse effects and therefore no specific monitoring is required

Disadvantages - Alemtuzumab has a higher immunosuppressive effect and therefore those with a higher immunogenic risk should be offered this in preference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are examples of patient’s who are at higher immunogenic risk following transplant?

A

Patient’s who have:
Received a previous blood transfusion
Antibodies are already present
The organ match is not close

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the mechanism of action of Alemtuzumab?

A

Alemtuzumab specifically binds to CD52 cell surface antigen which is expressed on monocytes, macrophages, natural killer cells and T and B lymphocytes causing cell lysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the therapeutic and toxic monitoring parameters for Alemtuzumab?

A

Therapeutic:
Lack of acute rejection

Toxic:
FBC - neutropenia, pancytopenia (although rare), anaemia and ability to develop haemolytic anaemia and thrombocytopenia
LFTs - hepatic injury and auto-immune hepatitis
TSH - autoimmune hyperthyroidism (hypothyroidism has also been seen)
Infusion associated reactions/first dose reaction - headache, rash, pyrexia, nausea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the advantages and disadvantages of using Alemtuzumab?

A

Advantages - very immunosuppressive, can be used in the treatment of rejection and can reduced the need to start maintenance therapy post-surgery

Disadvantages - prevalence of causing auto-immune conditions and first dose reactions therefore more intensive monitoring is required in comparison to Basiliximab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the mechanism of action of anti-thrombocyte globulin (ATG)?

A

Anti-thrombocyte globulin is IgG which is derived from horses and rabbits that is then immunised with human thrombocytes. It specifically blocks CD2, 3 and 45 causing the altered function, cell lysis and prolonged T-cell depletion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are some of the symptoms a patient who has received ATG is expected to experience and why?

A

When ATG causes cell lysis due to binding and blocking cell surface antigens this can result in the release of cytokines, leading to cytokine release syndrome. Symptoms are due to a systemic inflammatory response against these cytokines.
Symptoms include:
Fever
Chills
Hypotension
Rash
Dyspnoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How long does cytokine release syndrome last?

A

Usually develops shortly its administration and can last up to several hours. Patient will recover usually after stopping the administration of the medication.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Aside from cytokine release syndrome what are some of the other side effects associated with ATG?

A

Thrombocytopenia
Leukopenia
Serum sickness (Type 3 hypersensivity)
Allergic reactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the appropriate management for attempting to reduce the side effects associated with ATG administration?

A

Usually patient will be given pre-medication which includes paracetamol, chlorphenamine and corticosteroids.

However despite pre-med administration side effects may still occur.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the therapeutic and toxic monitoring parameters for anti-thrombocyte globulin (ATG)?

A

Therapeutic:
Lack of acute rejection

Toxic:
FBC - thrombocytopenia, leukopenia
Cytokine release syndrome - could monitor Bp and temperature
Symptoms of an allergic reaction

Patients should be monitored every 15mins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is an important dosing consideration for ATG?

A

Use ideal body weight in obese patients to avoid excessive dosing and therefore increased risk of side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

When is ATG used more commonly now?

A

In episodes of rejection, less common to have at induction now

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the mechanism of action of corticosteroids?

A

Binds to glucocorticoids receptors, causing changes in gene expression, causing multiple downstream effects. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10 and inhibit T-cell activation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the therapeutic and toxic monitoring parameters for steroids?

A

Therapeutic:
Lack of transplant rejection

Toxic:
Adrenal insufficiency
Weight gain/fluid retention
Bp - Hypertension
Psychiatric behaviours
Acne
Hyperlipidaemia
Blood glucose
U+Es – hypernatremia, hypokalaemia
Mineral bone density
GI – taken in the morning (match cortisol levels) after breakfast
Eye examination - glaucoma
Cushing syndrome - mooning of the face, thinning of the skin
Increased risk of malignancy
Increased infection risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the dosing regimen for steroid use in transplant patients?

A

Steroids can be used both at induction and carried on as maintenance therapy.
The once daily dose should always be taken in the morning to match the body’s natural cortical levels.
The dose should be tapered dose gradually, avoiding adrenal suppression. The tapering rate is done on a patient by patient basis depending on the level of organ match, graft function and overall patient condition.
Usually at a dose of 20mg post-transplant, 15mg at discharge (usually Day 5).
Steroid use is reviewed at twice weekly outpatient transplant clinics to decide any further reduction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the mechanism of action of Ciclosporin?

A

Ciclosporin is a calcineurin inhibitor. It binds to cyclophilin (which is an immunophilin) to form a complex. This complex inhibits calcineurin phosphatase supressing T-cell activation by inhibiting IL-2 production.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the therapeutic and toxic monitoring parameters for Ciclosporin?

A

Therapeutic:
Lack of rejection
Serum Ciclosporin level of 100-300 ng/mL which is measured at a trough level

Toxic:
Urea & electrolytes (including calcium &
phosphate)
Full blood count
Mid-stream urine (for culture & sensitivities)
Serum level of Ciclosporin above or below the therapeutic level of 100-300 ng/mL
Liver function tests
Blood pressure required at least twice before initiation
Serum creatinine (for creatinine clearance) · required at least twice before starting treatment or Calculated glomerular filtration rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What else should you check before initiation of Ciclosporin?

A

If a patient’s cervical screening is up to date, if appropriate
Check vaccination status and screen for Hep B, Hep C, HIV or Varicella Zooster immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

How frequent is the monitoring of Ciclosporin?

A

Initially patients have to report to the outpatient transplant clinic for monitoring 2-3 times a week, daily when in hospital

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are the concentration dependent side effects of Ciclosporin?

A

Nephrotoxicity
Hypertension
Hyperlipidaemia
Gingival hyperplasia
Hirsutism
Tremor
Neurotoxicity

32
Q

When should patients seek urgent medical attention when on Ciclosporin?

A

Skin or mucosal reaction (rash, pruritus, mouth or throat ulceration)
Sore throat
Fever
Unexplained bruising or bleeding
Nausea, vomiting, diarrhoea or weight loss
Diffuse alopecia
Breathlessness, infection or cough
Peripheral neuropathy

33
Q

What is the management strategy if Nephrotoxicity occurs with Ciclosporin use?

A

Reduce the dose

34
Q

What is the management strategy if hypertension occurs with Ciclosporin use?

A

Initiate anti-hypertensives, however if remains uncontrolled this is a contra-indication to Ciclosporin use and the patient may have to be switched on to another immunosuppressive.

35
Q

What are the conditions that Ciclosporin can induce?

A

Haemolytic uraemic syndrome
Diabetes mellitis - about 5% of patients, even within the therapeutic level

36
Q

What is the dosing regimen for Ciclosporin?

A

Ciclosporin is a twice daily regimen, with dosing titrated to the patient’s trough Ciclosporin level between 100-300 ng/mL.

37
Q

What is a key consideration regarding brands of Ciclosporin?

A

Patient’s must be maintained on the same brand of Ciclosporin, therefore it should be prescribed as brands either NeOral or named generic.

38
Q

What are the major drug interactions for Ciclosporin?

A

It is metabolised by CYP 450 and therefore CYP450 inducers and inhibitors will affect the concentration of Ciclosporin.
Also include avoiding grapefruit juice.

39
Q

What are the advantages of using Ciclosporin?

A

It has a major positive impact on rejection and survival following transplant.

40
Q

What liquids can Ciclosporin be mixed with?

A

Orange or apple juice (Neoral)
Milk, chocolate milk, or orange juice (Sandimmune)

Preferably all liquids should be at room temperature

41
Q

What is the mechanism of action of Tacrolimus?

A

Binds to FK506 (binding protein 12 which is immunophilin). This inhibits calcineurin which is involved in the transcription of genes encoding IL-2 and other cytokines. This prevents early T-cell activation.

42
Q

What are the therapeutic and toxic monitoring parameters for Tacrolimus?

A

Therapeutic:
Lack of transplant rejection
Trough tacrolimus levels 5-15 (20) ng/mL

Toxic:
Blood glucose (fasting) - Diabetes
Nephrotoxicity – creatinine, eGFR, urine output and itself causes nephrotoxicity (dose dependent)
Blood pressure - hypertension
Neurotoxicity – peripheral neuropathy, dose dependent
U & Es- hyperkalaemia
Lipids
Clotting screening
ECG for hypertropic changes
FBC
LFTs
Plasma proteins

May also want to screen for HIV, Hep B or Hep C infections before initiation

43
Q

How frequently should for Tacrolimus occur?

A

At least weekly for the first 3 months following a cardiac, renal or liver transplant and then:
Indicatively from 3 months, every 2-4 weeks; from 4 months, every 4-6 weeks; from 12 months, every 3-6 months

In addition to the above patient’s should also receive periodic skin examinations, lipids and Hep B surface antibodies to inform whether revaccination is required.

44
Q

What advice would you give to patients taking Tacrolimus or Ciclosporin?

A

Avoid UV sun exposure due to increased risk of malignancy
Report any signs of high blood sugar such as confusion, feeling sleepy, increased thirst, increased hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit
Ensure vaccination status is up to date before initiation and patient’s should be advised to avoid live vaccines during treatment
Pregnancy should be excluded before starting treatment

45
Q

What are some of the other side effects of Tacrolimus?

A

Other side effects:
Headache
Tremour
Seizures
GI disturbances
Haemolytic uraemic syndrome

46
Q

Are all the side effects of Tacrolimus dose dependent?

A

Side effects are more likely above the therapeutic range but they can be idiosyncratic, occurring at a therapeutic level.

47
Q

Compare the side effect profile of Tacrolimus and Ciclosporin.

A

Tacrolimus has a lower incidence of hypertension, hyperlipidaemia and cosmetic side effects

Tacrolimus has a higher incidence of diabetes and neurotoxicity

48
Q

Does Tacrolimus also need to be prescribed by brand?

A

Yes it must be prescribed by brand as swapping between brands or generics leads to toxicity and graft rejection.
The only exception to this is in a hospital environment when it must be done under close supervision.

49
Q

Compare the bioavailability between formulations of Tacrolimus and Ciclosporin.

A

PO Ciclosporin is equivalent to 3x the IV dose
PO Tacrolimus is 3-5x the IV dose

50
Q

Describe the dosing regimen for Tacrolimus.

A

The dosing of Tacrolimus is once or twice daily depending on the brand and transplant type.
In renal transplant - Advagraf is used, this is once daily dosing
In liver transplant - Adoport is used, this is twice daily dosing

Either brand should be taken on an empty stomach for better absorption
Dose is titrated based on the trough level 5-15 (20) ng/mL however this can vary depending on the age of the transplant, can be decreased in later years
Any dose changes requires increased monitoring

51
Q

What are some of the interactions of Tacrolimus?

A

Again like Ciclosporin, Tacrolimus is metabolised by CYP 450 and thereforeCYP450 inducers and inhibitors will affect the concentration of Tacrolimus.
Also include avoiding grapefruit juice.

52
Q

When would you use Tacrolimus in preference to Ciclosporin?

A

Due to consideration of the side effect profile but also in patients requiring higher amounts of immunosuppression due to Tacrolimus being more potent than Ciclosporin.

53
Q

What is the mechanism of action of Azathioprine?

A

Azathioprine is a pro-drug of 6-MP is metabolised to thioguanine nucleotides which interfere with DNA synthesis. Another metabolite inhibits de novo purine synthesis.*** This inhibits the production of both B and T cells.

54
Q

What are the therapeutic and toxic monitoring parameters for Azathioprine?

A

Therapeutic:
Lack of transplant rejection

Toxic:
Hypersensivity
FBC - myelosuppression, leukopenia, neutropenia, thrombocytopenia
Serum creatinine (for creatinine clearance) or calculated glomerular filtration rate
Liver function tests
Blood pressure
TPMT assay

55
Q

What is the management required for haematological disturbances with Azathioprine use?

A

Dose dependent myelosuppression occurs in 50% of patients
Both leukopenia and thrombocytopenia can be reversed by reducing or stopping the dose

56
Q

What is the appropriate management for nausea and vomiting associated with Azathioprine?

A

Taking the dose with meals or dividing the dose during the day

57
Q

What is the dosing regimen for Azathioprine?

A

Once daily dosing usually 1–2.5 mg/kg daily, adjusted according to response. Preferably administered by mouth, if not can given by IV injection.

58
Q

What is a key interaction for Azathioprine?

A

Manufacturer advises reduce dose to one-quarter of the usual dose with concurrent use of allopurinol.

59
Q

What is the mechanism of action of Mycophenolic acid?

A

Mycophenolic acid blocks inosine monophosphate dehydrogenase the enzyme required for the de novo synthesis of guanosine monophosphate nucleotides. This blocks purine synthesis, preventing B and T cell proliferation.

60
Q

What is an advantage of using Mycophenolic acid over Azathioprine?

A

Mycophenolic acid is more potent than Azathioprine so it has a greater reduction in acute rejection. Would prefer its use over Azathioprine in patients at a higher risk of rejection.

61
Q

What are the therapeutic and toxic monitoring parameters for Mycophenolate acid?

A

Therapeutic:
Lack of rejection

Toxic:
FBC - anaemia, leukopenia, neutropenia
Renal function
LFTs
GI - diarrhoea and vomiting

62
Q

What are some of the counselling points you would provide to patients on MPA?

A

Firstly the drug is teratogenic meaning that if female the patient must be on an effective form of contraception.
Avoid live vaccines whilst on the medication
UV light exposure should also be limited due to the increased risk of skin malignancies

63
Q

What side effect of MPA is dose limiting and what is the appropriate management?

A

Diarrhoea, patient can be converted to the enteric coated MPA formulation which was improved GI side effects

64
Q

What is the dosing regimen for MPA?

A

Dose is dependent upon the type of transplant and whether it is used for prophylaxis or treatment of rejection.
However it is always a twice daily dosing regimen.

65
Q

What are some of the interactions of MPA?

A

Antacids, iron supplements and Rifampcin all decrease the serum mycophenolate mofetil levels whereas

Aciclovir and Ganclovir increase mycophenolate mofetil levels, increasing the risk of haematological toxicity

66
Q

What is Sirolimus an alternative to?

A

It is an alternative to calcineurin inhibitors + anti-proliferative drug or a calcineurin inhibitor combination.

67
Q

What is the mechanism of action of Sirolimus?

A

In target cells, sirolimus binds to the cytoplasmic receptor FK506-binding protein-12 (FKBP12), an immunophilin, to form an immunosuppressive complex. FKBP12-sirolimus complex binds to and inhibits the activation of the mammalian target of rapamycin (mTOR) which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, survival, mobility, and angiogenesis.

mTOR regulates the downstream signalling pathways involved in cell survival, such as the phosphatidylinositol-3 kinase (PI3K)/Akt signalling pathway. Inhibition of mTOR leads to the suppression of cytokine-driven T-cell proliferation such as IL-2, 4 and 15, preventing G1 to S phase of the cell cycle.
Also inhibits antibody production.

68
Q

What are the therapeutic and toxic monitoring parameters for Sirolimus?

A

Therapeutic:
Lack of transplant rejection
Target blood serum range of 12-20 ng/mL

Toxic:
Blood pressure- hypertension
FBC - thrombocytopenia
Blood lipid profile - hyperlipidaemia
Pneumonitis
Renal function - eGFR, CrCl
GI-diarrhoea
LFTs

69
Q

Compare the side effects of Sirolimus with the other Calcineurin inhibitors.

A

Less likely to cause nephrotoxicity but proteinuria is present
Less likely to cause diarrhoea

70
Q

What is the appropriate management if pneumonitis occurs?

A

It is life threatening and therefore treatment withdrawal should occur. Should resolve after that.

71
Q

Why is Sirolimus not initiated immediately after surgery?

A

Sirolimus causes alteration to fibroblast response to their growth factors and therefore causes impaired wound healing.

72
Q

What are some of the interactions of Sirolimus?

A

Like the Calcineurin inhibitors, Sirolimus is metabolised by CYP 450 and therefore CYP450 inducers and inhibitors will affect the concentration of Sirolimus.
Also include avoiding grapefruit juice.

73
Q

What is the mechanism of action of Belatacept?

A

Belatacept specifically binds to CD80 and CD86 receptors that are found on the antigen-presenting cell (B cells, macrophages, dendritic cells) to block selective T-cell lymphocyte costimulation.

74
Q

Compare the use of Belatacept to calcineurin inhibitors.

A

It is used as an equivalent to calcineurin inhibitors.
It has equivalent patient and graft survival associated but has a higher incidence of acute rejection particularly those of higher immunogenic risk.

75
Q

What are the therapeutic and toxic monitoring parameters for Belatacept?

A

Therapeutic:
Lack of transplant rejection

Toxic:
TB screening
FBC - WBC, neutropenia, anaemia, thrombocytopenia, leukopenia
Regular skin examinations
Blood pressure
GI - diarrhoea, nausea, vomiting
Renal function
LFTs

76
Q

What is the dosing regimen for Belatacept?

A

It is split into two phases:

Initial phase- IV Day 1 and 5 at the end of Weeks 2, 4, 8 and 12

Maintenance phase - IV Week 16 and every 4 weeks afterwards

77
Q

What is an uncommon but important side effect of Balatacept?

A

Patients being administered Belatacept are at risk of post-transplant lymphoproliferative disease. Associated with the EBV, this is when white blood cells multiply out of control.

Solid organ transplants (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions