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Pre-reg exam > Immunosuppression > Flashcards

Immunosuppression Flashcards

1
Q

Ciclosporin

Indications

A
  • Severe acute ulcerative colitis refractory to corticosteroids
  • Severe active rheumatoid arthritis
  • Severe active rheumatoid arthritis (In combo with MTX)
  • Short term treatment of severe atopic dermatitis
  • Severe psoriasis
  • Organ transplant
  • Prevention/treatment of graft-versus-host disease
  • Nephrotic syndrome
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2
Q

Ciclosporin

MOA

A
  • Ciclosporin is a cyclic polypeptide of 11 amino acids
  • It is a potent immunosuppressive agent
  • Ciclosporin inhibits the development of cell-mediated reactions, including allograft immunity
  • At cellular level ciclosporin inhibits the production and release of lymphokines including IL-2 (T-cell growth factor)
  • Ciclosporin appears to block the resting lymphocytes in phase G0 or G1 in the cell cycle and inhibits the Ag triggered release of cytokines from activated T cells
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3
Q

Ciclosporin

Warnings

A
  • Active/suspected ocular infection
  • Malignancies
  • Uncontrolled HTN (in non-transplant indications)
  • Uncontrolled infections
  • Cautioned in
    • Elderly- reduced renal function
    • Hyperuricaemia
    • HSV- allow infection to clear prior to initiation
    • MRSA skin infection
    • Lymphoproliferative disorders
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4
Q

Ciclosporin

Adverse effects

A
  • When used on the eye TOP- visual disturbances
  • Blood- Leucopenia
  • Metabolism- Hyperlipidaemia, hyperkalaemia, hypomagnesaemia, hyperglycaemia
  • CNS- tremor, headache, convulsions
  • Vascular disorder- HTN
  • Hepatic- Elevated LFTs
  • Skin- Hirsutism, acne, hypertrichosis
  • Renal- Renal dysfunction
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5
Q

Ciclosporin

Interactions

A
  • Ciclosporin is a CYP inhibitor
  • All other CYP PgP inducers are going to decrease plasma levels
    • CBZ, barbs, phenytoin, rifampicin, SJW
  • CYP inhibitors- Erythromycin, clarithromycin, fluconazole, verapamil- increase risk of nephrotoxicity
  • Amiodarone increase ciclosporin exposure
  • Any med that increases risk of nephrotoxicity- aminoglycosides, NSAIDs, Amphotericin B, Cipro, Vanc, H2-antagonists, MTx
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6
Q

Ciclosporin

Monitoring

A
  • FBC- Especially WCC
  • Dermatological examination
  • Obs- BP
  • U&E- K, Mg, Renal function
  • LFTs-
  • Lipids
  • Renal biopsy- monitor for nephrotic syndorme annually
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7
Q

Ciclosporin

Pt advise

A
  • Patient should be aware that ciclosporin should be prescribed by brand. Different formulations can lead to changes in blood-ciclosporin concentration
  • Manufacturer suggests avoid excessive exposure to UV light, including sunlight
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8
Q

Azathioprine

Indications

A
  • Severe Chrons disease (including maintenance)
  • Maintenance of remission of acute ulcerative collitis
  • Rheumatoid arthritis not responding to DMARDs
  • Severe systematic lupus erythematosus
  • Auto-immune conditions
  • Suppression of transplant rejection
  • Severe refractory eczema
  • Generalised myasthenia gravis
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9
Q

Azathioprine

MOA

A
  • Azathioprine is a metabolised into the active 6-mercaptopurine
  • 6-MP is metabolised by xanthine oxidase enzyme (inhibited by allopurinol)
  • 6-MP acts as a purine anti-metabolite
  • The possible blockade of -SH groups by alkylation
  • Inhibition of many pathways including nucleic acid biosynthesis, preventing proliferation of cells involved in determination and amplification of the immune system
  • DNA through incorporation of purine thio-analogues
    *
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10
Q

Azathioprine
Warnings

A
  • Absent TioPurineMethylTransferase (TPMT) activity
  • Very low TPMT activity
    • Cautioned in
    • Reduced dose in elderly
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11
Q

Azathioprine

Adverse effects

A
  • Bone marrow suppression (dose related)
  • Increased risk of infection
  • Pancreatitis
  • Hypersensitivity reaction (malaise, dizziness, vomiting, diarrhoea, fever, rash, hypotension and renal dysfunction
  • Neutropenia and thrombocytopenia- neutropenia is dose-depndent. This requires careful monitoring and dose adjustment
  • Nausea- common in early treatment, dividing daily dose can resolve nausea
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12
Q

Azathioprine

Monitoring

A
  • Prescreening for TPMT activity must occur prior to treatment- low levels increase risk of myelosuprresion
  • Monitor for toxicity throughout
  • FBC weekly for 1st 4 weeks then 3 monthly thereafter
  • Monitor for signs of myelsuppresion
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13
Q

Tacrolimus

A
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14
Q

Tacrolimus

MOA

A
  • Tacrolimus’ effect seems to be mediated by cytosolic protein (FKBP12) which is responsible for intracellular accumulation of the compound
  • The FKBP12-tacrolimus complex specifically and competitively binds to and inhibits calcineurin, leading to a calcium-dependent inhibition of T-cell signal transduction pathways, thereby preventing transcription of a discrete set of lymphokine genes
  • Tacrolimus inhibits the formation of cytotoxic lymphocytes, which are mainly responsible for graft rejection
  • Tacrolimus suppresses T cell activitation and T-helper dependent B-cell proliferation, as well as the formation of cytokines (IL-2,3) and expression of IL-2 receptors
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15
Q

Tacrolimus

Warnings

A
  • Cautioned in
    • UV light- avoid excessive exposure to sunlight
    • Increased risk of infection
    • Lymphoproliferative disorders
    • Malignacy
    • Neurotoxicity
    • QT-interval prolongation
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16
Q

Tacrolimus

Adverse effects

A
  • Increased risk of infection
  • Increased risk of developing malignancies
  • Blood disorders
  • Metabolic- hyperglycaemia, diabetes, hyperkalaemia. General electrolyte disturbances
  • Eye- blurred vision
  • CV- Ischaemic coronary artery disease, tachycardia, HTN, thromboembolic events
  • Resp- Dyspnoea, inflammations, pleural effusion
  • GI
  • Renal impairment
  • Investigations abnormalities- LFTs, Alk Phos, weight, ECG
  • Cardiomyopathy has been reported in children with high tacrolimus levels
17
Q

Tacrolimus

Monitoring

A
  • After initial dosing and for maintenance treatment, tacrolimus doses should be adjusted according to whole-blood concentration
  • Monitoring whole blood-tacrolimus trough coenctration (especially during diarrhoea)
  • Monitor BP, ECG (hypertrophic changes- risk of cardiomyopathy)
  • BG
  • Neurological (inc visual)
  • Coagulation
  • U&E
  • Hepatic function
18
Q

Tacrolimus

Patient info

A
  • Tacrolimus must be prescribed by brand
  • Switching between brands is associated with reports of toxicity and graft rejection
19
Q

Mycophenolate

Indications

A
  • Prophylaxis of graft rejection in renal, hepatic and cardiac transplant in combo with corticosteroids and ciclosporin
20
Q

Mycophenolate

MOA

A
  • Mycophenolate mofetil is the 2-morpholinoethyl ester of MPA (Mycophenolate Acid)
  • MPA is a potent selective, uncompetative and reversible inhibitor of inosine monophosphate dehydrogenase and therefore inhibits the pathyway of guanosine nucleotide synthesis without incorporation into DNA
  • Because T and B-lymphocytes are critically dependent for their prolifieration on the synthesis of purines whereas other types of cells can utilise salvage pathways, MPA has more potent cytostatic effects on lymphocytes than on other cells
21
Q

Mycophenolate

Warnings

A
  • Cautioned in
    • Active serious GIT (risk of haemorrhage, ulceration and perforation)
    • Children- increased risk of side effects
    • Delayed graft function
    • Eldery- increased risk of infection, GI haemorrhage, pulmonary oedema
    • Increased susceptibility to skin cancer (Avoid exposure)
    • Risk of hypogammaglobulinaemia or bronchiectasis when in combo with other immunosuppressants- measure Ig levels if recurrent infection occurs and consider bronchiectasis or pulmonary fibrosis
22
Q

Mycophenolate

Adverse effects

A
  • Malignancies- increased risk
  • Infection- increased risk
  • Blood- Leukopenia, anaemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia
  • GI- ulceration, haemorrhage
  • Respiratory- ILD, pulmonary fibrosis, bronchiectasis
  • Electrolyte disturbance + hyperglycaemia
  • CV- tachycardia, HTN
23
Q

Mycophenolate

Interactions

A
  • Aciclovir- increased risk of haematological toxicity
  • Vaccines
  • CYP inducers
24
Q

Monitoring

Mycophenolate

A
  • FBC every 4 weeks then twice monthly then monthly in the first year
25
Q

Mycophenolate

Patient info

A
  • Pregnancy must be excluded prior to treatment.
  • Encourage effective contraception due to the risk of congenital malformations and spontaneous abortions

Pre-reg exam (113 decks)

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