1 - CYCLOSPORINE Flashcards by My Co Tran

Cyclosporine is also known as cyclosporine A (CsA)

True

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CsA was originally discovered and isolated from the soil fungus Tolypocladium inflatum gams

True

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Sandimmune and Neoral are both formulations of CsA

True (only Neoral is approved for the treatment of psoriasis)

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Neoral is a more bioavailable and more consistently absorbed microemulsion formulation of CsA

True (only Neoral is approved for the treatment of psoriasis)

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CsA is not cytotoxic

True (in contrast to other drugs used to treat psoriasis I.e. MTX)

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CsA is not immunosuppressive

True (in contrast to other drugs used to treat psoriasis I.e. MTX)

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CsA is not teratogenic

True (in contrast to other drugs used to treat psoriasis I.e. MTX and Acitretin)

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CsA is nephrotoxic

True
N - Neoplasm
E - Epilepsy
O - Oral (gingival hyperplasia)
R - Renal Toxicity leading to Hypertension
A - Anorexia due to GI effects
L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

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CsA may cause lymphoproliferative malignancies

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CsA is a neutral cyclic peptide available in oral solution or in capsules

True

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Concomitant intake of Grapefruit juice with CsA should be avoided as Grapefruit juice affects the metabolism of CsA through inhibiting the CYP 450 enzyme system

True (to make the oral solution more palatable, Neoral should be diluted with Apple juice or orange juice instead)

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Neoral has a 10-50% higher bioavailability than Sandimmune

True

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Neoral is less dependent on bile, food, diet and the GI environment for proper absorption

True

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CsA is excreted in breast milk and breastfeeding should be avoided while on CsA

True

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CsA is extensively metabolised by the CYP3A4 enzyme in the liver

True

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CsA is excreted mainly in the bile and faeces

True

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Only 6% of CsA and its metabolites are excreted in urine

True (mainly excreted in bile and faeces)

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Hepatic insufficiency may prolong the half life of CsA

True (CYP3A4 metabolism in the liver)

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CsA dose needs to be adjusted in hepatic insufficiency

True (metabolised in the liver through CYP3A4)

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Dialysis and renal failure does not significantly alter CsA’s clearance

True (mainly metabolised in the liver and excreted in the bile and faeces)

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90% of CsA is protein bound

True

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The exact mechanism of action of CsA is not fully understood although there is an effect on T lymphocytes in psoriasis

True

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CsA inhibits T cell secretion of cytokines (IL-2, IFN-gamma, ICAM-1), lymphocyte infiltration and inflammation

True

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CsA inhibits production of IL-2 by inhibiting calcineurin that results in decreased T cell proliferation

True

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CsA inhibits IFN-gamma production by T lymphocytes that results in reduced keratinocyte proliferation

True

Neoral has a more complete and more predictable absorption than Sandimmune

True

CsA is effective in patients who present with widespread, intensely inflammatory psoriasis

True

CsA is effective in patients who present with a sudden severe flare of their psoriasis

True

CsA may be used in patients with moderate to severe or disabling psoriasis who are unable to tolerate, have contraindications to or have failed other systemic therapies

True

CsA may be useful in psoriasis patients experiencing major life events where substantial clearing of psoriasis for a short period of time is important

True

CsA may also be strongly considered for erythrodermic psoriasis

True

CsA may also be strongly considered for pustular psoriasis

True

CsA is generally effective for all forms of psoriasis

True

CsA may be used for Severe atopic dermatitis

True

CsA is ideally given for 3-6 months and 12 months at the most due to risk of nephrotoxicity

True

CsA, tacrolimus and pimecrolimus are calcineurin inhibitors

True

Significantly decreased renal function is a contraindication for CsA

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

Uncontrolled hypertension is a contraindication for CsA

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

Clinically cured or persistent malignancy (except NMSCs) is a contraindication for CsA

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

Cutaneous T-cell lymphoma is a contraindication for CsA

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

Patients with cutaneous T cell lymphoma progressed after treatment with CsA

True

The risk of nephrotoxicity and hypertension from CsA increase with increasing dose and duration of therapy

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

Neurological effects I.e. Tremor, headaches, paraesthesia and hyperesthesia are the most common adverse effects noted in patients using CsA for 2 months or less

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout

CsA may cause hypertrichosis

True

CsA may cause gingival hyperplasia

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

CsA may cause GI side effects I.e. Nausea, diarrhoea, abdominal discomfort

True N - Neoplasm E - Epilepsy O - Oral (gingival hyperplasia) R - Renal Toxicity leading to Hypertension A - Anorexia due to GI effects L - Lab abnormalities (hyperkalaemia, hyperlipidaemia, hypomagnesaemia, hyperuricaemia leading to Gout)

A reduction of CsA dose is recommended when there is a 30% increase from the baseline creatinine value

True

The development of hypertension due to CsA is not a contraindication to continuing therapy with CsA

True (CsA can be continued as long as the hypertension can be controlled using the calcium channel blocker nifedipine)

The risk of NMSCs is probably increased in psoriasis patients undergoing long term treatment with CsA

True

Hyperlipidaemia is a common adverse effect of CsA

True

The hyperlipidaemia from CsA may be treated using a lipid lowering agent

True

Fluvastatin (lipid lowering agent) is suitable to be used for CsA induced hyperlipidaemia as it is not a substrate of CYP3A4 and does not interact with CsA

True (CsA is metabolised by CYP3A4)

Rosuvastatin (lipid lowering agent) is suitable to be used for CsA induced hyperlipidaemia as it is not a substrate of CYP3A4 and does not interact with CsA

True (CsA is metabolised by CYP3A4)

Pravastatin (lipid lowering agent) is suitable to be used for CsA induced hyperlipidaemia as it is not a substrate of CYP3A4 and does not interact with CsA

True (CsA is metabolised by CYP3A4)

Lovastatin (lipid lowering agent) should not be used for CsA induced hyperlipidaemia as similar to CsA, it is also a substrate of CYP3A4 and interacts with CsA

True

Simvastatin (lipid lowering agent) should not be used for CsA induced hyperlipidaemia as similar to CsA, it is also a substrate of CYP3A4 and interacts with CsA

True

Atorvastatin (lipid lowering agent) should not be used for CsA induced hyperlipidaemia as similar to CsA, it is also a substrate of CYP3A4 and interacts with CsA

True

CsA may cause hypomagnesaemia

True

CsA may cause hyperuricaemia and potentially gout

True

Macrolide antibiotics (erythromycin, clarithromycin, azithromycin) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Fluoroquinolones antibiotics (Ciprofloxacin) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Cephalosporins may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Doxycycline may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Azole antifungals (ketoconazole, itraconazole, fluconazole) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

HIV-1 protease inhibitors (Ritonavir, Idinavir) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Calcium channel blockers (Diltiazem, Verapamil) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4) - but not nifedipine

H2 antihistamines (cimetidine) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Diuretics (thiazides, frusemide) may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Grapefruit juice may increase CsA levels due to CYP3A4 inhibition

True (CsA is metabolised by CYP3A4)

Rifampicin may reduce CsA levels due to CYP3A4 induction

True (CsA is metabolised by CYP3A4)

Carbamazepine may reduce CsA levels due to CYP3A4 induction

True (CsA is metabolised by CYP3A4)

Phenytoin may reduce CsA levels due to CYP3A4 induction

True (CsA is metabolised by CYP3A4)

Nephrotoxic drugs should be used with caution with CsA as this may potentiate renal toxicity

True

ACE-inhibitors may increase the CsA risk of hyperkalaemia when used concurrently with CsA

True

Potassium sparing diuretics may increase the CsA risk of hyperkalaemia when used concurrently with CsA

True

Discontinuation of CsA should be gradual while an alternative therapy is instituted to reduce the risk of rebound in psoriasis disease activity

True (cases of pustular psoriasis when CsA stopped cold turkey)

CsA is a very good clearing agent for psoriasis

True (The ideal sequential therapy approach is to use CsA first to induce clearing, followed by Acitretin with a slow onset of action as maintenance therapy)

When converting Sandimmune to Neoral, a 1:1 dose conversion strategy is recommended even though Neoral is more readily absorbed than Sandimmune

True

Warfarin may increase CsA levels due to competitive binding to CYP3A4 (both warfarin and CsA are CYP3A4 substrates)

True (CsA is also metabolised by CYP3A4)

The overall ratio of bioavailability between Sandimmune and Neoral is 5:4

True