Immune System

Question 1

Patients with chronic inflammatory diseases and autoimmune diseases as well as those who have received organ transplants are often maintained on regimens containing which drugs?

Answer 1

Antiproliferative drugs, calcineurin inhibitors, corticosteroids and sirolimus.

Question 2

Should the use of ciclosporin or azathioprine be stopped during pregnancy? Who should supervise such use?

Answer 2

No. Use should be supervised by specialist units.

Question 3

In what cases is azathioprine used?

Answer 3

In transplant recipients and those with autoimmune conditions.

Question 4

What is azathioprine metabolised into?

Answer 4

Mercaptopurine.

Question 5

Doses of azathioprine should be reduced when used concomitantly with which other drug? Why is this?

Answer 5

Allopurinol due to the increased risk of marrow suppression.

Question 6

With which antiproliferative immunosuppressants has red cell aplasia been seen?

Answer 6

Azathioprine and mycophenolate mofetil.

Question 7

What course of action should be taken should red cell aplasia be seen with the use of azathioprine or mycophenolate mofetil?

Answer 7

Dose reduction or discontinuation should be considered under specialist supervision.

Question 8

What are the symptoms of hypersensitivity occasionally seen with the use of azathioprine? What course of action should be taken should hypersensitivity occur?

Answer 8

Malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension, interstitial nephritis. The drug should be withdrawn if this occurs.

Question 9

Patients on azathioprine should be warned to report any signs or symptoms of bone marrow suppression. What are these symptoms?

Answer 9

Unexplained bleeding or bruising, infections.

Question 10

What is red cell aplasia?

Answer 10

A bone marrow disorder characterized by a reduction of red blood cells (erythrocytes) produced by the bone marrow.

Question 11

What side effects may be seen during the early stages of treatment with azathioprine?

Answer 11

Nausea, vomiting, diarrhoea.

Question 12

If nausea, vomiting, diarrhoea occur during the early stages of rheumatoid arthritis treatment, what can be done?

Answer 12

The drug can be discontinued.

Question 13

What monitoring is required during azathioprine treatment?

Answer 13

FBC for 4 weeks then every 3 months, monitor throughout treatment, blood tests and monitoring for myelosuppression in long-term treatment.

Question 14

What screening is required before beginning treatment with azathioprine or mercaptopurine?

Answer 14

The activity of the TPMT enzyme, that which metabolises azathioprine and mercaptopurine. Greater risk of myelosuppression where reduced activity is seen

Question 15

What is mycophenolate licensed for?

Answer 15

Prophylaxis of acute rejection in renal, hepatic, and cardiac transplantation when used with ciclosporin and corticosteroids.

Question 16

When taking azathioprine, which symptoms of bone marrow suppression should patients be made aware of?

Answer 16

Infection (sore throat), unexplained bleeding or bruising.

Question 17

When azathioprine is used with other immunosuppressants, what is there an increased risk of?

Answer 17

Hypogammaglobulinemia (recurrent infections) and bronchiectasis (respiratory symptoms such as cough and dyspnoea).

Question 18

Why should pregnancy be excluded immediately before and during treatment with azathioprine?

Answer 18

Due to the risk of congenital malformations and spontaneous abortions.

Question 19

Describe how contraception should be used whilst a patient is taking azathioprine.

Answer 19

Women should use two methods of effective contraception during treatment and for six weeks after discontinuation. Men and their partners should both use contraception during treatment and for at least 90 days after discontinuation.

Question 20

Describe the mechanism of action of ciclosporin.

Answer 20

Ciclosporin is a calcineurin inhibitor, a potent immunosuppressant which is virtually non-myelotoxic but markedly nephrotoxic.

Question 21

Are loading doses required with ciclosporin?

Answer 21

Loading doses may be required.

Question 22

What are the warning signs of ciclosporin toxicity?

Answer 22

Neurotoxicity (tremor, headache, encephalopathy), blood disorders (signs of infection, unexplained bleeding and bruising), liver toxicity (jaundice, nausea, vomiting, abdominal discomfort, dark urine), nephrotoxicity (elevated serum creatinine), vomiting, drowsiness, tachycardia, hypertension, benign intracranial hypertension, gingival hyperplasia.

Question 23

What monitoring is required when a patient is on ciclosporin?

Answer 23

FBC, liver function, serum electrolytes, blood lipids, renal function, blood pressure, dermatological and physical examination.

Question 24

What is required when ciclosporin is used during pregnancy?

Answer 24

Specialist supervision.

Question 25

What dietary considerations should be made when a patient is on ciclosporin?

Answer 25

The patient should be advised to avoid a high potassium diet and to avoid grapefruit juice. Oral solution formulations can be taken with a fruit juice such as orange or apple juice to improve taste.

Question 26

What special consideration is required when patients on ciclosporin require vaccination?

Answer 26

Patients must not receive live vaccines.

Question 27

Why should patients on ciclosporin be advised to avoid exposure to UV light and wear a wide spectrum sun screen?

Answer 27

To reduce the risk of developing secondary skin malignancies.

Question 28

Patients on ciclosporin should be stabilised on a particular brand to avoid changes in blood-ciclosporin concentration. How should this be achieved?

Answer 28

By prescribing by brand.

Question 29

What monitoring should be carried out when changing ciclosporin brands?

Answer 29

Blood-ciclosporin concentration, serum creatinine, blood pressure, transplant function.

Question 30

With which drugs is an increase in ciclosporin concentration seen?

Answer 30

Clarithromycin, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, miconazole, metoclopramide, verapamil, tacrolimus.

Question 31

An increased risk of nephrotoxicity and myotoxicity is seen when ciclosporin is seen with which drug?

Answer 31

Colchicine.

Question 32

With which drugs is a decrease in ciclosporin concentration seen?

Answer 32

Carbamazepine, orlistat, phenobarbital, phenytoin, rifampicin, St John’s wort.

Question 33

An increased risk of hyperkalaemia is seen when ciclosporin is given with which drugs?

Answer 33

ACEis, ARBs, aldosterone antagonists.

Question 34

An increased risk of nephrotoxicity is seen when ciclosporin is given with which drugs?

Answer 34

NSAIDs (plus increased plasma concentration of diclofenac).

Question 35

Ciclosporin increases the risk of plasma concentration of which drug?

Answer 35

Digoxin (increasing the risk of toxicity).

Question 36

An increased risk of myopathy is seen when ciclosporin is given with which drugs?

Answer 36

Statins (avoid).

Question 37

What is the mechanism of action of tacrolimus?

Answer 37

It is a calcineurin inhibitor similar to ciclosporin.

Question 38

Which has a greater risk of neurotoxicity; tacrolimus or ciclosporin?

Answer 38

Tacrolimus.

Question 39

What are the warning signs of tacrolimus toxicity, which should be reported immediately?

Answer 39

Neurotoxicity (tremor, headache), nephrotoxicity (elevated serum creatinine concentrations), eye disorders (blurred vision, photophobia), skin disorders (rash, toxic epidermal necrolysis), blood disorders (signs of infection, bleeding, bruising), hyperglycaemia (diabetes mellitus), cardiovascular disorders (cardiomyopathy, arrhythmias, hypertension), liver toxicity (jaundice, nausea, vomiting, abdominal discomfort, dark urine).

Question 40

What monitoring is required when a patient is on tacrolimus?

Answer 40

BP, ECG, fasting blood glucose, renal function, liver function, serum electrolytes (particularly K+), haematological, neurological and coagulation parameters.

Question 41

Should tacrolimus be avoided in pregnancy? Why?

Answer 41

Yes, due to the risk of premature delivery.

Question 42

Why should patients on tacrolimus be advised to avoid UV exposure and wear wide spectrum sunscreen?

Answer 42

To reduce the risk of secondary skin malignancies.

Question 43

What may tacrolimus use affect?

Answer 43

The performance of skilled tasks such as driving.

Question 44

What special consideration should be taken when patients on tacrolimus require vaccination?

Answer 44

Patients must not receive live vaccines.

Question 45

What dietary advice should be given to patients on tacrolimus?

Answer 45

To avoid high potassium diets and grapefruit juice.

Question 46

Switching brands of oral tacrolimus has been associated with toxicity and graft rejection, what should be done to avoid this?

Answer 46

Oral tacrolimus should be dispensed and prescribed by brand only.

Question 47

An increase in plasma concentration is seen when tacrolimus is used with which drugs?

Answer 47

Clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, nifedipine, omeprazole, ranolazine.

Question 48

A reduction in plasma concentration is seen when tacrolimus is used with which drugs?

Answer 48

Phenobarbital, St. John’s wort, rifampicin, phenytoin.

Question 49

An increased risk of nephrotoxicity is seen when tacrolimus is given with which drugs?

Answer 49

Aminoglycosides, amphotericin, NSAIDs (especially ibuprofen), certain antivirals (acyclovir, ganciclovir).

Question 50

Which drug does tacrolimus increase the plasma concentration of?

Answer 50

Ciclosporin.

Question 51

An increased risk of hyperkalaemia is seen when tacrolimus is given with which drugs?

Answer 51

Potassium sparing diuretics (amiloride, spironolactone), potassium salts, angiotensin 2 receptor antagonists.