Immunosuppressants - DMARD, Antimetabolites

Question 1

Disease-modifying antirheumatic drugs (DMARDs) are typically the 1st line treatment for patients with a confirmed diagnosis of RA as they can reduce or prevent joint damage and to use preserve joint integrity and function.
How long do these drugs take before these drugs are effective?

1 - immediately
2 - 1-2 week
3 – 4-6 weeks
4 - 4-12 weeks

Answer 1

3 – 4-6 weeks

Some patients may stop taking them as they dont work straight away

Question 2

Disease-modifying antirheumatic drugs (DMARDs) are typically the 1st line treatment for patients with a confirmed diagnosis of RA. Are they always used in isolation?

Answer 2

• No

Can be used as a as a single agent or as a combination

Question 3

Disease-modifying antirheumatic drugs (DMARDs) are typically the 1st line treatment for patients with a confirmed diagnosis of RA. Which of the following is the least important to check at baseline before starting the DMARDs?

1 - FBC
2 - Cardiac enzymes
3 - Serum Creatinine
4 - Aminotransferases (liver enzymes)
5 - ESR and CRP

Answer 3

2 - Cardiac enzymes

• FBC = DMARDs can suppress bone marrow activity and can cause neutropenia and increased risk of infection
• Serum Creatinine = DMARDs can cause renal toxicity
• Aminotransferases (liver enzymes) = DMARDs can cause hepatoxicity
• ESR and CRP

Question 4

When starting DMARDs for a patient with RA, the following are measured at baseline:

• FBC
• Serum Creatinine
• Aminotransferases (liver enzymes)
• ESR and CRP

How often are these monitored in the 1st 6 weeks?

1 - daily
2 - every 72h
3 - weekly
4 - every 2 weeks

Answer 4

4 - every 2 weeks

Then monthly for 3 months
Then every 3 monthly afterwards

Question 5

What is generally the 1st line treatment for RA?

1 - Disease-modifying anti-rheumatic drugs (DMARDs) - Methotrexate
2 - non-steroidal drugs
3 - aspirin
4 - corticosteroids

Answer 5

1 - Disease-modifying anti-rheumatic drugs (DMARDs) - Methotrexate

Question 6

The first line treatment for RA is the disease-modifying anti-rheumatic drug (DMARDs) Methotrexate, typically prescribed SC, hut can be given orally as well. How often is this prescribed?

1 - daily 7.5 – 15mg SC
2 - daily 25mg orally
3 - weekly 7.5 – 15mg SC
4 - weekly 25mg orally

Answer 6

3 - weekly 7.5 – 15mg SC

Question 7

When starting methotrexate, what supplement are patients advised to take?

1 - Calcipotriol (vitamin D)
2 - Folic acid
3 - Omeprazole
4 - Vitamin C

Answer 7

2 - Folic acid
- given at 5mg/wk

Folic acid taken as methotrexate impairs folic acid synthesis

Question 8

Which of the following is NOT a common adverse event of methotrexate?

1 - GI problems – Nausea, Stomach upset
2 - Stomatitis (oral mucosa inflammation)
3 - Weight loss
4 - Hair loss
5 - Abnormal liver enzymes

Answer 8

3 - Weight loss

Question 9

Which of the following is NOT a common serious adverse event of methotrexate?

1 - cardiac toxicity
2 - hepatotoxicity
3 - nephrotoxicity
4 - pulmonary toxicity
5 - myelosuppression

Answer 9

1 - cardiac toxicity

Myelosuppression
1 - Anaemia
2 - Leukopenia
3 - Thrombocytopenia
4 - Pancytopenia

Question 10

Is methotrexate safe to take during pregnancy?

Answer 10

• no

Contraindicated in pregnancy as used as an abortifacient that can also induce congenital anomalies if taken during pregnancy

Question 11

Methotrexate is contraindicated in pregnancy as it is used as an abortifacient that can also induce congenital anomalies if taken during pregnancy. Prior to becoming pregnant, how long must patients have stopped taking it by?

1 - 24h
2 - 1 week
3 - 4 weeks
4 - 3 months

Answer 11

4 - 3 months

At least 3 months prior to coneption

Question 12

Which of the following is NOT an indication for the use of Methotrexate according to the BNF?

1 - RA
2 - Urticaria
3 - Psoriasis
4 - Crohn’s disease
5 - Neoplastic diseases

Answer 12

2 - Urticaria

Question 13

Leflunomide is a DMARDs used in rheumatology at a dose of 10-20mg/d. Which of the following is NOT a common side effect of this drug?

1 - GI - Diarrhoea, Nausea
2 - Hepatic – transaminitis
3 - Hypotension
4 - Pulmonary (ILD)
5 - Skin – rash, alopecia,
6 - Haematological – leucopoenia
7 - Drug interaction – warfarin

Answer 13

3 - Hypotension
- Causing hypertension

• BP monitoring during the first 3 months of treatment recommended

Monitoring is the same as methotrexate

Question 14

Leflunomide is a DMARDs used in rheumatology at a dose of 10-20mg/d. Is this a safe drug to take during pregnancy and lactation?

Answer 14

• no

Even when stopping, it can remain at low levels for up to 2 years

Cholestyramine, which binds to bile salts and prevents enterohepatic recirculation of Leflunomide

Question 15

Which 2 of the following are indications for the use of Leflunomide according to the BNF?

1 - RA
2 - Urticaria
3 - Psoriasis
4 - Crohn’s disease
5 - Neoplastic diseases

Answer 15

1 - RA
]3 - Psoriasis (must be active)

Question 16

Hydroxychloroquine is a DMARD that can be used to treat RA. What is the most important mechanism of action of Hydroxychloroquine in treating inflammatory conditions such as RA?

1 - inhibit COX1 and 2
2 - lysosomotropic actions
3 - inhibit prostoglandins
4 - inhibit immunoglobulin formation

Answer 16

2 - lysosomotropic actions

Accumulate in lysosomes, organelles that can degrade proteins, carbs, nucleic acids, lipids etc..

• can inhibit MHC-II auto-antigen presentation so body doesn’t attack itself
• interfere with autophagy, disrupt membrane stability and alter signalling pathways and transcriptional activity.
• inhibition of immune activation by reducing Toll-like receptor signalling and cytokine production and, in T cells, reducing CD154 expression, essentially resulting in anti-inflammatory response

Question 17

What is the maximum dose of Hydroxychloroquine?

1 - 1mg/day
2 - 5mg/kg
3 - 3g/day
4 - 50mg/kg

Answer 17

2 - 5mg/kg

Question 18

Which of the following is NOT an adverse effect of Hydroxychloroquine?

1 - GI upset
2 - hepatotoxicity
3 - hyperpigmentation
4 - nephrotoxicity
5 - retinal toxicity
6 - cardiotoxicity
7 - neuromuscular toxicity

Answer 18

4 - nephrotoxicity

Does not cause this, but CKD must be monitored, as it is cleared by kidneys

Baseline examination within a year of starting treatment, subsequent screening in 5 years and yearly thereafter.
More frequent screening required in patients on higher doses of HCQ, presence of renal disease, presence of macular disease and concomitant use of tamoxifen

Question 19

Although Hydroxychloroquine can be used in RA, which of the following is it also used as 1st line treatment for?

1 - pericarditis
2 - rosacea
3 - SLE
4 - giant cell arteritis

Answer 19

3 - SLE

Question 20

Which 2 of the following are indications for the use of Hydroxychloroquine according to the BNF?

1 - RA
2 - Urticaria
3 - Psoriasis
4 - SLE

Answer 20

1 - RA
4 - SLE

Can also be used for dermatological conditions irritated by the sun

Question 21

If a patient has RA and is already on disease-modifying anti-rheumatic drugs (DMARDs), namely Methotrexate. What drugs can be given to help with flare ups?

1 - paracetamol
2 - non-steroidal drugs
3 - aspirin
4 - corticosteroids

Answer 21

2 - non-steroidal drugs for short periods

Question 22

The 1st line treatments for RA are disease-modifying anti-rheumatic drugs (DMARDs). The core drug is methotrexate, but other drugs include sulfasalazine, hydroxychloroquineand leflunomide. If DMARDs are not successful patients can be prescribed Biologic Agents, such as anti-B, anti-T and anti-TNF-a. How many DMARDs do patients need to have tried prior to being prescribed Biologic Agents?

1 - can go straight to Biologic Agents
2 - >4 drugs
3 - >3 drugs
4 - >2 drugs

Answer 22

4 - >2 drugs

Question 23

Which of the following are are the major side effects of Disease Modifying Anti-Rheumatic Drugs?

1 - bone marrow suppression
2 - increased risk of infection
3 - liver dysfunction
4 - all of the above

Answer 23

4 - all of the above

Question 24

When should treatment for RA be started?

1 - as soon as the patient asks for it
2 - if the suspicion of RA is high
3 - clinical experience only
4 - immediately once the diagnosis is confirmed

Answer 24

4 - immediately once the diagnosis is confirmed

Question 25

If a patient presents to the GP with symptoms of RA, what is the time frame from when treatment should be started? 1 - 3 days 3 - 3 weeks 3 - 3 months 4 - 3 years

Answer 25

3 - 3 months

Question 26

Mycophenolate Mofetil is another DMARD that can be used to treat SLE. What is the mechanism of action of this drug? 1 - inhibition of COX1 and 2 2 - prevents T and B cell proliferation 3 - inhibits all WBCs 4 - all of the above

Answer 26

2 - prevents T and B cell proliferation Active metabolite of mycophenolate, mycophenolic acid, prevents T-cell and B-cell proliferation and the production of cytotoxic T-cells and antibodies Dose 500mg – 1500mg twice a day

Question 27

Mycophenolate Mofetil is another DMARD that can be used to treat SLE. Which of the following is NOT an adverse event of Mycophenolate Mofetil? 1 - Bone marrow suppression, 2 - GI upset 3 - Infections 4 - Lymphoproliferative diseases 5 - Seizures 6 - Pure Red cell aplasia

Answer 27

5 - Seizures

Question 28

Is Mycophenolate Mofetil safe in pregnancy and breastfeeding?

Answer 28

- no Planned 6 weeks after stopping the medication

Question 29

How often should Is Mycophenolate Mofetil be monitored by FBC to assess renal and liver function? 1 - weekly during first month 2 - fortnightly during second and third month 3 - monthly for the first year 4 - all of the above

Answer 29

4 - all of the above

Question 30

Azathioprine is another DMARD that can be used to treat SLE. Azathioprine reduces intracellular purine synthesis, which results in which of the following? 1 - decreased numbers of circulating B and T lymphocytes 2 - reduced immunoglobulin synthesis 3 - diminished interleukin (IL) 2 secretion 4 - all of the above

Answer 30

4 - all of the above

Question 31

Azathioprine can be haematologic toxicity due to AZA and 6-mercaptopurine (6-MP). What must be measured prior to using Azathioprine? 1 - pancreatic lipase 2 - thiopurine methyltransferase 3 - reductase 4 - RNA polymerase

Answer 31

2 - thiopurine methyltransferase -TPMT TPMT is an enzyme that breaks down (metabolizes) a class of drugs called thiopurines

Question 32

The starting dose of Azathioprine is 25 to 50 mg/day. How often should FBC be measured initially to assess for haematologic toxicity? 1 - daily 2 - weekly 2 - every 2 weeks 4 - monthly

Answer 32

2 - every 2 weeks Can increase the daily dose by 50 mg (or approximately 0.5 mg/kg/day) every four weeks to 1.5 mg/kg/day. Maximum of 3 mg/kg/day

Question 33

Which of the following is NOT an adverse effect of Azathioprine? 1 - GI upset 2 - anorexia 3 - eye inflammation  4 - myelosuppression 5 - infection

Answer 33

3 - eye inflammation myelosuppression = bone marrow suppression, both RBCs and WBCs

Question 34

All of the following drugs are safe in pregnancy, EXCEPT which one? 1 - Hydroxychloroquine 2 - Methotrexate 3 - Sulfasalazine 4 - Azathioprine 5 - Low dose steroids (5 – 15mg)

Answer 34

2 - Methotrexate

Question 35

Which of the following can be used selectively in pregnancy? 1 - Steroids 2 - NSAIDs 3 - TNF alpha inhibitors 4 - Ciclosporin 5 - Tacrolimus 6 - all of the above

Answer 35

6 - all of the above

Question 36

All of the following drugs should NOT be used in pregnancy, EXCEPT which one? 1 - Mycophenolate mofetil 2 - Leflunomide 3 - Hydroxychloroquine 4 - Methotrexate 5 - Cyclophosphamide

Answer 36

3 - Hydroxychloroquine