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Rheumatology > DMARDs > Flashcards

DMARDs Flashcards

1
Q

Name the conventional synthetic DMARDs (csDMARDs)

A

Methotrexate

Hydrochloroquine

Sulfosalazine

Leflunomide

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2
Q

What are the indications for methotrexate?

A

Rheumatoid arthritis

Tx of psoriasis that has not responded to topical, steroids or phototherapy

Psoriatic arthritis

Crohn’s disease

Ectopic pregnancies

Neoplastic disease

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3
Q

What is the pharmacodynamic of methotrexate?

A

Inhibits dihydrofolate reductase, essential for the synthesis of purines and pyrimidines (i.e., nucleotides)

This prevents cell division and leads to anti-inflammatory action

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4
Q

What is the pharmacokinetic of methotrexate?

A

Bioavailability = 64-90%

Protein binding = 46.5-54% plasma proteins

Half-life = 3-10 hours (low dose), 8-15 hours (high dose)

Metabolism = hepatic (via folylpolyglutamate synthase)

Excretion = kidney (via urine), some in bile (8.7-26%) with IV administration

N.B: methotrexate has a narrow therapeutic index and should not be taken everyday

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5
Q

What are the contraindications for methotrexate?

A

Acute infection

Pregnancy and breastfeeding

Ascites

Immunodeficiency syndrome

Significant pleural effusion

Severe hepatic impairment

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6
Q

What are the side-effects of IV/Oral methotrexate?

A

Anaemia

Liver cirrhosis

Decreased appetite

Pulmonary fibrosis

GI symptoms (i.e., vomiting, diarrhoea)

Nausea

Leucopenia/bone marrow disorders/agranulocytosis

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7
Q

What are the side-effects specific to IV methotrexate?

A

Necrotising demyelinating leukoencephalopathy

Neurotoxicity

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8
Q

According to NICE guidelines what monitoring should be done for patients with blood dyscrasias (i.e., any disorder of the blood e.g., leukaemia etc) or liver cirrhosis on low-dose methotrexate?

A

FBCs + Us&Es every 1-2 week until therapy is stabilised then every 2-3 months thereafter

Also patients should be advised to report all symptoms and signs suggestive of infection, especially sore throat

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9
Q

How is methotrexate monitoring done at the Royal Sussex?

A

Once a week for 6 weeks

Then once a month for 3 months

Then 3 monthly thereafter

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10
Q

What are the significant drug interactions for methotrexate?

A

Methotrexate + trimethoprim = depletion of folic

Methotrexate + PPIs = increased clearance of Methotrexate

Methotrexate + NSAIDs = increased risk of toxicity

Methotrexate + Phenoxymethylpenicillin/Piperacillin/Piroxicam/Pivmecillinam = increased risk of toxicity

Methotrexate + live vaccines (e.g., infleunza, MMR) = increased risk of generalised infection (possibly life threatening)

Methotrexate + Levetiracetam = decreased clearance of Methotrexate (this can cause toxicity as Methotrexate has a narrow therapeutic window)

Methotrexate + Nitrous oxide = increased risk of toxicity

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11
Q

What other supplement should be prescribe in conjunction with methotrexate and why?

A

Folic acid

Decreases mucousal and GI side-effects (no evidence it reduced haematological side effects)

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12
Q

When should methotrexate be withdrawn?

A

If the patient has:

ulcerative stomatitis

diarrhoea

Suggests GI toxicity

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13
Q

What drug may be required in acute methotrexate toxicity?

A

Folinic acid (as calcium folinate)

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14
Q

A patient has moderate-severe active rheumatoid arthritis. What dose of methotrexate would they be given?

A

7.5g once weekly

(max dose = 20mg)

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15
Q

A patient has severe active rheumatoid arthritis. What dose of methotrexate would they be given?

A

Initially 7.5mg

Then increase in steps of 2.5mg once weekly

Max 25mg per week

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16
Q

A patient has severe Crohn’s. What dose of methotrexate would they be given?

A

Initially 25mg once weekly until remission

Maintenance = 15mg once weekly

17
Q

What dose of methotrexate would be given for maintenance of remission of severe Crohn’s?

A

10-25mg once weekly

18
Q

A patient has severe psoriasis not responding to conventional treatments. What dose of methotrexate would they be given?

A

Initially 2.5–10 mg once weekly

Then increased in steps of 2.5–5 mg, adjusted according to response

dose to be adjusted at intervals of at least 1 week

19
Q

What is the usual dose of methotrexate for severe psoriasis not responsive to conventional treatment?

A

Usual dose 7.5–15 mg once weekly

Stop treatment if inadequate response after 3 months at the optimum dose

Maximum 30 mg per week.

20
Q

TRUE OR FALSE

Methotrexate is not licenced for use in severe Crohn’s disease

A

TRUE

21
Q

What investigations should you do before starting methotrexate?

A

Chest X-ray (look for latent TB)

Renal function

Liver function

22
Q

What are the indications for sulfasalazine?

A

Tx of acute attack of mild to moderate and severe UC

Maintenance of remission of mild to moderate and severe UC

Active Crohn’s disease

Active Rheumatoid arthritis (on expert advice)

23
Q

Sources for sulfasalazine

A

https://bnf.nice.org.uk/drugs/sulfasalazine/

https://go.drugbank.com/drugs/DB00795

https://en.wikipedia.org/wiki/Sulfasalazine

24
Q

A patient is being treated for an acute attack of mild to moderate and severe UC. What dose of sulfasalazine would they be given?

A

By mouth
1-2g QDS until remission occurs (corticosteroids may also be given if necessary)

By rectum
0.5-1g BD (given alone or with oral therapy, morning and night after a bowel movement)

25
Q

A patient is being treated for active Crohn’s. What dose of sulfasalazine would they be given?

A

By mouth
1-2g QDS until remission occurs (corticosteroids may also be given if necessary)

By rectum
0.5g-1g BD (can be given alone or with oral therapy, morning and night after bowel movement)

26
Q

What dose of sulfasalazine would be given for maintenance of remission of mild to moderate and severe UC?

A

By mouth
500mg QDS

By rectum
0.5-1g BD (given alone or with oral therapy, morning and night after a bowel movement)

27
Q

What dose of sulfasalazine would be given for Tx of active RA?

A

By mouth
Initially 500mg daily

Increased in steps of 500mg every week

Increased to 2-3g daily in divided doses

Enteric coated tablets to be administered

28
Q

What is the pharmacodynamic of sulfasalazine?

A

Anti-inflammatory

Broken down into 5-aminosalicylic acid (5-ASA) and sulfapyridine (SP) whose mechanism of action are still being studied

29
Q

What is the pharmacokinetic of sulfasalazine?

A

Bioavailability = <15%

Protein binding = not available

Half-life = 5-10 hours

Metabolism = colon by bacteria

Excretion = faeces (but majority of 5-ASA stays in the colonic lumen)

30
Q

What are the contraindications for sulfasalazine?

A

CAUTIONS include:
- acute porphyrias
- G6PD deficiency
- Hx of allergy
- Hx of asthma
- maintain adequate fluid intake
- risk of haematological toxicity
- risk of hepatic toxicity
- slow acetylator status

31
Q

What are the common/very common side-effects of sulfasalazine?

A

Insomnia

Stomatitis

Altered taste

Tinnitus

Urine abnormalities - can colour the urine

32
Q

What are the uncommon side-effects of sulfasalazine?

A

Face oedema

Seizure

Vasculitis

Vertigo

33
Q

What are the frequency unknown side-effects of sulfasalazine?

A

Hepatic failure

Anaemia

Decreased appetite

Ataxia

Cyanosis

Encephalopathy

Haematuria

Hallucination

Hypoprothrombinaemia

Lymphadenopathy

Macrocytosis

Aseptic meningitis

Methaemoglobinaemia

Nephrotic syndrome

Severe cutaneous adverse reactions (SCARs)

Smell disorders

SLE

Yellow discolouration of body fluids

34
Q

If haematological abnormalities occur usually in the first 3 to 6 months of treatment on sulfasalazine, what should you do?

A

Discontinue sulfasalazine

35
Q

What should you advice patients receiving aminosalicylates (which includes sulfasalazine) and their carers to report?

A

Any unexplained:
- bleeding
- bruising
- purpura
- sore throat
- fever
- malaise

that occurs during Tx

36
Q

What monitoring should be done for all patients on aminosalicylates (including sulfasalazine)?

A

Renal function

Before starting

At 3 months of Tx

Then annually during Tx

37
Q

What monitoring should be done for all patients on sulfasalazine?

A

Bloods
Close monitoring of FBC (inc. differential WCC and platelet count) initially

Then at monthly intervals during the 1st 3 months

Renal function
Although recommended by the manufacturer, evidence of practical value is unsatisfactory

LFTs
Should be done at monthly intervals for the 1st 3 months

38
Q

What are the significant drug interactions for sulfasalazine?

A

Sulfasalazine + darolutamide (new type of hormone therapy for men whose prostate cancer has stopped responding to other types of hormone therapy - an androgen receptor inhibitor) = increased exposure to Sulfasalazine

Sulfasalazine + tepotinib (kinase inhibitor used in treating small cell lung cancer) = could increase exposure to sulfasalazine

Sulfasalazine + voxilaprevir (reversible inhibitor of the NS3/4A protease an important protein in HCV) = increases [sulfasalazine]

Rheumatology (6 decks)

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