ARTHRITIS Flashcards by Maddie YEAR 3 & 4

First line analgesia for OA?

Step 1 - Topical NSAIDs
Step 2 - oral NSAIDs +/- PPI
Step 3 - weak opioids or paracetamol - infrequently or short-term

Adjuncts: topic capsaicin cream or intra-articular steroid injection

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how does topical capsaicin relieve pain?

Capsaicin is taken from chilli peppers
It works by reducing the amount of substance P associated with inflammation. It also defunctionalises nociceptor fibres by inducing a topical hypersensitivity reaction of the skin

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What is the MOA of NSAIDs?

Non-selectively inhibit COX 1 and COX 2
COX 2 inhibition decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling
COX1 inhibition leads to the SE

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Side efefcts of NSAIDs?

GI disturbance - indigestion + stomach ulcers
Renal insufficiency
Salt and water retention
Hyponatraemia and hyperkalaemia
cardiovascular events
Hypersensitivity reactions
Headaches
Dizziness
Skin reactions
Bronchospasm in asthmatics

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Why does the side effect profile of NSAIDs vary?

Different selectivity for COX-1 or COX-2

More side effects for those with greater inhibitory selectivity for COX-1 than COX-2

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What is an example of NSAIDs that have are selective for COX-2?

Celecoxib

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whats the problem with celecoxib?

It can increase the risk of serious cardiovascular problems because COX-1 pathway is not inhibited at all

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When prescribing NSAIDs, how can you attempt to reduce the GI side effects?

Use a COX-2 inhibitor e.g. celecoxib
Prescribe a PPI alongside

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Contra-indications for NSAIDs?

Active GI bleeding or ulcer
History of GI bleeds or GI perf related to previous NSAID therapy
History of recurrent GI haemorrhage or ulceration
History of hypersensitivity or severe allergic reaction
Severe HF
Severe hepatic impairment
Severe renal impairment
Third trimester of pregnancy
Varicella infection

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Why are NSAIDs contraindicated in the 3rd trimester of pregnancy?

May be associated with increased risk of oligohydramnios and premature closure of the ductus arteriosus

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Drug-drug interactions for NSAIDs?

Alendronate - risk of GI bleed
ACEi - increase bp, renal impairment risk, rarely hypokalaemia
Anticoagulants - worsen bleeding
SSRIs and SNRIs - risk of GI bleed
Antiplatelets - increase risk of GI bleed
Beta blockers - may reduce efficacy
Corticosteroids - GI bleed
Cisplatin - nephrotoxicity
Ciclosporin - reduce renal function
Lithium - can increase risk of toxicity
Loop and thiazide diuretics - may reduce Antihypertensive effects
Methotrexate - risk of toxicity
Nicorandil - GI bleed
Potassium sparing diretics - acute renal impairment

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Does a normal uric acid value rule out gout?

No - you can have drops in uric acid levels in acute flares of gout

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XR findings in pseudogout?

Chondrocalcinosis in the joint space

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Joint aspiration findings in gout?

Negatively birefringent, needle-shaped monosodium urate crystals
No mirobial growth

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What medications can increase the risk of gout?

Diuretics
Low dose aspirin
Immunosuppressants e.g. cyclosporin

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Management of an acute flare of gout?

NSAIDs or colchicine
(Continue the allopurinol if already taking it)

If both contraindicated then oral steroids can be considered

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Moa of colchicine?

Inhibits microtubule polymerization by binding to tubulin and interfering with mitosis of neutrophils = prevention of activation, migration and action of neutrophils within the joint space

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Side effects of colchicine?

GI disturbance - abdominal pain, diarrhoea, n&v
Blood disorders
GI haemorrhagic
Hepatic or renal impairment
Myopathy

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Contraindications of colchicine?

Blood diorders

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Interactions with colchicine?

The following drugs can increase toxicity risk due to CYP3A4 inhibition:
Macrolides
Antivirals
Antifungals
CCB
Grapefruit juice

Lipid lowering therapies e.g. simvastatin - increase risk of myopathy

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What is the length of the colchicine course?

500 micrograms 2-4 times a day until sympotms resolved (max 6mg per course)

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Lifestyle advice for a pt with gout?

Healthy, balanced diet - avoid food high in purines e.g. liver, seafood, oily fish
Reduce weight
Reduce alcohol consumption

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How soon after a gout attack would you repeat the uric acid blood test?

6 weeks later

Indication for urate-lowering therapy following an attack of gout?

All pt after their first attack

What urate-lowering therapy can be given following an attack od rout?

2 weeks after the acute attack… Start allopurinol

When should you not start allopurinol and why? What should you cover the drug with when first starting and why?

Dont start during an acute attack as it can case a transient rise in uric acid levels Ensure adequate fluid intake Cover with NSAIDs/colchicine when starting to prevent a flare

Side effects of allopurinol?

Rash Hypersensitivity reactions GI disturbances Blood disorders

Drug interactions for allopurinol?

Amoxicillin (rash) ACEi (leukopenia) Azathioprine (toxicity) Bendroflumethiazide (hypersensitivity) Warfarin (can increase the anticoagulant effect)

Why does azathioprine interact with allopurinol?

Inhibition of xanthine oxidase by allopurinol decreases the rate of conversion of azathioprine and mercaptopurine to inactive metabolites = the subsequent increased plasma concentration of active metabolites may lead to life-threatening leukopenia, thrombocytopenia or pancytopenia

Should you ever stop allopurinol following a gout attack?

No - should be on it for life but may be able to tailor the dose down

Examples of DMARDs?

Affect immune process: Methotrexate Hydroxychloroquine Ciclosporin Azathioprine Leflunomide Affect disease process: Gold Penicillamine Sulfazalazine Biological agents: Infliximab Etanercept Adalimumab Abatacept Rituximab

Moa of sulfasalazine?

not fully understood, it is thought to be mediated through the inhibition of various inflammatory molecules.19 Research have found that sulfasalazine and its metabolites, mesalazine and sulfapyridine, can inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathway

Side effects of sulfasalazine?

GI disturbances Orange secretions e.g. urine or may stain contact lenses Pnemonitis and lung fibrosis Pancreatitis Blood disorders - myelosuppression, Heinz body anaemia, Megaloblastic anaemia Hepato-renal toxicity Skin reactions e.g. Steven Johnson syndrome Reversible oligospermia

Contraindication for sulfasalazine?

A salicylate drug allergy e.g. aspirin G6PD deficiency

Examples of tumour necrosis factor inhibitors?

Infliximab Adalimumab Etanercept

Anti-CD20 agent?

Rituximab

Anti-IL1 therapy agent?

Anakinra

Anti-IL6 receptor agent?

Tocilizumab

T cell co-stimulator modulator agent?

Abetacerpt

Contraindications for infliximab?

Severe infections HF

Side efefcts of infliximab?

Hypersensitivity reactions HF and arrhythmias Skin disorders Lung problems GI disorders Blood disorders Infections - due to immunosuppression

Cautions for starting infliximab?

Malignancy Hep B Pregnancy TB Not up to date with vaccinations

Moa of methotrexate?

Dihydrofolate reductase enzyme inhibitor

Side efefcts of methotrexate?

GI disturbances Stomatitis - discontinue if this happens Myelosuppression Pulmonary, GI,m renal, liver toxicity Skin reactions Pneumonitis Pulmonary fibrosis

Contraindications for methotrexate?

Active infection Ascites and pleural effusion - will worsen this Liver disease & alcoholism Severe renal impairment Teratogenic in pregnancy - must be on contraception for 6 months after

Interactions for methotrexate?

NSAIDs - toxicity Trimethoprim and co-trimoxazole - can cause severe bone marrow depression

Considerations for methotrexate?

Avoid live vaccines Co-prescribe folic acid (not on the same day as methotrexate!) Contraception Pre-screening tests Monitoring requirements -

Monitoring requirements for methotrexate?

FBC, renal and liver tests every 1-2 weeks until therapy stabilised and then every 2-3 months Advise them to report any symptoms and signs of infection, esp a sore throat May require a pregnancy test pre starting Tx

When should treatment for RA be started?

ASAP - within 3 months of onset of persistent symptoms

Why might you need a short-term treatment with corticosteroid when starting a DMARD?

As DMARDs can take 2-3 months to take effect

How does pneumonitis secondary to methotrexate Tx present?

Within1 year of starting treatment… non-productive cough, dyspnoea, malaise, fever

Treatment of choice for methotrexate toxicity?

Folinic acid

What is sulfasalazine a pro-drug for?

5-ASA

Which DMARD is safe in pregnancy and breastfeeding?

Sulfasalazine

Management for RA?

DMARD monotherapy +/- a short-course of bridging prednisolone Most common methotrexate is used

How can you monitor the response to treatment in RA?

NICE recommends using a combination of CRP and disease activity (using a composite score such as DAS28) to assess response to treatment

How are flares of RA managed?

Oral or IM corticosteroids