ARTHRITIS Flashcards
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
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
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
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
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
What is an example of NSAIDs that have are selective for COX-2?
Celecoxib
whats the problem with celecoxib?
It can increase the risk of serious cardiovascular problems because COX-1 pathway is not inhibited at all
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
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
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
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
Does a normal uric acid value rule out gout?
No - you can have drops in uric acid levels in acute flares of gout
XR findings in pseudogout?
Chondrocalcinosis in the joint space
Joint aspiration findings in gout?
Negatively birefringent, needle-shaped monosodium urate crystals
No mirobial growth
What medications can increase the risk of gout?
Diuretics
Low dose aspirin
Immunosuppressants e.g. cyclosporin
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
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
Side effects of colchicine?
GI disturbance - abdominal pain, diarrhoea, n&v
Blood disorders
GI haemorrhagic
Hepatic or renal impairment
Myopathy
Contraindications of colchicine?
Blood diorders
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
What is the length of the colchicine course?
500 micrograms 2-4 times a day until sympotms resolved (max 6mg per course)
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
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
