Chapter 10: Musculoskeletal Flashcards
What is rheumatoid arthritis?
- Autoimmune disease where the immune system mistakenly attacks the synovium (lining of the joints)
- systemic
RA symptoms?
- joint pain and swelling
- usually affects the hands, feet and wrists
- stiffness is worse after periods of inactivity, especially in the morning, when it can be severe and last for more than thirty minutes.
RA treatment ?
- DMARDS (Disease Modifying Anti-Rheumatic Drugs)
- new diagnosis of RA: methotrexate + other dmard + temporary corticosteroid
DMARD treatment drugs?
- Oral methotrexate, leflunomide or sulfasalazine should be given first line
- hydroxychloroquine (weak conventional DMARD) is an alterntive in patients with mild RA or palindromic rheumatism
- dose should be titrated up to maximum tolerated effective dose
- TNF alpha inhibitors can also be used (e.g. adalimumab, inflixumab) when inadequate response to combination therapy
- rituximab in combo with methotrexate alternative option for severe RA
What is gold?
- sodium aurothiomalate: no longer commonly used in RA in practice due to availability of newer, more effective drugs
- same goes for azathioprine, ciclosporin and penicillamine
Pain relief in rheumatoid arthritis?
- short term use of NSAID or COX 2 inhibitor should be considered for additional control of pain and stiffness
- offered PPI to minimise GI side effects
- in patients already taking low dose aspirin, other treatments should be considered before NSAID
What is methotrexate?
- high risk drug
- anti-folate; inhibits the conversion of dihydrofolate (folic acid) to tetrahydrofolate needed to make purines and pyrimidines and therefore DNA; prevents cellular replication
*anti-folate drugs are teratogenic and cause blood dyscrasias
Methotrexate uses?
- RA
- cancer
- psoriasis
- crohn’s disease
Methotrexate dose?
- Once weekly (on same day each week)
- prescription must state: dose and frequency (Xmg weekly) and prescribe only one strength
What should be used alongside methotrexate to help reduce side effects?
- folic acid
Possible regimens:
- 5mg once weekly on day after methotrexate day (BNF)
- 5mg daily except on methotrexate day
- 1mg daily except on methotrexate day
Methotrexate missed doses?
- if >3days, take next scheduled dose on normal day
Methotrexate patient counselling?
- weekly dose and avoid OTC NSAIDs (risk of toxicity)
- annual flu vaccination (methotrexate causes immunosuppression)
- methotrexate treatment booklet
Methotrexate side effects?
BLOOD DYSCRASIAS
- low WBCs; susceptible to infection, report mouth ulcers, fever, malaise, sore throat
- low RBCs; anaemia, report extreme tiredness, pallor, dizziness
- low platelets; thrombocytopeonia, report bruising and bleeding easily
HEPATOTOXICITY
- report nausea, vomiting, dark urine, jaundice, abdominal pain (upper right), pruritus, malaise, pale coloured spots
NEPHROTOXICITY
- also renally excreted
PULMONARY TOXICITY
- report SOB, cough and fever
GI TOXICITY
- report stomatitis, first sign of GI toxicity (inflamed and sore mouth)
MTX-INDUCED SIDE EFFECTS/TOXICITY: Folinic acid residue
Methotrexate and contraception?
- TERATOGENIC
- effective contraception during and 3 months after; both men and women
Handling methotrexate?
- CYTOTOXIC
- pregnant women should avoid handling at all
What interacts with methotrexate to increase risk of blood disorders?
- phenytoin
- trimethoprim/co-trimoxazole (anti-folates)
- clozapine (neutropoenia)
What is the interaction between methotrexate and NSAIDs?
- reduces renal excretion (vasoconstriction of afferent renal arteriole) = methotrexate toxicity
What interacts with methotrexate to increase risk of hepatotoxicity?
- isotretinoin
- phenothiazine antipsychotics
- rifampicin
- ketoconazole
(hepatotoxic drugs)
What is osteoarthritis ?
- most common form of arthritis
- caused by wear and tear of joints
- tends to only affect individaul joints (not systemic)
- symptoms often occurs towards the end of the day, after using the affected joint
- Osteoarthritis can affect the lower parts of the spine, and the finger joints closest to the nailbeds, both of which are areas of the body rarely affected in RA
What is gout?
- gout is a condition that causes sudden severe pain, swelling and redness in the joints, caused by the accumulation of uric acid crystals forming in the joints
Gout drug causes?
(HYPERURICAEMIA)
- diuretics (loop and thiazides)
- ciclosporin, tacrolimus
- cytotoxics
- cancer
Gout treatment for acute attack?
- relive pain
- first line: NSAIDs e.g. diclofenac, naproxen
- *aspirin not indicated in gout
- alternative: colchine
- do not repeat course in 3 days
- max dose: 500mcg every 2-4 times a day
- max 6mg per dose
Gout treatment for prevention?
(correct hyperuricaemia)
XANTHINE OXIDASE INHIBITORS:
- first line: allopurinol
- second line: feboxustat, side effects: serious hypersensitivity reactions: anaphylaxis, SJS
URICOSURIC DRUGS
- sulfinapyrazone , side effects: makes urine alkaline, allows urea crystals to form, ensure adequate renal function and urine output
When shouldnt prevention treatment be started?
- never start during acute attack - wait 1-2 weeks after
- initiation may precipitate an acute attack: NSAID/colchine for 1 month after hyperuricaemia corrected
- if attack occurs during prophylaxis, continue as normal and treat attack separately
Allopurinol class and use?
- xanthine oxidase inhibitor
- first line in prophylaxis of gout
Allopurinol side effects?
- rashes (if mild re-introduce slowly, stop if it occurs again)
How to take allopurinol?
- take with or after food
Allopurinol interactions?
- reduce dose of mercaptopurine/azathioprine by 1/4-/12 with allopurinol (increased risk of toxicity)
What is myasthenia gravis and what is used for treatment?
- characterised by muscle weakness
- It most commonly affects the muscles that control the eyes and eyelids, facial expressions, chewing, swallowing and speaking. But it can affect most parts of the body
- anticholinesterases: neostigmine, pyridostgmine (first line in ocular)
- immunosuppressants: corticosteroids, azathioprine, methotrexate
What do anticholinesterase drugs do?
- they enhance neuromuscular transmission in voluntary and involuntary muscle in myasthenia gravis
- excessive dosage of these drugs can impair neuromuscular transmission and precipitate cholinergic crises by causing a depolarising block - may be difficult to distinguish from worsening myasthenic state
Anticholinesterase side effects?
- Muscarinic side effects: increased sweating, increased salivary and gastric secretions, increased GI and uterine motility, and bradycardia
- parasympathomimetic effects are antagonised by atropine sulfate
What is lambert-eaton mysathenic syndrome?
- rare disorder of neuromuscular transmission
- acetylcholine-release enhancers = amifampridine, fampridine used
What is used for nocturnal leg cramps?
quinine
What restricts use of quinine?
- sleep is regularly disturbed
- cramps are very painful or frequent
- treatable causes of cramps are excluded
- non-pharmacological treatments have not worked e.g. passive stretch exercises
Serious side effects to quinine?
- QT prolongation, convulsions, arrhythmias
- quinine is toxic in overdose
MHRA/CHM: reminder of dose-dependent QT-prolonging effects. Caution in patients with risk factors for QT prolongation or in those with atrioventricular block
Quinine monitoring?
- interrupt treatment every 3 months to assess further need
- may take up to 4 weeks for improvement
What is baclofen?
- GABA analogue; works at spinal level and depresses CNS
- used in chronic severe spasticity
Baclofen side effects?
- drowsiness, muscular hypotonia
Baclofen cautions?
- drowsiness - may affect driving
- withdrawal reations: hyperactive state, exacerbates muscle spasticity and precipitates autonomic dysfunction, hyperthermia, psychiatric reactions, convulsions
- avoid abrupt withdrawal; gradually reduce over at least 1-2 weeks
- intrathecal use: test dose, closely monitor, have resusitation immediately available and initiate within 3 months of test dose
What does intrathecal mean?
Intrathecal administration is a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF) and is useful in spinal anesthesia, chemotherapy, or pain management applications.
What other drugs can be used for spasticity?
- baclofen (skeletal muscle relaxants)
- cannabis
- tizanidine
- dantrolene
- diazepam
- methocarbamol
NSAID mechanism of action?
- inhibits COX enzymes involved in prostaglandin synthesis
- mild to moderate pain relief with first dose
- analgesic full effect takes one week
- anti-inflammatory effect takes 3 weeks
Non selective COX1/2 inhibitors?
- aspirin
- diclofenac
- etodolac
- ibuprofen
- indometacin (headache, GI disturbance, driving)
- mefenamic acid (haemolytic anaemia/diarrhoea)
- meloxicam
- naproxen: choice drug for inflammation
- piroxicam (high risk of GI side effects; must give PPI, serious skin reactions)
Selective COX-2 inhibitors?
- celecoxib
- etorocoxib
- parecoxib (post-op pain)
NSAIDs side effects?
- hypersensitivity: c/i’d if history of sensitivity to NSAIDs or aspirin; bronchospasms, rash, angioedema, hives and rhinitis
- photosensitivity with topical NSAIDS especially ketoprofin
- Take caution may worsen asthma; bronchospasms. c/i if history of asthma attack with NSAIDs
- nephrotoxicity: caution in renal impairment , NSAIDs reduce eGFR and are renally cleared. Temporarily stop on “sick days” = acute kidney injury
- sodium and fluid retention: caution in renal and liver impairment, CHF, hypertension
NSAIDs and GI toxicity?
- commonly causes stomach irritation: take with or after food
- GI bleeding/ulcers/perforation
- c/i’s:
- active Gi bleeding/ulcers
- piroxicam/ketoprofen/ketolorac = any history
- other non-selective NSAIDs > 2 episodes
- history of NSAID-induced ulcer/bleeding
- gastroprotection for high risk patietns e.g. elderley
Which NSAIDs have the highest risk of GI toxicity?
HIGHEST RISK
- ketoprofen, ketolorac, piroxicam
MIDDLE RISK
- naproxen, diclofenac, indometacin
LOW RISK
- ibuprofen
LOWEST RISK
- cox2 selective “coxibs”
CVD events and NSAIDs?
- small increased risk of thrombotic effects e.g. MI or stroke
- severe heart failure: all NSAIDs c/i’d
- Highest risk = high dose ibuprofen 2.4g daily, dexibuprofen, cox2 selective, diclofenac, acelofenac
- additional c/i’s
- ishaemic heart disease
- cerebrovascular disease
- peripheral arterial disease
- mild to severe heart failure
- left ventricular dysfunction
- hypertension
- patients with oedema for any other reason may precipitate CHF
NSAIDs and pregnancy?
AVOID
- especially in third trimester
- delays labour
- causes pulmonary hypertension in new-born child
- premature closure of foetal ductus arteriosus
NSAID interactions that increase risk of acute kidney injury?
- ACE inhibitors
- ciclosporin
- tacrolimus
- diuretics
NSAID interactions that increase risk of bleeding?
- warfarin (displaced by NSAID; higher free-drug concentrations)
- NOACs
- antiplatelets
- low dose aspirin
- heparin
- SSRI
- venlafaxine
- steroid
NSAID interaction that reduces renal excretion = increased risk of toxicity?
- methotrexate
- lithium
NSAID interaction that increases risk of hyperkalaemia?
- potassium sparing diuretics
NSAID interaction that increases risk of convulsions?
- quinolones
What is extravasation?
- extravasation injury follows leakage of drugs or IV fluids from the veins or inadvertent administration into the subcut or subdermal tissue
- must be dealt with promptly to avoid tissue necrosis
Extravasation prevention?
- drugs likely to cause injury should be given through a central line and patients receiving repeated doses of hazardous drugs should preferably have the cannula resited at regular intervals
- placing a GTN patch distal to the cannula may improve patency of the vessel in patients with small veins or veins prone to collapse
Extravasation management?
- infusion should be stopped immediately but cannula should not be removed until after an attempt has been made to aspirate the area
- corticosteroids used to reduce inflammation
- antihistamines may be used for symptom relief
