BNF - Chapter 10 - Musculoskeletal System Flashcards
What is used for pain relief in osteoarthritis?
Simple analgesics such as paracetamol or topical NSAID (particularly for hand or knee involvement) is first-line treatment
What if treatment with simple analgesic is ineffective?
Then consider oral NSAID when required (topical NSAID use should be discontinued), or a weak opioid analgesic (such as codeine phosphate) when required or topical Capsaicin 0.0025%, particularly in the knee or hand osteoarthritis
What about in patients with osteoarthritis who are taking low-dose aspirin?
In these patients, other analgesic treatment options should be considered before using a NSAID
What can be considered for relief of moderate to severe pain associated with osteoarthiritis?
Intra-articular corticosteroid injections
What are some non-drug measures for osteoarthriris?
Weight reduction (in overweight or obese patients) and exercise including local muscle strengthening and aerobic exercise, should also be encouraged
Are Glucosamine containing products recommended for osteoarthrirtis?
No - Glucosamine, chondroitin, and topical rubefacients (which may contain nicotinate compounds, salicylate compounds, essential oils, and camphor) are not recommended for the treatment of osteoarthritis
What is rheumatoid arthritis?
It is an autoimmmune disease where the immune system mistakenly attacks the synovium (lining of the joints)
What are the symptoms of RA?
Joint pain and swelling, usually affects hands, feet an wrists
What does DMARDs stand for?
Disease modifying anti-rheumatic drugs
Which DMARDs are used in Arthritis?
Sulfasalzine (blood dyscrasis, colours bodily secretions orange/yellow)
Penicillamine (Blood dyscrasis)
Gold (Blood Dyscrasis)
Which anti-malarial is considered a DMARD?
Hydroxychloroquine/ Chloroquine (Screening for ocular toxicity)
Which DMARDs are used which affect the immune response? (they all cause blood dyscrasis)
- Methotrexate
- Azathioprine
- Ciclosporin (nephrotoxic)
- Leflunamide (hepatoxic, Effective contraception for 2 years after treatment for women and 3 months after treatment for men)
- Cyclophosphamide (cytotoxic drug, urothelial toxicity i.e. haemorrhagic cystitis and permanent male sterility)
List the Cytokine modulators - DMARDS?
- Infliximab
- Etanercept
(Blood dyscrasis, report symptoms of tuberculosis e.g. persistent cough, weight loss and fever)
With which drugs if given with methotrexate can increase the risk of hepatoxicity?
- Isotretinoin
- Phenothiazine antipsychotics
- Rifampicin
- Ketoconazole
All are hepatoxic drugs
What is the treatment for juvenile idiopathic arthritis?
Methotrexate is effective;
Sulfasalazine is an alternative (unlicensed)
What type of immunosuppressant is etanercept?
Tumour necrosis factor alpha(TNF-alpha) inhibitor
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
BNF - Gout is a common form of inflammatory arthritis characterised by raised uric acid concentration in the blood (hyperuricaemia) and the deposition of urate crystals in joints and other tissues.
Which drugs can cause hyperuricaemia?
- Diuretics (loop and thiazides)
- Ciclosporin, Tacrolimus
- Cytotoxic
- Cancer
The management of gout under what age requires specialist supervision?
Under the age of 30
What are acute attacks of gout treated with?
With either colchicine or high doses of an NSAID (excluding aspirin)
What should be co-prescribed in patients prescribed an NSAID?
A gastro-protective drug (such as a proton pump-inhibitor)
What is the use of colchicine limited by?
By the development of toxicity at higher doses;
However, unlike NSAIDs it does not induce fluid retention, moreover it can be co-administered with anticoagulants
What can be considered in those who cannot tolerate NSAIDs or colchicine and when intra-articular injection is not suitable for acute attack of gout?
A short course of oral corticosteroid
For long-term control of gout, the formation of uric acid from purines may be reduced with which drugs?
xanthine-oxidase inhibitors
- allopurinol or febuxostat
Which is recommended as first-line urate-lowering therapy?
Allopurinol where renal function allows;
Febuxostat can be used as an alternative when allopurinol is contra-indicated or not tolerated
If an acute attack develops during urate-lowering therapy long term therapy, what should happen to the urate-lowering therapy?
the urate-lowering therapy should continue at the same dosage and the acute attack treated separately.
What is the instruction directions for gout?
Max dose - 500micrograms 2-4 times a day
Max 6mg per course
Do not repeat course within 3 days
What should be noted about starting a prevention treatment (urate-lowering therapy) for gout?
Never start during an acute attack - start preventative treatment 1-2 weeks after an acute attack
Initiation may precipitate an acute attack - may need to continue colchicine for up to 6 months
What side effect with allopurinol should you look out for?
Rash - if mild reintroduce slowly. Stop if it occurs again
How should you take allopurinol?
With or after food
What should you do if allopurinol is given with mercaptopurine/ azathioprine?
Reduce dose of mercaptopurine/ azathioprine (half the dose) - increased risk of toxicity
What has been reported with febuxostat?
rare but serious reports of hypersensitivity reactions, including Steven’s-Johnson syndrome and acute anaphylactic shock
What is myasthenia gravis (MG)?
It is a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles.
Myasthenia gravis affects the voluntary muscles of the body, especially those that control the eyes, mouth, throat and limbs
What is used first line for treatment in ocular myasthenia gravis as an adjunct to immunosuppressant therapy for generalised myasthenia gravis?
Anticholinesterases (Drugs that enhance neuromuscular transmission)
When anticholinesterases do not control symptoms completely then which drugs are used next?
Corticosteroids are used when anticholinesterases do not control symptoms completely. A second line immunosuppressant such as azathioprine is frequently used to reduce the dose of corticosteroid.
Excessive dosage of anticholinsterase can cause what?
Can impair neuromuscular transmission and precipitate cholinergic crises by causing a depolarising block
This may make it difficult to distinguish from a worsening myasthenic state
What are the Muscarinic side effects of anticholinesterases?
- increased sweating
- increased salivary and gastric secretions
- increased gastro-intestinal and uterine motility
- bradycardia
These parasympathomimetic effects are antagonised by which drug?
By atropine sulfate
Which anticholinesterase can be used for myasthenia gravis?
Neostigmine
How long does neostigmine produce its therapeutic effect for?
For up to 4 hours
Why is the pronounced muscarinic action of neostigmine a disadvanatge?
Its pronounced muscarinic action is a disadvantage, and simultaneous administration of an antimuscarinic drug such as atropine sulfate or propantheline bromide may be required to prevent colic, excessive salivation, or diarrhoea
In severe disease, neostigmine can be given how often?
every 2 hours
What is the maximum daily dose of neostigmine that patients can tolerate?
180mg daily
Compare neostigmine to pyridostigmine bromide in terms of onset of action and duration of action?
Pyridostigmine bromide is less powerful and slower in action than neostigmine but it has a longer duration of action
Why is pyridostigmine preferred over neostigmine?
It is preferable to neostigmine because of its smoother action and the need for less frequent dosage.
It is particularly preferred in patients whose muscles are weak on waking
It has a comparatively mild gastrointestinal effect but an antimuscarinic drug may still be required.
When corticosteroids are used for myasthenia gravis is it given daily?
Commonly given on alternate days
In generalised myasthenia gravis which corticosteroid is used?
Prednisolone is given alone
How many patients may experience a transient but very serious worsening of symptoms in the first 2-3 weeks, especially if the corticosteroid is started at a high dose?
About 10%
Is larger or smaller doses required in ocular myasthenia gravis?
Smaller doses of corticosteroids
In generalised myasthenia gravis which drug is usually started at the same time as the corticosteroid which allows a lower maintenance dose of the corticosteroid to be used?
Azathioprine
What are skeletal muscle relaxants used for?
They are used for the relief of chronic muscle spasm or spasticity associated with multiliple sclerosis or other neurological damage; they are not indicated for spasm associated with minor injuries
Which skeletal muscle relaxants act principillay on the central nervous system?
- Baclofen
- Diazepam
- Tizanidine
What about dantrolene?
Peripheral site of action
Where does cannabis extract act?
both central and a peripeheral action
What is the major disadvantage of treatment with these drugs?
The reduction in muscle tone can cause a loss of splinting action of the spastic leg and trunk and sometimes lead to an increase in disability
What does baclofen inhibit?
Baclofen inhibits transmission at spinal level and also depresses the central nervous system. The dose should be increased slowly to avoid the major side-effects of sedation and muscular hypotonia (other adverse events are uncommon).
Does dantrolene sodium cause alot of Central adverse effects?
No - Dantrolene sodium acts directly on skeletal muscle and produces fewer central adverse effects making it a drug of choice. The dose should be increased slowly.
What drug class does tizanidine belong to?
It is an alpha2-adrenoceptor agonist indicated for spasticity associated with multiple sclerosis or spinal cord injury
When can cannabis extract be tried?
Cannabis extract can be trialled as an adjunct treatment for moderate to severe spasticity in multiple sclerosis if other pharmacological treatments are not effective. Treatment must be initiated and supervised by a specialist.
Has the clinical efficiacy of methocarbamol and meprobamate as a muscle relaxant been established?
No not well established
What drug class does riluzole belong to?
It is a neuroprotective drug - used to extend life in patients with amyotrophic lateral sclerosis
What is the MAO of anticholinesterases?
They prolong the action of acetylcholine by inhibiting the action of the enzyme acetylcholinesterase
which drug may be used to reduce the frequency of nocturnal leg cramps?
Quinine salts such as quinine sulfate
Can quinine be used for routine treatment?
because of potential toxicity, quinine is not recommended for routine treatment and should not be used unless cramps cause regular disruption to sleep
Quinine should only be considered when cramps are very painful or frequent, when other treatable causes of cramp have been excluded, and when non-pharmacological treatments have not worked (e.g. passive stretching exercises).
How many weeks may it take to see benefit of quinine?
Up to 4 weeks; if there is benefit then quinine treatment can be continued
Which drugs are used for Lambert-eaton myasthenic syndrome (a rare disorder of neuromuscular transmission)?
Amifampridine
Fampridine
What are the serious side effects of quinine?
- QT prolongation
- Convulsions
- Arrhythmias
Quinine is toxic in overdose
Dose dependent QT prolonging effects - caution in patients with risk factors for QT prolongation or in those with atrioventricular block
Where does baclofen work?
It is a GABA analogue - works at spinal level and depresses CNS
What are some side effects of baclofen?
- Drowsiness,
- Muscular hypotonia
Avoid abrupt wothdrawl, can exacerbate muscle spasticity
What should be noted about intrathecal use of baclofen?
Test dose
Closely monitor
Have resucitation immediately available and intitiate within 3 months of test dose
What is sciatica?
Sciatica (radicular pain or radiculopathy) is neuropathic leg pain secondary to compressive lumbosacral nerve root pathology. Sciatica can also be present in about 5–10% of individuals with non-specific back pain, and where they coexist, the symptoms of sciatica tend to predominate.
What is the non-drug management of back pain and sciatica?
Exercise programmes, manual therapy (spinal manipulation, mobilisation, or soft-tissue techniques such as massage), and psychological therapies should be considered for managing low back pain with or without sciatica.
Spinal decompression may be considered in patients with sciatica when pain and function has not improved with non-surgical treatment (including drug treatment).
What is first line drug for managing acute back pain?
An oral NSAID
What if NSAID is CI, not tolerated or ineffective?
A weak opioid, either alone or with paracetamol, can be used to manage acute low back pain only if an NSAID is contra-indicated, not tolerated or ineffective
Is paracetamol alone effective in managing low back pain?
No - so paracetamol alone is not effective for managing back pain
Which drugs should not be offered for managing low back pain?
Selective serotonin re-uptake inhibitors (SSRIs), serotonin and noradrenaline re-uptake inhibitors (SNRIs), tricyclic antidepressants, gabapentinoids, and antiepileptic drugs
In osteoarthritis which is preferred, NSAID or paracetamol?
although paracetamol often gives adequate pain control in osteoarthritis, NSAIDs are more appropriate than paracetamol or the opioid analgesics in the inflammatory arthritides (e.g. rheumatoid arthritis) and in some cases of advanced osteoarthritis.
but paracetamol is preferred, particularly in the elderly.
Is there much difference in anti-inflammatory activity between NSAIDs?
No
Pain relief starts soon after taking the first dose of NSAID but how long will the full analgesic effect normally take?
Should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks.
How do NSAIDs work?
They work by recuding the production of prostaglandins by inhibiting the enzyme cyclo-oxygenase.
What do enzymes vary in (site of action)?
They vary in their selectivity for inhibiting different types of cyclo-oxygenase; selective inhibition of cyclo-oxygenase-2 (COX-2) is associated with less gastro-intestinal intolerance
Does ibuprofen have antipyretic properties?
Yes as well as anti-inflammatory and analgesic effect
Is Ibuprofen a selective or non-selective NSAID?
A non-selective
It has fewer side effects than other non-selective NSAIDs but it’s anti-inflammatory properties are weaker
Does ibuprofen or naproxen have more incidence of side effects?
Naproxen
Which is more effective, Flurbiprofen or naproxen?
Flubiprofen
What is etodolac licensed for?
the symptomatic relief of osteoarthritis and rheumatoid arthritis
What side effects may be associated with indometacin?
- Headaches, dizziness and GI disturbances
Does mefenamic acid have a high or low anti-inflammatory
Minor anti-inflammatory properties
associated with diarrhoea and haemolytic anaemia which require discontinuation of treatment
Compare piroxicam to naproxen?
Piroxicam is as effective as naproxen and has a long duration of action which permits once-daily administration. However, it has more gastro-intestinal side-effects than most other NSAIDs, and is associated with more frequent serious skin reactions.
Which NSAIDs are licensed for the short-term management of post-operative pain?
- Ketorolac trometamol
- Selective COX-2 inhibitor - Parecoxib
Which other NSAIDs are COX-2 selective?
- Etoricoxib
- Celecoxib
Do selective Cox-2 inhibitors cause more or less GI side effects?
Although selective inhibitors can cause serious gastro-intestinal events, available evidence appears to indicate that the risk of serious upper gastro-intestinal events is lower with selective inhibitors compared to non-selective NSAIDs; this advantage may be lost in patients who require concomitant low-dose aspirin.
Which COx-2 inhibitor is licensed for the relief of pain from acute gout?
Etorixocib
Which NSAIDs are used for dental pain?
- Ibuprofen
- Diclofenac sodium and diclofenac potassium
What is the risk of anticoagulant plus NSAID?
with a vitamin K antagonist, direct thrombin inhibitor or factor Xa inhibitor in combination (risk of major gastrointestinal bleeding);
What is the risk of NSAID with concurrent antiplatelet agent without proton pump inhibtor (PPI)?
(increased risk of peptic ulcer disease);
What’s the risk of corticosteroids with NSAID without PPI prophylaxis?
Increased risk of peptic ulcer disease
What is the risk of NSAID with an eGFR less than 50ml/min/1.73m2?
Risk of deterioration in renal function
What is the risk of NSAID in severe hypertension or severe heart failure?
Risk of exacerbation
What is the link between NSAID and CVD events?
All NSAID use (including COX-2 selective inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke) independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those receiving high doses long term.
What is a disadvantage of COX-2 selective NSAID?
concurrent cardiovascular disease (increased risk of myocardial infarction and stroke).
Which NSAIDs have a greater risk of thrombotic events?
COX-2 selective inhibitors
Ibuprofen (2.4g daily)
Diclofenac (150mg daily)
Naproxen (1 g daily) is associated with a lower thrombotic risk, and low doses of ibuprofen (1.2 g daily or less) have not been associated with an increased risk of myocardial infarction.
Which non-selective NSAIDs are associated with the greatest risk of GI events?
piroxicam, ketoprofen, and ketorolac trometamol are associated with the highest risk;
Which non-selective NSAID have a intermediate risk of GI side effects?
indometacin, diclofenac, and naproxen are associated with intermediate risk,
Which non-selective NSAID has the lowest risk of GI side effects?
Ibuprofen
What are the recommendations to reduce risk with NSAIDs?
Recommendations are that NSAIDs associated with a low risk e.g. ibuprofen are generally preferred, to start at the lowest recommended dose and not to use more than one oral NSAID at a time.
What’s the risk of taking alcohol with NSAIDs?
Alcohol increases the risk of gastro-intestinal haemorrhage associated with NSAIDs.
Specialist sources recommend that concurrent use need not be avoided with moderate alcohol intake, but greater caution is warranted in those who drink more than the recommended daily limits.
List all the non-selective NSAIDs (COX-1/COX-2)?
Aspirin Ibuprofen Indometacin (headache, GI disturbance, dizziness, driving caution) Aceclofenac Acemetacin Dexibuprofen Dexketoprofen Etodolac Fenoprofen Flurbiprofen Ketoprofen Mefenamic acid (Haemolytic, anaemia/ diarrhoea) Meloxicam Nabumetone Naproxen (choice of drug for inflammation) Piroxicam (highest risk of GI side effects; serious skin reactions) Phenybutazone (haematologicak reactions) Sulindac Tenoxicam Tiaprofenamic acid (severe cystitis)
List the selective COX-2 inhibitors?
Celecoxib
Etorocoxib
Parecoxib (post-operative pain)
What is the caution with NSAID in asthmatics?
- Take caution may worsen asthma; bronchospasms;
- Contraindicated if history of asthma attack with NSAIDs
When are NSAIDs contraindicated?
If history of sensitivity to NSAIDs or Aspirin; bronchospasm, rash, angiodema, hives and rhinitis
With which NSAID would there be photosensitivity with topical NSAIDs?
Ketoprofen
Are NSAIDs nephrotoxic?
Yes - take caution in renal impairment
NSAIDs reduce eGFR and are renally cleared.
When would you temporarily stop NSAIDs?
Stop on ‘sick days’ = acute kidney injury
What retention does NSAIDs cause?
Sodium and fluid retention
Hyperkalaemia
caution in renal and liver impairment, congestive heart failure, hypertension
What counselling should you give with NSAID to reduce GI side effects?
Take with or after food
With which NSAIDs is any even one history of GI bleed mean it is contraindicated?
- Piroxicam
- Ketoprofen
- Ketolorac
= Any history
What about the other non-selective NSAID?
2 or more episodes of GI bleed means contraindicated
Which patients are at highest risk of GI bleed with NSAID?
Elderly patients
Which NSAIDs have the highest risk of GI effects?
- Piroxicam
- Ketoprofen
- Ketolorac
Which NSAID have middle risk of GI effects?
Naproxen
Diclofenac
Indometacin
Which NSAID has the low GI effects?
Ibuprofen
Which class of NSAIDs have the lowest risk of GI effects?
COX-2 selective NSAIDs
‘Coxibs’
Are all NSAIDs contraindicated in severe heart failure?
Yes
Which NSAIDs have the highest risk of GI side effects?
Ibuprofen 2.4g daily Dexibuprofen, COX-2 selective Diclofenac Acelcofenac
What are additional contra-indications of NSAIDs?
- Ischaemic heart disease
- Cerebrovascular disease
- Peripheral arterial disease
- Mild to moderate heart failure for some NSAIDs
- Left ventricular dysfunction
- uncontrolled hypertension
- Patients with oedema for any other reason; may precipitate congestive heart failure
- Patients with risk factors for CVD events
Are NSAIDs safe in pregnancy?
AVOID
Especially in the third trimester:
-delays labour
- Causes pulmonary hypertension in new born child
- Premature closure of foetal ductus arteriosus
NSAID interactions -increased risk of acute kidney injury with which drugs?
- ACE inhibitors
- Ciclosporin
- Tacrolimus
- Diuretics
NSAID interactions- increased risk of bleeding with which drugs?
- Warfarin (displaced by NSAID, higher free drug concentrations)
- NOACs (apixaban, dabigatran, edoxaban, rivaroxaban)
- antiplatelet
- low-dose aspirin
- Heparin
- SSRI
- Venlafaxine
- Corticosteroids
NSAID interactions - reduced renal excretion with which drugs?
- Methotrexate
- Lithium
Reduced renal excretion = increased risk of toxicity
NSAID interactions - increased risk of hyperkalaemia with which drugs?
Potassium sparing diuretics
ACE inhibitors
NSAID interactions - increased risk of convulsions with which drugs?
Quinolones
What are the symptoms of ibuprofen overdose?
nausea and vomiting,
epigastric pain,
tinnitus but more serious toxicity is uncommon
What is the antidote to ibuprofen?
Charcoal, activated followed by symptomatic measures are indicated if more than 100mg/kg has been ingested within the preceding hour
Piroxicam dose should not exceed daily what mg?
20mg daily max
With which NSAID has there been an association in risk of causing severe cystitis?
Tiaprofenic acid
should not be given to patients with urinary-tract disorders and should be stopped if urinary symptoms develop (such as increased frequency, noctunria, urgency, pain on urinating or blood in urine.
Polymyalgia rheumatica giant cell (temporal) arteritis are always treated what?
With corticosteroids
Relapse is common if therapy is stopped prematurely
Are corticosteroids injections given locally?
Corticosteroids are injected locally for an anti-inflammatory effect
In inflammatory conditions of the joints particularly in RA, how are corticosteroid injections given?
By intra-articular injection to relieve pain, increase mobility and reduce deformity in one or a few joints
In tendinitis, corticosteroid injections should be made into where?
into the tendon sheath and not directly into the tendon (due to the absence of a true tendon sheath and a high risk of rupture, the Achilles tendon should not be injected).
Each joint should not be treated more than how many times a year?
Each joint should not be treated more than 4 times a year
What is extravasation?
Extravasation injury follows leakage of drugs or intravenous fluids from the veins or inadvertent administration into the subcutaneous or subdermal tissue. It must be dealt with promptly to prevent tissue necrosis.
Which preparations can cause extravasation?
Acidic or alkaline preparations and those with an osmolarity greater than that of plasma can cause extravasation injury;
excipients including alcohol and polyethylene glycol have also been implicated.
Cytotoxic drugs commonly cause extravasation injury
Which patients may suffer more from extravasation?
certain patients such as the very young and the elderly are at increased risk. Those receiving anticoagulants are more likely to lose blood into surrounding tissues if extravasation occurs, while those receiving sedatives or analgesics may not notice the early signs or symptoms of extravasation.
How can you avoid extravasation?
Precautions should be taken to avoid extravasation; ideally, drugs likely to cause extravasation injury should be given through a central line and patients receiving repeated doses of hazardous drugs peripherally should have the cannula resited at regular intervals
What patch can improve the patency of the vessel in patients with small veins?
Placing a glyceryl trinitrate patch distal to the cannula may improve the patency of the vessel in patients with small veins or in those whose veins are prone to collapse.
What signs of extravasation should patients report immediately?
Patients should be asked to report any pain or burning at the site of injection immediately
What is collagenase?
Collagenases are proteolytic enzymes that are derived from the fermentation of Clostridium histolyticum and have the ability to break down collagen.
What is hyaluronidase used for in soft-tissue disorders?
Hyaluronidase is used to render the tissues more readily permeable to injected fluids, e.g. for introduction of fluids by subcutaneous infusion (termed hypodermoclysis).
