MSK Flashcards
Non-Steroidal Anti-inflammatory Drugs - Examples
Naproxen (low risk of CV events)
Ibuprofen (lowest GI effects)
Etoricoxib
NSAIDs - Indications
1) Mild-to-moderate pain
(alternate to paracetamol or in addition)
2) Pain related to inflammation
- Rheumatoid arthritis, severe osteoarthritis, acute gout
NSAIDs- MOA
- NSAIDs inhibit prostaglandin synthesis from arachidonic acid by inhibiting cyclo-oxygenase (COX).
COX exists as two main isoforms:
- COX-1 is the constitutive form. It stimulates prostaglandin synthesis that is essential to preserve integrity of the gastric mucosa; maintains renal perfusion (by dilating afferent glomerular arterioles) + inhibits thrombus formation at the vascular endothelium.
- COX-2 is the inducible form, expressed in response to inflammatory stimuli. It stimulates production of prostaglandins that cause inflammation and pain.
- The therapeutic benefits of NSAIDs are principally mediated by COX-2 inhibition and adverse effects by COX-1 inhibition, although there is some overlap between the two. - Selective COX-2 inhibitors (e.g. etoricoxib) were developed in an effort to reduce the adverse gastrointestinal effects of NSAIDs.
NSAIDs - Contraindications
- Severe renal impairment
- Heart failure
- Liver failure
- NSAID hypersensitivity
NSAIDs- Caution
- Peptic ulcer disease
- GI bleeding
- CV disease
- Renal impairment
NSAIDs - Interactions
Peptic ulceration:
- Low dose aspirin & corticosteroids
GI bleeding:
- Anticoagulant - warfarin, DOAC
- SSRIs - venlafaxine
Renal Impairment:
- ACEi
- Diuretics
NSAIDs - Prescription
- Taken orally, there also topical gels, suppositories, injectable
- Dose dependent on condition, patient choice, safety considerations
NSAIDs - Monitoring
- Assess efficacy by enquiring about symptoms
- Monitor renal function in patients with renal impairment
NSAIDs - Patient Education
- Help improve symptoms of pain, swelling and fever
Most common SE is indigestion –> seek help - Long term use is not recommended, stop if acutely unwell or dehydrated to reduce risk of damage to kidneys.
NSAIDs - Adverse Effects
- GI toxicity
- Renal impairment
- Increased risk cardiovascular events
- Hypersensitivity reaction (bronchospasm & angioedema & fluid retention)
Bisphosphonates - Examples
- Alendronic acid
- Disodium pamidronate
- Zolendronic acid
Bisphosphonates - Indications
1) 1st line for osteoporotic fragility fractures
2) Severe hypercalcaemia of malignancy –> Pamidronate & zolendronic
3) Myeloma & breast cancer with bone metastases
4) 1st line for metabolically active Paget’s disease (reduce bone turnover & pain)
Bisphosphonates - MOA
- Bisphosphonates reduce bone turnover by inhibiting the action of osteoclasts, the cells responsible for bone resorption.
- Bisphosphonates have a similar structure to naturally occurring pyrophosphate: hence they are readily incorporated into bone.
- As bone is resorbed, bisphosphonates accumulate in osteoclasts, where they inhibit activity and promote apoptosis.
- The net effect is reduction in bone loss and improvement in bone mass.
Bisphosphonates - Adverse Effects
Common:
- Oesophagitis (oral intake)
- Hypophosphateamia
Rare:
- Osteonecrosis of the jaw
- Atypical femoral fracture
Bisphosphonates - Contraindications
- Severe renal impairement (Bisphosphonates are renally excreted)
- Hypocalcaemia
- Oral administration in people with active upper GI disorders
Bisphosphonates - Caution
- Smokers
- Dental disease
Bisphosphonates - Interactions
Bisphosphonates bind calcium. Their absorption is therefore reduced if taken with: - calcium salts (including milk) - antacids - iron salts
Bisphosphonates - Prescribing
For osteporosis:
- alendronic acid - oral intake
For severe hypercalcaemia & bone metastases:
- pamidronate or zolendronic acid - slow IV infusion
Bisphosphonates - Monitoring
Osteoporosis :
- check & replace calcium & vit D before treatment
- DEXA scan every 1-2 years to check bone density
Enquire about symptoms _ bone pain & complications
Safety net about oesophagitis, osteonecrosis of the jaw, atypical femoral fracture.
Monitor calicum & phosphate
Bisphosphonates - Patient Education
- Taken whole at least 30 mins before breakfast & plenty of water
- Remain upright for 30 mins after taking to reduce GI irritation
Allopurinol - Indications
1) To prevent recurrent attacks of gout.
2) To prevent uric acid and calcium oxalate renal stones.
3) To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy.
Allopurinol - MOA
- Allopurinol is a xanthine oxidase inhibitor.
- Xanthine oxidase metabolises xanthine (produced from purines) to uric acid.
- Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys.
Allopurinol - Adverse Effects
Can trigger or worsen an acute attack of gout.
- can avoid this by co-prescription with NSAID or colchicine
Common:
- skin rash –> mild or more serious hypersensitivity reaction e.g. Stevens-Johnson syndrome or toxic epidermal necrolysis
Rare:
- Allopurinol hypersensitivity syndrome –> e.g. fever, eosinophilia, lymphadenopath
Allopurinol - Contraindications
- During acute attack of gout
- Recurrent skin rash
- Signs of more severe hypersensitivity to allopurinol
Allopurinol - Caution
Lower dose for:
- renal impairment
- hepatic impairment
Allopurinol - Interactions
- The active metabolite (mercaptopurine) of the pro-drug ▴azathioprine is metabolised by xanthine oxidase. Concurrent administration increases the risk of toxicity.
- Co-prescription of allopurinol with ▴ACE inhibitors or thiazides increases the risk of hypersensitivity reactions
- With amoxicillin increases the risk of skin rash.
Allopurinol - Prescribing
- Orally : start low dose and titrate according to serum uric acid conc
- For gout: prescribe with NSAID or colchicine for at least 1 month to avoid triggering acute attack (when initiating)
Allopurinol - Monitoring
- Serum acid concentration - 4 weeks after intiation or change in dose
- Lower uric acid conc to > 300 µmol/L
- Stop if there is a rash
- Mild rash - reintroduced cautiously once rah resolves
Allopurinol - Patient Education
- Taken after meals, maintain good hydration with fluid intake
- Purpose is to reduce attack of gout
- Safety net: seek medical advise if they develop a rash
- Do not stop if they get an acute attack of gout- can make it worse
Colchicine - Indications
1) Acute Gout
2) Short-term prophylaxis during initial therapy with allopurinol
3) Prevent flare-ups of symptoms of familial Mediterranean fever (FMF) – an inherited inflammatory condition
Colchicine - MOA
For gout, colchicine works by reducing the inflammation caused by crystals of uric acid in your joints. This also helps to reduce pain.
Colchicine - Contraindications
- Blood disorders
Colchicine - Caution
- Cardiac disease
- Elderly
- Gastro-intestinal disease
Colchicine - Caution
- Cardiac disease
- Elderly
- Gastro-intestinal disease
- Renal & hepatic impairment
Colchicine - Interactions
- Amiodarone
- Erythromycin
- Simvastatin - rhabdomyolysis
- Antiviral
- Verapamil or diltiazem
Colchicine - Monitoring
- Monitor symptoms & side effects
DMARD : Methotrexate -
Indications
1) As a disease-modifying treatment for rheumatoid arthritis.
DMARD : Methotrexate -
MOA
- Methotrexate also has anti-inflammatory and immunosuppressive effects.
- These are mediated in part by inhibition of inflammatory mediators such as interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, although the underlying mechanisms are not fully understood.
DMARD : Methotrexate -
Adverse Effects
- Mucosal damage (sore mouth, GI upset)
- Bone marrow suppression (neutropenia, increased risk of infection)
Rare:
- hypersensitivity reactions (cutaneous reaction, hepatitis or pneumonitis)
- Long- term use : hepatic cirrhosis & pulmonary fibrosis
- Accidental overdose: if given daily
DMARD : Methotrexate -
Contraindications
- Pregnancy: methotrexate is teratogenic
- Severe renal impairment
- Abnormal liver function due to it causing hepatotoxicity.
DMARD : Methotrexate -
Interactions
Methotrexate toxicity:
if prescribed with drugs inhibiting its renal excretion e.g. NSAIDs, penicillins
Increase risk of haematological abnormalities :
- Co prescription with other folate antagonists e.g. trimethoprim & phenytoin
Neutropenia:
- combined with clozapine
DMARD : Methotrexate -
Prescribing
- Prescribed by only specialists
- Oral
- Folic acid can be given to limit adverse effects.
- Given once-weekly
DMARD : Methotrexate -
Monitoring
- Efficacy monitored by symptoms, examination & blood test (inflammatory markers)
DMARD : Methotrexate -
Patient Education
- Improve swollen painful joints -may take time for maximal effect
- Taken ONCE A WEEK
Safety Net: seek help if:
- sore throat or fever (infection)
- Bruising or bleeding ,
- Nausea, Abdo pain or dark urine (liver poisoning)
- Breathlessness (lung toxicity)
Advice about contraception.
Patients should receive a methotrexate treatment booklet & warning card.
