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
