BASIC - MSK Flashcards
Names of NSAIDs?
Ibuprofen, diclofenac, etoricoxib
Indications of NSAIDs?
- PRN for mild-to-moderate pain
- Regular treatment of pain related inflammation
Mechanism of NSAIDs?
- Inhibit synthesis of prostaglandins from arachidonic acid by inhibiting cyclooxygenase (COX
- COX-1 stimulates prostaglandin synthesis essential to preserve gastric mucosa, maintain renal perfusion (by dilating afferent glomerular arterioles) and inhibit thrombus formation at the vascular endothelium
- COX-2 expressed in response to inflammatory stimuli stimulates production of prostaglandins that cause inflammation and pain
- Therapeutic benefits of NSAIDs are principally COX-2 inhibition and adverse effects by COX-1 inhibition
- Selective COX-2 inhibitors (e.g. etoricoxib) developed to reduce the adverse effects
Side effects of NSAIDs?
- GI ulcers/gastritis
- Renal impairment
- Increased risk of MI/CVA
- Fluid retention
Interactions of NSAIDs?
- GI Ulceration o Aspirin, corticosteroid - GI bleeding o Anticoagulants, SSRIs, venlafaxine - Renal Impairments o ACEi, diuretics
Contraindications of NSAIDs?
o Severe renal impairment
o Heart Failure
o Liver failure
Cautions of NSAIDs?
o Peptic ulcer disease
o GI bleeds
o CVD
Prescription of NSAIDs?
- Available as tablets, suspensions, gels, suppositories, injectable
- Acute pain treatment should be stopped when resolved
- Taken with food to minimise GI upset
- Can use gastroprotection for patients at increased risk
Names of oral glucocorticoids?
Prednisolone, hydrocortisone, dexamethasone
Indications of oral glucocorticoids?
Allergic or inflammatory disorders (anaphylaxis, eczema, asthma, COPD)
Severe croup
Autoimmune disease (IBD, ITP, inflammatory arthritis)
Cancer treatment
Myasthenia Gravis, Polymyalgia rheumatica, GCA, Lupus
Proctitis
Joint injections
Adrenal insufficiency/Hypopituitarism
Mechanism of oral glucocorticoids?
- Bind to cytosolic glucocorticoid receptors which upregulate anti-inflammatory genes and downregulate pro-inflammatory genes (cytokines, TNFa)
- Suppression of circulating monocytes and eosinophils
- Metabolic effects
o Increased gluconeogenesis
o Increased catabolism - Mineralocorticoid effects
o Stimulate Na and water retention and K excretion
Side effects of oral glucocorticoids?
- Immunosuppression
- Diabetes mellitus
- Insomnia, psychosis and suicidal ideas
- Osteoporosis
- Metabolic
o Proximal muscle weakness, skin thinning with easy bruising and gastritis - Mineralocorticoid
o Hypertension, hypokalaemia and oedema - Prolonged
o Adrenal atrophy leading to Addisonian crisis if withdrawn suddenly
Cautions of oral glucocorticoids?
- Infection
- Children (suppress growth)
- Hepatic or Renal impairment
Interactions of oral glucocorticoids?
Risk of peptic ulceration – NSAIDs
Hypokalaemia – B2-agonists, theophylline, loop and thiazide diuretics
Affected by CYP450 enzymes
Prescription of oral glucocorticoids?
o Can be given orally, IM, IV
o OD, taken in the morning to mimic natural circadian rhythm
o Consider use of bisphosphonates and PPIs if long-term and risk
Monitoring of oral glucocorticoids?
o For children – height and weight monitored annually – refer to paediatrician if slow
o Prolonged treatment – HbA1c or DEXA scan
Cessation of oral glucocorticoids?
o Abrupt withdrawal can lead to adrenal insufficiency
o Gradual withdrawal used if treatment >3 weeks, received >40mg, repeated evening doses
Communication of oral glucocorticoids?
o Should feel better in 1-2 days
o Do not stop immediately
o Steroid card to carry round at all times
Indications of methotrexate?
- Rheumatoid arthritis
- Crohn’s disease
- Chemotherapy – e.g. leukaemia, lymphoma and some solid tumours
- Severe psoriasis
Mechanism of methotrexate?
- Inhibits dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4)
o FH4 needed for DNA and protein synthesis, so lack of it prevents cellular replication
o Actively dividing cells particularly sensitive so good for cancer - Anti-inflammatory and immunosuppressive effects
o Inhibition of IL-6, IL-8 and TNF alpha
Side Effects of methotrexate?
- Sore mouth, GI upset (diarrhoea, nausea, vomiting)
- Neutropenia, leukopenia, thrombocytopenia (Agranulocytosis)
- Hepatitis, pneumonitis
- Long term use – hepatic cirrhosis, pulmonary fibrosis
Contraindications of methotrexate?
- Active infection
- Pregnancy – teratogenic (both men and women taking drug need effective contraception during and for 3 months after stopping treatment
- Severe renal impairment
- Hepatic impairment in non-malignant conditions
Cautions of methotrexate?
- Abnormal liver function
Interactions of methotrexate?
- Methotrexate toxicity more likely with:
o NSAIDs, penicillins - Risk of haematological abnormalities in trimethoprim and phenytoin
- Risk of neutropenia increased in clozapine
Prescription of methotrexate?
- Oral dose, once weekly 7.5-20mg, adjusted according to response
- Folic acid prescribed to be taken on the other 6 days when methotrexate isn’t taken
- For cancer – given IV/IM/intrathecal
Important communication to patient of methotrexate?
- Report symptoms of sore throat, fever, bruising, bleeding, nausea, abdominal pain, dark urine, breathlessness
- Need contraception
- Give folic acid to reduce side effects
Monitoring of methotrexate?
- Before treatment – FBC, LFT, U&E and a pregnancy test
- 1-2 weekly until established
- 2-3 monthly thereafter
Indications of allopurinol?
- Prophylaxis of gout and uric acid/calcium oxalate renal stones
- Prophylaxis of hyperuricaemia in cancer
Mechanism of allopurinol?
- Xanthine oxidase inhibitor
- Reduces xanthine to uric acid – lowers concentrations of uric acid
Side effects of allopurinol?
- Skin rash – mild to severe SJS or TENs
- Drug hypersensitivity syndrome
o Fever, eosinophilia, lymphadenopathy - Acute gout triggered
Contraindications of allopurinol?
- Acute gout
- Recurrent skin reaction
Cautions of allopurinol?
- Ensure adequate fluid intake (2-3 litres/day)
- Start allopurinol before cancer treatment
Dose changes in renal/hepatic impairment of allopurinol?
- Dose reduction
Interactions of allopurinol?
- Allopurinol and amoxicillin risk of rash
- Allopurinol and ACEi/thiazides – risk of hypersensitivity reactions
Prescription of allopurinol?
- Oral start at low dose and titrate according to uric acid levels to maintenance dose
- Typical 100mg initial and then up to 200-600mg
- Take after food
- NSAID or colchicine prescribed for 1 month after serum uric levels normalise to avoid acute attack
Communication of allopurinol?
- Take after meals
- Seek advice if rash develops
- Do not stop allopurinol in acute attack
Monitoring required of allopurinol?
- Uric acid levels checked 4 weeks after start/dose change
- Aim for uric acid <300 and titrate dose
Names of calcium salts?
Calcium carbonate, calcium gluconate
Names of vitamin D analogue?
Colecalciferol
Indications of calcium salts and vitamin D?
- Osteoporosis
- Chronic kidney disease
- Severe hyperkalaemia (calcium gluconate)
- Hypocalcaemia if symptomatic or severe (<1.9)
- Vitamin D used in prevention and treatment of Vitamin D deficiency, including rickets (children) and osteomalacia (adults)
Mechanism of action in calcium and vitamin D?
- Calcium needed for muscles, nerves, bone and clotting
- Homeostasis controlled by PTH and vitamin D, which increase serum Ca and calcitonin which reduces Ca level
- Restoring positive Ca balance reduces rate of bone loss, restores Ca level in CKD
- In hyperkalaemia, calcium gluconate raises myocardial threshold potential, reducing excitability
Side effects of calcium salts?
- Dyspepsia
- Constipation
- Nausea
Interaction of oral calcium?
- Oral calcium reduces absorption of:
o Iron, bisphosphonates, tetracyclines and levothyroxine
Prescription of calcium salts & vitamin D?
- Adcal D3 BDS contains calcium and vitamin D (cholecalciferol)
- Chew then swallow tablets
- Separate doses by 4 hours to medicines that interact
Monitoring in calcium salts?
- Check calcium levels regularly
Names of bisphosphonates?
Alendronic acid, disodium pamidronate, zoledronic acid
Indications of bisphosphonates?
- Alendronic acid – patients at risk of osteoprotic fragility fractures
- Pamidronate/Zoledronic acid – severe hypercalcaemia of malignancy, myeloma, breast cancer with bone mets
- Paget’s Disease
Mechanism of bisphosphonates?
- Reduce bone turnover by inhibiting action of osteoclasts, cells responsible for bone resorption
- Reduction in bone loss and improvement in bone mass
Side effects of bisphosphonates?
- Oesophagitis
- Hypophosphatemia
- Osteonecrosis of jaw
- Osteonecrosis of external auditory canal
- Atypical femoral fractures
Contraindications of bisphosphonates?
- Severe renal impairment (<35)
- Hypocalcaemia
- Upper GI disorders
Cautions of bisphosphonates?
- Smokers
- Dental disease
Interactions of bisphosphonates?
- Absorption reduced if taken with calcium salts (including milk), antacids and iron salts
Prescription of bisphosphonates?
- For osteoporosis – alendronic acid oral 70mg once weekly
- For severe hypercalcaemia – slow IV infusions
Communication to patient of bisphosphonates?
- Alendronic acid – swallowed whole >30 mins before breakfast or other medications with plenty of water, patient remain upright for 30 minutes afterwards to reduce oesophageal irritation
Monitoring of bisphosphonates?
- Osteoporosis – check Ca and Vit D before and during treatment, DEXA every 1-2 years
- Hypercalcaemia – Ca levels
