Musculoskeletal - Pharmacology

Question 1

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Answer 1

• act as anti-inflammatory, antipyretic & analgesia
• have anti-platelet actions - inhibit platelet aggregation & reduce risk of thrombus (make platelets less sticky)
• inhibit prostaglandin synthesis & release
• effective for low to moderate pain, used in providing symptomatic relief (bone & muscle pain), progression of disease is unchanged

Question 2

NSAIDs - Action

Answer 2

• inhibits enzyme cyclo-oxygenase (COX)
• COX is enzyme involved in cell walls, damage to the walls initiates the release of COX, inhibiting COX stops the inflammatory response
• prostaglandins are made at the site of tissue damage and lead to pain

Question 3

NSAIDs - GI Problems

Answer 3

• stomach & intestines produce cytoprotective prostaglandins to maintain integrity of the GI mucosa
• inhibiting release of prostaglandins puts the GI at risk of ulceration due to acidic environment of stomach

Question 4

NSAIDs - COX2

Answer 4

• COX1 is expressed in most tissues (including GI)
• COX2 is only released from some cells (synovial & macrophages) and is induced by inflammation
• COX2 inhibitors should be questioned in patients with cardiac history

Question 5

NSAIDs - Indications

Answer 5

• reduce inflammatory response & provide pain relief
• acute or chronic RA
• OA
• other rheumatic diseases
• mild to moderate pain
• gout
• fever
• non-rheumatic inflammation
• dysmenorrhoea

Question 6

NSAIDs - Adverse Reactions

Answer 6

• GIT disturbances
  
  • diarrhoea
  • constipation
  • dyspepsia
  • gastritis
  • nausea & vomiting
  • ulceration
  • bleeding
• skin reactions
  
  • rashes / urticaria
• renal damage
  
  • nephrotoxicity
  • dysuria
  • haematuria
• sodium retention
• asthma attacks in sensitive persons

Question 7

NSAIDs - Interactions

Answer 7

• drugs that affect
  
  • inflammatory responses
  • kidney or liver functions
  • blood pressure
  • blood coagulation mechanisms
  • acid-base balance
  • hearing

Question 8

NSAIDs - Asprin

Answer 8

• inhibits prostaglandin synthesis and release
• analgesic, anti-inflammatory, antipyretic, anti-platelet
• A/E: nausea, vomiting, gastric ulceration, bleeding, hypersensitivity
• interactions: multiple, significant are warfarin & other NSAIDs
• absorbed across stomach wall, reaches peak serum levels 20-40mins

Question 9

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

Answer 9

• diverse group of drugs, each that have an impact on the disease progression rather than symptoms
• first line treatment in RA

Question 10

DMARDs - Gold Salts

Answer 10

• gold attached to sulfur (to increase solubility)
• seems to suppress synovitis of the acute stage of RA
• A/E: skin & mucous membrane reactions
• A/E with Auranofin: above plus abdominal distress or pain, gas, diarrhea, nausea, vomiting
• interactions: toxicity when used concurrently with penicillamine
• used in caution in patients with: inflammatory bowel disease, skin rash, diabetes, heart failure
• onset of action: oral: 3-4 months, parenteral: 6-8 weeks, variable half life, excreted in faeces or via kidneys

Question 11

DMARDs - Penicillamine

Answer 11

• a chealating agent for heavy metals such as mercury, lead, copper & iron (causes things to clump together & precipitate so they can be excreted), makes the metals more soluable
• unknown mechanism of action, indicated for moderate to severe RA not responding to other treatments
• A/E: anorexia, diarrhoea, loss of taste senses, nausea & vomiting, abdominal pain, allergic reactions, stomatitis, avoid use in pregnancy & breastfeeding
• interactions: may impair renal and haematological function, not to be used cocurrently with gold or phenybutazone
• onset of action 2-3 months, metabolised by the liver & excreted in faeces & urine

Question 12

DMARDs - Sulfasalazine

Answer 12

• consists of both an asprin-like anti-inflammatory & a sulphur antibiotic-like component (sulphoamide)
• unknown action, recommended first line management for RA as has least side effects
• A/E: dose dependent: nausea, vomiting, rashes, tinnitus, dizziness, headache
• haematological A/E: haemolytic anaemia, agranulocytosis, thrombocytopenia
• contraindicated in people with haematological disorders or known sulphoamide sensitivity
• close monitoring required in people with renal or hepatic impairment

Question 13

DMARDs - Leflunomide

Answer 13

• inhibits pyridine synthesis, reducing cells involved in the inflammatory response
• A/E: diarrhoea, nausea, rashes, alopecia, rare: pancytopenia, epidermal necrolysis
• converted in the liver to active metabolite, excreted in the urine (30%) & the faeces (70%), has a half life of 2-3 weeks

Question 14

Symptom-Modifying Antirheumatic Drugs (SMARDs) - Paracetamol

Answer 14

• modify the symptoms, improve quality of life
• inhibits prostaglandin release, but has no anti-inflammatory affect, is analgesic, antipyretic
• indicated in mild to moderate pain, fever, headache
• peak levels - 15-60 minutes, half-life - 1-3 hours
• overdose - irreversible liver & kidney damage
• antidote - acetycysteine (parvolex) if >1 hour and <10 hours