MSK/Pain

Question 1

name three common NSAIDs

Answer 1

naproxen, ibuprofen, diclofenac

Question 2

what are the indications to take NSAIDs?

Answer 2

‘As needed’ treatment of mild-to-moderate pain

Regular treatment for pain related to inflammation, particularly of the musculoskeletal system, e.g. in rheumatoid arthritis, severe osteoarthritis and acute gout.

Question 3

how do NSAIDs work?

Answer 3

NSAIDs inhibit synthesis of prostaglandins from arachidonic acid by inhibiting cyclooxygenase (COX)

Question 4

what are the two types of COX and whaat do they do?

Answer 4

COX-1: stimulates prostaglandin synthesis that
is essential to preserve integrity of the gastric mucosa; maintain renal perfusion (by dilating afferent glomerular arterioles); and inhibit thrombusformation at the vascular endothelium

COX-2: 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

Question 5

what are the side effects of NSAIDs?

Answer 5

GI toxicity
renal impairment
increased risk of cardiovascular (CV) events
fluid retention - worsen hypertension and heart failure

Question 6

what are the contraindications to taking NSAIDs?

Answer 6

severe renal impairment, heart failure,
liver failure and known NSAID hypersensitivity
peptic ulcer disease or GI bleeding

Question 7

what are the interactions with NSAIDs?

Answer 7

increased risk of NSAID-related adverse effects -
GI ulceration: low-dose aspirin, corticosteroids;
GI bleeding: anticoagulants, SSRIs, venlafaxine;
renal impairment: ACE inhibitors, diuretics.

NSAIDs increase the risk of bleeding with warfarin and reduce the therapeutic effects of antihypertensives and diuretics

Question 8

what class of drug is codeine?

Answer 8

weak opioid

Question 9

how does codeine work?

Answer 9

metabolised by cytochrome P450 enzymes to morphine and morphine-related metabolites - agonists of opioid µ-receptors,

Question 10

what are the indications to take codeine?

Answer 10

Mild-to-moderate pain: as second-line agents when simple analgesics, such as paracetamol, are insufficient

Question 11

what are the side effects of codeine?

Answer 11

nausea, constipation, abdo pain and drowsiness

neurological and respiratory depression

Question 12

what are the contraindications to taking codeine?

Answer 12

significant respiratory disease, renal impairment and hepatic impairment, and also in the elderly.

Question 13

what are the interactions with codeine?

Answer 13

other sedating drugs (e.g.antipsychotics, benzodiazepines and tricyclic antidepressants)

Question 14

name two strong opioids

Answer 14

morphine, oxycodone

Question 15

how do opioids work?

Answer 15

from activation of opioid µ (mu) receptors in the central nervous system. overall, reduce neuronal excitability and pain transmission

in the medulla, they blunt the response to hypoxia and hypercapnoea, reducing respiratory drive and breathlessness.

in MI and acute pulmonary oedema they may reduce cardiac work and oxygen demand, as well as relieving symptoms

Question 16

what are the indications to take opioids?

Answer 16

For rapid relief of acute severe pain

For relief of chronic pain, when paracetamol, NSAIDs and weak opioids are insufficient

For relief of breathlessness in the context of end-of-life care.

To relieve breathlessness and anxiety in acute pulmonary oedema, alongside oxygen, furosemide and nitrates.

Question 17

what are the side effects of opioids?

Answer 17

respiratory depression
neurological depression
nausea and vomiting
constipation
itching
dependence

Question 18

what are the contraindications to taking opioids?

Answer 18

hepatic failure and renal impairment and elderly
respiratory failure
biliary colic

Question 19

what are the interactions with opioids?

Answer 19

other sedating drugs (e.g. antipsychotics, benzodiazepines and tricyclic antidepressants)

Question 20

how does paracetamol work?

Answer 20

weak inhibitor of cyclooxygenase (COX)
appears to increase the pain threshold
reduce prostaglandin (PGE) concentrations in the thermoregulatory region of the hypothalamus, controlling fever
has specificity for COX-2 rather than COX-1

Question 21

what are the indications to take paracetamol?

Answer 21

first-line analgesic for most forms of acute and
chronic pain
antipyretic that can reduce fever and its
associated symptoms

Question 22

what are the side effects of paracetamol?

Answer 22

Steven-Johnson syndrome, toxic epidermal necrolysis

In overdose, paracetamol causes liver failure.
metabolised by cytochrome P450 enzymes to NAPQI
conjugated with glutathione before elimination
elimination. After overdose, this elimination pathway is
saturated, and NAPQI accumulation causes hepatocellular necrosis

Question 23

how do you treat paracetamol overdose?

Answer 23

glutathione precursor - acetylcysteine

Question 24

what are the contraindications to taking paracetamol?

Answer 24

Chronic excessive alcohol use (increased risk of liver toxicity); malnutrition, low body weight (reduced glutathione stores); severe hepatic impairment

Question 25

what are the interactions with paracetamol?

Answer 25

Cytochrome P450 inducers, e.g. phenytoin and

carbamazepine, increase the rate of NAPQI production and risk of liver toxicity after paracetamol overdose.

Question 26

what class of drug is allopurinol?

Answer 26

Xanthine oxidase inhibitor

Question 27

how does allopurinol work?

Answer 27

metabolises xanthine to uric acid – inhibition lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys

Question 28

what are the indications to take allopurinol?

Answer 28

Prevent attacks of gout, prevent uric acid and calcium oxalate renal stones, prevent hyperuricaemia and tumour lysis syndrome

Question 29

what are the contraindications to taking allopurinol?

Answer 29

Not for acute episodes of gout, allergy/recurrent rash, renal/hepatic impairment

Question 30

what are the side effects of allopurinol?

Answer 30

Skin rash, Stevens-Johsons syndrome, toxic epidermal necrolysis, starting during an acute attack of gout can worsen it, GI disorders

Question 31

what are the interactions with allopurinol?

Answer 31

Mercaptopurine, azathrioprine (require xanthine oxidase for metabolism – increased risk of toxicity); amoxicillin (increased risk of skin rash); ACE inhibitors, thiazides (increased risk of hypersensitivity)