Pain

Question 1

What is the usual dose of paracetamol given?

Answer 1

1g QID

Question 2

How is paracetamol metabolised?

Answer 2

Liver - by both conjugation and CYP2E1

Question 3

How do non-selective inhibitors of COX work?

Answer 3

Decrease in production of prostaglandins and thromboxane –> anti-inflammatory + anti-pyretic + analgesic effect

Question 4

List 5 adverse effects of non-selective NSAIDs.

Answer 4

1. Increased bleeding time and blood loss (due to inhibition of COX1 in platelets causing impaired platelet function)
2. GIT ulceration/PUD (due to loss of GI mucosal protective mechanisms that are usually stimulated by prostaglandin)
3. Renal failure (due to loss of prostaglandin control of GFR)
4. Exacerbation of asthma in susceptible individuals
5. Exacerbation of CCF due to sodium (and hence water) retention

Question 5

List 4 examples of non-selective NSAIDs.

Answer 5

Ibuprofen, indomethacin, diclofenac, ketorolac

Question 6

List 2 examples of COX 2 inhibitors

Answer 6

celecoxib (oral) and parecoxib (IV)

Question 7

What needs to be considered in giving celecoxib and parecoxib as pain relief?

Answer 7

Both are sulphonamides so should be avoided in patients with sulphur allergies - alternative e.g. meloxicam

Question 8

What is the difference between tolerance and dependence?

Answer 8

Tolerance - The predictable and physiological decrease in the effect of a drug over time

Dependence - a state in which the use of a drug is necessary for either physical or psychological well-being

Question 9

How is morphine metabolised and excreted?

Answer 9

Metabolised in liver via demethylation and glucuronidation

Metabolites renally excreted (therefore duration of action of morphine can be prolonged in setting of renal impairment due to metabolite accumulation)

Question 10

What class of drugs does fentanyl belong to?

Answer 10

A synthetic opioid approximately 100x more potent than morphine

Question 11

How is fentanyl metabolised and excreted? How is it different to morphine?

Answer 11

Metabolised in liver and excreted by kidneys BUT no active metabolites therefore no risk of accumulation in setting of renal impairment (unlike morphine - active metabolites)

Question 12

Describe the action of codeine

Answer 12

Synthetic opioid that is a pro-drug. converted to morphine within liver - percentage of population does not have adequate liver enzymes which can result in both poor analgesic efficacy and opioid toxicity

Question 13

When is tramadol used?

Answer 13

Useful in treatment of moderate pain and neuropathic pain

Question 14

When should tramadol be avoided? (2)

Answer 14

1. In patients with history of seizures (can lower seizure threshold)
2. In patient who use drugs that increase serotonin levels e.g. SSRIs (risk of serotonin syndrome)

Question 15

How is pethidine metabolised and why is this important?

Answer 15

Hepatic metabolism produces norpethidine which can result in seizures and cerebral excitation, risk is greater in setting of prolonged use and renal failure as the metabolite can accumulate

Question 16

What is the mechanism of action of buprenorphine?

Answer 16

Opioid partial agonist (transdermal, oral, sublingual)

Question 17

When is buprenorphine used?

Answer 17

Can be used in management of persistent pain (patch) and also in larger doses for management of opioid dependence and withdrawal (sublingual)

Question 18

What is naloxone?

Answer 18

Competitive opioid antagonist used to treat opioid overdose

Question 19

What is MS Contin?

Answer 19

Slow-release morphine

Question 20

What is oyxcontin?

Answer 20

Slow-release oxycodone

Question 21

What is endone or oxynorm?

Answer 21

Immediate-release oxycodone

Question 22

What is Targin?

Answer 22

Oxycodone + naloxone

Question 23

What is the mechanism of action of ketamine?

Answer 23

NMDA receptor antagonist

Question 24

How can ketamine be delivered? (3)

Answer 24

Intranasal, IM and IV

Question 25

List 3 indications for the use of ketamine for analgesia

Answer 25

1. Poorly controlled with opioids 2. When severe pain is anticipated 3. In treatment of neuropathic and persistent pain Only to be used as adjuvant

Question 26

What is the mechanism of action of clonidine?

Answer 26

Alpha-2 receptor agonist; reduces sympathetic tone (decreases noradrenaline release)

Question 27

What are the side effects of clonidine?

Answer 27

Drowsiness and hypotension

Question 28

What is the mechanism of action of local anaesthetics?

Answer 28

Produce analgesia by blocking Na+ channels and preventing propagation of action potentials along nerves involved in pain pathways

Question 29

List five agents used as local anaesthetics. Which of these are the most short-acting?

Answer 29

``` Lignocaine (SA) Ropivacaine Bupivacaine Levobupivacaine Prilocaine (SA) ```

Question 30

Describe the symptoms that occur in local anaesthetic toxicity. (2 major groups)

Answer 30

1. Excitation (blocking of inhibitory neurons in CNS - happens in trigeminal distribution): perioral tingling, tinnitus, agitation, muscle twitchiness, grand mal seizures 2. Depression - apnoea, cardiac collapse, unconscious

Question 31

How is local anaesthetic toxicity treated? (3)

Answer 31

1. BZDs for seizure control 2. CPR, amiodarone for CV toxicity 3. Lipid emulsion therapy DON"T USE LIGNOCAINE TO TREAT VF

Question 32

What is the rationale behind the use of lipid emulsion therapy in the treatment of local anaesthetic toxicity?

Answer 32

Creates a lipid phase that extracts the lipid-soluble molecules of the LA from the aqueous plasma phase - decreases free drug concentration available to free tissues

Question 33

List 5 side effects of opioids.

Answer 33

1. Cardiovascular - hypotension may occur due to decreased sympathetic tone 2. Respiratory - involves direct inhibition of brainstem respiratory centres and a decreased responsiveness to pCO2. 'Ondine's curse' - if you go to sleep, you don't breathe 3. GI - directly stimulates CTZ resulting in N&V/ Can cause biliary spasm, delayed gastric emptying and constipation 4. GU - urinary retention 5. Pruritus esp. in obstetric patients