Analgesia nociceptive

Question 1

what are the four components of pain

Answer 1

1. Physical pain
2. Psychological pain
3. Social pain
4. Spiritual pain

Question 2

what are the steps of the WHO analgesic ladder

Answer 2

Step 1: non-opioids (eg paracetamol or NSAIDS) +/- adjuvants

Step 2: weak opioids (eg codeine, dihydrocodeine or tramadol) +/- adjuvants

Step 3: Strong opioid (e.g morphine, oxycodone, methadone, buprenorphine, fentanyl) and non-opiod +/- adjuvants

Question 3

What are the 5 key principles of the WHO analgesic ladder

Answer 3

By mouth - PO where possible
By the clock - regular intervals
For the individual - according to pain character, type and intensity
By the ladder - follow ladder and start with lowest doses and titrate according to response
Attention to detail

Question 4

what are some non-pharmacological methods of pain management

Answer 4

education, explanation and reassurance, physiotherapy, electrotherapy, mindfulness, or acupuncture

Question 5

rung 1/3 of WHO analgesic ladder

Answer 5

Step 1: Consider regular paracetamol use
0.5g – 1g every 4-6 hours; maximum 4g daily

step 2: Add an NSAID (+/- PPI)
Typical drug dosing for (oral) ibuprofen:
Mild to moderate pain: initially 300-400mg 3-4 times a day; increased up to 600mg 4 times a day if necessary; maintenance 200-400mg three times a day

Question 6

rung 2/3 of WHO analgesic ladder

Answer 6

Step 3: Add codeine/co-codamol
codeine Mild to moderate pain: 30-60mg every 4 hours as required

Step 4: Stop codeine/co-codamol & trial tramadol
Moderate to severe acute pain: initially 100mg, then 50-100mg every 4-6 hours; usual maximum 400mg/24 hours

Question 7

rung 3/3 WHO analesic ladder

Answer 7

Step 6: Stop tramadol & start morphine
Before prescribing any strong opiate, consider ABC:
Start Antiemetic metoclopramide
Consider Breakthrough pain
Prescribe laxatives for Constipation senna

To titrate morphine:
1. Prescribe the dose on a regular basis/PRN every four hours eg 5mg
2. Reassess after 24 hours, if pain free the total dose that has been administered over the past 24
hours should be added up and converted into a twice-daily sustained/modified release
(SR/MR) dose by dividing the total 24 hour dose by two.
3. If the patient is still reporting pain first confirm adherence and then consider increasing
the dose prescribed and re-assessing after another 24 hours.

Once their MR has been established, add morphine for breakthorugh pain to take ‘PRN’. Commonly 1/10th to 1/6th of
the equivalent total daily dose of the drug every 4 hours PRN

Step 7: Refer to pain management specialists

Question 8

how to convert from morphine in mg to oxycodone in mg

Answer 8

divide by 2!

Question 9

why does acetylcysteine work for paracetamol overdose

Answer 9

Acetylcysteine (treatment for overdose) is a glutathione precursor

Cytochrome P450 metabolises it into NAPQI (toxic metabolite) which is conjugated with glutathione before elimination.

Question 10

which patients should avoid paracetamol

Answer 10

paracetamol should be reduced in ppl with liver failure (due to increased NAPQI production eg in excess alcohol intake, OR reduced glutathione stores (malnutrition, low body weight, severe hepatic impairment) - this is particularly important for IV infusion paracetamol

Question 11

interactions paracetamol

Answer 11

cytochrome p40 inducers eg phenytoin, carbamazepine increase the rate of NAPQI production and risk of liver toxicity after paracetamol overdose

Question 12

dosing paracetamol

Answer 12

0.5-1g PO 4-6 hourly (maximum 4g/24 hours)

Question 13

interactions NSAIDs

Answer 13

many drugs when combined, increase the risk of NSAID adverse effects. Eg gastric ulceration: aspirin and corticosteroids. Gastric bleeding: anticoagulants, SSRIs, venlafaxine. RENAL IMPAIR: ACEi, diuretics. NSAIDs increase the risk of bleeding with warfarin and reduce the therapeutic effects of anti-HTNs and diuretics

Question 14

Adverse effects NSAIDs

Answer 14

COX-1 inhibition
Peptic ulceration (decreased PGE2),
Bleeding (decreased TXA2), this is more prominent in selective COX-1 inhibitors
Renal impairment (decreased PGE2 and PGI1)

COX-2 inhibition
Increased risk of cardiovascular events (decreased PGI1) this is more prominent in selective COX-2 inhibitors as TXA from COX-1 is unopposed whilst PGI2 is suppressed

LOX upregulated
Importantly, if the COX system is being inhibited, there is more arachidonic acid to be directed to LOX - this makes leukotrienes and can ppt bronchospasm in asthmatics! Caution!

Question 15

name some COX-1 selective NSAIDs

Answer 15

Ketorolac
Indomethacin
Low dose aspirin

Question 16

name some non-selective NSAIDS

Answer 16

Ibuprofen
Naproxen

Question 17

name some COX-2 selective NSAIDs

Answer 17

Diclofenac
Etoricoxib

Question 18

contraindications to NSAIDs

Answer 18

active bleeding, thrombocytopenia, peptic ulcer, history of adverse effects with NSAIDs, severe heart failure, varicella infection, severe renal impairment eGFR<40, liver failure, asthma, uncontrolled HTN

Question 19

dosing ibruprofen

Answer 19

Ibuprofen 300-400mg tds-qds
Normal tablet is 200mg but check as there are many different types

Question 20

what is the risk NSAIDs asthma

Answer 20

Importantly, if the COX system is being inhibited, there is more arachidonic acid to be directed to LOX - this makes leukotrienes and can ppt bronchospasm in asthmatics! Caution!

Question 21

name some weak opioids

Answer 21

codeine, dihydrocodeine, tramadol

Question 22

how does codeine work?

Answer 22

codeine and dihydrocodeine are metabolised in the liver to produce small amounts of morphine

Question 23

why is tramadol unique compared to other opioids

Answer 23

Tramadol is a synthetic analogue of codeine. Tramadol, unlike other opioids, also acts on serotonergic and adrenergic pathways where it is thought to act as a serotonin and noradrenaline reuptake inhibitor- contributes to analgesic effect

It can be used for both nociceptive and neuropathic pain. Therefore if responsive, consider whether the pain is truly nociceptive.

Question 24

adverse effects opioids

Answer 24

nausea, constipation, dizziness, drowsiness, neurological and respiratory depression when taken in overdose.

Question 25

what drugs should tramadol be avoided with

Answer 25

try to avoid other sedating drugs eg benzodiazepines, antipsychotics, TCA. don’t give tramadol with other drugs that lower seizure threshold eg SSRIs and TCAs. Tramadol can also cause serotonin syndrome especially when combined with other serotonergic drugs eg many antidepressants

Question 26

what specific condition must tramadol be avoided in

Answer 26

Tramadol lowers seizure threshold so avoid in epilepsy

Question 27

what should be prescribed alongside a weak opioid

Answer 27

advise the person of the risks of constipation, and prescribe a stimulant laxative (such as senna or dantron-containing laxative) at the time of first prescription. Just think that opioids turn the gut off so you need to turn it back on with a stimulant laxative

Question 28

examples of strong opioids

Answer 28

morphine and oxycodone

Question 29

indications strong opioids

Answer 29

Rapid relief of acute severe pain eg post-operative or pain associated with MI
Chronic pain where rest of WHO ladder is exhausted
Relief of breathlessness in EOLC
To relieve breathlessness and anxiety in acute pulmonary oedema , alongside oxygen, furosemide and nitrates

Question 30

moa opioids

Answer 30

Activation of opioid mu receptors in the CNS. activation of these G coupled receptors reduces neuronal excitability and pain transmission.

In the medulla they blunt the response to hypoxia and hypercapnia, reducing respiratory drive and breathlessness. By relieving pain, breathless and associated anxiety, opioids reduce sympathetic nervous system activity. The theory extends that in Mi and acute pulmonary oedema they may decrease cardiac work and oxygen demand,a s wella s relieving symptoms

Question 31

why do opiods cause nausea and vomiting? management?

Answer 31

stimulation of CTZ

Haloperidol, metoclopramide or levomepromazine

Question 32

how does opioid overdose present?

Answer 32

neurological depression and drowsiness, respiratory depression and associated cyanosis (blue lips and peripheries) , pupil constriction, flushing of the skin, itching,

Question 33

how does opioid withdrawal present?

Answer 33

Opioid withdrawal is the opposite of the opioid effects

anxiety, pain, breathlessness, pupil dilation, skin is cool and dry with piloerection pt has gone “cold turkey” and appears like a “cold turkey”

Question 34

cautions strong opioids

Answer 34

rely on liver and kidneys for excretion so dose reduce in renal and hepatic impairment and in the elderly. Do not give in resp failure (unless expert guidance in palliative care), avoid opioids in biliary colic as they may cause spasm of sphincter of oddi and make pain worse.

Question 35

interactions strong opioids

Answer 35

dont use with other sedating drugs eg antipsychotics, benzodiazepines, TCA

Question 36

ABC of strong opioid prescribing

Answer 36

Start Antiemetic (metoclopramide)
Consider Breakthrough pain
Prescribe laxatives for Constipation (stimulant - senna)

Question 37

?opioid overdose, what do you prescribe?

Answer 37

Naloxone
small incremental dose 200-400 mcg IV every 2-3 minutes until satisfactory reversal has been achieved. In patients who develop[ opioid toxicity in the context of chronic use (especially in palliative care) - smaller incremental doses should be used e.g. 40-100mcg.

Question 38

why is it important to monitor aptients that you needed to give naloxone to?

Answer 38

closely monitor patient fot at least an hour. This is beacuse the action of naloxone (20-60 mins) is shorter than most opioids so opioid toxicity can reoccur

Question 39

MoA naloxone

Answer 39

binds to opioid receptorsa s a competitive antagonist. It has little to no effect in the absence of exogenous opioids.

Question 40

How do you titrate morphine

Answer 40

To titrate morphine:
1. Prescribe the dose on a regular basis/PRN every four hours eg 5mg oromorph
2. Reassess after 24 hours, if pain free the total dose that has been administered over the past 24
hours should be added up and converted into a twice-daily sustained/modified release
(SR/MR) dose by dividing the total 24 hour dose by two.
3. If the patient is still reporting pain first confirm adherence and then consider increasing
the dose prescribed and re-assessing after another 24 hours.

Question 41

How do you prescribe for breakthorugh pain- morphine?

Answer 41

Once their MR has been established, add morphine for breakthorugh pain to take ‘PRN’. Commonly 1/10th to 1/6th of
the equivalent total daily dose of the drug every 4 hours PRN

Question 42

NSAIDS and renal issues?

Answer 42

dont use if eGFR <40 !!!!

Question 43

NSAID lowest risk of cardiac events?

Answer 43

naproxen

Question 44

what to do if renal impairment and on morphine for pain relief and showing signs of toxicity? how to control pain

Answer 44

Because morphine is renally excreted, it is generally avoided in patients with renal impairment. Oxycodone is typically used as a substitute as it is metabolised by the liver.

eg if were on morphine 30mg bd
switch to oxycodone 15mg bd