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What are the types of pain and how are they managed?
Nociceptive: Pain caused by damage to the body tissues,
described as sharp, aching or throbbing sensation
Neuropathic pain: Pain caused by damage to neurones,
described as prickling, pins and needles, shooting or
stabbing sensation
What is visceral pain?
Pain originating from internal organs
What are the types of nociceptive pain and how are they
managed?
> Musculoskeletal pain: non-opioids,
especially NSAIDs (as this pain normally has an
inflammatory origin)
> Dental pain: Find route cause e.g. infection which
needs to be treated with antibiotics, NSAIDs (as this pain
normally has an inflammatory origin)
> Moderate to severe visceral pain: opioids
> Period pain: oral contraceptives, antispasmodics or
non-opioids - especially NSAIDs
> Pain in palliative care: ???
How is neuropathetic pain managed?
> Use TCAs (amitriptyline, nortriptline - both unlicensed)
antiepileptics (gabapentin, pregabalin - both unlicensed)
nerve compression by tumour = dexamethasone
why is dexamethasone used for nerve compression
tumour?
To reduce the oedema, inflammation and cord
compression caused by the tumor mass and to thereby
relieve the pain
Outline the WHO pain ladder
1. Non opioids: paracetamol, NSAIDs, aspirin
+/- adjuvant
2. Weak opioids: Codeine, tramadol, dihydrocodeine
+/- non-opioid +/- adjuvant
3. morphine, diamorphine, oxycodone, hydromorphone,
methadone, buprenorphine, fentanyl
+/- non-opioid +/- adjuvant
Adjuvants:
Neuropathic pain: amitriptyline, nortriptyline,
gabapentin, pregabalin
Bone metastases: bisphosphonates, sodium ranelate
Nerve compression by tumour:
Dexamethasone
*Consider prophylactic laxatives the further up the
ladder you go
Note: tramadol is better classified as a moderate opioid
State examples of non-opioid analgesics
Paracetamol
NSAIDs
Aspirin
Nefopam
What is the indication for paracetamol?
Mild-moderate pain and fever
Post immunisation pyrexia
Why is paracetamol preferred in the elderly?
Does not cause gastric irritation like aspirin and NSAIDs
What is the adult dosing or paracetamol?
0.5-1g every 4 to 6 hours as required. Maximum 4g/day
What are the cautionary and advisory labels for
paracetamol?
Do not take more than 2 at any one time. Do not take
more than 8 in 24 hours
Contains paracetamol. Do not take anything else
containing paracetamol while taking this medicine. Talk
to a doctor at once if you take too much of this medicine
even if you feel well
How does overdose of paracetamol effect the body?
Liver damage (Higher risk of hepatotoxicity <50kg)
What are the symptoms of paracetamol overdose?
Nausea, vomitting, right subcostal pain/tenderness
What is the treatment for paracetamol overdose?
Acetylcysteine
What is the mechanism of action of aspirin?
Acetylates and irreversibly inhibits cyclooxygenase (COX
I and COX II) to prevent the conversion of arachidonic
acid to prostaglandins.
What is the indication for aspirin?
As antiplatelet:
Medical emergencies: ACS, ischaemic stroke/tia
300mg dispersible tablets (chewed or dispersed in
water)
Secondary prevention of thrombotic arterial events:
Low-dose aspirin 75mg daily for life
As an NSAID:
Fever and pain e.g. headache, musculoskeletal pain,
dysmenorrhea 300-900mg every 4 to 6 hours as
required. Max 4g per day
What are the cautionary and advisory labels for aspirin?
Take with or just after food, or a meal
Contains aspirin. Do not take anything else containing
aspirin while taking this medicine
What are the side effects of aspirin?
Gastric irritation
> Use enteric-coated formulations help with this but
avoid in medical emergencies/when rapid pain relief is
needed because it has a slower onset of action
> Patient should take with or just after food or a meal
Tinnitus (at high doses)

What are the contraindications for aspirin?
Under 16; risk of Reyes syndrome
EXCEPTION if being used in Kawasaki disease or as an
antiplatelet
Salicylate or NSAID hypersensitivity
e.g. bronchospasm, asthma attacks, rhinitis, urticaria,
angioedema
What is reyes syndrome?
A rare syndrome of rapid liver degeneration and
encephalitis in children treated with aspirin during a viral
infection
What are the interactions with aspirin?
Increased risk of bleeding;
Antiplatelets, anticoagulants e.g. warfarin, SSRIs
NSAIDs Refer to Chapter 10:MSK
What is the mechanism of action of opioids?
Acts on various opioid receptors located in the brain,
spinal cord and other nervous tissue to relieve pain
State examples of opioids according to their potency
Weak opioids
Codeine (CD5, Injections=CD2)
Dihydrocodeine (CD5)
Meptazinol (POM)
Moderate opioids
Tramadol (CD3, exempt from safe custody)
Strong opioids
Morphine (CD2, Oral morphine solution 13mg/5ml or
less = CD5)
Oxycodone (CD2 = alternative to oral morphine; similar
efficacy & S/E profile)
Diamorphine (CD2 - given IV, also known as heroin)
Buprenorphine (CD3 = S/L or 3/4/7 transdermal patch.
Opioid dependence)
Fentanyl (CD2, 72hr transdermal patch, injection in
intra-operative analgesia)
Methadone (CD2 - Use in opioid dependence)
Hydromorphone (CD2)
Others
Aldentanil (CD2 - intraoperative analgesia)
Remifentanil (CD2 - intraoperative analgesia)
Pethidine (CD2 - Used in labour, if accumulates causes
convulsions)
Dipipanone (CD2 - only preparation which comes with an
antiemetic; unsuitable for regular regimens)
Papaveretum (CD2 - Partial agonist precipitates
withdrawal symptoms and pain)
Pentazocine (CD3)
Sufentanil (CD2)
Tapentadol (CD2 - less N/V/C than other strong opioids)
In what situations would oxycodone be used as an
alternative to morphine?
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Morphine hypersensitivity
Renal impairment
What are the contraindications for use of opioids?
Comatose patients (opioids cause neurological
depression and sedation)
Risk of paralytic ileus - paralysis of the intestinal muscles
(Opioids reduce GI motility and can cause fatal intestinal
obstruction), cautioned in inflammatory bowel disease
as there is an increased risk of paralytic ileus and as a
result intestinal obstruction and toxic megacolon
Respiratory depression (opioids reduce respiratory
drive), cautioned in respiratory disease; avoid in asthma
attacks and COPD
Head injury or raised intracranial pressure (opioids
interfere in pupillary responses vital for neurological
assessment)
What are the side effects of opioids?
Dry mouth
Constipation
> Treat/prevent with faecal softer and peristaltic
stimulant e.g. Senna + lactulose
Drowsiness/sedation
> Driving may be impaired and the effects of alcohol
enhanced
Nausea and vomiting
> Common with morphine. anti-emetic drug at start of
treatment; pro kinetic drug e.g. metoclopramide
Reduced concentration and confusion
Euphoria, hallucinations
> Euphoria can be common with morphine
Dependence and tolerance
> With tolerance, higher doses will be required to
achieve the same effect
> With physical dependence the body cannot survive
without the substance, when the body is depleted of the
drug substance withdrawal effects will occur so avoid
abrupt withdrawal after long term treatment
Respiratory depression
> Treated with artificial ventilation or reversed by
naloxone
Larger doses can cause respiratory depression,
hypotension, pupil constriction, muscle rigidity
With long term use can cause hypogonadism e.g.
reduced fertility, amenorrhea, erectile dysfunction
Adrenal insufficiency
Hyperalgesia - abnormal respond to pain (reduce the
dose or switch to a different treatment - specialist)
MORPHINE
Miosis (pinpoint pupils), muscle rigidity
Out of it (sedation/drowsiness)
Respiratory depression
Postural hypotension
Hallucinations, hyperalgesia
Infrequency (urinary retention, constipation)
Nausea and vomiting
Euphoria

What are the symptoms of opioid withdrawal?
Tremors, shaking, breathlessness, body aches, chills,
nausea, vomitting, diarrhoea
What are the cautionary and advisory labels for opioids?
Warning: this medicine may make you sleepy. If this
happens, do not drive or use tools or machines. Do not
drink alcohol
What advice is there for driving and taking opioids?
Avoid driving when newly started on an opioid or after a
dose change
What is the indication for morphine?
Pain, 1st choice oral opioid for severe pain in palliative
care
Coughs in palliative care
What is the dosing frequency for morphine?
IR: Every 4 hours
MR: 12hrly/24hrly
When pain is controlled patients can be transferred from
I/R morphine to M/R morphine.
When are patients given a dose for M/R morphine after
being transferred from I/R morphine?
With or within 4 hours of last I/R dose
What are the maximum dose increments for morphine?
1/3 or 1/2 of the total daily dose per 24 hour
Should not be increased more than every 24 hours
Compare the side effects of morphine to other opioids
Morphine causes the most euphoria, nausea and
vomiting
What the the equivalence for morphine PO:Parenteral?
Parental dose (IM/SC/IV) = half oral dose
What is the legal category for morphine?
Oral morphine = CD5; if over 13mg/5ml = CD2
Which opioid has the most similar efficacy and side
effect profile to morphine?
Oxycodone
What is the indication for diamorphine?
Preferred over morphine when administering
parenterally (more soluble and smaller volumes can be
injected in emaciated patients in palliative care - this is
better for them as you do not want to overload them
with fluid)
What is the equivalence between morphine and
diamorphine?
Diamorphine (only parenteral) = 1/3 of oral morphine
dose
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Compare the side effects of diamorphine and morphine
Diamorphine causes less nausea and hypotension than
morphine
What is the mechanism of action of buprenorphine?
Partial opioid agonist (Also has antagonistic properties,
therefore precipitates withdrawal symptoms e.g. pain in
opioid-dependent patients and those who have taken
another opioid)
How is buprenorphine administered?
Sublingual for opioid dependence e.g. Subutex
IV,IM
Transdermal
How long do buprenorphine patches last?
Long lasting - 72 hours, 96 hours, 7 day
How long should you wait before taking an opioid after
removal of a buprenorphine patch?
Other opioids should not be administer within 24 hours
of patch removal due to the long duration of action
What are the risks associated with fentanyl use?
Risk of fatal respiratory depression in opioid-naive
patients not previously treated with a strong opioid;
manufacturer recommends use only in patients who are
opioid tolerant
What counselling information should be given to
patients taking fentanyl?
Immediately remove patch in cause of breathing
difficulties, asked drowsiness, confusion, dizziness or
impaired speech. Seek prompt medical attention (opioid
overdose)
What dose adjustment is needed if an opioid is being
switched due to hyperalgesia?
Reduce dose of new opioid by 1/4 to 1/2
When is the transdermal route unsuitable for use in pain
management?
The transdermal route is unsuitable in acute pain or
rapidly changing pain because it takes a long time to
reach steady state which prevents rapid titration of the
dose, so its given when the dose and pain level is stable
What counselling information should be given to
patients using patches?
Apply to dry, non-irritated and non-hairy skin on upper
torso or upper arm
Rotate patch site after each use
Avoid exposure to external heat (hot baths/sauna)
because there is increased absorption and more side
effects and possible toxicity. And monitor if fever
present because there will be more absorption
What are the indications for codeine?

Mild to moderate pain: 30 - 60mg every 4 hours
Codeine linctus in dry or painful cough
Acute diarrhoea
What are the MHRA alerts for codeine?
Codeine for analgesia: restricted use in children due to
reports of morphine toxicity
> Can be used for acute moderate pain in children above
12 years only if it cannot be relieved by other painkillers
such as paracetamol or ibuprofen alone
> Children aged 12-18 years: max 240mg daily for 3 days.
Dosage: up to four times a day with no less than 6 hour
intervals
> NOT RECOMMENDED IN CHILDREN WITH
COMPROMISED BREATHING: severe cardiac or
respiratory conditions, respiratory infections, multiple
trauma or extensive surgical procedures, neuromuscular
disorders
Codeine is not recommended in children aged 12 -18
years for cough and cold in patients with breathing
problems
What are the contraindications for codeine?
Ultra rapid metabolisers (CYP2D6) - will lead to
morphine toxicity
Children under 18 years who undergo removal of tonsils
or adenoids for treatment of obstructive sleep apnoea
because serious life threatening reactions can occur
Children under 12 years (risk of respiratory side effects)
Breastfeeding mothers
Can codeine be taken during breastfeeding?
Codeine should not be given to breastfeeding mothers;
passes to baby through breast milk
What are the routes of administration for codeine?
PO
IM (CD2 in this form)
NEVER give codeine intravenously because it causes
severe reactions similar to anaphylaxis
What counselling information should be given to
patients taking codeine?
Recognise signs and symptoms of morphine toxicity
Stop taking and seek medical attention if experiencing
reduced consciousness, lack of appetite, somnolence,
respiratory depression, constipation, pinpoint pupils,
nausea and vomiting
What are the MHRA alerts for dihydrocodeine?
Co-dydramol must be prescribed and dispensed by
strength to minimise risk of medication error and risk of
accidental overdose
What are the routes of administration for
dihydrocodeine?
4
PO IM (CD2 in this form)
NEVER give codeine intravenously because it causes
severe reactions similar to anaphylaxis
What is the mechanism of action of tramadol?
Noradrenaline and serotonin reuptake inhibitor =
amplifies descending inhibitory pathway
Weak mu opioid agonist = decreases ascending pain
pathway
What are the side effects of tramadol?
Increased risk of bleeding
Lowers seizure threshold
Psychiatric reactions
Less likely to cause normal opioid S/Es e.g. constipation,
respiratory depression
What are the interactions for tramadol?
Lowers seizure threshold;
SSRIs, TCAs, anti epileptics (effect antagonised)
Increased serotonergic effect when taken with
serotonergic drugs, risk of serotonin syndrome;
SSRIs, TCAs, 5HT1 agonist, MAOIs
Increased risk of bleeding;
Warfarin (enhances anticoagulant effect of coumarins)
Which opioid effects be reversed by naloxone?
All opioid except: buprenorphine effects are only
partially reversed by naloxone in opioid toxicity
How are breakthrough pain doses calculated and what
formulation is used to give breakthrough pain doses?
Rescue doses 1/10th or 1/6th of the total daily dose of
strong opioid. Given every 2-4 hours as required (may
require hourly dosing in palliative care)
Doses are given by immediate release preparations e.g.
oral morphine solution, oxycodone oral solution
What are the signs of opioid toxicity?
Coma, pinpoint pupils, respiratory depression
What is the antidote for opioid toxicity?
IV Naloxone
What is the mechanism of action of naloxone?
Opioid receptor antagonist.
Reverses respiratory depression which is the main life-
threatening effect of opioids (Effects of buprenorphine
are only partially reversed)
Can naloxone be supplied without a prescription?
POM therefore cannot be sold OTC
But can be supplied by without a prescription by
pharmacies which provide drug treatment services (e.g.
ones that provide needle exchange programme or opioid
substitution treatment) for the purpose of saving a life in
an emergency e.g. heroin overdose - can be supplied to
their friend/family member/key worker

What are the interactions with opioids?
Increase sedation with taken concomitantly with;
Antidepressants, antihistamines, alcohol, Z-drugs,
antipsychotics, antiepileptics,
[benzodiazepines - also causes respiratory depression]
When taken with MAOIs can cause possible CNS
excitation or depression (hypertension or hypotension)
What is a migraine?
A moderate-severe headache felt as throbbing pain in
one side of the head
What are the symptoms of a migraine?
Intense throbbing headache on one side of the head
which gets worse on movement
Nausea and vomtiing
Sensitivity to light or sound
May have aura (temporary warning symptoms before a
migraine):
> Visual disturbance: flashing lights, zig-zag patterns or
blind spots
> Numbness or pins and needles: starting in one hand,
moves up arm before affecting face, lips and tongue
> Dizziness, feeling off-balance
> Difficulty speaking
What are triggers for migraine?
Stress
Lack of sleep
Chemical triggers (e.g. nitrates, alcohol, contraceptives)
What is the drug treatments for migraine?
5HT1 receptor agonists "triptans"
Ergot alkaloids (Rarely used)
NSAID (tolfenamic acid - specifically licensed to treat
acute migraine attack)
When are prophylactic treatments for migraine used?
Suffer at least 2 attacks a month
Increasing frequency of headaches
Significant disability despite treatment for migraine
attacks
Cannot take suitable treatment for migraine attacks
Patients at risk of migraine induced stroke
What drugs are used for prophylaxis of migraine?
Beta blockers (propanolol, atenolol, metoprolol, nadolol,
timolol)
Antiepileptics (topiramate, sodium valproate,
gabapentin)
TCAs
Valproic acid
Antihistamine serotonin receptor antagonist (Pizotifen -
limited value, causes weight gain)
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What treatment is used for acute migraine attacks?
1. Simple analgesic e.g. aspirin, paracetamol or NSAID
(preferably soluble/dispersible/effervescent)
2. 5HT1 agonist e.g. sumatriptan
> For frequent, prolonged attacks despite treatment:
Combine with NSAID
Ergotamine (ergot alkaloid) - Rarely used
Antiemetics: pro kinetics - metoclopramide,
domperidone
Antihistamines - buclizine, phenothiazines -
prochlorperazine
Why are soluble/dispersible/effervescent formulations
preferred in migraine?
During a migraine there is delayed gastric emptying and
peristalsis is often reduced which increases the
absorption time
Since these formulations are better absorbed they are
ideal
What is the cause of nausea during migraines?
Delayed gastric emptying
Reduced perstalsis
What happens if a patient doesn't respond to
sumatriptan for migraines?
Try a different triptan
Why is ergotamine rarely used?
Side effects and difficulties in absorption
What are the side effects of ergotamine?
Nausea, vomiting, abdominal pain, muscle cramps,
peripheral vasospasm (numbness, tingling of
extremities)
When is ergotamine (ergot alkaloid) contraindicated?
Cerebrovascuar and cardiovascular disease
When should ergotamine (ergot alkaloids) be
discontinued?
If numbness or tingling of extremities occurs
What is the mechanism of 5HT1 receptor agonists
'triptans'?
They are selective serotonin receptor agonists. Act on
5HT1D and 5HT1B present on cranial arteries and veins
to cause vasoconstriction
How are triptans dosed during an acute migraine attack?
Take one dose ASAP after onset, followed by a second
dose at least 2 hours later (4 hours if naratriptan) if
migraine recurs. Do not take a second dose for the same
attack
Not for hemiplegic, basilar or ophthalmoplegic migraines
 6

What are the contraindications for use of triptans?
Ischaemic heart disease, previous MI, coronary
vasospasm, prinzmetal's angina, uncontrolled or
moderate-severe hypertension, peripheral vascular
disease, previous stroke/TIA
Not for hemiplegic migraine (one side of the body
goes numb), basilar migraine (caused by blood vessel
at the base of the brainstem going into spasm), or
ophthalmoplegic migraine (pain is felt around the eye
and causes brief attacks of blindness or visual
problems e.g. flashing lights in one eye)
What are the side effects of triptans?
Coronary vasoconstriction or anaphylaxis
warm sensations
tightness
tingling
flushing
feelings of heaviness in the face, limbs or chest
nausea
drowsiness
dry mouth
Nortriptyline (may be better tolerated than
amitriptyline)
Antiepileptics:
Gabapentin
Pregabalin
If there is inadequate response to other drugs, opioids
can be given. Morphine and oxycodone are prescribed
by a specialist only. Tramadol can be prescribed with a
non-specialist in the meantime whilst waiting for a
specialist assessment
Can amitriptyline and gabapentin be used together?
Yes if pain is not controlled by one alone taken at the
maximum tolerated dose
Which drugs are used for compression neuropathy?
Corticosteriods
What is trigeminal neuralgia?
A sudden and severe nerve disorder that causes a
stabbing or electric-shock-like pain in parts of the face
(jaw, teeth, gums)

When should triptans be discontinued? How is trigeminal neuralgia treated?

Stop if intense tingling, heat, heaviness, pressure or Carbamazepine - can reduce frequency and severity of
tightness in any part of the body occur attacks when taken in the acute stages of trigeminal
neuralgia
What is a cluster headache? Phenytoin - may be given IV in a crisis
A neurological disorder characterized by recurrent Surgery may be required
severe headaches on one side of the head, typically
around the eye. There is often accompanying eye How is chronic oral and facial pain managed?
watering, nasal congestion, or swelling around the eye Specialist referral as may require prolong use of
on the affected side. These symptoms typically last 15 analgesics
minutes to 3 hours
How is localised pain treated?
What are the treatments for the acute attack of a Topical local analgesic or capsaicin cream
cluster headache?
1st line: SC sumatriptan Initially 6 mg for 1 dose,
followed by 6 mg after at least 1 hour if required, to
be taken only if headache recurs (patient not
responding to initial dose should not take second dose
for same attack), dose to be administered using an
auto-injector; not for intravenous injection which may
cause coronary vasospasm and angina; maximum 12
mg per day.
2nd line: zolmitriptan nasal spray, 100% oxygen
What is used for the prophylaxis of a cluster
headache?
Prophylaxis for frequent attacks lasting more than 3
weeks: verapamil, lithium, prednisone, ergotamine

What drugs are used for the treatment of neuropathic

pain?
TCAs:
Amitriptyline