Pharmacology of pain control

Question 1

Acute pain

Answer 1

Minutes, hours, days

Well defined onset

Associated with objective and subjective physical signs

Hyperactivity of the autonomic nervous system

Responds well to analgesia and treatment of underlying problem

Question 2

Chronic pain

Answer 2

Weeks, months

Associated with significant changes in lifestyle, function and personality

More challenging management

Question 3

Types of nociceptive pain

Answer 3

Somatic

Visceral

Question 4

Somatic pain

Answer 4

Causes: activation of nociceptors in skin, muscle and bone

Symptoms: localised, aching, throbbing, gnawing

Examples: bone metastasis, tumour invasion into soft tissue, muscle spasticity

Question 5

Visceral pain

Answer 5

Causes: activation of nociceptors from stretching, distension or inflammation

Symptoms: poorly localised, deep aching, cramping, pressure, referred pain

Examples: bowel obstruction, pancreatic cancer, liver metastases, capsular pain

Question 6

Neuropathic pain

Answer 6

Causes: direct damage to PNS or CNS

Symptoms: burning, shooting, stabbing, electric shock, altered sensation

Examples: damage to nerve plexus, post hepatic neuralgia, spinal cord compression, diabetic neuropathy

Question 7

Ascending pain pathways

Answer 7

Nociceptors

C fibres and A-delta fibres

Spinal ganglia

Dorsal horn

Lateral spinothalamic tract

Pain perception point

Question 8

Descending

Answer 8

Brain (cortex and thalamus)

Periaqueductal grey

Rostral ventral medulla

Dorsal root ganglion

Question 9

WHO analgesic ladder

Answer 9

Step1: non-opiod analgesic + adjuvant

Step 2: weak opioid + non-opioid + adjuvant

Step 3: Strong opioid + non-opioid + adjuvant

Question 10

Non-opioid

Answer 10

Paracetamol

Aspirin

NSAIDs

Question 11

Weak opioid

Answer 11

Tramadol

Codeine

Dihydrocodeine

Question 12

Strong opioid

Answer 12

Morphine

Oxycodone

Fentanyl

Diamorphine

Alfetanil

Hydromorphone

Question 13

Types of adjuvants

Answer 13

Pharmacological

Non-pharmacological

Question 14

Pharmacological adjuvants

Answer 14

Corticosteroids

Antidepressants

Antiepileptics

Anti-muscarinics

Benzodiazepines

Bisphosphonates

Ketamine

Question 15

Non-pharmacological adjuvants

Answer 15

TENS

Acupuncture

Massage

Heat

Psychological support and relaxation

Radiotherapy

Interventional techniques

Question 16

Opioid receptors

Answer 16

G protein coupled receptors

3 main subtypes (Mu, kappa, delta)

Locations

• CNS (cortex, thalamus, hypothalamus, PAG, RVM)
• other (enteric plexus of gut, peripheral sensory afferent nerves, dorsal root cells, immune cells)

Question 17

Mu opioid receptors

Answer 17

Endogenous opioid
- beta- endorphins

Drug effects of receptor binding
- analgesia, respiratory depression, euphoria, miosis, constipation

Question 18

Kappa opioid receptor

Answer 18

Endogenous opioid
- dynorphins

Drug effects of receptor binding
- analgesia, dysphoria, miosis, diuresis

Question 19

Delta opioid receptor

Answer 19

Endogenous opioid
- enkephalins

Drug effects of receptor binding
- analgesia, respiratory depression

Question 20

Opioid effects: analgesia

Answer 20

Anti-nociception and effect on emotional response

Direct inhibition of ascending transmission of nociceptive information from the spinal cord dorsal horn

Activation of descedning pain control circuits from the midbrain to the dorsal horn

Question 21

Opioid effects: psychotropic

Answer 21

Anxiolysis and euphoria may also help with analgesic properties

Question 22

Opioid effects: respiratory depression

Answer 22

Direct effect on respiratory centre in medulla

Example: oramorph for SOB in patients with ed stage COPD

Question 23

Opioid effects: suppression of cough reflex

Answer 23

Example: codeine linctus for cough

Question 24

Opioid effects: constipation

Answer 24

Delayed gastric emptying and inhibition of peristalsis

Example: codeine for high output stoma

Question 25

Opioid toxicity: symptoms

Answer 25

Drowsiness

Myoclonic jerks

Pinpoint pupils (miosis)

Respiratory depression

Agitation

Confusion

Vivid dreams

Hallucinations

Question 26

Opioid toxicity: management

Answer 26

Mild-moderate

• reduce or stop opioid
• check renal and hepatic function
• ensure adequate hydration

Severe toxicity

• RR <8, decreased O2 sats, unresponsive
• naloxone

Question 27

Codeine

Answer 27

Action: Mu receptor

Dose: 15-60mg PO QDS (240mg/24 hrs)

Major side effects: constipation

Morphine equivalence: ÷10

Question 28

Dihydrocodeine

Answer 28

Action: Mu receptor

Dose: 15-60mg PO QDS (240mg/25 hrs)

Major side effects: constipation

Morphine equivalence: ÷10

Question 29

Tramadol

Answer 29

Action: Mu receptor monoaminergic

Dose: 50-100mg PO QDS (400mg/24 hrs)

Major side effects: N&V, sedation

Cautions: elderly, MAOIs, seizures

Morphine equivalence: ÷5-10

Question 30

Morphine pharmacology

Answer 30

Mu and kappa receptor agonist

Good oral absorption

Metabolised in the liver

Excreted in the urine

Immediate release preparations

• oramorph
• sevredol

Modified release preparations

• MST
• zomorph

Question 31

Oxycodone

Answer 31

Semi-synthetic opioid

Full opioid agonist

Metabolised by the liver

Given orally

Immediate release and modified release preparations

Question 32

Hydromorphone

Answer 32

Similar action to morphine through more selective mu-receptor agonism

Metabolised in the liver

Can be used in caution in patients with mild to moderate renal impairment

Given orally

Immediate and modified release preparations

Question 33

Fentanyl

Answer 33

High potent, only consider in patients tolerant to opioids

Patches

• not suitable with unstable/ rapidly escalating pain
• depot will remain in skin for 24hrs post removal

Lozenges

• rapid onset of action
• shorter duration of effect

Question 34

Alfentanil

Answer 34

Third line opioid used with specialist advice

Very potent, short acting

Synthetic derivative of fentanyl

Metabolised in the liver, inactive metabolites

Opioid of choice when eGFR <30ml/min