Pharmacology of pain control Flashcards by Holly O'Flanagan

Acute pain

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

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Chronic pain

Weeks, months

Associated with significant changes in lifestyle, function and personality

More challenging management

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Types of nociceptive pain

Somatic

Visceral

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Somatic pain

Causes: activation of nociceptors in skin, muscle and bone

Symptoms: localised, aching, throbbing, gnawing

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

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Visceral pain

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

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Neuropathic pain

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

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Ascending pain pathways

Nociceptors

C fibres and A-delta fibres

Spinal ganglia

Dorsal horn

Lateral spinothalamic tract

Pain perception point

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Descending

Brain (cortex and thalamus)

Periaqueductal grey

Rostral ventral medulla

Dorsal root ganglion

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WHO analgesic ladder

Step1: non-opiod analgesic + adjuvant

Step 2: weak opioid + non-opioid + adjuvant

Step 3: Strong opioid + non-opioid + adjuvant

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Non-opioid

Paracetamol

Aspirin

NSAIDs

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Weak opioid

Tramadol

Codeine

Dihydrocodeine

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Strong opioid

Morphine

Oxycodone

Fentanyl

Diamorphine

Alfetanil

Hydromorphone

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Types of adjuvants

Pharmacological

Non-pharmacological

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Pharmacological adjuvants

Corticosteroids

Antidepressants

Antiepileptics

Anti-muscarinics

Benzodiazepines

Bisphosphonates

Ketamine

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Non-pharmacological adjuvants

TENS

Acupuncture

Massage

Heat

Psychological support and relaxation

Radiotherapy

Interventional techniques

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Opioid receptors

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)

Mu opioid receptors

Endogenous opioid
- beta- endorphins

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

Kappa opioid receptor

Endogenous opioid
- dynorphins

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

Delta opioid receptor

Endogenous opioid
- enkephalins

Drug effects of receptor binding
- analgesia, respiratory depression

Opioid effects: analgesia

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

Opioid effects: psychotropic

Anxiolysis and euphoria may also help with analgesic properties

Opioid effects: respiratory depression

Direct effect on respiratory centre in medulla

Example: oramorph for SOB in patients with ed stage COPD

Opioid effects: suppression of cough reflex

Example: codeine linctus for cough

Opioid effects: constipation

Delayed gastric emptying and inhibition of peristalsis

Example: codeine for high output stoma

Opioid toxicity: symptoms

Drowsiness Myoclonic jerks Pinpoint pupils (miosis) Respiratory depression Agitation Confusion Vivid dreams Hallucinations

Opioid toxicity: management

Mild-moderate - reduce or stop opioid - check renal and hepatic function - ensure adequate hydration Severe toxicity - RR <8, decreased O2 sats, unresponsive - naloxone

Codeine

Action: Mu receptor Dose: 15-60mg PO QDS (240mg/24 hrs) Major side effects: constipation Morphine equivalence: ÷10

Dihydrocodeine

Action: Mu receptor Dose: 15-60mg PO QDS (240mg/25 hrs) Major side effects: constipation Morphine equivalence: ÷10

Tramadol

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

Morphine pharmacology

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

Oxycodone

Semi-synthetic opioid Full opioid agonist Metabolised by the liver Given orally Immediate release and modified release preparations

Hydromorphone

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

Fentanyl

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

Alfentanil

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