The pharmacology of pain control Flashcards
What is pain?
Subjective
Complex
“What the patient says hurts”
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”
Describe 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
Describe chronic pain
Weeks, months
Associated with significant changes in lifestyle, function and personality
More challenging management
State a cause of somatic nociceptive pain
Activation of nociceptors in skin, muscle and bone
State a cause of visceral nociceptive pain
Activation of nociceptors from stretching, distension or inflammation
State a cause of neuropathic pain
Direct damage to PNS or CNS
What are the symptoms of somatic nociceptive pain
Localized, aching, throbbing, gnawing
What are the symptoms of visceral nociceptive pain
Poorly localized, deep aching, cramping, pressure
also referred pain
What are the symptoms of neuropathic pain
Burning, shooting, stabbing, electric shock. May be associated altered sensation. Often dermatomal
Give examples of neuropathic pain
Damage to nerve plexus, post herpetic neuralgia, spinal cord compression, diabetic neuropathy
Give examples of visceral nociceptive pain
Bowel obstruction, pancreatic cancer, liver metastases
(capsular pain)
Give examples of somatic nociceptive pain
Bone metastasis, tumour invasion into soft tissue, muscle spasticity
Name two types of pain classified in terms of pattern
Background pain
Breakthrough pain
What is total pain?
The cumulative of social, psychological, physical and spiritual pain
Describe the ascending pain pathways
Nociceptors (receptors)
A-delta fibres (fast transmission of sharp localised pain)
C-fibres (slow transmission of dull burning chronic pain)
Spinal ganglia
Dorsal horn (pain signal is modified)
Lateral spinothalamic tract
Pain perception point
Somatosensory cortex and other areas of the brain
Where does pain processing occur in the brain?
Somatosensory cortex
Prefrontal cortex
Thalamus
What factors play a role in pain processing?
Mood
Beliefs
Cognition
Genetics
Describe the descending pain pathway
Cortex Thalamus Periaqueductal grey matter Rostral ventral medulla Dorsal root ganglia Spinal cord
What do the periaqueductal grey matter and the rostral ventral medulla contain?
High levels of opioid receptors
What does the 5HT/NA neuron control?
Controls/inhibits communication between the 1st and 2nd order neuron in the ascending pathway
Describe the WHO analgesic ladder
Non-opioid analgesic +/- adjuvant
Weak opioid analgesic +/- Non-opioid analgesic +/- adjuvant
Strong opioid analgesic +/- Non-opioid analgesic +/- adjuvant
List some non opioid analgesics
NSAIDs
Paracetamol
Aspirin
List some weak opioid analgesics
Tramadol
Codeine
Dihydrocodeine
List some strong opioid analgesics
Morphine Oxycodone Fentanyl Diamorphine Alfentanil Hydromorphone
List some pharmacological adjuvants
Corticosteroids
Antidepressants - duloxetine, amitriptyline, mirtazapine
Antiepileptics - gabapentin, pregabalin
Antimuscarinics - Mebeverine and hyoscine
Benzodiazepines
Bisphosphonates
Ketamine
List some non-pharmacological adjuvants
TENs Acupuncture Massage Heat Psychological support and relaxation Radiotherapy Interventional techniques
What type of receptor are opioid receptors?
G protein coupled
Name the 3 main subtypes of opioid receptor
Mu
Kappa
Delta
Where are opioid receptors located?
CNS - cortex, thalamus, PAG, RVM Enteric plexus of the gut Peripheral sensory afferent nerves Dorsal root cells Immune cells
Name the endogenous opioid of mu receptors
Beta-endorphins
Describe the drug effects of mu receptor binding
Analgesia - spinal cord and brain
Name the endogenous opioid of kappa receptors
Dynorphins
Describe the drug effects of kappa receptor binding
Analgesia - spinal cord
Dysphoria
Miosis
Diuresis
Name the endogenous opioid of delta receptors
Enkephalins
Describe the drug effects of delta receptor binding
Analgesia - spinal cord
Respiratory depression
List the effects of opioids
Analgesia Psychotropic Respiratory depression Suppression of the cough reflex Constipation
Describe the analgesic effect of opioids
Anti-nociception and effect on emotional response
Direct inhibition of ascending pathway from spinal cord to dorsal horn
Activation of descending pathway from midbrain to dorsal horn
Describe the psychotropic effect of opioids
Anxiolysis and euphoria may also help with analgesic properties
When is an opioid used to induce respiratory depression?
SOB in a patient with end stage COPD (oramorph)
When is an opioid used for its constipative effect?
High output stomas (codeine)
List the adverse effects of opioids
Constipation Nausea and vomiting Sedation Dry mouth Pruritus
What are the symptoms of opioid toxicity?
Drowsiness Myoclonic jerks Pinpoint pupils (miosis) Respiratory depression Agitation Confusion Vivid dreams Hallucinations Tolerance Addiction Physical dependence
Describe the management of mild to moderate toxicity
Reduce or stop opiod
Check renal and hepatic function
Ensure adequate hydration
Describe the management of severe opioid toxicity
Naloxone
What are the signs of severe opioid toxicity
RR <8
Decreased O2 sats
Unresponsive
What is tolerance?
Increased dose required over time to produce a given pharmacological response. Related to receptor down regulation
What is addiction?
Pattern of behaviour characterised by craving of the psychic effect of the drug or the need to avoid withdrawal
Which receptor does codeine act on?
Mu receptor
Which receptor does Dihydrocodeine act on?
Mu receptor
Which receptor does tramadol act on?
Mu receptor
Monoaminergic
State the dose of codeine
15-60mg PO qds
240mg/24hrs max
What is the biggest side effect of codeine?
Constipation
State the does of dihydrocodeine
15-60mg PO QDS
240mg/24hrs max
What is the biggest side effect of codeine?
Constipation
State the dose of tramadol
50-100mg PO QDS
400m/24hrs max
What is the biggest side effect of tramadol?
Nausea and vomiting
Sedations
Who do you have to be cautious of prescribing tramadol?
Elderly
Seizures
MAOIs
What is the morphine equivalent of codeine?
/ 10
What is the morphine equivalent of dihydrocodeine?
/ 10
What is the morphine equivalent of tramadol?
/5-10
Which strong opioid is the 1st line on step 3 of WHO analgesic ladder?
Morphine
Describe the mechanism of action of morphine
Mu and kappa receptor agonist
Where is morphine metabolised?
Liver
How is morphine excreted?
Urine
List some immediate release preparations of morphine
Oramorph (suspension)
Sevredol (tablets)
List some modified release preparations of morphine
MST (tablets and suspension)
Zomorph (capsules)
How long does morphine IR take to peak onset?
15-30 mins
How long does morphine IR take for peak effect?
30mins-1hr
What is the half life of morphine IR?
2-4hrs
What is the duration of action of morphine IR ?
4hrs
How long does morphine IR take to reach steady state?
24hrs
How long does morphine SR take to peak onset?
2 hrs
How long does morphine SR take for peak effect?
3-4hrs
What is the half life of morphine SR?
2-4hrs
What is the duration of action of morphine SR?
12hrs
How long does morphine SR take to reach steady state?
24hrs
Describe oxycodone
Semisynthetic
Full opioid agonist
How is oxycodone metabolised?
By the liver
How is oxycodone given?
Orally
What preparations does oxycodone come in?
Immediate release
Modified release
Describe the mechanism of action of hydromorphone
Similar mechanism of action to morphine (mu and kappa agonist) though more selective for mu receptor agonism
Name a highly potent strong opiod that comes in a patch, lozenge or intranasally
Fentanyl
How long do fentanyl depto patches remain in the skin for?
24hrs post removal
What are fentanyl patches not suitable for?
Rapidly escalating/unstable pain
Describe the lozenge/intranasal/SL fentanyl
Rapid onset of action
Shorter duration of action
No relationship between most effective dose and effective background dose
Describe Alfentanil
3rd line opioid used with specialist advice Very potent Short acting (half life 30mins) Metabolised in liver Injectable
What is the opioid of choice when eGFR <30ml/min
Alfentanil
In whom may alfentanil clearance be reduced?
Liver impairment
Older patients
What is the breakthrough dose of opioid?
1/6 total daily dose
Which patients are required to have a breakthrough dose?
Any being prescribed a regular opioid
How should opioids be switched?
Dosing varies greatly between different opioids
Therefore care must be taken when switching between different opioids
Describe a method that opioids are administered
Opioid syringe pumps