Opiods Flashcards
What is nociception?
Non-conscious neural traffic due to trauma or potential trauma to tissue
What is pain?
Complex, unpleasant awareness of sensation modified by experience, expectation, immediate context and culture.
How do you feel pain?
- Nociceptors stimulated
- Release of substance P and glutamate.
- Afferent nerve stimulated
- Fibres decussate
- Action potential ascends
- Synapses in thalamus
- Project to post central gyrus
How can we modulate pain?
Have modulators in peripheral system and in central system.
Peripherally: Substantia Gelatinosa
Centrally: Peri-aqueductal grey
How can we modulate pain peripherally?
Tissue damage then through Ad and C fibres to the substantia gelatonosa then up spinothalamic tract to the thalamus.
Also, if we ‘rub it better’ it stimulates the Ab fibres which simulate the lamina and cause inhibition of Ad and C fibres.
How do we modulate pain centrally?
Pain acting on thalamus and cortex stimulate the Periaqueductal grey matter.
MOP
Supraspinal / GI tract
Decreased cAMP
Outward flux of potassium
Hyperpolarisation and decrease Substance P release
Enkephalins and B-endorphins
Analgesia, depression, euphoria, dependence, respiratory sedation
DOP
Wide distribution
Decreased cAMP
Influx of Ca
Hyperpolarisation and decrease of substance P release
Enkephalins
Analgesia, inhibit dopamine, modulate u
KOP
Spinal cord / Brain / Periphery
Decreased cAMP
Efflux of potassium, Influx of calcium.
Hyperpolarisation and decrease substance P release.
Describe the WHO analgesic ladder
Simple analgesia e.g. paracetamol / NSAIDs
Weak opioid e.g Codeine
Strong opioid e.g. Morphine, fentanyl
What do you take for arthritic pain?
NSAIDS
What do you take for neuropathic pain?
Anticonvulsants
Tricyclics
SSRIs
SNARIs
Describe the opiods as a class
Exploit natural opioid receptors either agonise or antagonise
Main therapeutic effects via u-receptors
Aim to modulate pain
Also indicate in cough, diarrhoea, palliation
How can you give morphine?
PO, IV, IM, SC, PR
But, gut absorption can be erratic
Significant first pass effect - 40% oral bioavailability.
IV and SC tend to be better.
Describe distribution, metabolism and elimination of morphine
Distribution: Rapidly enters all tissues including foetal
Struggle to cross blood-brain barrier.
Metabolism: Morphine + glucuronic acid - M6G + M3G
Eliminated renally.
On what receptors does morphine mostly act?
U (MOP) receptors - complete activation of u.
How does morphine work?
Analgesia
Euphoria
What are the side effects of morphine?
Respiratory Depression - medullary resp centre less responsive to CO2.
Emesis - stimulate CTZ
GI tract - decrease motility, increasing sphincter tone
Cardiovascular
Miosis
Histamine release - careful with asthmatics.
Describe the absorption, distribution, metabolism and elimination of Fentanyl
Absorption: IV, epidural, Intrathecal, Nasal
Distribution: Highly lipophilic, highly protein bound, high level of CNS crossing
Metabolism: Hepatic via CYP3A4
Elimination: Half life 6 minutes, renally excreted
How is fentanl different to morphine?
100% potency - MUCH more potent
Higher affinity fo u receptor.
Actions of fentanyl
Analgesia
Anaesthetic
What are the side effects of fentanyl?
Respiratory distress
Constipation
Vomitting
Describe the absorption, metabolism and elimination of codeine
Absorption: PO, SC administration
Metabolism: Codeine to morphine via CYP2D6. This enzyme has extremely variable expression. CYP2D6 inhibited by fluoxetine.
Elimination: Glucoronidation of morphine and renal excretion
How potent is codeine compared to morphine?
Approx 1/10th potency
Describe the actions of codeine
Mild to moderate analgesia
Cough depressant
What are the side effects of codeine?
Constipation
Respiratory depression - worse in children
Describe absorption, metabolism and elimination of Buprenorphine
Absorption: Transdermal, Buccal, Sublingual
Distribution: Very lipophilicity
Metabolism: Hepatic via CYP3A3 then glucoronidation before biliary excretion.
Elimination: Biliary > Renal
Safe in renal impairment
Half life 37 hours.
How does buprenorphine compare to morphine?
Very high affinity for u receptor. Low Kd. Long duration of action Not easily displaced Lower Emax as partial agonist, lower efficacy Antagonist at k receptors.
What can you use buprenorphine for?
Moderate to severe pain
Opioid addiction treatment
What are the side effects of buprenorphine?
Respiratory depression
Low Bp
Nausea
Dizziness
Describe the absorption, metabolism and elimination of Naloxone
Absorption: IV, IM, Intranasal, PO
Very low oral bioavailability as extensive first pass effect
Rapid onset of action
Distribution:
Rapid distribution as very lipophilic
Metabolism: Hepatic - naloxone-3-glucuronide
Renal excreted
Elimination: Duration of action 30-60mins
How does naloxone compare to morphine?
Affinity u>d>k
Greased affinity than morphine
Affinity less than buprenorphine
What are the actions of naloxone?
Competitive antagonism of opioids.
What are the side effects of naloxone?
Short half life
Slow infusion
Describe how opioid tolerance occurs
Up-regulate by making more receptors so synthetic bind and endogenous no longer cause a response.
What do you use for opioid withdrawal?
Methadone - reduced E(max) and reduced side effects
Why is overdose a growing problem?
As abusing drugs prescribes and abusing drugs need as not got opioids anymore.
Prescribe short courses a much as you can.
Describe an overdose of opioids
u receptor
Variable effects of doses
Respiratory depression most common cause of death
Can decrease effects - d agonist, 5HT4 agonists
Naloxone infusion as treatment.
What symptoms do you get in an overdose of opioids?
Dependace Vomiting Constipation Hypotension and bradycardia Decreased sex drive Histamine release Miosis Drowsiness Respiratory depression Apnoea
What groups of patients require special consideration?
Manual labourers / drivers Elderly Bedbound Asthmatics Biliary tract obstruction Respiratory disease Renal impairment Pregnancy
In who are opioids completely contraindicated?
Hepatic failure Acute respiratory distress Comatose Head injury - as already disrupt blood brain barrier Raised ICP
How do you prescribe opioids in palliative prescribing>
Difficult as Harold Shipman
Tend to ignore special considerations
Indications: Pain, Shortness of breath
Manage side effects: Nausea, constipation
What do opioids prescriptions have to include?
Date and prescribers address and full name.
Patient address and name
Form of the drug - tablets, syrup, capsules, catches, ampoules ect.
Units - mg, mls, ect.
Total volume - words and figures
Clearly defined doses.
Why are opioids controlled under the misuse of drugs legislations?
Aim to prevent:
Misuse
Illegal obtainment
Harm being caused
