Opoids Flashcards
What are included in the WHO’s step 1 in the analgesic ladder?
- Nonopoid
- Analgesics
- NSAIDs
What are included in the WHO’s step 2 in the analgesic ladder?
Weak opioids
What are included in the WHO’s step 3 in the analgesic ladder?
- Strong opioids
- Methadone
- Oral administration
- Transdermal patch
What are included in the WHO’s step 4 in the analgesic ladder?
- Nerve block
- Epidurals
- PCA pump
- Neurolytic block therapy
- Spinal stimulators
What is opium?
Natural extract of the poppy Papaver somniferum. It contains morphine and other related compounds
What is an opioid?
Any substance (natural or synthetic) that produces morphine like effects which are blocked by a morphine antagonist
What is an opiate?
A naturally occuring opioid (e.g. morphine)
What is the “ceiling effect”?
- Seen in opioids
- Escalation of dose typically causes side effects without improving analgesia
What are examples of strong opioids?
- Morphine
- Oxycodone
- Diamorphine (heroin) (highly lipid soluble)
- Fentanyl (most commonly used IV opioid)
- Pethidine (also anticholinergic, tachycardic, will not give pinpoint pupils)
- Remifentanil (short acting, used in intensive care and anesthesia)
- Methadone
Conversion factors
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What are examples of weak opioids?
- Codeine
- Dihydrocodeine
- Loperamide (immodium) (not analgesic, opioid receptors in myenteric plexus, used for diarrhoea)
What is significant property of weak opioids?
- Partial agonsits
- Have a ceiling effect
What opioid is used to treat diahhroea?
Loperamide
What is tramadol?
- First developed as anti-depressant
- Found to have analgesic actions
- Serotonin and opioid receptors
- Pro-convulsant drug
What opioid should be avoided in epilepsy?
Tramadol
By what route are opioids given post-operatively?
- IV
- IM (through buttock)
What nerve must be avoided during IM injection through the buttocks?
Sciatic
By what route are opioids given in palitive care usually?
- Oral (most common)
- Trans-dermal patches (fentanyl)
When in labour, how can opioids be delivered?
The extra-dural route
- Catheter is placed in extra dural space, either by bolus or infusion, usually with mixture of local anesthetic
What drug can be given via lozenges often in military settings?
Fentanyl (oral transmucosal route)
What is oral bioavailibility?
Percentage of total dose that reaches systemic circulation
Give an example of a prodrug?
Codeine (has to be metabolised in liver)
Where does the vast majority of opioid action take place?
Mu opioid receptor (MOP)
What are 4 different types of opioid receptors?
- Mu opioid peptide receptor (MOP)
- Kappa (KOP)
- Delta (DOP)
- Nociception
Where are mu opioid receptors found?
All over the NS
- Specifically pain, peripheral afferent nerve terminals, dorsal horn, PAG, thalamus, cerebral cortex
On the primary afferents where are the opioid receptors?
Pre-synaptic
- Inhibit the release of glutamate on dorsal horn (diminish the transmission of nociceptor stimulus)
What are examples of endogenous opioids?
- Endorphins (produced in pituitary)
- Dinorphins
- Enkephalins
Describe the structure of the opioid receptor?
- Proteins with a serpentine formation with 7 transmembrane spanning proteins
- Couples to G proteins
Following activation by an opioid what happens to the receptor at a cellular level?
- Closure of voltage sensitive Ca2+ channels
- Opening of K+ channels, K+ efflux causes hyperpolarisation of the cell, less likely to depolarise
- Ca2+ influx reduces Neurotransmitter release
- Inhibition of adenylate cyclase (ATP not converted to cAMP)
- Reduction in neurotransmitter release (principally glutamate)
What is the effect of opioids on the respiratory rate?
- Brain becomes less sensitive to rising CO2 levels and Respiratory Rate depressed, tidal volume depressed also
- Anti tussive (codeine linctus)
- Morphine can cause bronchoconstriction in patients with asthma - histamine release
What is the effect of opioids on the cardiovascular system?
- Bradycardia (pethidine exception)
- Direct action on SA node
- Decreased sympathetic drive
- Peripheral vasodilation (morphine due to histamine release)
What is the effect of opioids on the GI system?
- Delayed motility - nausea and constipation
- Direct action on CTZ and vestibular sensitisation increased
- Constipation (usually prescribed with laxatives)
What are other side-effects of opioids?
- Urticaria, due to Ach release, causes itch
- Urinary retention
- Abcesses, immune supression
- Decreased ACTH, Prolactin, increased ADH
What percentage of people metabolise codeine at a slow rate?
- Western europeans (8-10%)
- Africans (0-20%)
- East Asian (0-1%)
A mutation in what causes a defect in codeine metabolism?
CYP2D6
What percentage of people are ultra fast codeine metabolisers?
- Western europeans: 1-4%
- Southern europeans: 7-10%
- Africans: 5-30%
- Arabians: Up to 20%
Death in children due to codeine was though to be due to what?
Ultra-fast metabolism
Where are active opioid metabolites excreted?
Kidneys (renal imapairment may lead to toxicity)
What is usually the opioid of choice for people with renal impairment?
Fentanyl (not metabolised to active metabolites)
What can pinpoint pupils indicate?
Opioid toxicity
What is the starting dose for morphine in adults?
Parenteral dose:
- 10mg (0.1mg/kg)
Oral dose:
- 30mg (0.3mg/kg)
What is the starting dose for fentanyl in adults?
Parenteral dose:
- 100 micrograms (1 - 2 micrograms / kg)
What is an opioid antagonist that is used to treat opioid overdose and what are some of its properties?
Naloxone
- High affinity for the receptor but no intrinsic activity
- Titrated in
What is an opioid antagonist that can be used to treat addiction?
Naltrexone
How can methadone affect a patient’s dental hygiene?
- Sugary
- Dries mouth and stops secretions in mouth
- Can give patients “munchies”
What is methadone’s biovailibility?
High oral
- Low first pass metabolism
