Narcotic analgesics Flashcards
Where can you prevent transmission of pain?
You can prevent the transmission of noxious stimuli in the dorsal horn of the spinal cord (in the substantia gelatinosa). The neurotransmitter here is substance P.
What are the classification of endogenous and exogenous opioids?
Endogenous opioids include:
• Enkephalins
o Met-enkephalin
o Leu-enkephalin
• Endorphins
o Β-endorphin
• Dynorphins
Exogenous opioids can be classified by their pharmacodynamic profile into:
• Agonists – for example morphine
• Partial agonists – for example buprenorphine
• Agonist/antagonist – for example nalbuphine
• Antagonist - naloxone
What are the opioid receptors?
- μ – supraspinal distribution, responsible for analgesia
- δ – can be stimulated by enkephalins
- κ – found in spinal cord, responsible for analgesia
How do opiates reduce pain?
Opioid receptors are expressed both pre and post synaptically. Binding the receptors results in:
• outward flux of potassium which makes the resting membrane potential more negative and reduces excitability
• reduced influx of calcium preventing release of neurotransmitter
• decreased cAMP synthesis so less phosphorylation activating calcium channels
• As a result, pain transmission is reduced and in the gate control theory there is less substance P released at the synapse so pain signal propagated less to the brain
What are major therapeutic uses of opitates?
- Analgesia – moderate to severe pain, particularly of visceral origin – eg codein for moderate or morphine for severe
- Terminal illness analgesia – no need to worry about dependence as will be on it until end of life
- Diarrhoea – slow nervous transmission in bowel – eg morphine or loperamide is an opioid that cannot cross the BBB so only acts on the bowel to reduce motility
- Maintenance in dependence – prevent use of more potent heroin whilst preventing withdrawal symptoms – eg methadone or buprenorphine (partial agonist)
- Anaesthesia – numbs pain so much can be used as anaesthesia – eg fentanyl, alfentanil or remifentanil but can all cause histamine release as ADR
- Labour analgesia – however controversial as relaxes smooth muscle when you need uterine contraction? – eg pethidine
What are ADRs of opiates?
ADRs due to binding of the μ-opioid receptor include: • Nausea • Vomiting • Constipation • Drowsiness • Miosis • Dependence and tolerance - people need higher doses to get same effects • Respiratory depression • Hypotension
What should be used in opiate overdose?
Naloxone - opiate antagonist
an opioid receptor antagonist very useful at blocking the effects of opioid agonists in overdoses to reduce the toxicity and reverse respiratory depression. Has a half-life of just 1 to 1.5 hours so needs to be repeatedly administered until the opioid agonist has cleared to prevent recurrence of symptoms
What is morphine used for?
gold standard analgesic that all new ones have to be compared against. Not very lipid soluble so low oral bioavailability. Half-life of 4 hours. Its metabolites can be screened for in urine.
What is tramadol used for?
moderate analgesic with 5-HT and NA re-uptake blocking effects thus also having antidepressant actions which can improve the gate control theory
What is diamorphine used for?
Analgesia - lipid soluble so crosses BBB easily and just half-life of 5 minutes before metabolised to morphine which is then in brain to exert actions
What is codeine used for?
moderate analgesic that gets metabolised to morphine by CYP2D6, an enzyme that has lots of polymorphisms so codeine may be ineffective in individuals lacking this enzyme as morphine not produced (eg Chinese population particularly)
What is methadone used for?
used in opioid addiction as weaker agonist but still gives relief preventing withdrawal symptoms, but is highly protein bound (90%) so potential for DDIs when used with other protein bound drugs such as NSAIDs and sulphonylureas
What is opioids are used for anaesthesia?
Fentanyl, alfentanil, remifentanil.
