Opioids Flashcards
What the 3 main opioid receptors and their function?
- They are all G-protein coupled receptors – opens K+ channels & closes Ca2+ channels.
- Widely distributed in CNS, spine, GI tract
- Mu (µ) – analgesia, euphoria (but also constipation, respiratory depression)
- Kappa (κ) – analgesic at periphery (but dysphoria, hallucinations)
- Delta (δ) – analgesia at spine?
How does morphine work as an analgesic?
- Morphine attaches to opioid receptor e.g. mu, kappa or delata.
- Morphine reduces membrane excitability & therefore decreases frequency of action potential firing
- Opioids act on dorsal horn & peripheral terminals of nociceptive afferent neurones
- This prevents pain signals travelling up the spinal column.
- Morphine also increases release of enkephalins (endogenous opioid) & 5-HT onto the dorsal horn neurones, via stimulation of the periaqueductal grey matter (PAG) & raphe nucleus.
Define pharmacokinetics and Pharmacodynamics
Pharmacokinetics – how the body affects the drug e.g. absorption, clearance.
Pharmacodynamics – how the drug affects the body.
When might you prescribe an opioid?
Morphine= moderate-severe pain acutely.
Morphine or diamorphine = chronic pain, usually palliative.
Codeine= mild pain or when paracetamol/ NSAID are not effective or suitable.
How are opioids used in the pain ladder?
- Non-opioid e.g paracetamol
- Adjuvant e.g. NSAIDS -Ibuprofen, Diclofenal
- Opioid (mild) e.g. Codeine, Dihydrocodeine, Tramadol
- Opioid (mod-severe) e.g. Morphine
Commonly used opiates?
- Morphine
- Diamorphine
- Oxycodone
- Methadone
- Fentanyl
- Codeine
- Tramadol
- Naloxone
When not to prescribe an opioid?
Neuropathic pain- tingling or electric shock pain in peripheral nerves.
Migraine or tension headaches.
Morphine: use, pharmacological effects, side effects, pharmacokinetic considerations & prescribing considerations?
Use:
- severe pain, particularly by injection.
- Acute & chronic pain.
Pharmacological effects:
- CNS: analgesia, euphoria, sedation, pupillary constriction (caused by µ and κ receptor-mediated stimulation of the oculomotor nucleus)
- GI: nausea & vomiting (chemoreceptor trigger zone in medulla), constipation (from reduced motility & muscle tightening in gut)
- Respiratory- Depression (inhibits respiratory centres in brainstem),
Suppress cough reflex
Side effects:
Acutely – sedation, respiratory depression, vomiting.
Chronic – constipation.
Tolerance w/ recurrent use:
- Desensitisation of mu receptors
- Increasing doses needed to achieve sufficient analgesia
Dependence causes problems w/ opioid withdrawal
- Physical withdrawal – restlessness, aggression, runny nose, diarrhoea, shivering - when opioid is abruptly withdrawn.
- Psychological withdrawal – cravings may persist months or years.
Pharmacokinetic considerations:
- Short half-life (3-4 hrs) = given several times a day
- Metabolised in liver & then excreted in urine.
- Oral absorption relatively slow & inconsistent- requires higher dose than injection.
- Active metabolite morphine-6-glucuronide eliminated by kidney
- Liver & kidney failure= morphine may not be removed quick enough = builds up = toxicity
Prescribing considerations:
- IV/IM morphine – choose lower dose compared to oral.
- If changing from 1 opioid to another, must check BNF ‘Prescribing in Palliative Care’ section to ensure equivalence in dosing
- Synthetic opioid patches release drug for days & days- Must check & remove if toxicity suspected
Prescribe morphine w/:
- Anti-emetic e.g. metoclopramide, ondansetron - stops vomiting.
- Laxatives if long-term use- stops constipation.
What are examples of opioid receptor antagonists (to counteract effects of opioids)?
- Naloxone
- Reverses opioid actions on mu receptor
- Given IV/SC in acute opioid toxicity e.g. drowsy patient w/ small pupils & poor respiration.
- Can trigger acute physical withdrawal = aggressive & irritable. - Naltrexone – aids detox in opioid & alcohol withdrawal programmes.
- Methylnaltrexone, naloxegol – peripheral action to prevent GI problems w/ morphine e.g. constipation.
Diamorphine: use & pharmacodynamics?
Use:
- palliative care when high doses need to be given in small volume syringe
Pharmacodynamics:
- More potent & soluble than morphine- so can use half the dose you would w/ morphine.
- Is pro-drug – converted in body to 6-monoacetylmorphine & morphine
- Crosses blood-brain barrier easily – rapid ‘high’ favoured by IV users.
Codeine: Use, pharmacodynamics & problems?
Use:
- Mild-moderate pain
- Sometimes in combination of co-codamol (paracetamol & codeine together in one tablet)
- Used when NSAIDs are contraindicated e.g. peptic ulcers.
- Chronic diarrhoea
Pharmacodynamics:
- Pro-drug that is demethylated by liver CYP2D6 to become morphine.
Problems:
1. Reasonably well-absorbed orally but only limited fraction converted to morphine, thus cannot provide strong analgesia.
2. Genetic variation in liver CYP enzymes – so less predictable response.
- Serious toxicity noted in susceptible children
- Other patients – poor analgesic benefit
- Depends on the variation in the liver enzymes
Methadone: use, pharmacokinetics & caution?
Use:
- Substitution therapy to reduce IV drug abuse
- Often part of supervised regime where community patients go to local pharmacy to pick up methadone.
- Safer to used oral methadone than using needles for heroin.
Pharmacokinetics
- Synthetic opioid
- Good oral absorption
- Half-life may exceed 24 hrs w/ regular dosing
Caution
- Highly toxic in overdose because of very long half-life
How can risk of addiction be reduced and managed?
Addiction should be discussed w/ all patients being considered for long term opioid treatment
Opioids should be used only after other evidence based interventions have been tried
Clear aim of therapy should be agreed w/ patient before starting opioids
Advice from specialist in pain medicine & addiction medicine should be readily available
What are the risk factors for developing opiate addiction?
Current or past history of substance misuse including alcohol
Family member w/ history of misuse
Poor social support
Co-morbid psychiatric disorders
What is tolerance? How can we reduce tolerance?
Increasing dose to get the same pharmacological response
- i.e. receptor desensitisation or removal of receptors.
By swapping the drug for another.
