Bone Pain - Pharmacology and Prescribing Flashcards
What is an opiate?
Compounds that are found in te opium poppy e.g., morphine and codeine
What is an opiod?
Any substance, whether endogenous or synthetic, produces morphine - like effects that are blocked by anatagonists
Where does opium come from?
Extract from seed capsule of opium poppy (papaver somnifermu)
Describe products directly derived from opium
Opium poppy
- White milky latex containing alkaloids
- Varying proportion of morphine, codeine, thebaine
Purification
- Extraction focused on obtaining morphine
- Further processing to obtain morphine derivatives
Chemical modification
- Heroin (3,6-diacetylymorphine or diamorphine)
- Codeine (3-methylmorphien)
Other opiods can be synthesised. What are the two products thebaine is synthesised to?
- Oxycodone
- Hydrocodone
There are laboratory production of substances that act on similar receptors to natural opiods. List 3 examples of these substances
- Fentanyl
- Methadone
- Buprenorphine
Describe the chemical structure of opiods
Opioid activity comes from free hyrdoxyl on benzene ring, linked with carbon atoms to a nitrogen
There are three main types of receptors. Name the three receptors and describe their role
- Mu (for morphine) - analgesia, euphoria (but also constipations and respiratory depression)
- Kappa (for ketocyclazocine) - analgesic periphery (also dysphoria and hallucinations)
- Delta [for (vas) Deferencs in mice] - analgesics at spine
What type of receptors are the Mu-opiod peoptide receptors and describe their role
The Mu-opioid peptide receptors are G-protein coupled receptors. They open K+ channels and close Ca++ channels
List 6 of the most common opiods
- Morphine
- Codeine
- Diamorphine
- Methadone
- Oxycodone
- Fentanyl
What systems does morphine have an effect on?
- CNS
- GI
- Respiratory
List the pharmacological effects of morphine on the CNS
- Analgesia
- Euphoria (particularly with IV administration)
- Sedation
- Pupillary construction (stimulation of oculomotor nucleus brainstem)
List the pharmacological effects of morphine on the GI
- Nausea and vomiting - chemoreceptors trigger zone in
- Constipation - from reduced motility and muscle tightening
List the pharmacological effects of morphine on the respiratory
- Depression - inhibits respiratory centres in brainstem
- Suppress cough reflex
Describe some of the safety problems regarding morphine
- Acute - sedation, respiratory depression, vomiting
- Chronic - constipation
- Tolerance with recurrent use - causes desensitisation of mu receptors therefore increasing doses needed to achieve sufficience analgesisa
- Dependance causes problems with opioid withdrawal - Physical e.g., restlessness, aggression, runny nose, diarrhoea, shivering and also psychological eg., cravings may persist months and years
Morphine
a) Indications
b) Pharmacokinetic problems
c) Often given together with:
a) Most important opioid for acute and chronic severe pain, particularly by injection
b)
- Oral absorption relatively slow and inconsistent so requires higher dose than injection
- Broken down by liver, half-life 3-4 hours only
- Active metabolite morphine-6-glucuronide elimanted by kidney
c)
- Anti-semetic (anti sickness) e.g., metoclopramide or ondansetron which prevents nause and vomiting
- Laxatives if long-term use (for constipation)
When is diamorphine used?
Palliative care
When is methadone used?
To help stop IV opiod abuse
Diamorphine
a) Indications
b) Comparison with morphine
c) Why is it favoured by iv users?
a) Typically used in palliative care when high doses need to be given in small volume syringes
b) More potent and soluble than morphine, so half the dose you would use for morphine can be used
c) It crosses blood-brain barrier easily, providing a rapid ‘high’
Codeine
a) What is codeine?
b) Indications
c) Provide a pro and con
a) Codeine is a pro-drug that is demethylated by liver CYP2D6 to become morphine
b) Mild-moderate pain (sometimes in combination with co-codamol), chronic diarrhoea
c) Pro - reasonably well-absored orally
Con - only a limited fraction is converted to morphine, thus cannot provide strong analgesia
Methadone
a) What is methadone?
b) Indications
c) Pro?
d) Caution
a) Synthetic opiod
b) Used as substitution therapy to reduce iv drug abuse
c) Good oral absorption
d) Highy toxic in overdose as it has a very long half-life
Oxycodone
a) Indications
b) Problem?
a) Used for acute and chronic pain
b) Has become a major drug of abuse
Fentanyl
a) Indications?
b) Advantage
a) Acute pain and anaesthesia
b) High potency so allows transdermal administration
What is the most important opioid receptor antagonist?
Naloxone
Naloxone
a) What is naloxone
b) Indications
c) Problem?
d) List 3 drugs related to naloxone and describe their role
a) Opioid receptor antagonist so reverses opioid actions on mu receptor
b) Given iv/sc in acute opioid toxicity e.g., drowsy patients with small pupils and poor respiration
c) Can trigger acute physical withdrawal
d) Other antagonists related to naloxone
- Methylnaltrexone, naloxegol - peripheral action to prevent GI problems with morphine
- Naltrexone - aids detox in opioid and alcohol withdrawal programme
What must you if you’re changing a patient from one opiod to another?
You must check BNF ‘Prescribing in Palliative Care’ section to ensure equivalence in dosing
What must you be careful of with synthetic opioid patches?
Synthetic opioid patches go on releasing the drugs for days so you must check and remove if toxicity suspected, or if a change in drug/dose is needed
a) What is the starting dose of morphine?
b) What is the starting dose if the patient has been regularly havign strong opiods
c) What should you increase the dose by if there is no response
d) When a patient is on regular use, what should you do?
a) 5-10 mg
b) 10-30mg
c) Increase dose by 30-50% if no response
d) Review dose every few days,and increase 30-50% if pain recurs
Describe the WHO pain relief ladder
- Mild pain = Non-opioid (Paracetamoal) +/- adjuvant (NSAIDs)
- Mild to moderate pain = Weak opioid (e.g., codeine) +/- non-opioid (paracetamol) & +/- adjuvant
- Moderate to severe pain = Strong opioid (e.g., morphine) +/- non-opioid & +/- adjuvant
