9.1.2 Opioids Flashcards
What are the different types of opioids?
Endogenous ligands
B-endorphins
Endonorphins
Dynorphins
Enkephalins
Opiates
Codeine
Morphine
Diacetyl morphine
Semi-synthetic
Hydrocodone
Synthetic
Methadone
Fentanyl
What is codeine metabolised to?
5% is metabolised to morphine by CYP2D6
How do opioids work?
Many endogenous opioid peptides but only 4 receptors
All Gai
µ opioid receptor responsible for most analgesic effects
What is effect of opioid binding at different neurones?
Pre-synaptic
Opioid binds causing a reduction in calcium entering the neurone
Reduction of glutamate released
Post-synaptic
Opioid binds causing K+ to move out causing hyperpolarisation, decrease, now further away from threshold potential
What are some examples of opioids?
Codeine &
Buprenorphine
Diamorphine
Fentanyl
Morphine
Tramadol &
&-considered to be a weaker opioid
What are opioids used for?
Analgesia
Antitussive (cough suppression)
Dyspnoea- pulmonary oedema
Anaesthetic
Anti-diarrhoeal
Palliation
What are the features of morphine?
Less lipid soluble
Slower onset
Long duration
PO,IV,IM,SC,PR
What are the features of fentanyl?
Highly lipid soluble
Fast onset
Short duration
100x potency of morphine
Less itching
Transdermal,IV,epidural,intrathecal
What are the features of codeine?
Prodrug
Primary metabolite less potent than morphine 10% of potency
Morphine as second metabolite~5%
Mediated by CYP2D6
What is the pain ladder?
Tool used to determine what pain relief should be given
What are the adverse drug reactions of opioids?
MORPHINE
Miosis
Overly sweaty (hyperhidrosis)
Respiratory depression
Pee retention and constipation
Itching
Nausea
Euphoria and dysphoria
When should you be careful in giving opioids?
HEROIN because heroin is bad
Head injury/ raised ICP
Exacerbates asthma
Respiratory depression
cOmatose patients
paralytic Ileus
Neonatal abstinence syndrome caused if pregnant
What are some important drug to drug interactions with opioids?
- CNS depressants- including anti-epileptics and benzodiazepines
- Other opioids
- Drugs that reduce gut motility
- Clarithromycin (buprenorphine)
- Opioid receptor antagonists
What opioids are used in disorder or overdose?
Buprenorphine
Methadone
Naloxone (overdose)
What is buprenorphine?
Partial agonist
50x potency of morphine
Long action
Why is methadone so useful for opioid abuse?
Methadone is much more lipophilic than morphine and has a longer duration of action
Has some NMDA receptor antagonism
What is naloxone?
Competitive opioid receptor antagonist used in overdose
Rapid distribution
Duration is 30-60 minutes
Why may naloxone need to be administered many times in respiratory depression?
Short duration only 30-60 minutes
Opioids may still be in the system and act on their receptors again
What are the signs of opioid overdose?
Airways- blue lips and nails
Breathing- slow, irregular or stopped
Cardiac- slow heart rate, weak pulse, low BP
Doesn’t respond to voice or touch
Eyes- pinpoint pupils
How can naloxone be given?
Nasal sprays
Pre-filled injections
Why are opioids addictive?
Reduction in GABA from GABA interneurones
Increased in dopamine as GABA is blocked
Dopamine is associated with please
What is tolerance?
More of the drug needed to elicit same response
Can need 100x the amount to reduce pain significantly increase risk of death
Why does tolerance happen?
cAMP compensation
Receptor phosphorylation
Internalisation and uncoupling
What happens in cAMP compensation?
Increased cAMP without opioid inhibition
Excess of normal function particularly mediated in ventral tegmental area, locus coerules and gut
How does withdrawal present?
Excess of normal neuronal activity
GABA break is no longer blocked which may lead to overdrive, increased firing and reduced dopamine release
Leads to insomnia, anxiety, excessive sweating, enlarged pupils, tachycardia, tachypnoea and diarrhoea
How do people avoid cAMP compensation?
Keep taking opioids at higher and higher doses to feel normal
Breathing stops
Anyone can become addicted
What are controlled drugs?
Classified from A-C based on how harmful it is
These drugs are prohibited in manufacture, supply and possession
What are schedules?
Controlled drugs are further divided into schedules 1-5 which dictates how they are made, stored, sourced, prescribed etc.
Schedule 1 is not used medicinally
Schedule 2-5 decreasing controls and requirements
Where are opioids placed as controlled drugs?
Opioids sit in class A-C
Schedule 2,3 and 5
Depending on the drug, preparation and route of admission
