Opioids Flashcards
What are the different types of endogenous opioid peptides? What receptors do they bind to? Where are they distributed?
Endorphins:
- miu (MOP) receptors
- supraspinal distribution, immune cells (long-term opioid use can cause immunosuppression)
- increase efflux of potassium —> reduced excitability
- main therapeutic effects of exogenous opiates are mediated by miu receptors
Enkephalins:
- delta (DOP) receptors
- widely distributed
- reduced influx of calcium
Dynorphins:
- kappa (KOP) receptors
- distributed in spinal cord
- reduce c.AMP synthesis
Give some examples of ADRs associated with opioids.
- nausea and vomiting (stimulates vomiting centre in medulla)
- constipation (inhibits nerve plexus of stomach —> reduced gut motility)
- miosis (pupil constriction) - “pin-point pupils”
- resp. depression (effect on CO2 sensitivity)
- hypotension
- psychosis
- coma
- anaphylaxis
- immunosuppression (long-term)
- dependence
- tolerance (tachyphylaxis reduces efficacy —> repeated doses req.)
- dysphoria (kappa receptors)
Define tachyphylaxis.
Acute rapid decrease in response to a drug after its administration
Define dysphoria.
State of unease/dissatisafaction
OR confusion/disrupted thought processes
What increases the risk of resp. depression in therapeutic doses of opioids?
- sleep
- pulmonary deficit
- anaesthetics
- alcohol
- sedatives
Give examples of opioid agonists. What are their pharmacokinetics and pharmacodynamics? When are they indicated? Give examples of ADRs associated with their use.
Morphine (gold standard)
- metabolised via glucocuronidation
- prodrug and metabolite are active (artificially lengthens half-life)
- can measure metabolites in urine
- t1/2 = ~4hrs (lengthened in hepatic/renal failure)
- poor oral bioavailability (hydrophilic - does not cross blood-brain barrier)
- indicated for acute diarrhoea, terminal illness, post-op analgesia
- ADRs = constipation, N&V, dysphoria, tolerance
Diamorphine (heroin):
- legal to prescribe in U.K.
- hydrolysed to morphine
- t1/2 = ~5min
- lipophilic (crosses blood-brain barrier; morphine can then reach brain faster and in higher conc.)
- indicated for analgesia in terminal illness
Methadone
- oral
- t1/2 = ~15-30hrs
- indicated for chronic pain, heroin dependence (reduced risk of blood-borne infections)
Tramadol
- affects 5-HT (anti-depressant effect to relieve pain)
- affects noradrenaline (sympathetic inhibition —> increased desc. inhibition)
Tapentadol
- specific miu agonist
- noradrenaline reuptake inhibitor (anti-depressant effect and sympathetic inhibition)
Codeine
- oral
- mild analgesic
- metabolised to morphine by CYP2D6 (polymorphisms; Chinese pop. = higher doses req.; Caucasians = unable to convert to morphine)
Fentanyl/alfentanil/remifentanil
- potent anaesthetics
- rapid onset but short half-life (analgesia req. post-op)
- ADRs = histamine release —> pruritis, rash
Pethidine
- used to be used as analgesia in labour (smooth muscle relaxant) BUT crosses placenta (baby requires naloxone once delivered)
- metabolised to norpethidine (active metabolite)
- ADRs = convulsions, drowsiness (DO NOT GIVE FREQ./REPEATED DOSES)
What restrictions are in place for prescribing controlled drugs?
Schedule 2 (diamorphine, morphine, pethidine, remifentanil) - legal requirements regarding prescribing, storage, and disposal
Schedule 5 (codeine) - pharmacists have to keep a record of prescriptions
Give some examples of opioid agonist-antagonists.
Nalbuptine
Buprenorphine
Pentazocine
Analgesia without euphoria
Give some examples of opioid antagonists. What are their pharmacokinetics? When are they indicated? Give examples of ADRs associated with their use.
Naloxone
- t1/2 = ~1-1.5hrs (shorter half-life than morphine, therefore multiple doses req.)
- IV only
Naltrexone
- t1/2 = ~4hrs
- oral
Indications:
- opioid toxicity
- resp. depression
- dependence
ADRs = WITHDRAWAL (therefore supervision is req.)
- sweating
- N&V
- restlessness
- trembling
- headache
- arrhythmias
- seizure
- pulmonary oedema
What are the actions of opioids? When are they indicated?
Central:
- euphoria (don’t care/pay attention to pain)
- reduced perception of pain
Peripheral:
- inhibits release of substance P from nerve terminals
Indicated for moderate-severe pain relief (particularly that of visceral origin)
Give examples of acute, chronic, and non-analgesic uses of opiates.
ACUTE
- acute diarrhoea
- cough (codeine is anti-tussive)
- MI (coronary artery vasodilatation)
CHRONIC
- dependence (methadone)
NON-ANALGESIC = ?
