Opioids Flashcards
What type of receptors are all opioid receptors
G protein coupled that. Inhibit adenylyl cyclase Gi
- reducing Ca2+ influx
- reducing k+ efflux
- reducing neuronal firing and transmitter release
What doses are needed to control pain
High doses
What are the symptoms of acute opioid toxicity
Respiratory depression Pinpoint pupils Coma Cyanosis Apnea
Opioid toxicity treatment
Ventilation and opioid antagonist -naloxone i.v
What is morphine contraindicated in
In asthma and severe brain injury
Adverse effects of morphine
- MIOSIS (pinpoint eyes) - little tolerance - patho genomic for morphine in coma
- out of it (sedation)
- respiratory depression - tolerance develops
- pneumonia (antitussive) - cough suppression
- hypotension
- infrequency (constipation and urinary retention)
- nausea
- emesis
- causes release of histamine and euphoria. Analgesic.
Most common cause of death with morphine
Respiratory depression
Morphine therapeutic uses
Analgesic, treatment of diarrhea, relief of cough (antitussive), to treat acute pulmonary edema and anaesthesia.
Effect of morphine on pregnant women
It can cross through the placenta and can cause addiction in infants and withdrawal symptoms
Can morphine cross BBB
No it can’t
Metabolites of morphine
M6G ( very potent analgesic)
M3G (Neurotoxic)
Which side effects is it impossible to develop tolerance against
MIOSIS and Constipation
What’s an opiate black box warning
Don’t give with benzodiazepines
What’s a naturally occurring opiate
Codeine
What is codeine used for
Used in mild to moderate pain
What is codeine converted to and why
Morphine to show analgesic action
What is codeine combined with for pain
Acetaminophen
What’s a better alternative than codeine for antitussive effects and why
Dectromethorphan synthetic cough depressant with much lower abuse potential
What is oxycodone
A semisynthetic analog
What can oxycodone be used with
APAP, aspirin or ibuprofen - it can be used on its own too!
When is hydromorphine preferred over morphine
In patients with renal dysfunction due to less active metabolite accumulation
Hydrocodone uses and what can it be combined with
A good antitussive also combined with NSAIDs and APAP for pain
What is Fentanyl related to
Chemically related to meperidine and is 100x more potent than morphine
What is fentanyl used for
Used in anaesthesia and pain
- can be given as a transdermal patch used in reliefing cancer pain
Fentanyl duration of action and uses
Rapid onset and short duration
- Can be used with local anaesthetic
- to provide analgesia for labour and post operative pain
When is fentanyl used as patches
For chronic pain (like cancer) with late offset and long duration
Meperidine structure in comparison with morphine
Is it structurally unrelated to morphine
Meperidine contraindications
Patients with impaired renal function
Meperidine special unique effect
AntiMuscarinic effect so have increased chance of delirium and mydriasis
What is meperidine metabolite
Normeperidine which is an active metabolite and is neurotoxic -> it is renally eliminated hence it is contraindicated in kidney failure
Meperidine clinical uses
Used in labour
Used in acute pain for a short time
Methadone receptors
Mu agonist as well as NMDA receptor antagonist
Effect of methadone on serotonin and norepinephrine
Uptake inhibitor
Methadone clinical uses
Used in the control of withdrawal effects of addicts and maintenance therapy because withdrawal symptoms with methadone are milder and prolonged
Methadone mode of elimination
Excreted in feces
Methadone adverse effects
It can cause QT prolongation and torsades des pointes
What are partial agonists and mixed agonist antagonist used for
Partial agonists given to opioid
What are partial agonists and mixed agonist antagonist used for
Partial agonists given to opioid naive can show agonistic response but when given to opioid addicts can show withdrawal symptoms
What are diphenoxylate and loperamide used for
Management of diarrhea
Petazocin receptors
Kappa agonist and weak atagonist or partial agonist of mu
Petazocin a mixed agonist and antagonist- effect
Can produce withdrawal symptoms in morphine abusers
Petazocin adverse effects
Increase in concentration can cause respiratory depression, tachycardia and hallucinations so it is rarely used
When is Petazocin used with caution
With angina and CAD
Buprenorphine receptors
Agonist at mu receptor and antagonist at Kappa receptor
Buprenorphine clinical uses
Used in the treatment of addiction—> used in opiate detoxification because it has a less severe and shorter duration of withdrawal than methadone
Buprenorphine mode of administration
Sublingual and subdermal formulation approved in treatment of opioid addiction due to providing prolonged suppression of opioid withdrawal
Why is Buprenorphine better than methadone at detoxification
Shorter and less severe
Buprenorphine adverse effects
Respiratory depression not easily reversed by naloxone also QT prolongation
Tramadol receptors
Centrally acting mu agonist which undergoes extensive metabolism to an active metabolite more affinity to mu receptors than parent compound
When is tramadol used
Used in moderate to severe pain
Tramadol adverse effects
Anaphylactoid reaction
Tapentadol receptors
Centrally acting analgesic and antagonist of mu receptors and NET inhibitor
Tapentadol clinical uses
Manage moderate to severe acute to chronic pain
Including neuropathic pain associated with diabetic peripheral neuropathy
Tapentadol should be avoided in which patients
Patients taking MAOIs within the last 2 weeks
Tapentadol metabolism
Metabolised by glucuronidstion —> low drug interactions
Tramadol drug drug interactions
SSRI MAOIs AND TCAs leading to CNS toxicity
Tramadol should be used with caution in people with
Seizures
Opioid antagonist
Naloxone and naltrexone
Naloxone mode of administration
IV
Naloxone receptors
Competitive antagonist at mu kappa and deltts receptors
10 time fold at mu> kappa
Naloxone clinical use
- Quick onset of action
- Reverses respiratory depression and coma by opioid over dose 1-2 mins after IV administration
- Could be used for withdrawal symptoms
Naltrexone difference than naloxone
Longer duration of action and slower onset of actions and can be given orally
Naltrexone mode of administration
Can be given as a sustained release IM/month
Naltrexone clinical use
Opioid dependence and alcohol addiction
