Neuroscience Week 3: Opioid Actions Flashcards
Understand the general pharmacokinetics of opioid compounds
Oral/Parenteral potency ratio
Absorption - routes of administration
Distribution - localize to highly perfused tissues
Metabolism
Excretion
Examples of strong opioid agonists
- Morphine
- Oxycodone (AKA oxycontine)
- Fentanyl
- Methadone
- Meperidine
Examples of partial opioid agonists
- Codeine
- hydrocodone
Examples of mixed opioid agonist-antagonist actions
Buprenorphine
Other clinical uses of Opioid Analgesics:
Treating dyspnea from acute pulmonary edema
Morphine
Other clinical uses of Opioid Analgesics:
Example for antitiussive
Dextromethorphan
antitussive Definition
To prevent or relieve a cough
Other clinical uses of Opioid Analgesics:
Example for anti-diarrhea
- Diphenoxylate
- Loperamide
Other clinical uses of Opioid Analgesics:
Examples for shivering
Meperidine
Other clinical uses of Opioid Analgesics:
adjuncts to anesthesia
Fentanyl (regional)
Positive effects of opioids on CNS
Analgesia
Adverse effects of opioids on CNS
- Mental clouding & Sedation
- Respiratory depression
- Antidiuresis
- Emesis
- Bradycardia
- Miosis
- constipation
- seizures
Opioid antagonists
- Naloxone
- Naltrexone
Opioid drug interactions
Sedative-hypnotics - increased respiratory depression (CNS depression)
Antipsychotic tranquilizers - increased sedation and accentuates cardiovascular effects (antimuscarinic and α-blocking actions
Monoamine oxidase inhibitors - increased for hyperpyrexic coma and hypertension
Oral/Parenteral Potency Ratio
1st pass metabolism (elimination) upon oral administration
Parenteral route: elsewhere than mouth or alimentary canal; e.g. IV, IM, Sub, Q, intrathecal, etc)
Example of low to parenteral ratio
Morphine
Example of high oral to parenteral ratio
Methadone
Codeine Absorption
- reduced 1st pass metabolism, remains effectively orally
- acts as a partial agonist at the mu receptor
- High O/P ratio
Oxycodone Absorption
moderate 1stpass metabolism, but remains effective orally Acts as a moderately strong agonist at the mu receptor. Medium O/P ratio In sustained release form:OxyContin In tablets containing acetaminophen: Percocet
In tablets containing aspirin: Percodan
Other routes of administration
Nasal insufflation
of some opioids can result in rapid therapeutic blood levels by avoiding 1st pass elimination
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Oral mucosa via lozenges
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Transdermal via transdermal patches, which can deliver potent analgesics over many days
Opiods are converted mostly to?
Opioids are converted mostly to polar metabolites (e.g. glucuronides
How are opioids typically distributed?
Opioids rapidly leave the blood compartment and localize in
highest concentrations in highly perfused tissues such as:
Brain
Lungs
Liver
Kidney
Spleen
Opioids and muscle
Concentrations in skeletal muscle may be lower, but muscle can
serve as a main reservoir due to its bulk
Opiods and fatty tissue
Low blood flow in fatty tissue but accumulation occurs with highly lipophilic drugs in fatty tissue especially after frequent high dose delivery eg fentanyl
Morphine Metabolism
Pay special attention to renal failure resulting in high circulating levels
Fentanyl metabolism
Fentanyl Absorption
Absorption: Highly lipophilic and slowly metabolized via transdermal route. Transdermal system: improved iontophoretic (localized electric current) allowing needle-free delivery.
Polar metabolits such as glucoronide conjugates: M3G and H3G are excreted how?
In the urine
small amounts are present in the bile; a very minor amount of the excretory process
Remifentanil Metabolism
bolus IV dose for a very quick procedure (cataract removal)
Codeine is metabolized to
Codeine demethylated → morphine
Hydrocodone is metabolized to
Hydrocodone → hydromorphone → H3G
Oxycodone is metabolized to?
Oxycodone → Oxymorphone → O3G
Codeine
hydrocodone
Oxycodone
Metabolism
Poor metabolizers of codeine
wont experience an effect as codeine itself doesnt have strong affinity to the mu receptor
clinical uses of opioids
Mild-moderate agonist Clinical Use of Opioids
Clinical uses of other opioids
Opioid effects and tolerance
Opioid Drug Interactions
Non-opioid Therapeutics used to manage pain
draw attention to gabapentin and pregabalin
ketamine
tramadol however it is a weak mu opiod agonist
