Narcotics Flashcards
Morphine
- Chemical Properties: Natural opioid, least lipophilic of opioids.
- Mechanism of Action: Mu-opioid receptor agonist, inhibits nociceptive transmission at the spinal cord and activates descending pain control pathways.
- Metabolism: Liver via glucuronidation to M3G (inactive) and M6G (active, potent). Prolonged effect in renal failure due to M6G accumulation.
- Uses: Moderate to severe pain, more effective for dull pain than sharp intermittent pain.
- Dosage: IV (0.03 - 0.15 mg/kg), IM (0.05 - 0.2 mg/kg).
- Onset: 20 min IV.
- Peak: 30-60 min.
- Duration: 4-5 hrs.
- CNS Effect: Sedation occurs before analgesia. Miosis due to inhibition of GABA and stimulation of Edinger-Westphal nucleus.
- Cardiovascular Effect: Bradycardia via medullary vagal stimulation. Minimal effect on BP in healthy patients, but peripheral vasodilation can occur.
- Respiratory Effect: Dose-dependent respiratory depression (mu/delta receptor action in brainstem). Reduces CO₂ responsiveness.
- Other Notes: Causes constipation, urinary retention, muscle rigidity with rapid administration. Pruritus common with neuraxial use.
Fentanyl
- Chemical Properties: Synthetic opioid, highly lipid-soluble, rapid onset.
- Mechanism of Action: Mu-opioid receptor agonist, inhibits ascending nociception. Most widely used opioid analgesic in anesthesia.
- Metabolism: Significant first-pass uptake in the lungs with temp accumulation before release. Liver via N-dealkylation and hydroxylation to inactive metabolites, excreted in urine and bile. Elimination prolonged in elderly and neonates.
- Uses: Profound dose-dependent analgesia, sedation, intra-op and post-op pain management.
- Dosage: Intra-op 2 - 50 mcg/kg, Post-op 0.5 – 1.5 mcg/kg. Transdermal: 25-100 mcg/hr for 24-72 hrs.
- Onset: Immediate IV.
- Duration: Short (20-40 min).
- CNS Effect: Minimal effect on EEG, used in neurophysiologic monitoring.
- Cardiovascular Effect: Minimal effects, can cause bradycardia.
- Respiratory Effect: Ventilatory depression, dose-dependent.
- Other Notes: Rapid redistribution terminates action for single doses; prolonged infusion shifts elimination to metabolism.
Alfentanil
- Chemical Properties: Less lipid-soluble but highly nonionized (90%) at physiological pH, small volume of distribution, rapid onset, short duration.
- Mechanism of Action: Mu-opioid receptor agonist.
- Metabolism: Liver via CYP450 (N-dealkylation, O-demethylation), inactive metabolites excreted renally.
- Uses: Intra-op anesthesia, effective epidural opioid but short duration limits popularity.
- Dosage: 8 - 100 mcg/kg, Maintenance: 0.5 – 3 mcg/kg/min.
- Onset: Immediate IV.
- Duration: Short.
- CNS Effect: Dose-dependent sedation, analgesia.
- Cardiovascular Effect: Minimal, but caution in hypovolemic patients.
- Respiratory Effect: Profound respiratory depression and sedation prolonged if combined with erythromycin (inhibits metabolism).
Hydromorphone
Chemical Properties: Semisynthetic opioid, more potent than morphine, highly lipid-soluble.
Mechanism of Action: Mu-opioid receptor agonist.
Metabolism: Liver, no active metabolites (safer in renal failure).
Uses: Moderate to severe pain.
Dosage: IV (0.01 – 0.02 mg/kg), IM (0.02 – 0.04 mg/kg).
Onset: IV: 15-30 min.
Peak: 30-90 min.
Duration: 4-5 hrs.
CNS Effect: Similar to morphine, sedation before analgesia.
Cardiovascular Effect: Minimal effect.
Respiratory Effect: Dose-dependent depression.
Other Notes: Recommended in renal failure due to lack of active metabolites.
Meperidine
Chemical Properties: Synthetic mu receptor agonist, structurally similar to atropine.
Mechanism of Action: Mu-opioid receptor agonist, kappa receptor activity.
Metabolism: Liver via demethylation to normeperidine (active, neurotoxic, long half-life).
Uses: Analgesia, antispasmodic (atropine-like), shivering reduction (kappa receptor effect).
Dosage: Variable, IV preferred.
Onset: IV rapid.
Duration: Moderate.
CNS Effect: Accumulation of normeperidine leads to CNS excitation, tremors, seizures.
Cardiovascular Effect: Mild vasodilation.
Respiratory Effect: Mild depression.
Other Notes: Avoid in renal failure, elderly, and chronic use due to neurotoxicity. Interacts dangerously with MAOIs (hyperthermia, seizures, death).
Remifentanil
Chemical Properties: Piperidine-derived opioid with ester linkage, ultra-short acting. moderate lipophilic, water soluble.
Mechanism of Action: Mu-opioid receptor agonist.
Metabolism: Rapid hydrolysis by blood/tissue esterases, not dependent on liver or kidney. Small Vd
Uses: Short procedures
Dosage: Intra-op: 1 mcg/kg, Maintenance: 0.05 - 2 mcg/kg/min, post op 0.05 - 0.3 mcg/kg/min
Onset: Immediate.
Duration: Ultra-short (elimination half-life 8-20 min).
CNS Effect: No accumulation, rapid clearance.
Cardiovascular Effect: Minimal.
Respiratory Effect: Severe depression, muscle rigidity if given as bolus.
Other Notes: Not used epidurally/intrathecally due to glycine content (neurotoxic).
Buprenorphine
Chemical Properties: Partial mu agonist, high receptor affinity.
Mechanism of Action: Partial mu agonist, kappa antagonist.
Metabolism: Liver, slow receptor dissociation.
Uses: Opioid use disorder, moderate-severe cancer pain (transdermal).
Dosage: 8-hour duration, slow dissociation.
CNS Effect: Less euphoria than full agonists.
Cardiovascular Effect: Minimal.
Respiratory Effect: Ceiling effect on depression (safer in overdose).
Other Notes: Minimal GI side effects.
Butorphanol
Chemical Properties: Highly lipophilic opioid.
Mechanism of Action: Kappa agonist, weak mu antagonist.
Metabolism: Liver.
Uses: Migraine headaches, postop pain, epidural pain.
Dosage: Varies.
Onset: Rapid.
Duration: Moderate.
CNS Effect: Sedation.
Respiratory Effect: Ceiling effect for depression.
Nalbuphine
Chemical Properties: Mixed agonist-antagonist.
Mechanism of Action: Kappa agonist, mu antagonist.
Metabolism: Liver.
Uses: Pain, opioid-induced pruritus, respiratory depression reversal.
Dosage: Varies.
CNS Effect: Analgesia, mild sedation.
Cardiovascular Effect: Minimal.
Respiratory Effect: Ceiling effect, not fully reversible with naloxone.
Morphine lipophilicity
Least lipophilic of the opioids: Slow to cross the BBB, slow onset, and less accumulation in fatty tissues
Morphine metabolism
Glucuronidation in the liver to M3G (inactive) and M6G (active, more potent than parent drug)
Morphine in renal failure
Prolonged therapeutic effect due to M6G accumulation
Morphine clinical uses
Moderate to severe pain, especially dull pain; can be given IV, IM, subQ, oral, intrathecal, and epidural
Morphine dosage (IV)
0.03 - 0.15 mg/kg
Morphine onset and duration
Onset 20 min, peak 30-60 min, duration 4-5 hrs
Morphine respiratory effect
Dose-dependent respiratory depression; reduces responsiveness to CO₂ and O₂
Morphine cardiovascular effect
Bradycardia from medullary vagal stimulation, minimal BP effect in healthy patients
Fentanyl usage
Most widely used opioid analgesic in anesthesia: NO active metabolites
Fentanyl metabolism
N-dealkylation and hydroxylation to inactive metabolites, excreted in urine and bile
Fentanyl elimination in elderly and neonates
Prolonged due to decreased metabolism
Fentanyl clinical uses
Profound dose-dependent analgesia, sedation; given IV, intradermal, intrathecal, epidural, and PCA
Fentanyl intra-op dosage
2 - 50 mcg/kg
Fentanyl post-op dosage
0.5 – 1.5 mcg/kg
Fentanyl onset and duration
Short duration of action (20-40 min)
Fentanyl respiratory effect
Ventilatory depression; single dose terminated by redistribution, but repeated doses require elimination
Fentanyl cardiovascular effect
Minimal BP effect in healthy patients, peripheral vasodilation (dose-dependent)
Alfentanil onset and duration
Rapid onset and shorter duration than fentanyl: NO active metabolites
Alfentanil metabolism
Liver metabolism via oxidative N-dealkylation and O-demethylation (CYP450)
Alfentanil drug interaction
Erythromycin prolongs metabolism, increasing respiratory depression and sedation
Alfentanil clinical use
Limited due to prolonged respiratory depression and sedation
Alfentanil intra-op anesthesia dosage
8 - 100 mcg/kg
Alfentanil maintenance infusion dosage
0.5 – 3 mcg/kg/min
Alfentanil respiratory effect
Profound respiratory depression, risk of prolonged apnea
Hydromorphone origin
Semisynthetic opioid derived from morphine: NO active metabolites
Hydromorphone metabolism
No active metabolites: Preferred opioid in renal failure patients
Hydromorphone clinical uses
Management of pain
Hydromorphone IV dosage
0.01 – 0.02 mg/kg
Hydromorphone IM dosage
0.02 – 0.04 mg/kg
Hydromorphone onset and duration
Onset 15-30 min, peak 30-90 min, duration 4-5 hrs
Meperidine classification
Synthetic mu receptor agonist with declining use: ACTIVE metabolite (normeperidine)
Meperidine metabolism
Demethylation in the liver to normeperidine, which lowers seizure threshold and induces CNS excitability
Meperidine clinical uses
Analgesia, antispasmodic effect, and postoperative shivering reduction via kappa receptor stimulation
Meperidine contraindications
Avoid in renal failure, elderly, and chronic cancer patients due to normeperidine accumulation
Meperidine drug interaction
Significant interactions with first-generation MAO inhibitors → Risk of hyperthermia, seizures, and death
Remifentanil classification
Piperidine-derived opioid with ester link: NO active metabolites
Remifentanil metabolism
Rapidly hydrolyzed by blood and tissue esterases to a less active compound
Remifentanil elimination half-life
8-20 min
Remifentanil clinical uses
Ultra-short duration and titratability make it ideal for intra-op use
Remifentanil intra-op anesthesia dosage
1 mcg/kg
Remifentanil maintenance infusion dosage
0.05 - 2 mcg/kg/min
Remifentanil respiratory effect
Profound respiratory depression; bolus dosing not recommended due to muscle rigidity risk
Remifentanil epidural use
Contraindicated due to potential glycine neurotoxicity
Buprenorphine classification
Potent partial agonist at mu receptors, kappa antagonist
Buprenorphine clinical uses
Opioid use disorder treatment, moderate to severe cancer pain (transdermal system)
Buprenorphine duration
Long duration (~8 hrs) due to slow receptor dissociation
Buprenorphine respiratory effect
Ceiling effect prevents respiratory depression at high doses
Buprenorphine GI effect
Minimal constipation compared to full mu agonists
Butorphanol classification
Highly lipophilic opioid: Kappa agonist, weak mu antagonist
Butorphanol clinical uses
Migraine headaches, postoperative pain, epidural pain (under study)
Butorphanol analgesic effect
More potent than morphine but has a ceiling effect
Butorphanol respiratory effect
Ceiling effect prevents severe respiratory depression
Butorphanol side effects
Significant sedation
Nalbuphine classification
Mixed opioid agonist-antagonist (kappa agonist, mu antagonist)
Nalbuphine clinical uses
Pain treatment, opioid-induced pruritus, opioid-induced respiratory depression
Nalbuphine respiratory effect
No respiratory depression even with increased dose (ceiling effect)
Nalbuphine cardiovascular effect
No adverse circulatory changes
Nalbuphine reversal with naloxone
Difficult to reverse with naloxone
Naloxone classification
Pure opioid antagonist: Competitive antagonism at mu, kappa, and delta receptors
Naloxone clinical uses
Reversal of opioid-induced respiratory depression and analgesia
Naloxone duration
Shorter than most opioid agonists → Risk of respiratory depression recurrence
Naltrexone classification
Opioid antagonist similar to naloxone, but with higher oral efficacy and longer duration
Naltrexone clinical uses
Alcohol use disorder, prevention of opioid euphoria
Naltrexone duration
~24 hrs → Used for long-term opioid addiction management
Naltrexone metabolism
ACTIVE metabolite → Longer half-life than naloxone
Nalmefene classification
Long-acting parenteral opioid antagonist
Nalmefene clinical uses
Opioid overdose reversal, alcohol use disorder treatment
Nalmefene IV dosage
0.5 – 1.6 mg
Nalmefene elimination half-life
10 hrs
Nalmefene duration
8 hrs → Suitable for long-term overdose management
