Opioids Flashcards
Diphenoxylate, Loperamide Class
Opioids
Opioids
Antimotility agents
Diphenoxylate, Loperamide description
Opioids
Widely used in the treatment of diarrhea at doses that lack analgesic effects
Several mechanisms, but mostly act on mu and delta receptors
Dextromethorphan, Codeine class Opioids
Antitussives
Dextromethorphan, Codeine description
Opioids
Most effect cough suppressants
Lower dose than necessary for analgesia
Dextromethorphan, Codeine other
Opioids
Receptors are different than those associated with other action
Naloxone, Naltrexone class Opioids
mu and kappa antagonists
Naloxone, Naltrexone description
Opioids
Opioids
Nalaxone -> acute opioid overdose**
Naltrexone -> opioid addiction; also decrease EtOH craving in chronic alcoholics
Pentazocine, Butorphanol, Nalbuphine, Buprenorphine class opioids
Mixed agonist and antagonist
Pentazocine, Butorphanol, Nalbuphine, Buprenorphine description
Opioids
Potent analgesics in opioid naive patients, but precipitate withdrawal in patients that are physically dependent on opioids
Used in mild to moderate pain but are not routine due to ceiling effect
1st three may cause psychotomimetic effects, but not buprenorphine
Pentazocine, Butorphanol, Nalbuphine, Buprenorphine other
Opioids
Developed to reduce addiction potential of opioids especially buprenorphine
Tramadol description
Opioids
Weak mu agonist and NE/serotonin reuptake inhibitor
Useful for neuropathic pain
Tramadol other
Opioids
Increased risk of seizures
May cause serotonin syndrome
Propoxyphene class Opioids
mild to moderate agonist
Tramadol class Opioids
mild to moderate agonist
Propoxyphene description
Opioids
NOT recommended for routine dosing and withdrawn from market in 2010 due to cardiotoxicity
Metabolized to norpropoxyphene with a half life of 30hrs -> toxicity
Codeine, Oxycodone, Hydrocodone description
Opioids
Less efficacious than morphine
Usually combined with aspirin or acetaminophen
Codeine has low affinity for opioid receptors
Codeine, Oxycodone, Hydrocodone Metabolism
Opioids
Analgesic effect is due to metabolism by CYP2D6* to morphine
Metabolites have greater potency
Methadone, Levorphanol class Opioids
Strong agonist
Methadone, Levorphanol description
Opioids
Equal potency to morphine but with less euphoria and longer half life
- *mu agonist, NMDA antagonist and serotonin/NE reuptake inhibitor**
- *Levorphanol is even longer acting** than methadone
Methadone, Levorphanol other
Opioids
Used to manage opioid withdrawal in heroin addiction
Can cause QT prolongation, etc.
Fentanyl, Sufentanil, Alfentanil, Remifentanil class Opioids
Strong agonists
Fentanyl, Sufentanil, Alfentanil, Remifentanil description
Opioids
Rapid onset and short duration of action
100x more potent than morphine
Metabolized by CYP3A4 in the liver
No active metabolites
Meperidine class Opioids
Strong agonist
Meperidine description
Opioids
mu receptor agonist, but has high metabolite toxicity (normeperidine) ->tremor, twitching, mydriasis, hyperactive reflexes and convulsions*****
Serotonin syndrome -> delirium, hyperthermia, HA, rigidity, coma, dysregulation of BP, death (DO NOT combine with MAO-Is)
Meperidine mechanism
Opioids
Accumulation of normeperidine can occur in patients with decreased renal function and cause seizures
Meperidine other
Opioids
Normeperidine half life 15-20 hrs so it accumulates with frequent dosing
Meperidine half life = 3 hrs
Heroin description
Opioids
6-monoacetylmorphine and heroin are more liposoluble than morphine and cross BBB
Rapid hydrolysis to 6-MAM -> morphine which can then be conjugated
Pharmacological actions are due to 6-MAM and morphine
Hydromorphone, Oxymorphone description
Opioids
Severe pain
Morphine description
Opioids
High affinity for mu receptor; standard for analgesia
Morphine mechanism
Opioids
Conjugated to M3G -> neuroexcitation
10% -> M6G -> 4-6x more potent
Morphine other
Opioids
Metabolites are polar and do not readily cross BBB
Metabolite effects may be increased in renal impairment
Opioid analgesic mechanism
Produce analgesia primarily by activating receptors in the brain and spinal cord
Close voltage gates Ca2+ channels on presynaptic nerves and open K+ channels on postsynaptic nerves -> decreased NT release
Can also cause analgesia at peripheral mu receptors (i.e.knee)
Spinal analgesia
Opioids
Inhibit ascending pain transmission
Supraspinal analgesia
Opioids
Activate descending pain-inhibitory circuits* -> block inhibitory GABAergic neuron transmission
Systemic administration
Opioids
Both spinal and supraspinal are acted on concurrently increasing overall analgesic efficacy
Peripheral mu receptors also acted on
Opioid receptors
Mu, delta, kappa -> Gi
Majority act at the mu receptor and produce analgesia, euphoria, respiratory depression and physiologic dependence
delta and kappa are found primarily at the spinal level ->analgesia
kappa-> psychotomimesis (psychosis, delirium, hallucinations, etc)***
Opioid tolerance, dependence, addiction
Frequent use -> loss in effectiveness -> tolerance
Dependence -> physiologic withdrawal or abstinence syndrome
Addiction -> euphoria leads to compulsive use
Physical dependence is common when use therapeutically, but addiction is not
Opioid CNS effects
Analgesia -> reduce sensory and emotional components of pain
Euphoria -> floating sensation with decreased anxiety and distress
Sedation and drowsiness
Respiratory depression - decreased central response to CO2 -> not usually a life threatening complication, because pain is a power stimulus to breath
Cough suppression - decreased central cough center reflex
Miosis - excites PS -> pinpoint pupils are pathognomonic following toxic dose (mediated by mu receptor)
Truncal rigidity *
Nausea and vomiting -> activate brain stem trigger zone
Opioid use
Analgesia-> moderate to severe pain
Acute pulmonary edema -> decrease anxiety, preload and afterload
Cough -> dextromethorphan, codeine, levopropoxyphene and noscapine
Diarrhea - loperamide and diphenoxylate
Shivering - meperidine (activates alpha 2 receptors)
Anesthesia - premedication and intraoperatively
Opioids for cough
Dextromethorphan, codeine, levopropoxyphene and noscapine
Opioids for diarrhea
loperamide and diphenoxylate
Opioids for shivering
meperidine (activates alpha 2 receptors)
Opioid metabolism and excretion
Mainly converted to glucuronides and excreted by the kidney but small amounts of unchanged drug may be found in urine
Very small amount of enterohepatic circulation
*Codeine, oxycodone, hydrocodone are metabolized by CYP2D6 -> metabolites with increased potency
Supraspinal analgesia pathway
The descending pain inhibitory neuron is inhibited by GABA
Opioids inhibit the GABAergic neuron
This results in enhanced inhibition of pain transmission
Opioid AE
Nausea, vomiting, sedation itching *Constipation* Urinary retention Hypotension Respiratory depression
Opioid Peripheral effects
Hypotension -> due to peripheral vasodilation, inhibition of baroreceptor reflex and increase in histamine release
Constipation -> universal (concomitant laxative use)
Biliary colic -> contraction of biliary smooth muscle
Decreased renal function -> decreased renal blood flow
Prolong labor by unknown mechanism on uterus
Pruritus -> due to central effects and histamine release
Opioid contraindication/interactions
Using a pure agonist with a weak partial agonist -> diminishing analgesia or inducing a state of withdrawal
Head injuries -> CO2 retention causes cerebral vasodilation
Pregnancy -> fetal dependence
Impaired pulmonary function -> acute respiratory failure
Impaired hepatic function -> decreased metabolism of morphine
Impaired renal function -> longer half - life
Endocrine disease-> adrenal insufficiency or hypothyroidism can have prolonged or exaggerated response to opioids
Sedatives/hypnotics -> increase CNS depression (respiratory)
Antipsychotics -> increase sedation, variable effects on respiratory depression and accentuate CV effects of anti-M and alpha-blockers
MAO-I’s -> life threatening rxn especially with meperidine and tramadol*
