L40- Opioids Flashcards
list the endogenous opioids and their source
source- POMC (Proopiomelanocortin)
- endorphins
- enkephalins
- dynorphins
(1) are the clinically relevant opioid receptors, with (2) signaling and (3) as the end result
µ, κ, δ receptors:
-Gi receptors —> although no dec in cAMP
Presynaptic: closes Ca channels (no influx –> no neurotransmitter release)
Postsynaptic: opens K channels (inc efflux –> inc depolarization –> dec APs)
name the opioid receptors related to the following:
- (1) analgesia (supraspinal and spinal)
- (2) sedation
- (3) psychotomimesis (psychosis / delusions / delirium)
- (4) dec repiration
- (5) dec GI motility
1- µ, κ, δ 2- µ, κ 3- κ 4- µ 5- µ
list the all the CNS effects of opioid (therapeutic and adverse)
-analgesia
- sedation (µ, κ)
- euphoria
- respiratory depression (µ)
- cough suppression // anti-tussive
- n/v
- miosis (µ, κ)
- truncal rigidity
list all the PNS effects of opioids (therapeutic and adverse)
- hypotension
- constipation
- pruritus (via Histamine release)
- contraction of biliary smooth muscle – contraindicated with biliary colic
Opioids:
- (activates/inhibits) ascending pain pathway
- (activates/inhibits) descending pain pathway
1- inhibits
2- activates (serotonergic, adrenergic)
describe opioid effect on ascending pain pathway
Normal: stimulus in peripheral nerve–> neurotransmitter release –> spinal cord neuron fires AP to signal Pain
With Opioid:
- presynaptic Ca channels blocked –> no neurotransmitter release
- postsynaptic K channels opened –> inc depolarization, no AP
ascending pathway blockade = Spinal Analgesia
describe the normal functions of descending pain pathway and then how opioids change this pathway
- Serotonergic and Adrenergic neurons send descending fibers in order to inhibit ascending pain pathway
- Interneurons (GABAergic) will release GABA on Serotonergic and Adrenergic neurons to inhibit APs and their release of neurotransmitters –> disinhibition of ascending pain pathway => pain
OPIOIDS: inhibit neurotransmitter release in Interneurons –> therefore no inhibition of Serotonergic and Adrenergic fibers –> inhibition of neurotransmitter release in ascending pathway
descending blockade = supraspinal anagelsia
list the opioid agonists (not mixed):
- indicate most potent
- indicate least potent
- *morphine (hydromorphone, oxymorphone): most potent µ agonist + weak κ, δ agonist
- fentanyl (µ)
- meperidine (µ)
- methadone (µ)
- **codeine (hydrocodone, oxycodone): weak µ, δ agonists
- heroin
- levorphanol
list the mixed opioid agonists (describe general activity)
µ antagonists + κ agonists
- pentazocine
- butorphanol
- nalbuphine
-buprenorphine: weak µ agonist, κ antagonist
list the opioid antagonists
for all µ, κ, δ receptors:
- naloxone
- naltrexone
list the all clinical uses for Opioids
-analgesia
- anesthesia adjunct
- cough — anti-tussive
- diarrhea — causes constipation
- acute pulmonary edema (morphine- dec preload/afterload —> inc risk respiratory depression)
Opioid AEs:
- (1) common
- (2) less common
1- n/v, sedation, pruritus, constipation
2- urinary retention, hypotension, respiratory
______ are the only opioid effects that do not decrease in severity or disappear with prolonged use and drug tolerance
- constipation
- miosis
list the contraindications of Opioids with brief explanations
- Pregnancy: opioid withdrawal in fetus
- Head Injury: inc ICP (from injury) + hypoventilation (from opioid) –> inc CO2 –> vasodilation –> worse inc in ICP –> death
- Liver dysfunction: poor drug metabolism
- Renal dysfunction: poor clearance
- Pulmonary: not used in asthma and COPD –> higher risk of respiratory depression
list and explain the 2 main concerning drug interactions with opioids
1) Sedatives/Hypnotics => dec CNS and dec respirations
2) Serotonin Syndrome with MAOIs:
- delirium, hyper/hypo-tension, coma, death
- convulsions, HA, rigidity, hyperthermia
list the opioids that have the biggest risk for serotonin syndrome
- levophanol
- methadone
- meperidine
- tramadol
- fentanyl
______ is the drug of choice for severe pain, include receptor activity
Morphine, Hydromorphone, Oxymorphone:
- µ agonist, high affinity
- κ, δ agonist, low affinity
describe morphine metabolism
Morphine –>
- M3G
- M6G (10%): more potent, but no analgesic effects
- Normorphine –> Normorphine glucoronide
Note- none can cross BBB
describe Heroin effects and metabolism
Heroin (diacetylmorphine) –> rapidly hydrolyzed into 6-MAM (monoacetylmorphine) –> hydrolized into morphine
- 6-DAM, 6-MAM are more liposoluble than morphine –> crosses BBB
- 6-MAM, morphine are responsible for analgesia
Meperidine:
- (1) receptor activity
- (2) clinical use
- (3) AEs
1- µ agonist only
2- short-term pain
3- Metabolite (normeperidine) causes toxicity (worse in CKD) => hallucinations, muscle twitches, tremors, seizures
______ is an opioid that causes hallucinations, muscle twitches, tremors, seizures (worse in CKD)
Meperidine (3hr 1/2 life) –> Normeperidine toxic metabolite (20hr 1/2 life)
Fentanyl:
- (1) receptor activity
- (2) clinical use
- (3) describe unique pharmacokinetics
1- µ agonist only
2- severe acute pain
3:
- rapid onset –> short duration (15-30 mins)
- 100x more potent than morphine
Methadone:
- (1) receptor activity (hint- more than one)
- (2) clinical use
- (3) describe unique pharmacokinetics
- (4) important AE
1:
- µ agonist only
- NMDA antagonist
- SERT and NET inhibition
2:
- chronic pain
- opioid withdrawal Tx
3:
- longer duration / longer 1/2 life –> maintains constant levels
- less euphoria and sedation
4- QT prolongation / Torsades de pointes
Levorphanol:
- (1) receptor activity (hint- more than one)
- (2) clinical use
- (3) AE
1:
- µ, κ, δ agonist
- NMDA antagonist
- SERT and NET inhibitors
2- severe pain
3- less n/v than morphine
______ opioids have NMDA antagonist activity and SERT/NET inhibitor activity
- methadone
- levorphanol
(Oxy/Hydro)-codone is only available in combination with (2) and they are used to treat (3)
1- hydrocodone
2- acetaminophen / NSAID
3- moderate to severe pain
Oxycodone can be alone or in combination
Codeine:
- (1) receptor activity
- (2) clinical use
- (3) contraindication, explain
1- weak µ, δ agonists
2- mild to moderate pain
3- children: more rapid CYP2D6 metabolizers –> ineffective
list mixed opioid agonists and describe their clinical uses / effects
all can be used for Pain: opioid-naive Pts (no previous use) –> use is limited due to Ceiling Effect
1) Pentazocine, Nalbuphine, Butorphanol (µ agonist, κ antagonist) —> Psychotomimetric Effect
2) Buprenorphine (µ antagonist, κ agonist) –> opioid withdrawal
list the opioid antagonists and describe their clinical uses
Naloxone- acute opioid overdose
Naltrexone- opioid and alcohol addiction (reduces cravings via DA pathway)
Tramadol:
- (1) receptor activity
- (2) clinical uses
- (3) AEs
- (4) contraindication
1:
- µ agonist
- SERT, NET inhibitor
2- moderate pain and chronic neuropathic pain
3- seizures, serotonin syndrome
4- children
(1) is a common anti-tussive that can be combined with (2) opioid. (3)- describe actions of (1).
Dextromethorphan: lower dose needed than for pain, no opioid receptor activity
-acts centrally to inc threshold for coughing
-paired with Codeine
______ are a common anti-diarrheal agents that act on opioid receptors
Diphenoxylate-Atropine
Loperamide
