Opioid Analgesics Flashcards

1
Q

General characteristics of opioids

A
  • Opiods are peptides
  • Peptide systems appear to be distinct.
  • Peptides demonstrate some selectivity for different receptors, but there must also be more regulation at level of gene expression, protein processing, and peptide release.
  • Effects of peptides can be antagonized by naloxone.
  • Peptides can mediate all of responses seen with exogenous opiate drugs including analgesia, tolerance and dependance.
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2
Q

Classes of endogenous opioids + examples

A
  • Enkephalins: act as modulatory NT’s at synapses, found in brain and spinal cord, ex. methionine enkaphalin
  • Endorphins: NT and neurohormones, responsible for runners high, found in hypothalamus and pituitary, ß-endorphin is an example
  • Dynorphin: role unclear, ex. Dynorphin A
  • Endomorphin: μ-receptor selective
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3
Q

Opioid mechanisms @ CNS and PNS

A
  • Receptors = μ, δ, and κ
    • all are coupled to GTP-binding proteins- Gi and Go .
  • Binding decreases neuronal excitability in 3 ways:
  • Inhibits release of presynaptic NT’s through inhibition of Ca2+ channels.
  • They can also activate K+ channels leading to membrane hyperpolarization.
  • Finally, they inhibit cAMP synthesis, which also decreases NT action
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4
Q

Sites of opioid action @ CNS and periphery

A
  • analgesia: periaqueductal gray (descending pain), medulla nuclei (side effect-respiratory depression), spinal cord dorsal horn (ascending pain)
  • limbic and motor CNS regions: amygdala, hippocampus, striatum (affective response to pain)
  • “reinforcement” regions in CNS: ventral tegmentum, nucleus accumbens (addiction-abuse)
  • gut: myenteric plexus (side effect-constipation).
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5
Q

Opioid Agonists at μ receptors

A
  • Phenanthrines: Morphine, heroin (diacetylmorphine), codeine, oxycodone, ixtcibtub, percodan, percocet, hydrocodone (in vicodin), Tramadol
  • Phenylpiperidines: meperidine, loperimide, fentanyl
  • Phenylheptamines: methadone
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6
Q

Mixed opioid agonists/antagonists and partial agonists

A
  • Benzomorphans: bupernorphine - partial μ agonist and partial morphine antagonist
  • Pentazocine: A κ agonist, μ antagonist, spinal analgesia with less respiratory depression. Can also precipitate withdrawal in people dependant on μ agonists.
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7
Q

Opioid antagonists

A
  • Naloxone blocks all effects of opiods,
    • competitive antagonist, short duration
    • naltrexone, alvimopam
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8
Q

Life-threatening side effects of opioid drugs

A
  • **Respiratory depression - primary cause of opiod-induced death (overdose)*** Most important!
    • Respiratory function is depressed even at analgesic doses
    • Due to decrease in sensitivity of CO2 in brain stem respiratory centers
    • Increase in blood CO2 → cerebral vasodilation → exacerbate head injury
  • Opioids ==> histamine release ==> anaphylaxis
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9
Q

Other side effects of opioid drugs

A
  • behavioral effects
  • nausea/vomiting
    • activated @ low doses
    • depressed @ high doses
  • cough suppression
  • pupillary constriction
  • GI symptoms
    • consipation
  • urinary retention
  • mild CV effects
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10
Q

Medical indicaiton for opioid use

A
  • Pain associated with cancer
  • Painful diagnostic procedures (in combo with LA and tranquilizers)
  • Post-op pain
  • Obstetrical anesthesia
  • Patient controlled anesthesia
  • Cough (lower doses), separate from analgesic actions
  • Bile stones (pain treated with opiod), use atropine too to relax SM
  • MI: analgesia, alleviates apprehension, decreases cardiac load
  • Pulmonary edema associated with heart failure (unknown mechanism, only exception for respiratory conditions)
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11
Q

Contraindications for opioid use

A
  • Increased ICP and suspected head injury - can cause cerebral vasodilation
  • Depressed respiratory function (asthma, emhpysema, sleep apnea, severe obesity, etc.)
  • Hypotension - can cause further decrease in BP
  • Shock - opiod agonist might make worse b/c endogenous opiods may be active in shock response
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12
Q

Potential drug sources of adverse interaction with opioids

A
  • CNS depressants
  • phenothiazines (antipsychotics)
  • MAO inhibitors and tricyclic antidepressants
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13
Q

Opioid interaction w/CNS depressants

A
  • e.g. barbituates
  • Additive or synergistic CNS depression
  • Can increase metabolism of some opioids (meperidine)
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14
Q

Opioid interaction w/phenothiazines (antipsychotics)

A
  • Used to increase opioid analgesia, but also increases respiratory depression.
  • Can also increase hypotensive effects of opioids
  • Some can reduce analgesic actions of opioids.
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15
Q

Opioid interaction w/MAO inhibitors and Tricyclic Antidepressants

A
  • Increase respiratory depression.
  • Can induce CNS excitation, delirium and seizures.
  • However, combination therapies using antidepressant 5HT and NE
  • Reuptake inhibition and opiate agonist activities may be useful in chronic pain treatment by potentiating the inhibitory descending pain pathway (example: Tramadol)
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16
Q

Characteristics of tolerance

A
  • tolerance = a decrease in response to a drug as a result of previous exposure. Need an increased dose to achieve same pharmacological effect.
  • Linked to receptor desensitization
  • Frequency, dose, and duration of use all contribute
  • Significant tolerance not commonly seen over 2-3 weeks at normal therapeutic doses
  • Tolerance doesn’t develop for all symptoms:
    • no tolerance (GI, pupils)
    • tolerance(analgesia, respiratory depression, euphoria)
  • Can generalize to similar drugs such as all µ antagonists
  • Tolerance reverses following withdrawal (addict who quits and then relapses may then OD if goes back to old dose)
17
Q

Characteristics of dependence

A
  • Dependence = easily produced by opiods, most common in pain-free individuals abusing them or long term chronic pain treatment
  • Physical: the continued use of a drug to maintain a normal physiologic state
  • Psychic: the continued desire or craving for a drug (addiction)
18
Q

Characteristics of withdrawal

A
  • Withdrawal: occurs following cessation of opiod administration following prolonged use
  • Symptoms include dilated pupils, insomnia, restlessness, yawning, rhinorrhea, sweating, diarrhea, nausea, cramps, chills - a flu like syndrome
  • Can be prevented with opiod maintenance therapy
  • Can be precipitated in addicts with antagonists or even partial agonists and mixed antagonist/agonists
  • Clonidine used to treat withdrawal symptoms caused by sympathetic outflow
  • Withdrawal is not life threatening unlike in EtOH and barbituates
19
Q

Opioids vs. Small Molecule NTs

A
  • most neurons: produce conventional NTs and 1+ neuropeptides
    • peptides = w/in large dense-core vesicles found in all parts of neuron
    • vs. other NTs = w/in small synapitc vesicles
  • Ach- ion channel
  • NE - G protein
  • GABA - ligand gated ion channel (ionotropic)
  • Glutamate - ionotropic and metabotropic
  • 5HT - G protein
  • Opioids - G protein