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.
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
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
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).
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
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.
7
Q
Opioid antagonists
A
- Naloxone blocks all effects of opiods,
- competitive antagonist, short duration
- naltrexone, alvimopam
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
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
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)
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
12
Q
Potential drug sources of adverse interaction with opioids
A
- CNS depressants
- phenothiazines (antipsychotics)
- MAO inhibitors and tricyclic antidepressants
13
Q
Opioid interaction w/CNS depressants
A
- e.g. barbituates
- Additive or synergistic CNS depression
- Can increase metabolism of some opioids (meperidine)
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.
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)
