Twenty Four Flashcards
When and how should opioids be used and not used?
ῆ opioids are frequently the drug of choice for relief of short-term, severe pain (e.g. post-operative or post-myocardial infarct).
ῆ for chronic, non-malignant pain they should be considered the last choice, being selected only after aspirin, acetaminophen and other analgesics with little or no dependency potential have failed to provide adequate relief from pain.
ῆ opioids should be administered “by-the-clock,” not “as requested by patient.”
ῆ it requires less opioid to suppress the onset of severe pain than to relieve pain that has returned to a sever level.
What are 5 clinical indications for opiods?
analgesia
anesthesia
cough
diarrhea
detoxification
What are the 3 families of opioid receptors? How are they derived? What are the 3 opiod receptors? What kinds of receptors are they? What are their cellular/molecular effects? Overall effects on the cell? Where are they located? Which endogenous/exogenous opiods are they selective for?
endorphins, enkephalins and dynorphins
all are derived from longer precursors , e.g.preproenkephalin
ῆ pharmacological and molecular cloning experiments
demonstrate at least 3 genes encode opioid receptors
ῆ these are G-protein coupled receptors that couple to the G i and G o family of heterotrimeric G-proteins
ῆ these receptors attenuate adenylate cyclase activity, Ca 2+ channel activity and increase K + activity
ῆ combined, these actions result in decreased neuronal activity
MU named because morphine is selective for this class.
endorphins, enkephalins and dynorphins can all act as
endogenous ligands
DELTA first found in vas deferens, high in dorsal horn.
enkepahlins have greatest potency at this class
KAPPA ketocylcazocine is selective for this class.
dynorphins appear to be endogenous ligands
What are some examples of places in the body that have opiod receptors? What are 3 overall functions?
ῆ amygdala,hippocamppus, frontal/temporal cortex
ῆ PAG, central nucleus of the thalamus
ῆ hypothalamus
ῆ locus ceruleus
ῆ solitary, ambiguous, parabrachial nuclei
ῆ area postrema
ῆ substantia gelatinosa (laminae I,II)
• Gut: enteric nervous system has more neurons than spinal cord and is rich in opioid receptors
They inhibit transmission of peripheral nociceptive input, activate descending inhibitory pathways, and alter limbic system activity
Define narcotic, opioid, and analgesic.
Narcotic - induces sleep
Opioid - compounds that act on a specific set of receptors
Analgesic -relieves pain
Explain tolerance generally and how it works with opioids?
requirement for sequentially larger doses to obtain the same effectin the absence of changes in drug distribution or metabolism.
for opioids, occurs for some effects (analgesia and respiratory depression) to a greater degree than others (pupillary miosis and constipation)
Explain dependence, both physical and psychological both generally and how it works with opioids.
State of psychological and/or physical dependence on a drug that arises after periodic or continual administration.
Thus, drug taking not only suppresses withdrawal, but also
satisfies cravings
Abstinence after dependence develops results in the appearanceof withdrawal symptoms
Physical dependence - biological phenomenon
Psychological dependence - perceived need
These are characteristic of ALLopioids and are not predictors of abuse.
Explain cross tolerance in opiods.
Tolerance to one opioid can lead to tolerance to other opioids:
e.g., an individual tolerant to morphine will display toleranceto heroin, methadone and endorphins
This appears to be a receptor-mediated phenomenon
Therefore-
No cross-tolerance between mu- and kappa-selective opioids
What are some therapeutic uses and guidelines for opiods? Are they useful for post op pain relief? Why wouldn’t they be?
ῆ provide general relief of pain, cough and diarrhea
ῆ an equi-analgesic dose of opiate produces similar
levels of side effects
ῆ for moderate to severe pain, opioids are drugs of choice
ῆ if pain is chronic and due to non-malignant disease, opioids are not recommended to be used unless other compounds are not effective. instead use other treatments such as NSAIDs, nerve block, acupuncture,
useful for post-operative pain relief, but be aware that
they can prevent recognition of surgical complications
How ? Because:
- they decrease effectiveness of coughing
- predispose to pnuemonia
- reduce bowel motility
- increase urinary retentionetc.
What are 10 side effects produced by morphine?
respiratory depression
nausea and vomiting
dizziness
hypotension
increased intracranial pressure
crosses placenta into fetus
mental confusion
urinary retention
constipation
increased biliary pressure
What effects does morphine have on the CNS in general? In patients with pain? In pain free patients?
ῆanalgesia
ῆdrowsiness
ῆmood changes
ῆmental clouding
but doesn’t produce unconsciousness at analgesic doses
in patients with pain :
decreases or eliminates pain via spinal and supraspinal sites of action sometimes euphoria is present as well.
in pain-free patients
causes unpleasant feelings such as nausea, vomiting,
drowsiness, apathy and decreased activity.
What are 6 contraindications of morphine? Why? What are 3 drugs interactions? What happens with them?
Therefore - be careful in patients with:
- hepatic disease (metabolism of drugs)
- renal disease (excretion)
- poor respiratory function (interferes with compensatory mechanisms, such as increased respiratory rate)
- head injuries (ventilation corrects for drug effect)
ῆ hypotension
• biliary colic (increases pain !!)
drug interactions include phenothiazines, MAOI, TCA
(increase depressive effects of morphine)
What are 7 symptoms of morphine toxicity? How should they be treated? What special steps should be taken for dependent patients?
Can occur from accidental overdose, clinical overdose or suicide attempt
Symptoms:
ῆ stupor or coma
ῆ depressed respiration
ῆ decreased blood pressure (can lead to shock due to hypoxia)
ῆ pinpoint pupils
ῆ lowered body temperature
ῆ skeletal muscle relaxation, including tongue
ῆ convulsions (occasionally)
Treatment :
ῆ establish airway and ventilate patient
ῆ treat with antagonist
Note : for dependent patients,
ῆ start with low dose and treat slowly to avoid precipitating withdrawal
ῆ be aware of rebound sympathetic activity which can result in cardiac arrhythmias and pulmonary edema
What are 3 examples of MU agonists that are analgesics? How are they given? How are they metabolized? How do they differ from morphine?
Morphine
ῆ parenteral or oral for pain relief
ῆ metabolized by hepatic conjugation
Codeine
ῆ oral dose 50% as effective as parenteral dose in contrast to most opioids (little first-pass metabolism)
ῆ 10% of dose converted to morphine
ῆ commonly used in combination with aspirin
ῆ abuse liability somewhat lower than for morphine
Meperidine
ῆ short duration of analgesia - need to repeat at least every 4 hours
ῆ metabolized in liver to a convulsant - O.D.-see mixed stupor/convulsions
ῆ less constipating and antitussive than morphine
ῆ I.V. administration - can get large increase in heart rate
What is an example of a MU agonist that is given for anesthesia? How does its potency compare to morphine? How is it administered? What is it administered with?
Fentanyl • very potent (80 times more potent than morphine)
ῆ used IV as an anesthetic agent, often in combination with the neuroleptic droperidol (Innovar)
ῆ also available as a transdermal patch
ῆ accumulates with continued dosing, making it
slightly unpredictable
