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Flashcards in Twenty Four Deck (22)
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1
Q

When and how should opioids be used and not used?

A

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.

2
Q

What are 5 clinical indications for opiods?

A

analgesia

anesthesia

cough

diarrhea

detoxification

3
Q

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?

A

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

4
Q

What are some examples of places in the body that have opiod receptors? What are 3 overall functions?

A

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

5
Q

Define narcotic, opioid, and analgesic.

A

Narcotic - induces sleep

Opioid - compounds that act on a specific set of receptors

Analgesic -relieves pain

6
Q

Explain tolerance generally and how it works with opioids?

A

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)

7
Q

Explain dependence, both physical and psychological both generally and how it works with opioids.

A

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.

8
Q

Explain cross tolerance in opiods.

A

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

9
Q

What are some therapeutic uses and guidelines for opiods? Are they useful for post op pain relief? Why wouldn’t they be?

A

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.
10
Q

What are 10 side effects produced by morphine?

A

respiratory depression

nausea and vomiting

dizziness

hypotension

increased intracranial pressure

crosses placenta into fetus

mental confusion

urinary retention

constipation

increased biliary pressure

11
Q

What effects does morphine have on the CNS in general? In patients with pain? In pain free patients?

A

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.

12
Q

What are 6 contraindications of morphine? Why? What are 3 drugs interactions? What happens with them?

A

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)

13
Q

What are 7 symptoms of morphine toxicity? How should they be treated? What special steps should be taken for dependent patients?

A

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

14
Q

What are 3 examples of MU agonists that are analgesics? How are they given? How are they metabolized? How do they differ from morphine?

A

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

15
Q

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?

A

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

16
Q

What is an example of a MU agonist that is used as an antidiarhheal? Why is it a good antidiarrheal? What is it administered with? Why?

A

Diphenoxylate

ῆ very insoluble in aqueous solution - even salts are insoluble

ῆ administered with atropine

ῆ no central opioid effects at doses which are effective in theintestine, but higher doses will produce typical opioid effects

17
Q

What is an example of a MU agonist that is used for treating abuse? How does it compare to morphine?

A

Methadone

ῆ pharmacologically identical to morphine

ῆ similar potency to morphine but kinetics altered due to plasma protein binding (> 85% bound) which yields an average half-life of fifteen hours

ῆ overall abuse potential similar to morphine

ῆ more effective orally than morphine, can be given at widely spacedintervals - extended suppression of withdrawal symptoms in dependent individuals

18
Q

What is an example of an agent used for treating abuse that is a partial MU agonist and kappa antagonist? How does it compare to morphine? What are its approved uses?

A

Buprenorphine

ῆ similar to morphine but 25 to 50 times more potent as analgesic

ῆ longer acting compared to morphine

ῆ partial MU agonist and Kappa antagonist

ῆ approved as analgesic and treatment for opiate addiction

19
Q

What is the prototype Mixed agonist antagonist? What is its affect at its receptors? How is it used? What are its effects at low doses? Higher doses? How is it administered? How does its abuse potential compare to morphine? What might happen if given to a morphine dependent individual? What are its side effects? What is it administered with? Why?

A

Pentazocine

ῆ used primarily as an analgesic
ῆ at low doses, effects similar to morphine, but less potent
ῆ at higher doses, effects include anxiety, nightmares, hallucinations
ῆ oral administration preferred over parenteral (less abuse potential)
ῆ considerably less abuse potential than morphine or codeine, but dependence and abstinence syndrome do occur
ῆ may precipitate withdrawal symptoms in morphine dependent individual
ῆ appears to be a MU-receptor antagonist , and a Kappa-receptor agonist
ῆ increase in blood pressure and heart rate, increased cardiac work in patients with coronary artery disease due to Kappa-receptor activity
ῆ now formulated with naloxone (Talwin NX) to reduce likelihood of parenteral abuse.

20
Q

What are 2 other mixed antagonist/agonist agents? How do they compare to pentazocine?

A

Butorphanol

ῆsame as pentazocine except:
available parenterally only
• doesn’t produce withdrawal symptoms when given to morphine users

Nalbuphine
ῆsimilar to pentazocine except:
does not have adverse cardiovascular effects

21
Q

What is an example of a MU antagonist? What is its effect when administered to a drug free individual? An opioid dependent individual?

A

Naloxone

ῆ potent antagonist at MU-receptors
ῆ requires higher doses to reverse effects of agonist-antagonist opioids
ῆ very little or no effects when administered to healthy, drug-free individual
ῆ will rapidly produce withdrawal symptoms in opioid-dependent individual

22
Q

What is an example of a non-opiod antitussive? What does it not produce? What does it provide? When is it contraindicated due to drug interactions? Why?

A

Dextromethorphan

ῆ the d-isomer of the codeine analog of levorphanol

ῆ does not produce : analgesia, respiratory depression, dependence, or withdrawal syndrome

ῆ does provide: cough suppression equivalent to codeine

ῆ contraindicated when MAO inhibitors are on board due to possibly severe toxic reaction including excitation and hyperpyrexia.