Opioids

Front 1

presynaptic vs. post synaptic action of opioids

Back 1

presynaptic: Gi activation to decrease cAMp and therefore NT release (closure of Ca channels)
postsynaptic: open K channels to cause hyperolarization

Front 2

CNS effects of morphine: analgesia

Back 2

analgesia
-selectively interferes with nocioception, affective reaction; inhibits conduction; action mediated via receptors on the dorsal horn of the spinal cord, PAG, dorsal raphe nuclei, limbic regions

Front 3

CNS fx of morphine other than analgesia

Back 3

behavioral fx: dysphoria then euphoria
sedation
emetic d/t direct stimulation of CTZ
(chronic inhibits)
antitussive (direct action on medulla)
resp depression d/t dec sensitivity to CO2= dec rate and depth of respiration
hypothalamus: decreased body temp, ACTH, FSH, LH, TSH
miosis
trunchial rigidity d/t increased tone to spinal motoneurons

Front 4

peripheral actions of morphine

Back 4

GI tract- inc tone and dec peristalsis
biliary tract- gall bladder or bile duct spasm d/t increased biliary pressure
urinary tract increased muscle tone= decreased urinary output
CV: peripheral VD and orthostatic HTN; dose-dependent bradycardia
cerebral vasodilation, increased CSF pressure
indirect: histamine release-> itching, sweating, redness of eyes; bronchoconstriction and decreased secretions

Front 5

opiods and the placenta and fetus

Back 5

crosses placenta
fetal BBB not developed and baby is dependent

Front 6

mechanism of opioid elimination

Back 6

rapidly conjugated with glucuronide in liver- significant first pass fx

Front 7

pharmacogenetics: codeine and anesthesia

Back 7

codeine must be metabolized to morphine by Cyt 2D6 to be active
7% of caucasions lack this and will have no benefit

Front 8

tolerance to opioids

Back 8

marked: to depressant actions
little: stimulating actions

Front 9

how does tolerance develop? what is it related to/

Back 9

probably due to activity of adnylyl cyclase and receptor downregulation

degree of tolerance is related to : dose, frequency, exposure, duration of drug use

Front 10

cross tolerance occurs among__________ but not ________

Back 10

opioids but not other CNS depressants

Front 11

what is the significance of cross-dependence?

Back 11

can give another opioid to someone addicted

Front 12

what are the effects that have minimal or no tolerance?

Back 12

miosis
constipation
convulsions
antagonist actions

Front 13

does tolerance develop to bradycardia?

Back 13

moderate tolerance

Front 14

primary contraindications to opioid use

Back 14

asthma
emphysema
liver damage
head injuries
acute alcohol use
previous addiction
convulsive disorders
abdominal pain of unknown origin

Front 15

types of drugs that opioids interact with

Back 15

meperidine + MAOI can cause serotonin syndrome

methadone may cause torsades: careful with antiarrhythmics

depressant fx will be worsened with CNS depressants: phenothiazines, MAOI, TCA, cimetidine

amphetidine may enhance fx

Front 16

what is acute pure opioid OD and how do you treat it?

Back 16

triad: coma, pinpoint pupils, respiratory depression

tx: maintain respiration, give opioid antagonist, preferably naloxone

Front 17

what is the primary cause of death from opioid overdose

Back 17

respiratory failure

Front 18

what is the rationale of using methadone to treat opiate-dependent individuals?

Back 18

affects mu receptors
tolerance develops more slowly
withdrawal is long and mild

inverse relationship of half life to intensity of WDS

cheap

Front 19

indicate which opioid receptors are associated with:
analgesia
euphoria
miosis
dysphoria
physical dependence
respiratory depression

Back 19

mu (μ) – euphoria, analgesia, physical dependence, respiratory depression
kappa (κ) – miosis, analgesia of pentazocine, sedation, dysphoria
delta (δ) similar to μ receptors, enkephalins natural agonists; mediate neuro-endocrine effects
N/OFQ (pro-orphanin) – newest opioid receptor; orphanin natural agonists

Front 20

Distinguish between morphine, pentazocine and naloxone with respect to their actions at the µ receptor.

Back 20

morphine: agonist

pentazocine: pAg

naloxone: antagonist

Front 21

what is the primary difference between naloxone and naltrexone?

Back 21

naloxone is only parenterally effective

naltrexone is orally effective and longer lasting; can also be given as a monthly IM injection

Front 22

Compare the intensity of withdrawal syndrome from methadone when a patient stops taking the drug versus the intensity if precipitated by naloxone administration.

Back 22

methadone: mild

naloxone: causes immediate severe WDS

Front 23

which opioid analgesic is most likely to produce a serotonin syndrome if used in combo with monoamine oxidase inhibitors

Back 23

meperidine

Front 24

main difference between fentanyl and morphine

Back 24

short duration, much more powerful

Front 25

Indicate what unique pharmacokinetic aspects of remifentanil make it more useful for infusion anesthesia than the other meperidine congeners.

Back 25

ultra short duration due to metabolism and small Vd rather than redistribution

unique: rapidly metabolized by tissues and blood esterases to give it an extremely short half life and can have a titration of dose effect during anesthesia

Front 26

tolerance, physical dependence and withdrawal

Back 26

tolerance and physical dependence are directly related
greater PD; greater intensity of WDS

Front 27

what is the primary effect of morphine and most opioids on the heart

Back 27

CV system: peripheral VD and orthostatic hypotension as a result of CNS actions and histamine release

dose-dependent bradycardia (increased PNS and decreased SNS)

Front 28

risk of death: opioid withdrawal vs. alcohol/barbiturate withdrawal

Back 28

death can happen with alcohol or barbiturates
not with opioids

Front 29

which opioid is least likely to
1) produce constipation
2)suppress cough

Back 29

1) meperidine, codeine
2) meperidine

Front 30

what are the acitve metabolites of morphine and meperidine and what are the potential benefits or risks associated with each one?

Back 30

morphine 6 glucuronide contributes to analgesia

morphine 3 glucuronide causes dysphoric fx

meperidine: metabolite normeperidine is a stimulant and can cause seizures with accumulation

Front 31

analgesic potency: morphine, meperidine, fentanyl

Back 31

fentanyl>morphine>meperidine

Front 32

use, moa of methylnaltrexone and alvimopan

Back 32

both are antagonists

methylnaltrexone: reverses opioid-induced constipation but not analgesia (no CNS fx)

alvimopan is for post-op ileus, given before and after bowel resection (stays in GI tract)