3. Opioid Analgesics Flashcards
I. OPIOIDS A. Phenanthrenes 1. Agonists a. Naturally-occurring opium alkloids \_\_\_\_ Morphine
b. Semisynthetic derivatives of morphine
____ (DILAUDID) Oxymorphone (NUMORPHAN)
c. Semisynthetic derivatives of codeine
____
Oxycodone (ROXICODONE
- Partial Agonist
____ (BUPRENEX) - Agonist-Antagonist
____ (NUBAIN)
codeine hydromorphone hydrocodone buprenorphine nalbuphine
B. Phenylheptanes
____ (ORLAAM)
Methadone (DOLOPHINE) ____ (DARVON)
C. Morphinans
1. Agonist
____ (LEVO-DROMORAN)
- Agonist-Antagonist
____ (STADOL)
levomethadyl
propoxyphene
levorphanol
butorphanol
D. Phenylpiperidines \_\_\_\_ (ALFENTA) Fentanyl (SUBLIMAZE; DURAGESIC TRANSDERM) \_\_\_\_ (IMMODIUM) Remifentanil (ULTIVA) \_\_\_\_ (DEMEROL) Sufentanil (SUFENTA)
E. Benzomorphan
Agonist-Antagonist
____ (TALWIN)
F. Aminotetralin
Agonist-Antagonist
____ (DALGAN)
alfentanil
loperamide
meperidine
pentazocine
dezocine
Morphine – ____ occurring chemical
Codeine – also ____ occurring but the difference is a ____ group.
- DONT prescribe it to any of your ____ patients
- its demethylated to morphine.. some peds patients died from undergoing a TNA (?).. they were identified as ultra rapid ____.. and died from a morphine blood level
naturally naturally methyl pediatric metabolizers
Heroin – wanted a better analgesic aka get into the brain faster so they ____ it -Bayer (company that makes aspirin) made it
-rapidly acting and gives a big high, deacetlyated in the brain very quick
Hydromorphone – more ____ and lasts ____ than heroin -1 of the reasons why you cant prescribe heroin/we don’t need it is bc this drug that you can prescribe is even better if needed
acetylated
potent
longer
Meperidine - idk any docs prescribing this. I took this off DO boards.
-Not very potent (200-300mg), same group/very similar structure to ____
Methadone – used in ____ (medication assisted treatment) -same category as ____ (Darvon)
fentanyl
MAT
propoxyphene
Full Antagonist
Naloxone (Narcan) – every health professional should carry it, it has overburdened the city healthcare system
Naloxegol – only acting at the ____ level, goal is to block the constipation
Agonist-Antagonist
Pentazocine – sufficiently similar to the opioid receptor but more to the ____ receptor
-drug companies wanted to make a non-____ opioid analgesic.. will never occurs as long as people keep developing addictions
peripheral
kappa
addicting
Morphine – don’t really give it IM but this was a study
- what do these acute values tell us? High first ____ effect (will have to give more) -does that mean we can give morphine PO? ____
- most ____ used drug around the world for treating pain
- decrease its dose in cancer patients that start having ____ problems
*”Again im not going to ask you doeses Dr. hersh will tell you which ones you need to know”
Methadone – synthetic, not much of a first ____ effect
-no need to give via Parental, it is given ____ and to cancer pts
Heroin is at 5 when Hydromorphone is 1.5.. so ____ (trade: Dialudid) is more potent than heroin
pass
no
widely
liver
pass
PO
hydromorphone
Im not going to ask you to figure this out..
- FDA is centering around 90 MME/day to be a trigger
- some docs freaked out bc some pts on more than that.. can develop tremendous tolerance
- if you have a cancer pt you may have to use the chart
- remember though the chart conversions are 100% accurate, you have to go ____ than what the chart tells you to be safe
lower
Morphine Mg Equivalents
Do not use calculated dose in ____ to determine dosage for converting one opioid to another.
New opioid should be ____ to avoid unintentional overdose caused by incomplete cross-tolerance and individual differences in opioid pharmacokinetics. Consult medication label.
Dosages at or above ____ MME/day increase risk for OD by at least 2X.
Even relatively low dosages (20-50 MME per day) increase ____.
morphine milligram equivalents (MMEs)
lower
50
risk
-Some of the opioids out there are only Kappa compounds -Delta is more endogenous compounds
Morphine on all of these is an ____
Buprenorphine – ____, meaning there’s an upper ceiling to the respiratory depression which is good
____ and other compounds are not good to give to a pt that’s been on an opioid for over a week
Naloxone and Naltrexone are a ____ lasting form
agonist
partial agonist
butorphanol
longer
Mu-1
Primary action:
____
Euphoria
Mu-2 Primary action: \_\_\_\_ Respiratory depression \_\_\_\_
Kappa: Primary action: \_\_\_\_ Diuresis \_\_\_\_
Delta:
Primary action:
____
Spinal analgesia
supraspinal analgesia
spinal analgesia
constipation
spinal analgesia
dysphoria
supraspinal analgesia
Endogenous Opioids
Electrical stimulation of specific CNS areas (e.g., ____) produces strong ____.
Blocked by ____ antagonists.
Reason: presence of endogenous opioids—-> ____ receptors
Effects are very similar to ____ drugs.
periaqueductal gray (PAG)
analgesia
narcotic
opioid
narcotic
Endorphins
Presursor: propiomelanocortin ____—-> beta-endorphin
Beta-endorphin:
- 31-amino-acid peptide
- split from larger peptide that also yields ____
and alpha ____ - found primarily in pituitary gland
- binds predominantly to ____ and delta sites
Produce various behavioral and physiological responses to pain
propiomelanocortin
ACTH
MSH
mu
Enkephalins Precursor: \_\_\_\_ Pentapeptides; two types are: - \_\_\_\_ (met-enkephalin) - amino acid # 61-65 of beta-endorphin - leucine-enkephalin (leu-enkephalin)
Located in nerve endings throughout CNS (especially ____, dorsal horn - spinal cord, basal ganglia, portions of limbic sys.)
Appear to bind equally to ____ and mu1 sites
Probable mechanism:
- bind to opioid receptor
- decrease release of ____
- reduce transmission of pain signals
proenkephalin
methionine-enkephalin
brainstem
delta
substance P
Dynorphins
Precursor: ____
Located in neurons throughout the brain.
Bind primarily to ____ sites
Endorphins and enkephalins not of clinical value:
- not absorbed ____
- ____ biotransformation (e.g., blood & brain)
Synthetic enkephalins have been produced; are being evaluated.
prodynorphin
kappa
p.o.
rapid
Talking about chemical structure below (Fig 3)
When I was in grad school a long time ago there was a scientist named Beckett who proposed an opioid receptor
-people thought why is there a receptor in the brain to a drug that grows in a plant
-he was right bc he had a series of molecules and if they didn’t configure to a certain shape they weren’t really opioids
Point is morphine fits the ____ receptor (enkephalin receptor) – a pentapeptide
-how did they know this – that the opioid poppy would treat pain? By trial and error people learned a lot about plants
-same with the foxglove plant giving Digitalis
Every opioid that you will prescribe comes from the knowledge of this chemical structure -Terraneous (?) in 1978 said we know what this compound is its endorphin
Runners high – so much pain that endorphins are released
endorphin
CNS
Analgesia
Narcotics are powerful analgetics; decrease severe pain
Mechanism of Action
Stimulate ____receptors.
- Supraspinal
Act at ____ receptors in periaqueductal gray (PAG)
and related areas to stimulate ____ pathways of inhibition.
Result: dec transmission of pain signals from spinal cord to higher sites. - Spinal
Stimulate pre-synaptic ____ receptors.
Reduces availability of ____
Consequent reduction in release of ____ of pain (e.g., Substance P).
opioid / enkephalin/ endorphin opioid descending enkephalin neurotransmitters
Mu / Delta
dec ____ activity then dec in intracellular cAMP -> inc ____ efflux -> hyperpolarization -> dec ____ influx -> dec release of sub P
Kappa
skips to dec ____ influx -> dec release of sub P
adenylate cyclase
K+
Ca2+
Ca2+
CNS (continued)
____
Emesis
Narcotics often produce ____ and vomiting
Frequency increases when the patient becomes ambulatory:
Ø narcotics increase sensitivity to ____
Depression of ____
Respiratory Depression
Can be significantly ____; primary cause of death in ____
Therapeutic doses have minimal effect in most pts:
Ø not an issue unless pre-existing ____ problem (e.g., asthma).
sedation nausea motion cough reflex reduced OD respiratory
CNS (continued)
CV
Hypotension
Direct: depression of ____ center
Indirect: histamine release–> peripheral ____
GI
Hypomotility
Ø Decreased ____
Ø Delayed ____ emptying
Eye
____
Smooth Muscle Increased tone Primarily non-vascular smooth muscle Ø\_\_\_\_ Ø \_\_\_\_ tract Ø \_\_\_\_
Endocrine function
Pts receiving daily opioid therapy for > 1 a month may undergo ____ in cortisol, sex hormones & DHEA.
vasomotor
vasodilation
peristalsis
gastric
miosis
GI
biliary
urinary
reductions
USES
Analgesia
Relief of ____ pain (e.g., cancer, myocardial infarction, burns, fractures, postsurgical trauma)
Chronic use by legitimate patients does NOT cause ____ (psychological dependence).
Physical dependence, however, does develop after relatively short period of ____ use (e.g., one week).
Ultimate degree of physical dependence related to ____ used daily and ____ of use.
moderate to severe addiction daily amount duration
USES
Most effective dosing schedule in chronic pain, esp. cancer, is to administer doses on ____ schedule (e.g. Q6H ____).
Quality of sleep improves when patients receive ____ analgesia.
Also elevates their mood which, in turn, leads to a better ____ and improved interactions with relatives, friends and members of health care team.
In addition, pain control may also improve such that ____ narcotic is required (can therefore decrease ____).
fixed around the clock regular appetite less ADRs
