OPIOID ANALGESICS Flashcards
1
Q
name 2 strong opioid agonist drugs
1.
2.
A
- morphine
- methadone (dolophine)
2
Q
name a moderate opioid agonist drug
A
codeine
3
Q
name 2 mixed opioid agonist-antagonist drugs
1.
2.
A
- Pentazocine (Talwin)
- Buprenorphine (Buprenex)
4
Q
name 2 opioid antagonist drugs
1.
2.
A
- Naloxone (Narcan)
- Naltrexone (Re Via)
5
Q
name the two categories that pain can be divided into:
1.
2.
A
- acute pain
- chronic pain
6
Q
acute pain can be further divided into two more categories. name them:
1.
2.
A
- phasic pain
- tonic pain
7
Q
define phasic pain
A
sharp pricking types of pain
8
Q
define tonic pain
A
dull, throbbing, aching pain
9
Q
definition:
an unpleasant sensory and emotional experience that normally serves to alert an individual to actual or potential tissue damage
A
pain
10
Q
definition:
a state of not being able to fel pain, without the loss of consciousness
A
analgesia
11
Q
definition:
durgs that reduce pain and induce analgesia
A
analgesics
12
Q
definition:
durgs derived from the juice of the opium poppy, such as morphine and codeine
A
opiates
13
Q
definition:
natural or synthetic compounds with actions that mimic those of morphine
A
opioids
14
Q
definition:
endogenous opioid peptides, such as endorphins, dynorphins, and enkaphalins
A
opiopeptins
15
Q
definition:
a term dervied from the Greek word for stupor. used primarily as a legal term for drugs that cause dependence
A
narcotic
16
Q
indications for therapeutic uses of opioids:
1.
2.
3.
4.
A
- relief of intense pain
- relief of cough
- treatment of diarrhea
- treatment of acute pulmonary edema
17
Q
mechanism of action:
how do opioids produce analgesia?
A
opioids interact with (endogenous) opioid receptors, which are activated by endogenous opioid peptides (opiopeptins: endorphines, dynorphins, and enkaphalins)
18
Q
where are opioid receptors primary localized?
A
brain and spinal cord regions
19
Q
what purpose do opioid receptors serve?
A
opioid receptors are involved in the transmission and modulation of pain
20
Q
name the three major families of endogenous opioid peptides:
1.
2.
3.
A
- enkaphalins
- dynorphins
- endorphins
21
Q
when are opioid peptides released?
A
during stress such as pain or anticipation of pain
22
Q
what functions do endogenous opioid peptides serve?
A
act as peptide neurotransmitters, participating in the modulation of pain, stress, mood, reinforcement, dependence and homeostatic processes such as eating
23
Q
name the three types of opioid receptors
1.
2.
3.
A
- Delta receptors (OP1/DOP)
- Kappa receptors (OP2/KOP)
- Mu receptors (OP3/MOP)
24
Q
how many transmembrane domains to the three primary opioid receptors have?
A
7 transmembrane domains
25
what are the three major opioid receptors primarily attached to?
inhibitory types of G-proteins
26
describe the presynaptic action of the three major opioid receptors
inhibits voltage-gated calcium channels an d decreases the release of neurtransmitters from presynaptic terminals of nociceptive primary afferents
27
descibe the postsynaptic action of mu receptors
activates an inwardly rectifying potassium channel (leading to hyperpolarization) and thus inhibits postsynaptic, second-order pain transmission neurons
28
mu receptors have high affinity for:
1.
2.
3.
1. morphine and related opioid drugs
2. enkephalins
3. beta-endophin
endorphins\>enkephalins\>dynorphins
29
delta receptors have a high affinity for:
1.
2.
1. enkephalins
2. beta-endophin
enkephalins\>endorphins & dynorphins
30
kappa receptors have a high affinity for:
1.
1. dynorphin
dynorphins \>\> endorphins and enkephalins
31
what is the role of mu receptors?
mediate opioid-induced analgesia and positve reinforcement, as well as respiratory depression, miosis, decreased GI motility, and neuroendocrine effects
32
what is the role of delta receptors?
antinociception, motor integration, and cognitive function
33
what is the role of kappa receptors?
regulation of food uptake, temperature control, GI motility, pain perception, and neuroendocrine function
34
how is phasic pain produced?
noxious stimuli – heat, mechanical and chemical irritants
35
what pain pathway does phasic pain follow?
the ascending pain transmission pathway
36
describe A-alpha and A-beta fibers of primary afferent axons
myelinated
large diameter
detect proprioception and light touch
37
describe A-delta fibers of primary afferent neurons
lightly myelinated
medium diameter
detect nocioception (mechanical, thermal, chemical)
thermal threshold ~ 53ºC (type I)
thermal threshold ~ 43ºC (type II)
38
describe C fibers of the primary afferent axon
unmyelinated
small diameter
innocuous temperature, itch
nociception (mechanical, thermal, chemical)
thermal threshold ~43ºC
39
trace the ascending pain transmission pathway of phasic pain
the stimulus is transmitted through the fast-conducting, thinly myelinated A-delta fibers that enter the spinal through the dorsal horn. the pathway immediately crosses over and proceeds along the lateral spinothalamic tract
40
trace the ascending pain transmission pathway of tonic pain
sensory input is transmitted through the unmyelinated, slow-conducting C fibers that enter the spinal cord through the dorsal horn. the major ascending pathways for tonic pain are mutisynaptic pathways of the spinorectal and paleospinothalamic tracts
41
trace the descending pain modulatory pathways
the major descending pathways project from the cortex to midbrain periaquectoal gray (PAG), which then make connections to neurons extending into the rostroventral region of the medulla (RVM). the PAG and the RVM have extensinve reciprocal connections and provide descending projections to the dorsal horn of the spinal cord
42
what role do descending pathways play on ascending pain transmission neurons?
descending pathways play an inhibitory role on the ascending pain transmission neurons
43
how do opioids produce direct analgesic effect on the spinal cord?
inhibit the relase of excitatory nerutoransmitters from primary afferents and inhibit the dorsal horn pain transmission neurons
44
name two places where opioid receptors are found in the ascending pain transmission pathways
primary afferents
spinal cord pain transmission neurons
45
where are opioid receptors found in the descending pain modulatory pathway?
the PAG (periaqueductal gray) in the midbrain and the RVM (rostroventral region of the medulla)
46
how do opioids produce an indirect analgesic effect on the spinal cord?
inhibit the inhibitory (GABAergic) interneurons in the descending pathways, thus activating the pain inhibitory neurons that project to the spinal cord, leading to the inhibition of pain transmission neurons
47
what actions do opioid receptors produce at the brainstem?
cough center of the medulla
respiratory control center
chemoreceptor trigger zone
control of blood pressure
control of pupillary diameter
control of respiration
nausea and vomiting
48
name three sites where opioid receptor distribution/ action is linked to side effects
brain stem, hypothalamus, GI tract
49
what actions do opioid receptors produce at the hypothalamus?
neuroendocrine secretion
50
what actions do opioid receptors produce at the GI tract?
increase smooth muscle tone
decrease motility
51
what effects do opioids have on the CNS?
(7)
1. analgesia
2. euphoria or dysphoria
3. sedation
4. respiratory depression
5. cough suppression
6. miosis
7. emesis
52
what are the cardiovascular effects of opioids?
hypotension and vasodilation
53
what are the gastrointestinal effects of opioids?
(increased intestinal smooth muscle tone)
constipation and relief of diarrhea
54
what administration method can you use to minimize the negative cardiovascular effects of opioids?
epidural administration
55
what are the genitourinary effects of opioids?
urinary retention, prolongation of labor
56
what are the neuroendocrine effects of opioids?
stimulation of **antidiuretic hormone** and **prolactin** release
inhibition of **luteinizing hormone** release
57
what are the dermal effects of opioids?
flushing, pruritis, urticaria (hives)
58
define tolerance
decreased responsiveness to a drug
59
what effects of opioids can a tolerance be built up for?
analgesic, euphoric, sedative, emetic and respiratory dependent effects
60
what effects of opioid use can you not build a tolerance for?
miotic and constipating actions
61
can cross tolerance be built among opioid analgesics?
yes
62
definde dependence
an adaptive state that requires the presence of a drug to maintain cellular homeostasis
63
describe the effects of withdrawal syndrome
strong flu like symptoms,
goose flesh (cold-turkey)
muscle tremors and twitches (kicking the habit)
abdominal cramps and diarrhea
increased HR and BP
hyperventilation
anxiety and hostility
64
what are strong opioid agonists useful in treating?
severe pain
65
what receptors do strong opioid agonists show the highest affinity for?
mu-receptors
66
what is the major active ingredient in opium?
morphine (10%)
67
what is the duration of action of morphine?
4-6hr
68
what is morphine's active metabolite?
morphine-6-glucuronide
69
what is morphine most useful in treating?
severe pain associated with trauma, myocardial infarction, and cancer
70
acetylmorphine is better known as:
heroin
71
what effect does acetylation have on heroin?
makes it more lipid soluble and fast acting
72
what category of controlled substances is heroin?
heroin is a Schedule I Controlled Substance
73
what type of opioid agonists are methadone, meperidine, and fentanyl?
strong opioid agonists
74
dolophine is better known as:
methadone
75
what opioid is the most orally effective, and what is it's duration of action
methodone; orally, the duration of action is 15-20hr
76
what is methadone most commonly used to treat?
detoxification and controlled withdrawal of addicts from heroin and morphine
77
which strong opioid agonist is less potent than morphine?
meperidine
78
demerol is more commonly known as
demerol
79
what is the duration of action of meperidine
2-4hr
80
what is meperdine most commonly used to treat?
used as an obstetric or postsurgical analgesic
81
what opioid, otherwise known as sublimaze, is 80X more potent than morphine?
fentanyl
82
describe two characteristics that make fentanyl preferable as an adjunct to general anesthesia
rapid onset (\< 5min)
very short duration of action (15-30min)
83
describe how moderate opioid agonists compare to strong opioid agonists
moderate opioid agonsits are **less potent** and have **lower abuse potential**
84
what are moderate opioids most commonly used to treat?
moderate pain (in combination with non-opioid analgesics)
85
what opioid is present at ~ 0.5% concentration in opuim?
codeine
86
how is codeine metabolized to produce analgesic effects?
codeine is **metabolized to morphine** for analgesic activity
87
what is codeine commonly given with (orally) for treatment of mild to moderate pain?
aspirin and acetaminophen
88
what opioid is commonly mixed with cough syrups to alleviate or prevent coughs?
codeine
89
which moderate opioid agonist, otherwise known as Ralivia, is a synthetic analog of codeine?
tramadol
90
describe the mechanism of action of tramadol
moderate **mu-receptor agonist**
weak inhibitor of **NE and seratonin reuptake**
91
what moderate opioid agonist is a great alternative for patients who may not tolerate NSAIDs?
tramadol
92
definition:
drugs that have a partial agonist or antagonist activity at mu-receptors and show agonist or antagonist activity at kappa-receptors
mixed agonist-antagonist
93
definition:
drugs that can only produce a submaximal response
partial agonists
94
what action do partial agonists have in the absence of a full agonist?
agonist action
95
what action do partial agonists have in the presence of full agonists?
antagonist action
96
what are the advantages of mixed opioid agonist-antagonists?
ceiling to respiratory depression
lower abuse potential
97
what are the disadvantages of mixed opioid agonist-antagonists?
dysphoric at high doses
difficult to antagonize
98
which mixed agonist-antagonist, also known as talwin, is a kappa-receptor agonist with weak mu-receptor antagonist properties?
pentazocine
99
which mixed opioid agonist-antagonist, also known as buprenex, is a partial agonist at mu-receptors and an antagonist at kappa-receptors
buprenorphine
100
how is pentazocine formulated for use as a preanesthetic medication?
parenteral formulation
101
how is pentazocine administered for treating moderate to severe pain?
orally administered
102
which mixed agonist-antagonist precipitates withdrawal syndrome in a morphine abuser?
pentazocine
103
which mixed opioid agonist-antagonist is resistant to naloxone reversal?
buprenorphine
104
which mixed opioid agonist-antagonist is used to manage cocaine addicition and heroin abuse?
buprenorphine
105
which opioid antagonist has a half-life/duration of action of 1-2hrs?
naloxone
106
which opioid antagonist has a half-life of 10hr?
naltrexone
107
narcan is a competitive opioid antagonist otherwise known as
naloxone
108
ReVia is a competitive opioid antagonist also known as
naltrexone
109
describe how naloxone effects normal individuals vs. opiate abusers
no effects in normal individuals, but precipitates withdrawal symptoms in opiate abusers
110
how is naloxone most commonly used?
intravenous injection is used for reversing the coma and respiratory depression of opiod overdose.
111
which opioid antagonist has a 24 hr duration of action?
naltrexone
112
which opioid antagonist is used as a "maintenance" drug for addicts in treatment programs and used to treat chronic alcoholics by decreasing cravings for alcohol?
naltrexone
