Opioids: Nov 26th Flashcards
1
Q
where is opium derived from
A
Sap derived from the poppy (Papaver somniferum)
2
Q
how long have the properties of opium been known for
A
1000s of years over the contents (hot climate where you can grow it
3
Q
what is the difference between an analgesic and a narcotic
A
analegisic= pain relief narcotic= opium based pain killers
4
Q
anesthetics vs analgesics ?
A
anes= knock out analgesic= alieviate pain
5
Q
which is mj
A
analgesic
6
Q
narcotic is a subcategory od opium
A
t
7
Q
4 categories of opium
A
endogenous
alkaloids
semisynthetic
synthetic
8
Q
example of a endogenous opium
A
endorphin (release to alleviate pain during physical endurance)
9
Q
T: directly derived from sap
A
alkaloids
10
Q
example of alkaloids 2
A
morphine and codeine (potency difference)
11
Q
T: derivatives of directly extracted substance
A
semisyn
12
Q
2 examples of semi
A
heroine (from codeine)
oxycodone (from morphine)
13
Q
T: structurally different opiates (perfect molecule influence receptor)
A
synthetic
14
Q
2 examples of synthetics
A
methadone and fentanyl
15
Q
which class of drugs are opium
A
Exhibit euphoric (stimulant) and anxiolytic (depressant) effects, used as a medicine (anti-psychotic) NOT A HAL
16
Q
which category of opiate has different subjective effects
A
derived= semisyn
17
Q
since opium has no hallucinogenic properties we can rule what out
A
seretonin influence
18
Q
different intake methods depend on what property of the drug
A
potency and resistance to metabolism
19
Q
what effects do you have from oral opiod ingestion
A
mood alleviation (happy and relaxed), cough suppression (not coating throat)
20
Q
what form of intake causes euphoria
A
inhalation
21
Q
what are the 2 effects of intravenous
A
euphoria, pain relief
22
Q
what happens to body temp and pupils
A
Decreased body temp (risk of hypothermia), pupil constriction (hal=widen opioids close to prep you for sleep)
23
Q
how long does it take opioids to kick in when injected
A
2 min
24
Q
why would anyone put themselves through injection
A
“rush” “flash”: intense euphoria = emotion within 2 min
25
other than euphoria what happens in stage 1 injection
Tingling/warmth in “lower abdomen” resembling sexual
| orgasm = v reinforcing !!!
26
what is stage 2 after injection (2-3 hours after)
“on the nod”: tranquil drowsiness = soothed
27
what happens to sexual interest in stage 2
Reduction of sexual interest as a result of lowering testosterone levels
28
what is stage 3 after injection
withdrawal = SO RAPID
29
how does the injection cycle relate to poor outcomes for users
lower testosterone= low social dom and lack of interest in partner = isolation
30
T: street name China white, China girl, TNT, Apache, percopop
fentanyl (hit us before rest of world first)
31
trade name for fentanyl
Duragesic, Sublimaze around since the 70s
32
which opioids are which schedule
Schedule I = Heroin
| Schedule II = Morphine, Methadone, Fentanyl Schedule V = Codeine, Oxycodone
33
3 ways fentynol is given
```
Demerol – anaesthetic, “lollipop” – palliative care, Duragesic –
chronic pain (analgesia)
```
34
how does it compare to morphine in potency
100x (carfenanyl 1000x)
35
what is the fentaynol crisis
crisis of contamination
36
3 ways to intake fentanyl
oral, transdermal, insufflation
37
what is the problem and gain with fast fentanyl absorption
respiratory depression increases with faster
| absorption but less nausea and itching
38
what makes fentanyl so effective
potent and resistant to metabolism
39
what is the synthetic opid used for sedation and analgesia
Desomorphine
40
why was desomo created
powerful surgical anesthetic back in 1930s (8x more potent than morhpine
41
what were the downside of desomorphines potency
Increase in respiratory depression, septicemia, and
| cardiac arrest
42
what is septicaemia
arge amounts of bacteria are present in the blood from toxins in poop not going anywhere
43
how is crocodile related to desomorphine
synthesized version of desomorphine from codeine
44
3 street names for desomorphine synthesized from codeine
Krokodil, zombie, flesh-eating
45
krokodile has high toxicity from impure.. 2
preparation or reduction methods
46
2 things that are added to Kroc during preparation
paint thinner, HCL
47
what does the impure preparation cause 2
Inflammation liver, kidney
48
3 this created during impure reduction method
gasoline/ kerosine, iodine. phosphorus
49
3 things impure reduction methods cause
Thyroid damage, “Phossy Jaw”, gangrene
50
T: a condition that occurs when body tissue dies
gangrene
51
you can't get addicted to Kroc due to terrible adverse effects
f such a powerful painkiller you don't feel it until it wears off
52
how is Kroc related to desomorphine
when someone tries to create desomorphine
53
what is opium doing inside the body
agonizing the endogenous opiod system
54
Proopiummelancortin, proenkephalin, prodynorphin what are these
endogenous opiod chemicals= free floating in bodies but bound to other things= under high duress enzyme cuts active portion out from rest of molecule
55
T: separating the molecule into separate chains
cleavage
56
what are the 2 steps to cleavage
1. internal enzymatic action
| 2. active metabolite= morphine (cut morphine from molecule)
57
Enzyme ... converts codeine to morphine
CYP2D6 (responsible for endogenous functions as well)
58
2 ways opium macts as a agoist
1. cleavage
| 2. g protein metabotropic receptors
59
what enzyme is responsible for cleavage
CYP2D6
60
is the molecule after cleavage active
yes= double whammy!
61
ipiods become G-protein bound to Metabotropic receptors- what does this mean
it changes the system- makes neurons return to resting potential sooner- they don't fire
62
how does opium return neurons to resting potential sooner
allowing k to influx inwards
63
what is sensation vs perception
p: subjective interpretation of sensory signals
sensation: sensory experience
64
how fast do neurons fire when you feel pain
fast
65
how do opioids influence the system long term
makes neurons less likely to fire (depressant aspects)
66
how can this explain runners high
produce endogenous endorphins so you can endure physical pain
67
function of a pure agonist
pain relief
68
2 pure agonists of the endoginist system
fentanyl and morphine (medical)
69
function of partial agonism of endogenous system
Pain relief with no respiratory effect
70
example of partial agonist
Buprenorphine (less potent)
71
function of a mixed or agonist antagonist on endog system
Treating opioid addiction (occupy receptor s.o.a., block drug/other receptor)
72
2 examples of mixed agonist antagonists
Naloxone, methadone (no high but dependance)
73
why are they called mixed
they are agonizing receptors but they do nothing subjectively= antagonizing other chemicals e.g. the drug (implies how we use)
74
the mixed antag/ agnostics are used as ... in some countries
anxiolytic
75
what are the 3 areas of pain perception you can target
periphery, CNS, protections from brain (proximal= brain/ distal= body)
76
opioids agonism what?
endogenous opiod system
77
how do opioids agonise the endo opiod system
by antagonizing the gABA (antagonist) system which stops endo opioids pain relief
78
gaba supresses the inhibitory response of ... receptors
dopamine = influx= reinforcing
79
Suppression of the inhibitory response on dopamine receptors: where in brain does this happen
VTA
80
what does opioids do in the Nucleus accumbans
Activation of u opioid receptors that inhibit the GABA neurons (inhibit GABA all over)
81
as opium antagonists GABA what happens to dopamine
Allows dopamine to be released in VTA, and “enhancement” of the dopaminergic response
82
what does the enhacement of the dopamine system do
motor and reward control
83
ONE study in 1999 found relationship between opioids and reduce ... receptor as a secondary function
glutamate = reason they don't show excitement in response to down regulation of system 41:40
84
what mechanism is acting in the body
inhibitory
85
T: sensory pathways related to pain
| perception
nociception
86
T: in charge of sensory pain signal from receptor to spinal chord
Ad & C fibers
87
what do opioids do at ad and c fibers
Inhibition of neurotransmission
88
sensory pain signal
| from spinal chord to Thalamus what NT involved 2
Glutamate & substance P
89
what do opiods do to stop glutamate and substance p from sending pain signal to thalamus
Activation of medulla inhibits neurotransmission to thalamus
90
2 ways to stop pain from getting to the brain?
| 2 ways to stop pain once in the brain?
slides 7-8=. 4 ways to stop pain in the body
91
when pain meds targeting the PNS how is its effect on pain described
“dulling”/”blunting” of pain= take edge off
92
how long until you see withdrawl with opioids
3-4 hours
93
is there tolerance with opium
oh yes withdrawl tells you that
94
is the tolerance rapid? dose dependant?
not rapid but dose dep
95
what does it mean to say opiod tolerance is Accrued
the more you take the more tolerance
96
what does it mean to say tolerance is relational
proportional to the amount you take
97
opiod tolerance abides by allostatic principles what does this mean
system changes more permanently to adapt to enviro demands to try and achieve homeostasis
98
opiod tolerance is selective to which properties 3
analgesia, euphoria, and respiratory depression
99
how sensitive is opiod tolerance to conditioning effects
extremely= less of a dose in unfamiliar place= OD
100
how long does withdrawl last
5-10 days ( can stretch out or take full hit now)
101
what do you see in first 4-6 hours of withdrawl that intensifies at 3-4 day mark
craving = psycholigal
102
when does the physioligcal aspect kick in and what is it
8-12 hours with flu symptoms =respritory and hyperthermia
103
what is the third stage of withdrawl that kicks in at 48- 72 hours
secondary effects: pupil dilation (opposite of when on the drug), anorexia, piloerection (goosebumbs= cold turkey), spastic arm/leg movements (“kicking the habit”)
104
does pupil dilation happen similarly in hallucinogens and opioids
f when on Hal when coming off opioids
105
...% relapse after withdrawal associated with environment
90= evidence for conditioning
106
why 90% relapse if not as dangerous as alc and barbiturates withdrawl
not dealing with psychological component causing relapse
107
how long does LT vs short term detox last
LT 180 days
| ST 30 days
108
3 benefits to methadone and buprenorphine as detox
Prevent withdrawal, long-lasting effects, weak/no euphoria
109
how well does methadone and bupren work for ST detox
moderate withdrawal for short-term
110
what is the debate with using methadone clinics
Institutional control of addicts (i.e. not real treatment)
111
how long is rapid vs ultra rapid detox
```
rapid= 10 days
ultra= 2 days
```
112
can you go through rapid and ultra rapid awake
no induce coma
113
T: binds as an agonist and induces opposite pharmacological response
inverse agonist (mixed agonist antag)= lowers response
114
what inverse agonist is used in detox
naloxone
115
how is buprenorphine different from methadone
does have analgesic properties= better for those who have been using for long time
116
naloxone dereases withdrawal symptoms, decrease duration
f increases withdrawl
117
Ultra-rapid in conjunction with .... for first few hours
sedation/anesthetized
