Opiates and Opioids Flashcards
1
Q
Opiate
A
Natural narcotic opioid alkyloids found in the
opium poppy (Papaver somniferum)
2
Q
Opioid
A
Any natural or synthetic compound or the
endogenous peptides that exert biological
effects at the opioid receptors
3
Q
Opium Papaver somniferum
A
Latin ‘Sleep-bringing’
4
Q
Opium Cultivation and use
A
predates recorded history
5
Q
Opium Described for medical use in
A
Egyptian texts from 1500 BCE
6
Q
Ceramic opium pipes recovered from
A
m Cyprus dated to
1200 BCE
7
Q
Opium Reintroduced to Europe during
A
the Crusades
8
Q
Opium Tinctures common in
A
Victorian England
9
Q
- Laudanum (from Latin ‘to be praised’)
A
opium dissolved in
alcoho
10
Q
Natural opiates Major psychoactive opiates:
A
- Morphine
- Codeine
- Thebaine
11
Q
Other major opiates
A
Noscapine (anti-tussive, emetic)
* Papaverine (antispasmodic)
12
Q
Minor opiates
A
Hydrocodone (Zohydro, Vicodine)
* Hydromorphone (Dilaudid)
* Oxycodone (Oxycontin, Percocet)
13
Q
first opiate to be isolated was
A
Morphine first isolated in 1804.
14
Q
structure of morphine determined in
A
1925
15
Q
what is different about thebaine
A
its a stimulant
16
Q
Morphine and codine are
A
depressive and analgesic so they relieve pain and are psychoactive
17
Q
Pharmacological use of natural opiates Analgesic
A
still the most potent and effective pain relievers known,
widely used (both morphine and derivatives)
18
Q
Pharmacological use of natural opiates Antitussive
A
cough suppressant
19
Q
Pharmacological use of natural opiates Codeine has decreased
A
analgesic effect but retains antitussive effects
20
Q
Pharmacological use of natural opiates Decreased gastric motility of opiates
A
can be used to treat diarrhea esp.
pathogenic (e.g. dysentery)
21
Q
Loperamide is an opioid derivative that
A
does not penetrate the BBB and is
used to treat diarrhea
22
Q
Administration of opiates Natural opiates can be administered by a number of routes
A
- Oral administration
- Subcutaneous, intramuscular*, or intravenous**
Inhalation
23
Q
Administration of opiates Oral administration
A
morphine readily absorbed through GI but
high variability, codeine has more consistent oral absorption
24
Q
Administration of opiates Subcutaneous, intramuscular*, or intravenous**
A
more stable
systemic levels
25
Subcutaneous, intramuscular*, or intravenous** – more stable
systemic levels
*preferred route for morphine in clinical setting
* ** common recreational route
26
Administration of opiates Inhalation
historic route of (recreational) administration for raw
opium is smoking
27
Semi-synthetic opioids Diacetylmorphine
first synthesized in 1874 by C.R. Alder Wright who was
seeking morphine analogues with decreased addictive potential
28
Diacetylmorphine Marketed in 1898 by Bayer pharmaceutical under the trade name
Heroin
as a cough suppressant, analgesic, and cure for morphine addiction
29
Development of numerous semi-synthetic opioids followed the
solation of
morphine and codeine and subsequent discovery of the structures
30
Some semi-synthetic opioids are found
naturally but generally synthesized
from morphine or thebaine for pharmaceutical use
31
Some semi-synthetic opioids are found naturally but generally synthesized
from morphine or thebaine for pharmaceutical use
Hydrocodone, hydromorphone, and oxycodone
32
Administration of opioids Semi-synthetic opioids can generally be administered by the same routes
as morphine
Oral, Intravenous, Inhalation or intranasal
33
Administration of opioids Oral
heroin administration by oral route produces the same potency and
efficacy as morphine
34
First pass metabolism of heroin yields
morphine as the major metabolite
35
Administration of opioids Intravenous
IV heroin is dramatically more potent and rapid than morphine
due to increased lipophilic structure (increased BBB permeability)
36
ntravenous – IV heroin is dramatically more potent and rapid than morphine
due to increased lipophilic structure (increased BBB permeability)
Rapid uptake into the brain, where it is metabolized to morphine to exert psychoactive effects
37
Administration of opioids Inhalation or intranasal
occasional routes for recreational use
38
‘freebase’ heroin can be
smoked while other preparations can be finely ground and snorted
39
Therapeutic effects of opioids
Muscle relaxation
* Drowsiness
* Decreased sensitivity to external or internal
stimuli
* Pain relief
* Impaired concentration
* Constriction of pupils
* Dream-filled sleep
* Effects in the limbic system
40
Therapeutic effects of opioids Effects in the limbic system
Reduced anxiety
* Reduced inhibition
41
High doses of opioids Subjective effects at recreational doses:
Euphoria or elation
‘Rush"
Physiological effects:
42
Subjective effects at recreational doses: Euphoria or elation
(in contrast to relaxed state at lower
doses)
* Dysphoria in some users
43
High doses of opioids ‘Rush’
– most pronounced by IV
Rapid, intense state of euphoria
* Described by non-addicts as a sudden flush of warmth located in the pit of
the stomach
Described by others as a ‘whole-body orgasm’
Not the means of addiction but provides a strong reinforcement
44
High doses of opioids * Physiological effects:
* Pinprick pupils
Nausea and vomiting
Moderate respiratory depression
45
Nausea and Opioids can act at the
chemoreceptor trigger zone in the area postrema to
induce the vomit reflex
46
Recreational use of
opioids
Opium, morphine, heroin, fentanyl are well
known drugs of abuse
47
Prescription opioids (Oxycontin) are one of
the fasted growing classes of drugs of
abuse
Particularly among wealthy suburban
North Americans
Common among medical practitioners
(physicians and pharmacists)
48
Opioid tolerance
Tolerance to opioids develops quickly and reflects various modes of tolerance
49
Opioid tolerance lerance to respiratory and euphoric effects
develops more rapidly than
tolerance to analgesic effects
50
Tolerance to respiratory and euphoric effects develops more rapidly than
tolerance to analgesic effects
* Prolongs the usefulness in long-term pain management
* Unfortunately constipation does not develop tolerance
51
Metabolic tolerance
some increase in drug metabolism
52
Behavioural tolerance
highly relevant in addicts
53
Pharmacodynamic tolerance
– principal mechanism of tolerance – decreased
expression of opioid receptors
54
Opioid withdrawal
Somewhat exaggerated perception of opioid withdrawal due to
‘cinematic creative license’
55
During the early years of Hollywood heroin was more abundant,
cheaper, and higher purity and subsequently
addicts undergoing
withdrawal would have much more severe symptoms
56
Opioid withdrawal Current users will rarely take sufficient quantity to
match historic
depictions of withdrawal
57
Opioid withdrawal Much less severe than withdrawal from
barbiturates or alcohol
58
severe alcohol withdrawal can be
fatal, opioids never fatal
59
Withdrawal is heavily influenced by
mechanisms of
drug tolerance and
dependence
60
Withdrawal is heavily influenced by
mechanisms of drug tolerance and
dependence
Pharmacodynamic mechanisms
61
Receptor systems affected by opioids
compensate to restore homeostasis in the
continued presence of drug
62
Removal of drug upsets homeostasis in the
opposite direction of drug use
63
Withdrawal produces
neurochemical and
behavioural changes that are often opposite
the effects of intoxication
64
Stages of withdrawal
Begins 6-12 hours after last administration, peaks 26-72 hours, persists
less than 1 week
65
First stage of withdrawal
Restlessness and agitation is first sign
* Excess yawning, agitation, violence
* Chills, hot flashes, shortness of breath
* Intense piloerection (goosebumps) – origin of the term ‘cold turkey’
* Increasing drowsiness and deep sleep (often 8-12 hours)
66
Continued withdrawal effects Second stage
Cramps in stomach, back, legs
* Vomiting, diarrhea, profuse sweating
* Twitching of the extremities – shaking of hands and kicking of legs – origin of the term ‘kicking the habit’
* Symptoms become progressively less severe until gradually disappearing
67
Severity of withdrawal depends on
daily dose, less severe with less potent opiates (e.g. codeine)
68
For most, withdrawal resembles a
bad flu
69
Withdrawal symptoms stop
immediately by opioid administration, induced by opioid antagonists
70
Withdrawal symptoms reduced by
alcohol
71
Opioid overdose
High doses of opioids can cause death
72
Opioid overdose Usually IV
heroin or morphine
73
at high doses
Comatose state, pinpoint pupils, and severe respiratory depression occur
74
Opioid overdose convulsions common
Lowers seizure threshold
75
Opioid overdose Death occurs by
severe respiratory depression or combination of supressed cough reflex, unconsciousness,
and vomiting
76
Contaminants such as quinine (used to cut heroin) are a
probable cause of many overdoses – causes
frothing from mouth and nose and death by pulmonary edema
77
Opioid overdose Affected by behavioural tolerance
drug use outside conditioned environment can lead to
increased drug effects
78
OD can be treated using
opioid antagonists (i.e. naloxone)
79
Chronic effects of opioid use
constipation
Hormone imbalance
Opioid-induced hyperalgesia
80
Major side-effect of clinical (or recreational) opioid use is constipation
Does not develop tolerance, remains an issue with long-term use
81
Hormone imbalance
Hypogonadism in majority of chronic opioid users (up to 90%)
Amenorrhea by supressing luteinizing hormone
82
* Opioid-induced hyperalgesia
Chronic opioid use alters the homeostasis of pain signalling pathways
* With time pain thresholds decrease resulting in increased sensitivity to pain – often
mistaken for tolerance resulting in increased dosage
83
Management of addictions
* Maintenance therapies
* British system
84
Maintenance therapies
proposed on the premise that the real harm
of opioid abuse is caused by the illegality and expense of the drug
85
Many adverse health effects of opioid abuse are due to
impurities in drug and spread of
diseases (i.e. HIV, hepatitis) due to unsafe administration
86
British system
provides heroin prescriptions to addicts at public
expense
87
British system provides heroin prescriptions to addicts at public
expense * Cheap, reliable, and safe source allows users to
o maintain a healthy, normal life and career
88
British system provides heroin prescriptions to addicts at public
expense Decreased
death rates, reduced criminal behaviour, improved function and social
integration of addicts, decreased transmission of HIV and hepatitis
89
Decreased death rates, reduced criminal behaviour, improved function and social
integration of addicts, decreased transmission of HIV and hepatitis Effectively cheaper long-term to
prescribe heroin than to pay health care and judicial
costs associated with addictions
90
Methadone maintenance (US system)
* Synthetic opioid administered orally
* Decreased euphoric effects
* Effects last ~24 hours in preventing withdrawal symptoms
* Competitive for receptor sites with morphine (blocks euphoric
effects of heroin if co-administered)
* Reduces associated morbidity and mortality
* 80-90 % relapse rates
91
Methadone has decreased
potency and decreased
psychoactive effects but has
a much longer duration of
effect.
92
Methadone withdrawal is
much less severe than
heroin
93
LAAM (Levacetylmethadol) administration
Orally administrable maintenance drug
94
LAAM (Levacetylmethadol) Comparable to
methadone therapy but longer lasting – up to 72 hours (administration required only 3x per
week)
95
risks of LAAM (Levacetylmethadol)
Some risk of life-threatening ventricular rhythm disorders (not widely used)
96
Buprenorphine
Analgesic, mixed agonist-antagonist at different opioid receptors
97
Buprenorphine Similar to
methadone, but fewer adverse effects (no respiratory depression)
98
Buprenorphine Is itself addictive, but
thought to be easier to kick than heroin
99
* Buprenorphine Investigational use in
neonatal abstinence – infants born to opioid addicted mothers
100
Suboxone is currently
favored in Canada – buprenorphine and naloxone
