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Neuro-pharmacology > Opiates and Opioids > Flashcards

Opiates and Opioids Flashcards

1
Q

Opiate

A

Natural narcotic opioid alkyloids found in the
opium poppy (Papaver somniferum)

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2
Q

Opioid

A

Any natural or synthetic compound or the
endogenous peptides that exert biological
effects at the opioid receptors

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3
Q

Opium Papaver somniferum

A

Latin ‘Sleep-bringing’

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4
Q

Opium Cultivation and use

A

predates recorded history

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5
Q

Opium Described for medical use in

A

Egyptian texts from 1500 BCE

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6
Q

Ceramic opium pipes recovered from

A

m Cyprus dated to
1200 BCE

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7
Q

Opium Reintroduced to Europe during

A

the Crusades

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8
Q

Opium Tinctures common in

A

Victorian England

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9
Q
  • Laudanum (from Latin ‘to be praised’)
A

opium dissolved in
alcoho

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10
Q

Natural opiates Major psychoactive opiates:

A
  • Morphine
  • Codeine
  • Thebaine
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11
Q

Other major opiates

A

Noscapine (anti-tussive, emetic)
* Papaverine (antispasmodic)

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12
Q

Minor opiates

A

Hydrocodone (Zohydro, Vicodine)
* Hydromorphone (Dilaudid)
* Oxycodone (Oxycontin, Percocet)

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13
Q

first opiate to be isolated was

A

Morphine first isolated in 1804.

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14
Q

structure of morphine determined in

A

1925

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15
Q

what is different about thebaine

A

its a stimulant

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16
Q

Morphine and codine are

A

depressive and analgesic so they relieve pain and are psychoactive

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17
Q

Pharmacological use of natural opiates Analgesic

A

still the most potent and effective pain relievers known,
widely used (both morphine and derivatives)

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18
Q

Pharmacological use of natural opiates Antitussive

A

cough suppressant

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19
Q

Pharmacological use of natural opiates Codeine has decreased

A

analgesic effect but retains antitussive effects

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20
Q

Pharmacological use of natural opiates Decreased gastric motility of opiates

A

can be used to treat diarrhea esp.
pathogenic (e.g. dysentery)

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21
Q

Loperamide is an opioid derivative that

A

does not penetrate the BBB and is
used to treat diarrhea

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22
Q

Administration of opiates Natural opiates can be administered by a number of routes

A
  • Oral administration
  • Subcutaneous, intramuscular*, or intravenous**
    Inhalation
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23
Q

Administration of opiates Oral administration

A

morphine readily absorbed through GI but
high variability, codeine has more consistent oral absorption

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24
Q

Administration of opiates Subcutaneous, intramuscular*, or intravenous**

A

more stable
systemic levels

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25
Q

Subcutaneous, intramuscular*, or intravenous** – more stable
systemic levels

A

*preferred route for morphine in clinical setting
* ** common recreational route

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26
Q

Administration of opiates Inhalation

A

historic route of (recreational) administration for raw
opium is smoking

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27
Q

Semi-synthetic opioids Diacetylmorphine

A

first synthesized in 1874 by C.R. Alder Wright who was
seeking morphine analogues with decreased addictive potential

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28
Q

Diacetylmorphine Marketed in 1898 by Bayer pharmaceutical under the trade name

A

Heroin
as a cough suppressant, analgesic, and cure for morphine addiction

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29
Q

Development of numerous semi-synthetic opioids followed the

A

solation of
morphine and codeine and subsequent discovery of the structures

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30
Q

Some semi-synthetic opioids are found

A

naturally but generally synthesized
from morphine or thebaine for pharmaceutical use

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31
Q

Some semi-synthetic opioids are found naturally but generally synthesized
from morphine or thebaine for pharmaceutical use

A

Hydrocodone, hydromorphone, and oxycodone

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32
Q

Administration of opioids Semi-synthetic opioids can generally be administered by the same routes
as morphine

A

Oral, Intravenous, Inhalation or intranasal

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33
Q

Administration of opioids Oral

A

heroin administration by oral route produces the same potency and
efficacy as morphine

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34
Q

First pass metabolism of heroin yields

A

morphine as the major metabolite

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35
Q

Administration of opioids Intravenous

A

IV heroin is dramatically more potent and rapid than morphine
due to increased lipophilic structure (increased BBB permeability)

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36
Q

ntravenous – IV heroin is dramatically more potent and rapid than morphine
due to increased lipophilic structure (increased BBB permeability)

A

Rapid uptake into the brain, where it is metabolized to morphine to exert psychoactive effects

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37
Q

Administration of opioids Inhalation or intranasal

A

occasional routes for recreational use

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38
Q

‘freebase’ heroin can be

A

smoked while other preparations can be finely ground and snorted

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39
Q

Therapeutic effects of opioids

A

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

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40
Q

Therapeutic effects of opioids Effects in the limbic system

A

Reduced anxiety
* Reduced inhibition

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41
Q

High doses of opioids Subjective effects at recreational doses:

A

Euphoria or elation
‘Rush”
Physiological effects:

42
Q

Subjective effects at recreational doses: Euphoria or elation

A

(in contrast to relaxed state at lower
doses)
* Dysphoria in some users

43
Q

High doses of opioids ‘Rush’

A

– 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
Q

High doses of opioids * Physiological effects:

A
  • Pinprick pupils
    Nausea and vomiting
    Moderate respiratory depression
45
Q

Nausea and Opioids can act at the

A

chemoreceptor trigger zone in the area postrema to
induce the vomit reflex

46
Q

Recreational use of
opioids

A

Opium, morphine, heroin, fentanyl are well
known drugs of abuse

47
Q

Prescription opioids (Oxycontin) are one of
the fasted growing classes of drugs of
abuse

A

Particularly among wealthy suburban
North Americans
Common among medical practitioners
(physicians and pharmacists)

48
Q

Opioid tolerance

A

Tolerance to opioids develops quickly and reflects various modes of tolerance

49
Q

Opioid tolerance lerance to respiratory and euphoric effects

A

develops more rapidly than
tolerance to analgesic effects

50
Q

Tolerance to respiratory and euphoric effects develops more rapidly than
tolerance to analgesic effects

A
  • Prolongs the usefulness in long-term pain management
  • Unfortunately constipation does not develop tolerance
51
Q

Metabolic tolerance

A

some increase in drug metabolism

52
Q

Behavioural tolerance

A

highly relevant in addicts

53
Q

Pharmacodynamic tolerance

A

– principal mechanism of tolerance – decreased
expression of opioid receptors

54
Q

Opioid withdrawal

A

Somewhat exaggerated perception of opioid withdrawal due to
‘cinematic creative license’

55
Q

During the early years of Hollywood heroin was more abundant,
cheaper, and higher purity and subsequently

A

addicts undergoing
withdrawal would have much more severe symptoms

56
Q

Opioid withdrawal Current users will rarely take sufficient quantity to

A

match historic
depictions of withdrawal

57
Q

Opioid withdrawal Much less severe than withdrawal from

A

barbiturates or alcohol

58
Q

severe alcohol withdrawal can be

A

fatal, opioids never fatal

59
Q

Withdrawal is heavily influenced by
mechanisms of

A

drug tolerance and
dependence

60
Q

Withdrawal is heavily influenced by
mechanisms of drug tolerance and
dependence

A

Pharmacodynamic mechanisms

61
Q

Receptor systems affected by opioids

A

compensate to restore homeostasis in the
continued presence of drug

62
Q

Removal of drug upsets homeostasis in the

A

opposite direction of drug use

63
Q

Withdrawal produces

A

neurochemical and
behavioural changes that are often opposite
the effects of intoxication

64
Q

Stages of withdrawal

A

Begins 6-12 hours after last administration, peaks 26-72 hours, persists
less than 1 week

65
Q

First stage of withdrawal

A

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
Q

Continued withdrawal effects Second stage

A

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
Q

Severity of withdrawal depends on

A

daily dose, less severe with less potent opiates (e.g. codeine)

68
Q

For most, withdrawal resembles a

A

bad flu

69
Q

Withdrawal symptoms stop

A

immediately by opioid administration, induced by opioid antagonists

70
Q

Withdrawal symptoms reduced by

A

alcohol

71
Q

Opioid overdose

A

High doses of opioids can cause death

72
Q

Opioid overdose Usually IV

A

heroin or morphine

73
Q

at high doses

A

Comatose state, pinpoint pupils, and severe respiratory depression occur

74
Q

Opioid overdose convulsions common

A

Lowers seizure threshold

75
Q

Opioid overdose Death occurs by

A

severe respiratory depression or combination of supressed cough reflex, unconsciousness,
and vomiting

76
Q

Contaminants such as quinine (used to cut heroin) are a

A

probable cause of many overdoses – causes
frothing from mouth and nose and death by pulmonary edema

77
Q

Opioid overdose Affected by behavioural tolerance

A

drug use outside conditioned environment can lead to
increased drug effects

78
Q

OD can be treated using

A

opioid antagonists (i.e. naloxone)

79
Q

Chronic effects of opioid use

A

constipation
Hormone imbalance
Opioid-induced hyperalgesia

80
Q

Major side-effect of clinical (or recreational) opioid use is constipation

A

Does not develop tolerance, remains an issue with long-term use

81
Q

Hormone imbalance

A

Hypogonadism in majority of chronic opioid users (up to 90%)
Amenorrhea by supressing luteinizing hormone

82
Q
  • Opioid-induced hyperalgesia
A

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
Q

Management of addictions

A
  • Maintenance therapies
  • British system
84
Q

Maintenance therapies

A

proposed on the premise that the real harm
of opioid abuse is caused by the illegality and expense of the drug

85
Q

Many adverse health effects of opioid abuse are due to

A

impurities in drug and spread of
diseases (i.e. HIV, hepatitis) due to unsafe administration

86
Q

British system

A

provides heroin prescriptions to addicts at public
expense

87
Q

British system provides heroin prescriptions to addicts at public
expense * Cheap, reliable, and safe source allows users to

A

o maintain a healthy, normal life and career

88
Q

British system provides heroin prescriptions to addicts at public
expense Decreased

A

death rates, reduced criminal behaviour, improved function and social
integration of addicts, decreased transmission of HIV and hepatitis

89
Q

Decreased death rates, reduced criminal behaviour, improved function and social
integration of addicts, decreased transmission of HIV and hepatitis Effectively cheaper long-term to

A

prescribe heroin than to pay health care and judicial
costs associated with addictions

90
Q

Methadone maintenance (US system)

A
  • 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
Q

Methadone has decreased

A

potency and decreased
psychoactive effects but has
a much longer duration of
effect.

92
Q

Methadone withdrawal is

A

much less severe than
heroin

93
Q

LAAM (Levacetylmethadol) administration

A

Orally administrable maintenance drug

94
Q

LAAM (Levacetylmethadol) Comparable to

A

methadone therapy but longer lasting – up to 72 hours (administration required only 3x per
week)

95
Q

risks of LAAM (Levacetylmethadol)

A

Some risk of life-threatening ventricular rhythm disorders (not widely used)

96
Q

Buprenorphine

A

Analgesic, mixed agonist-antagonist at different opioid receptors

97
Q

Buprenorphine Similar to

A

methadone, but fewer adverse effects (no respiratory depression)

98
Q

Buprenorphine Is itself addictive, but

A

thought to be easier to kick than heroin

99
Q
  • Buprenorphine Investigational use in
A

neonatal abstinence – infants born to opioid addicted mothers

100
Q

Suboxone is currently

A

favored in Canada – buprenorphine and naloxone

Neuro-pharmacology (26 decks)

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