Opiates and Opioids Flashcards
Opiate
Natural narcotic opioid alkyloids found in the
opium poppy (Papaver somniferum)
Opioid
Any natural or synthetic compound or the
endogenous peptides that exert biological
effects at the opioid receptors
Opium Papaver somniferum
Latin ‘Sleep-bringing’
Opium Cultivation and use
predates recorded history
Opium Described for medical use in
Egyptian texts from 1500 BCE
Ceramic opium pipes recovered from
m Cyprus dated to
1200 BCE
Opium Reintroduced to Europe during
the Crusades
Opium Tinctures common in
Victorian England
- Laudanum (from Latin ‘to be praised’)
opium dissolved in
alcoho
Natural opiates Major psychoactive opiates:
- Morphine
- Codeine
- Thebaine
Other major opiates
Noscapine (anti-tussive, emetic)
* Papaverine (antispasmodic)
Minor opiates
Hydrocodone (Zohydro, Vicodine)
* Hydromorphone (Dilaudid)
* Oxycodone (Oxycontin, Percocet)
first opiate to be isolated was
Morphine first isolated in 1804.
structure of morphine determined in
1925
what is different about thebaine
its a stimulant
Morphine and codine are
depressive and analgesic so they relieve pain and are psychoactive
Pharmacological use of natural opiates Analgesic
still the most potent and effective pain relievers known,
widely used (both morphine and derivatives)
Pharmacological use of natural opiates Antitussive
cough suppressant
Pharmacological use of natural opiates Codeine has decreased
analgesic effect but retains antitussive effects
Pharmacological use of natural opiates Decreased gastric motility of opiates
can be used to treat diarrhea esp.
pathogenic (e.g. dysentery)
Loperamide is an opioid derivative that
does not penetrate the BBB and is
used to treat diarrhea
Administration of opiates Natural opiates can be administered by a number of routes
- Oral administration
- Subcutaneous, intramuscular*, or intravenous**
Inhalation
Administration of opiates Oral administration
morphine readily absorbed through GI but
high variability, codeine has more consistent oral absorption
Administration of opiates Subcutaneous, intramuscular*, or intravenous**
more stable
systemic levels
Subcutaneous, intramuscular*, or intravenous** – more stable
systemic levels
*preferred route for morphine in clinical setting
* ** common recreational route
Administration of opiates Inhalation
historic route of (recreational) administration for raw
opium is smoking
Semi-synthetic opioids Diacetylmorphine
first synthesized in 1874 by C.R. Alder Wright who was
seeking morphine analogues with decreased addictive potential
Diacetylmorphine Marketed in 1898 by Bayer pharmaceutical under the trade name
Heroin
as a cough suppressant, analgesic, and cure for morphine addiction
Development of numerous semi-synthetic opioids followed the
solation of
morphine and codeine and subsequent discovery of the structures
Some semi-synthetic opioids are found
naturally but generally synthesized
from morphine or thebaine for pharmaceutical use
Some semi-synthetic opioids are found naturally but generally synthesized
from morphine or thebaine for pharmaceutical use
Hydrocodone, hydromorphone, and oxycodone
Administration of opioids Semi-synthetic opioids can generally be administered by the same routes
as morphine
Oral, Intravenous, Inhalation or intranasal
Administration of opioids Oral
heroin administration by oral route produces the same potency and
efficacy as morphine
First pass metabolism of heroin yields
morphine as the major metabolite
Administration of opioids Intravenous
IV heroin is dramatically more potent and rapid than morphine
due to increased lipophilic structure (increased BBB permeability)
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
Administration of opioids Inhalation or intranasal
occasional routes for recreational use
‘freebase’ heroin can be
smoked while other preparations can be finely ground and snorted
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
Therapeutic effects of opioids Effects in the limbic system
Reduced anxiety
* Reduced inhibition
High doses of opioids Subjective effects at recreational doses:
Euphoria or elation
‘Rush”
Physiological effects:
Subjective effects at recreational doses: Euphoria or elation
(in contrast to relaxed state at lower
doses)
* Dysphoria in some users
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
High doses of opioids * Physiological effects:
- Pinprick pupils
Nausea and vomiting
Moderate respiratory depression
Nausea and Opioids can act at the
chemoreceptor trigger zone in the area postrema to
induce the vomit reflex
Recreational use of
opioids
Opium, morphine, heroin, fentanyl are well
known drugs of abuse
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)
Opioid tolerance
Tolerance to opioids develops quickly and reflects various modes of tolerance
Opioid tolerance lerance to respiratory and euphoric effects
develops more rapidly than
tolerance to analgesic effects
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
Metabolic tolerance
some increase in drug metabolism
Behavioural tolerance
highly relevant in addicts
Pharmacodynamic tolerance
– principal mechanism of tolerance – decreased
expression of opioid receptors
Opioid withdrawal
Somewhat exaggerated perception of opioid withdrawal due to
‘cinematic creative license’
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
Opioid withdrawal Current users will rarely take sufficient quantity to
match historic
depictions of withdrawal
Opioid withdrawal Much less severe than withdrawal from
barbiturates or alcohol
severe alcohol withdrawal can be
fatal, opioids never fatal
Withdrawal is heavily influenced by
mechanisms of
drug tolerance and
dependence
Withdrawal is heavily influenced by
mechanisms of drug tolerance and
dependence
Pharmacodynamic mechanisms
Receptor systems affected by opioids
compensate to restore homeostasis in the
continued presence of drug
Removal of drug upsets homeostasis in the
opposite direction of drug use
Withdrawal produces
neurochemical and
behavioural changes that are often opposite
the effects of intoxication
Stages of withdrawal
Begins 6-12 hours after last administration, peaks 26-72 hours, persists
less than 1 week
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)
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
Severity of withdrawal depends on
daily dose, less severe with less potent opiates (e.g. codeine)
For most, withdrawal resembles a
bad flu
Withdrawal symptoms stop
immediately by opioid administration, induced by opioid antagonists
Withdrawal symptoms reduced by
alcohol
Opioid overdose
High doses of opioids can cause death
Opioid overdose Usually IV
heroin or morphine
at high doses
Comatose state, pinpoint pupils, and severe respiratory depression occur
Opioid overdose convulsions common
Lowers seizure threshold
Opioid overdose Death occurs by
severe respiratory depression or combination of supressed cough reflex, unconsciousness,
and vomiting
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
Opioid overdose Affected by behavioural tolerance
drug use outside conditioned environment can lead to
increased drug effects
OD can be treated using
opioid antagonists (i.e. naloxone)
Chronic effects of opioid use
constipation
Hormone imbalance
Opioid-induced hyperalgesia
Major side-effect of clinical (or recreational) opioid use is constipation
Does not develop tolerance, remains an issue with long-term use
Hormone imbalance
Hypogonadism in majority of chronic opioid users (up to 90%)
Amenorrhea by supressing luteinizing hormone
- 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
Management of addictions
- Maintenance therapies
- British system
Maintenance therapies
proposed on the premise that the real harm
of opioid abuse is caused by the illegality and expense of the drug
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
British system
provides heroin prescriptions to addicts at public
expense
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
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
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
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
Methadone has decreased
potency and decreased
psychoactive effects but has
a much longer duration of
effect.
Methadone withdrawal is
much less severe than
heroin
LAAM (Levacetylmethadol) administration
Orally administrable maintenance drug
LAAM (Levacetylmethadol) Comparable to
methadone therapy but longer lasting – up to 72 hours (administration required only 3x per
week)
risks of LAAM (Levacetylmethadol)
Some risk of life-threatening ventricular rhythm disorders (not widely used)
Buprenorphine
Analgesic, mixed agonist-antagonist at different opioid receptors
Buprenorphine Similar to
methadone, but fewer adverse effects (no respiratory depression)
Buprenorphine Is itself addictive, but
thought to be easier to kick than heroin
- Buprenorphine Investigational use in
neonatal abstinence – infants born to opioid addicted mothers
Suboxone is currently
favored in Canada – buprenorphine and naloxone
