Opiates and Opioids Flashcards
1
Q
What is an opiate?
A
Natural narcotic opioid alkyloids found in the
opium poppy (Papaver somniferum)
2
Q
What are opioids?
A
- Any natural or synthetic compound or the
endogenous peptides that exert biological
effects at the opioid receptors
3
Q
Describe natural opiates
A
- Major psychoactive opiates:
- Morphine
- Codeine
- Thebaine
4
Q
Describe pharmacological use of natural opiates
A
- Analgesic– still the most potent and effective pain relievers known,
widely used (both morphine and derivatives) - Antitussive– cough suppressant
- Codeine has decreased analgesic effect but retains antitussive effects
- Decreased gastric motility – 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
5
Q
Describe semi-synthetic opioids
A
- Diacetylmorphine first synthesized in 1874 by C.R. Alder Wright who was
seeking morphine analogues with decreased addictive potential - Marketed in 1898 by Bayer pharmaceutical under the trade name Heroin
as a cough suppressant, analgesic, and cure for morphine addiction
6
Q
Describe opioid administration
A
- Semi-synthetic opioids can generally be administered by the same routes
as morphine - 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
- Intravenous– 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
- Inhalation or intranasal– occasional routes for recreational use
- ‘freebase’ heroin can be smoked while other preparations can be finely ground and snorted
7
Q
Describe high doses of opioids
A
- Subjective effects at recreational doses:
- Euphoria or elation (in contrast to relaxed state at lower
doses) - Dysphoria in some users
- ‘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
- Physiological effects:
- Pinprick pupils
- Nausea and vomiting
- Opioids can act at the chemoreceptor trigger zone in the area postrema to
induce the vomit reflex - Moderate respiratory depression
8
Q
Describe opioid tolerance
A
- Tolerance to opioids develops quickly and reflects various modes of tolerance
- 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
9
Q
Describe opioid withdrawal
A
- Much less severe than withdrawal from barbiturates or alcohol
- Severe alcohol withdrawal can be fatal, opioids never fatal
10
Q
Describe rebound hyperactivity
A
- 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 - Rebound hyperactivity
11
Q
Describe first stage withdrawal
A
- Begins 6-12 hours after last administration, peaks 26-72 hours, persists
less than 1 week - First stage:
- 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)
12
Q
Describe second stage withdrawal
A
- 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
13
Q
Describe opioid overdose
A
Comatose state, pinpoint pupils, and severe respiratory depression occur with high doses
Lowers seizure threshold – convulsions common
- Death occurs by severe respiratory depression or combination of suppressed cough reflex, unconsciousness, and vomiting
- Affected by behavioral tolerance – drug use outside conditioned environment can lead to
increased drug effects - OD can be treated using opioid antagonists (i.e. naloxone)
14
Q
Describe chronic effects of opioid use
A
- Major side-effect of clinical (or recreational) opioid use is constipation
- Does not develop tolerance, remains an issue with long-term use
- 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
15
Q
Describe management of addictions
A
- 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 - Cheap, reliable, and safe source allows users to maintain a healthy, normal life and career
- 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
