Topic 16: Opiates and Opioids Flashcards
What is an opiate?
natural narcotic opioid alkyloids found in the opium poppy
What is an opioid?
any natural or synthetic compound or the endogenous peptides that exert biological effects at the opioid receptors
What is the difference between opiates and opioids?
not all opioids are opiates, but all opiates or opioids
What are the major psychoactive opiates?
morphine
codeine
thebaine
How do opiate structures cause their effect?
natural opiates have greatly varied effects due to a number of relatively minor alterations in chemical structure
this lead pharmaceutical development of numerous semi-synthetic and synthetic opioids
What is the pharmacological use of natural opiates?
analgesic: still the most potent and effective pain relivers 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 especially pathogenic, loperamide is an opioid derivative that does not penetrate the BBB and is used to treat diarrhea
What are the routes of administration of opiates?
oral administration: morphine readily absorbed through GI but high variability, codeine has more consistent oral absorption
subcutaneous, intramuscular (morphine), or intravenous (common recreational route): more stable systemic levels
inhalation: historic route of (recreational) administration for raw opium is smoking
What are semi-synthetic opioids?
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
development of numerous semi-synthetic opioids followed the isolation 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
What is oral administration of heroin?
heroin administration by oral route produces the same potency and efficacy as morphine
first pass metabolism of heroin yields morphine as the major metabolite
What is intravenous administration of heroin?
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
What is inhalation or intranasal administration of heroin?
occasional routes for recreational use
“freebase” heroin can be smoked while other preparations can be finely ground and snorted
What are the therapeutic effects of opioids?
at small or moderate doses (5-10 mg morphine) opioids exert limited psychoactive effects
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
What are the subjective effects of recreational doses of opioids?
euphoria or elation (in contrast to relaxed state at lower doses)
dysphoria in some users
“rush” - most pronounced by IV
What is the “rush” experienced at recreational doses of opioids?
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
What are the physiological effects of high doses of opioids?
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
What the recreational use of opioids?
long history of recreational use
opium, morphine, heroin, fentanyl are well known drugs of abuse
prescription opioids (oxycontin) are one of the fasted growing classes of drugs of abuse
What is opioid tolerance?
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
What are the types of opioid tolerance?
metabolic tolerance: some increase in drug metabolism
behavioral tolerance: highly relevant in addicts
pharmacodynamic tolerance: principal mechanism of tolerance - decreased expression of opioid receptors
What is rebound hyperactivity?
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 produced neurochemical and behavioral changes that are often opposite the effects of intoxication: rebound hyperactivity
What is the timeline of opioid withdrawal?
begins 6-12 hours after last administration, peaks 26-72 hours, persists less than 1 week
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
What is the first stage of opioid 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)
What is the second stage of opioid withdrawal?
cramps in stomach, back, legs
vomiting, diarrhea, profuse sweating
twitching of the extremities - shaking of hands and kicking of legs
symptoms become progressively less severe until gradually disappearing
What is opioid overdose?
high doses of opioids can cause death
usually IV heroin or morphine
comatose state, pinpoint pupils, and severe respiratory depression occur with high doses
lowers seizure threshold - convulsions common
death occurs by sever respiratory depression or combination of suppressed cough reflex, unconsciousness, and vomiting
contaminants such as quinine (used to cut heroin) are a probable cause of many overdoses - causes frothing at the mouth and nose and death by pulmonary edema
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)
What are the chronic effects of opioid use?
major side-effect of clinical (or recreational) opioid use is constipation: does to develop tolerance, remains an issue with long-term use
hormone imbalance: hypogonadism in majority of chronic opioid users, amenorrhea by suppressing luteinizing hormone
opioid-induced hyperalgesia: chronic opioid use alters the homeostasis of pain signaling pathways, with time pain thresholds decrease resulting in increased sensitivity to pain - often mistaken for tolerance resulting in increased dosage
