Drug 1: Narcotics Flashcards
What are the major narcotics?
Opium, morphine, heroin
What makes a drug a narcotic?
Narcotic drugs are opiate derived and related drugs
What effect do narcotics have?
The word narcotic is derived from the Greek word ‘stupor’ because they produce dream-like effects, and at high doses can induce sleep.
What do narcotics do pharmacologically (in the medical setting)?
Have sedative-hypnotic and analgesic (pain killing) properties, they act stereo-typically on endorphin/enkephalin receptors and are antagonized by Naloxone
What drug reverses the effects of a narcotic drug?
Naloxone
What receptors do narcotics act on?
endorphin & enkephalin receptors
What are the 3 categories of narcotics
Opium & 3 natural components extracted from it: morphine, codeine, thebaine
Opium Derviatives: changes to chemical composition of morphine e.g. heroin
Synthetic Opiates: Not chemically related to morphine but produce opiate-like effects e.g. Meperidine (Demerol), Methadone, LAAM.
What is the purpose of creating synthetic opiates?
Synthetic opiates have been created in an attempt replicate the effects (analgesia) of the drugs without the abuse potential. Creating drugs which do not have abuse potential can help in the medical setting and also in rehabilitation of addicts e.g. heroin addicts taking Methadone
What are opium derivatives?
Drugs which have been created by making changed to te chemical composition of morphine e.g. heroin
What drug is an opium derivative?
Heroin
What are synthetic opiates?
Drugs which are not chemically related to morphine but produce similar effects e.g. Methadone
What drug is a synthetic opiate?
Methadone
What are the 3 natural components extracted from opium?
Morphine, codeine, thebaine
Where is opium sourced from?
The opium poppy, not the same as a normal poppy
How is opium sourced?
An incision is made on the seed capsule allowing a milky liquid to ooze out,
Oxidation causes the formation of a reddish, brown syrup which is collegected
What is the active ingredient in narcotics?
Opium
Out of morphine, codeine and thebaine, which is the most potent?
Morphine
Which type of narcotic is 10x more lipid soluble?
Opium derivatives e.g. Heroin
What is heroin often taken with?
Other drugs
What drug is often taken with other drugs such as cocaine?
Heroin
What countries harvest opium?
Fields in hot countries such as Peru, Afghanistan
How far backdated is opium cultivation?
1200BC
When did opium use peak?
19th Century
In china, how was opium primarily taken?
Through smoking
In 1856, the Hyperdermic syringe was invented, how did this change opiate use?
The hyperdermic syringe allowed opiates such as morphine to be injected, which was faster than oral delivery.
What was laudanum used for?
It was used to treat practically everything in the 11th and 16th century and was the most popular opiate up until the 19th Century
The 19th century saw opiate use peak, how was it taken?
In the 19th century opiate use peaked, it was orally delivered as a drink and was a socially acceptable construct
What stopped opiate use being so popular and social?
It stopped being a social popular thing once people realised it’s addictive qualities.
When was legislation put into place over narcotics?
1868.
In 1968, what was the legislation of narcotics?
That is was only allowed to be sold by pharmacists and shops.
In the US, the Harrison Narcotics Act was put into place. When and what was this?
The Harrison Narcotics Act was put into place in 1941, this made it illegal to be an addict, and it was illegal for pharmacists to prescribe opiates to addicts.
How were children affected in the history of opiod use?
During the time period when it was legal, children were exposed and took opiats to alleviate symptoms in collic and the pain of teething.
Why was heroin made?
Heroin was made when trying to create a drug which has the same effects of a narcotic (analgesic) but without the addictive/dependence properties.
When was heroin introduced into the world?
Introduced by the Bayer company in Germany in 1898
What was heroin first advertised as?
A cough suppressant and medication to relieve chest discomfort. It was also advertised as being similar to morphine without the nausea and dependency.
On a molecular level, what is heroin made up of?
2 acetyl groups joined to a basic morphine molecule.
Heroin is 10x more lipid soluble, what does that mean?
It is 10x more fat soluble than other narcotics, meaning it is rapidly absorbed into the brain and higher concentrations
What happens once heroin reaches the brain?
The 2 acetyl groups break off making the effects of heroin chemically identical to those of morphine.
When was the abuse potential for heroin recognised?
in 1910.
When was heroin banned in the USA?
In 1924.
In oral administration, is heroin more or less potent?
It is 100x less potent compared to IV
What narcotics are more effective if delivered orally?
Synthetic opiates - methadone and LAAN
What is IV?
Injecting something into the veins via a needle
What are the advantages of orally administrating heroin/morphine?
The user has more control of the drug through oral administration. But it does not survive well in the stomach and is less potent.
What is a disadvantage of oral administrating heroin/morphine?
Morphine and heroin are weak alkaloids and are not readily absorbed, meaning they do not survive well in the stomach and therefore less potent.
How can narcotics be administered?
Orally, IV, Subcutaneous Intranasally, Inhalation,
When heroin is injected it is _x more or less potent than morphine?
3x MORE potent
Why is heroin more potent than morphine if delivered through IV?
Because heroin can penetrate the blood brain barrier more rapidly, allowing it to accumulate in the brain quicker, giving more rapid and intense effects.
What is subcutaneous?
Injecting the drug under the skin
What is an advantage of subcutaneous delivery?
It allows the drug to be released at a slower rate.
What type of drug users use the subcutaneous method?
Chronic users who suffer from collapsed veins, and new users who can’t find a vein.
What is intranasally?
Taking the drug through the nose by snorting
How can heroin be taken intranasally?
Heroin can be snorted in the form of Snuff
What narcotic cannot be taken intranasally?
Morphine
What is inhalation delivery?
Taking the drug via breathing it in.
How is heroin inhaled?
By burining pure heroin until it vaporises then catching the smoke by inhaling, this is known as ‘chasing the dragon’
How did the chinese traditionally take opiates?
Via inhalation with an opium pipe
What can affect the intensity of a response to heroin?
Quality & quantity of the drug, How it is administered, Time elapsed since previous dose Degree of tolerance Psychological factors related to setting, circumstances, and expectation of the drug
What happens when heroin is administered through IV?
Immediate tingling sensation and a sudden feeling of warmth in lower abdomen, similar to sexual orgasm lasting 1-2 minutes
Intense euphoria followed by a state of tranquil drowsiness (3-4 hours), known as ‘the nod’ - during this time interest in sex is greatly reduced.
How do narcotics affect males?
Reduces testosterone levels.
What happens when a user takes heroin for the 1st time?
It can be unpleasant, causing nausea and vomiting. This can sometimes be so unpleasant it puts people off taking the drug again.
Why do first time heroin users experience vomiting and nausea?
The medulla is stimulated and vomiting and nausea are a reflex of this.
What are the acute affects of heroin?
Pinpoint pupils, depressed blood pressure, respiratory depression, constipation, all over body itching and reddening of eyes.
How does heroin affect respiratory?
Heroin reduces sensitivity of respiratory centres in the medulla to CO2 levels
Why is respiratory depression a risk factor in heroin use
Because in high doses, heroin can reduce the sensitivity of respiratory centres in the medulla to CO2 levels so much it causes death. This is how users die from overdose.
How does heroin cause constipation?
By slowing down the Gastrointestinal tract.
How do users get past the first time vomiting and nausea?
They build up a rapid tolerance to the effect.
What acute effects do users rarely become tolerant to?
Pupil constriction.
What is a sign of better quality heroin?
The more the user suffers from itching.
Why do users suffer from all over body itching?
Heroin causes a sudden release of histamine (released in response to foreign bodies) which causes the itching.
When were opiate receptors discovered?
In 1973.
Where are the opiate receptors?
In the brain, spinal cord and limbic system.
How were the opiate receptors discovered?
First found when studying rats.
What are the 3 types of endorphins?
Enkephalins, Beta-endorphins, Dynorphines
Why do we have endorphins and endorphin receptors?
They are our natural pain and stress fighters
What are endorphins made up of?
Peptide moldecules (amino acids strung together)
How do endorphins function?
They are opiate like in function
Where are endorphins produced?
Within the CNS (central nervous system)
What do endorphines function as?
Neurotransmitters, neurohormones or neuromodulators
What can activate the endorphines?
Acute stressors/ conditioning (Benedetti et al, 1999)
What are the 3 types of opiod receptors?
Mu, Kappa and Delta
Which type of opiod receptor does morphine readily bind to?
Morphine and naloxone.
Where is the Mu reptor located?
In the limbic syste, hippoacampus, amygdala, thalamus, locus coeruleus,
What does the Mu receptor do?
Mediates euphoric effects, spinal and supra spinal analgesia, respiratory depression, cardiovascular effects, slow GI motility and sedation
What endorphine is the Delta receptor selective to?
Enkephalin
Where is the Delta receptor located?
Cortex, hypothalamus, nucleus accumbens, regions of the medulla.
What does the Delta receptor do?
Euphoric effects and spinal analgesia.
What is the Kappa receptor involved in?
The adverse effects of narcotics such as sedation and psychosis.
Where is the Kappa receptor found?
Nucleus accumbens, ventral tegmental area, hypothalamus and regions of the thalamus
What does the Kappa receptor do?
May mediate spinal analgesia, sedation and psychotomimetric effects.
What is naloxone ?
An opiod antagonist
What does an antagonist do?
A substance that creates the same bodily response but does not bind to the same receptor.
What receptor does naloxone affect?
It is a pure antagonist at the Mu receptor.
What does naloxone do?
Blocks the action of any opiod at this receptor without having an opiod effect of its own, completely reversing the effects of a heroin overdose.
What is naloxone used for?
To treat victims of opiod overdose.
What happens when naloxone is given to a dependent person?
It causes withdrawal
How does naloxone work in the brain?
It replaces the opiod agonist by binding and blocking the Mu receptor, reversing the effects of opiods.
What narcotics will animals self administer?
Heroin and morphine
What has been observed when animals self administer heroin/morphine?
They will do it even if they have never experienced withdrawal symptoms.
They will self administer very regularly, not allowing themselves to enter withdrawal.
What narcotics will animals not self administer?
naloxone and naltrexone
What are naloxone and naltrexone
opiod antagonists
What will animals learn to avoid?
opiod antagonists naloxone and naltrexone
What agonists will animals self administer?
Mu agonists
To what extent will animals self administer mixed agonists and antagonists?
To a lesser extent than pure Mu agonists. (Zacny & Wlaker, 1998)
What can Mu antagonists block the self administration of?
Morphine and heroin (Trujillo, 1989)
What do animals do with Kappa agonists in self administration?
Do not self administer.
What evidence is there about Kappa agonists?
Evidence shows Kappa agonists block reinforcing effects of morphine and cocaine
What induces conditioned place preference?
Intra Ventral Tegmental Area morphine induces conditioned place preference. (Phillips, 1980)
What blocks the reinforcing effects of drinking water in thirsty rats in conditioned place preference paradigm?
Naloxone and Primozide (Agmo 1993)
What lowers Intracranial self stimulation reward thresholds?
Intra Ventral Tegmental Area morphine (Broekkamp, 1979)
What does Intra Ventral Tegmental Area morphine do?
Activates reward centres in the brain
What are the reinforcing actions of opiates?
Dopamine dependent and independent mechanisms of opiate action are the reinforcing actions of opiates
What do Mu receptor antagonists decrease in a dose-dependent manner?
Mu receptor antagonists decrease opiate reinforcement in a dose-dependent manner (Negus, 1993)
What do Mu receptor knock out mice don’t show?
Mu receptor knock-out mice do not show morphine induced analgesia or conditioned place preference (Matthes, 1996)
What are knock out mice?
Mice which are genetically modified to lack something e.g. mice genetically modified to lack Mu receptor.
What do opiates increase in the nucleus accumbens?
Dopamine release. Likely to be via Mu Receptors in Ventral Tegmental Area
Who discovered opioid receptors?
Mansour, 1987
What impairs opiate reward in intactranial self stimulation and conditioned place preference?
Dopamine lesions or D1 and D2 receptor antagonists
When all dopamine projections are destroyed, what happens in the Nucleus Accumbens in terms of the reinforcing effects of opiates?
Reinforcing effects of opiates in Nucleus Accumbens persists when all dopamine projections are destroyed (Pettit et al, 1984)
After several months of heavy use, how much can some users administer?
40x/50x the dose, this would kill non-toletant individuals.
After several months of heavy use, users can take 40-50x the dose which would kill a non-tolerant individual. What does this show?
That tolerance for narcotic drugs develops rapidly.
What effects of narcotic drugs do users become tolerant?
Users become tolerant to most effects of narcotic drugs e.g. analgesia, euphoria, respiratory depression. The decline of these effects is dose dependent.
Rats allowed to self administer heroin via IV increased their intake from less than 2mg to 336mg within how many days?
(Sim Selley, 2000) - 29-39 days.
Which effects only partially disappear?
Pupillary constriction
Which effects never subside?
Consipation
What is cross tolerance?
Tolerance of one thing reduces the effects of another, related thing.
What is the role of cross tolerance in narcotics?
Cross tolerance exists among all the narcotics, where tolerance to one reduces the effectiveness of the other e.g. using heroin can make you tolerant to morphine
What plays an important role in tolerance to narcotics?
Psychological processes such as conditioned tolerance (Seigal 1975)
Several cellular adaptations that involve receptor baring cells directly may contribute to opioid tolerance. What are these?
Receptor downregulation (Law et al, 1982) - Overtime, opioid receptors decrease to combat over stimulation.
Decrease in receptor affinity for opiod peptides (Evans and von Zastow, 1990)
List some signs/effects of heroin withdrawal…
Craving for drug, anxiety, yawning, sweating, runny nose, teary eyes, pupil dialation, goose bumps, tremors, hot and cold flashes, aching muscles and bones, loss of appetite, weight loss, spontaneous ejaculation or orgasm.
What is methadone and why is it useful in heroin rehabilitation?
Methadone is a synthetic narcotic which is used to rehabilitate heroin addicts. Addicts are prescribed the drug, often taken with orange juice. It is a useful drug in helping addicts get off heroin because of its longer lasting properties, it stays in the body due to having a longer half life and so the withdrawal symptoms are les severe and appear later than heroin
What makes heroin withdrawal more intense?
The more chronic the user the more intense the withdrawal.
What can give users a more intense craving?
Drug taking cues can make cravings more intense such as being in the environment where the drugs were typically taken.
What are affective symptoms of withdrawal?
Disphoria, depression and anadonia (inability to feel pain)
What is the basis of methadone in treating heroin addicts?
Cross-dependence is seen among the narcotics - withdrawal symptoms can be prevented by an appropriate dose of any narcotic. So substituting legal methadone prevents withdrawal symptoms for as much as a day.
