substance misuse 3 Flashcards
where is cocaine found?
Found in leaves of Erythorxylon coca (Andes)
- it is an alkaloid
what is the mechanism of action of cocaine?
CNS:
Blocks:
Dopamine active transporter (DAT)
Norepinephrine transporter (NET)
Serotonin transporter (SERT)
Increases synaptic levels of these three transmitters.
DAT: Nucleus accumbens – reward and reinforecment effects
SERT: cortex reward and reinforcement effects
NET: Activation of sympathetic system
Increased arterial pressure
Tachycardia
Ventricular arrhythmias
Production of illicit cocaine
Colombia is the main producer
Cocaine is extracted by
1. Mashing coca leaves in a gasoline and alkali mixture
2. Gasoline containing the dissolved alkaloid is drained into a barrel and a dilute acid added (sulphuric) to create aqueously soluble cocaine suphate
3. Gasoline layer is removed and NaHCO3 is added to neutralise the acid and cocaine hydrochloride precipitates out of solution
Cocaine base is filtered though a cloth and dried
This produces powder cocaine
what are the routes of administration of cocaine?
what can the route of administration indicate?
Transmucosal. Cocaine hydrochloride is absorbed through mucosal membranes
intranasally via insufflation
inhaled when free base is heated
Injected
Typically i.v.
Often mixed with other drugs (e.g. heroin = ‘speedball’)
The route of administration can be indicative of the level of dependence
Routes produce similar levels of DAT blockade but…
Users report stronger “highs” through inhaled cocaine (speed of delivery)
i.v. wastes less material
what are short term side effects of cocaine?
Increased sense of energy and alertness
Extremely elevated mood
Feeling of supremacy
Irritability
Paranoia
Restlessness
Anxiety
Dilated pupils
Excited, exuberant speech
Numerous peripheral effects (see right)
Duration of action: 0.5 to 2 hr
what are some long term side effects of cocaine?
Cardiac:
Increases heart rate and blood pressure
Lethal arrhythmia
CNS:
Central vasoconstriction
Increased risk of stroke
Seizures
Bizarre or violent behaviour
Lungs:
Caustic and can damage the nose and sinuses.
Gastrointestinal tract:
Vasoconstriction in gut leading to ulcers or perforation
Sexual function:
Impaired sexual function in men and women
what are withdrawal symptoms of cocaine?
Symptoms include:
Depression and anxiety
Fatigue
Difficulty concentrating
Inability to feel pleasure
Increased craving for cocaine
Physical symptoms including aches, pains, tremors, and chills
Formication (feeling of insects under the skin)
Withdrawal is rarely medically serious but very difficult to resist
Can cause suicidal thoughts.
Withdrawal symptoms resolve within 1-2 weeks but intense craving can return even years after the last use.
what are the treatments for cocaine addiction?
No FDA/EMA-approved medications to treat cocaine addiction
Some treatments are used off licence to target withdrawal symptoms rather than the underlying dependence
Psychotherapy: CBT, TCs (see first lecture)
Several medications marketed for other diseases have been claimed to show promise:
Antidepressant and tranquilizers
-(e.g. desipramine or diazepam) to reduce anxiety and depression
Amantadine
-Dopamine reuptake inhibitor used in Parkinson’s Disease may reduce cocaine craving
Bromocriptine
-D2 receptor agonist to decrease the craving for cocaine during detoxification and to reduce mood disturbance
propanolol
-A beta-blocker drug used to treat high blood pressure, may be useful for severe cocaine withdrawal symptoms, as it reduces peripheral effects of adrenaline, inhibiting the “fight or flight” response to stressful situations.
what are club drugs?
Amphetamines,
methamphethamine,
phenidates
methylene-dioxymethamphetamine (MDMA
what is the moa of Phenidates and Methyl phenidates
Mechanism of action similar to cocaine
“amphetamine-like”drug, with regards to the pharmacological, dopamine-releasing properties
Major effect in the basal ganglia (Volkow et al., 2002)
A rapid release of synaptic dopamine occurs, producing subjective effects of an instant “high” and an intensely gratifying euphoria
Localization of methylphenidate binding with dopaminergic pathways was “identical” with that of cocaine and a similar “high” was described by patients receiving both drugs intravenously (Volkow et al., 2002)
Amphetamines examples
what was it used for
Amphetamine-type stimulants include methamphetamine and amphetamine
Originally developed as synthetic alternatives to the naturally occurring stimulant ephedra (extract of Ephedra sinica)
Early amphetamine use was primarily via nasal insufflation. In 1932, Smith, Kline, and French began marketing the amphetamine inhaler Benzedrine for use in asthma and congestion
what is Dextro-amphetamine used for
moa
Dextro-amphetamine: ADHD, narcolepsy, obesity
Synthetic – indirect acting – sympathomimetic drugs
Cause release of endogenous biogenic amines (dopamine and noradrenaline)
Reverse action of biogenic amine transporters
Amphetamines are substrate of the transporters
increasing the amounts of dopamine, norepinephrine, and serotonin (to a lesser extent) in the synaptic cleft through a variety of mechanisms
why do people abuse amphetamine?
Recreationally, methamphetamine is abused to increase alertness, relieve fatigue, control weight, treat mild depression, and for its intense euphoric effects
what are the routes of administration for amphetamine?
duration effects
elimination
Administration:
- Methamphetamine users often begin with intranasal or oral use and progress to intravenous use, and occasionally smoking.
- Following oral administration, peak methamphetamine concentrations are seen in 2.6-3.6 hours and the mean elimination half-life is 10.1 hours (range 6.4-15 hours). The amphetamine metabolite peaks at 12 hours. Following intravenous injection, the mean elimination half-life is slightly longer (12.2 hours).
Duration of Effects:
Onset of effects is rapid following intravenous use and smoking, while effects onset more slowly following oral use. Overall effects typically last 4-8 hours; residual effects can last up to 12 hours.
Elimination:
-Methamphetamine is metabolized to amphetamine (active), p-OH-amphetamine and norephedrine (both inactive)
-Several other drugs are metabolised to amphetamine and methamphetamine and include benzphetamine, selegiline, and famprofazone
what are the side effects of amphetamine
and the side effects if they are overdosed?
Side Effect Profile:
Light sensitivity
Irritability
Insomnia
Nervousness
Headache
Tremors
Anxiety
Suspiciousness
Paranoia
Aggressiveness
Delusions
Hallucinations
Irrational behaviour
Violence
Overdose:
Hyperthermia
Tachycardia
Severe hypertension
Convulsions
Chest pains
Stroke
Cardiovascular collapse
Possible death
Tolerance, Dependence and Withdrawal Effects
Methamphetamine has a high potential for abuse and dependence
Tolerance may develop and users may quickly become addicted and use it with increasing frequency and in increasing doses
Abrupt discontinuation of use can produce extreme fatigue, mental depression, apathy, long periods of sleep, irritability, and disorientation
Treatment is by withdrawal and behavioural approaches
what is Methylene-dioxymethamphethamine (MDMA)
what does it cause?
MDMA (Ecstasy)
Synthetic, psychoactive drug that has similarities to both the stimulant amphetamine and the hallucinogen mescaline
Produces feelings of increased energy, euphoria, emotional warmth and empathy toward others, and distortions in sensory and time perception
Does MDMA Have Therapeutic Value?
use before
use now
MDMA was first used in the 1970s, not as a recreational drug but as an aid in psychotherapy—although without the support of clinical trial research or FDA approval.
It is currently in very early clinical trials as a possible pharmacotherapy aid to treat post-traumatic stress disorder (PTSD) and anxiety in terminal cancer patients.
what are the dangers of illegal market - ecstasy?
Ecstasy tablets and even capsules actually contain other drugs instead or in addition
Those may include ephedrine, dextromethorphan, ketamine, caffeine, cocaine, methamphetamine, synthetic cathinones (“bath salts”)
These substances are harmful alone and may be particularly dangerous mixed with MDMA
Most risks are associated with the use of the drug in the environment in which it is most often consumed
moa of LSD?
Similar to serotonin: indole ring
LSD is believed to exert its pharmacologic properties
primarily through its effects on the serotonin system
Binds to 5-HT1A/1B/1D, 5-HT2A/2C, 5-HT5A, 5-HT6,
and 5-HT7 receptors
Psychedelics share a common biochemical action
in that they all act as agonists at 5-HT2A receptors
Other mushroom/plant derivatives share these effects
what is the perceptual side effects of LSD?
150–250 micrograms of LSD p.o. typically produces:
Illusions; i.e., objects changing shape and color
Stationary objects seeming to move
Colors becoming brighter or more intense
Synaesthesia (i.e., one type of sensory experience is translated into another; e.g., one “sees” sound),
Emotional changes
Value judgment may be suspended
Time and spatial orientation are often affected
Events experienced while under the influence of LSD are given increased meaning
Memory is generally not affected
Transcendental experiences (“Psychedelic” term was coined)
what is the somatic side effects of LSD?
Effects may result from stimulation of both the sympathetic and parasympathetic nervous systems and tend to occur only at higher doses :
Changes in heart rate and blood pressure
Dilation of the pupils
Sweating
Hypersalivation,
Piloerection
Nausea, diarrhoea, vomiting
Fatigue
Increased muscular tension
Tremors
Headache, heaviness of the extremities
Analgesia may occur as well
Management of the symptomsof hallucinogen ingestion in LSD?
Side effect management is mainly through talk therapy
Volunteers at the Haight Ashbury Free Medical Clinic (HAFMC) developed techniques to “talk them down” from their drug frenzy observing that the individual’s environment had a lot to do with how the effects of LSD were perceived by the user
These techniques have been used and refined by the clinic’s Rock Medicine program at concerts with thousands of “trippers” at Grateful Dead and other concerts for over 40 years
Use of benzodiazepines and anti-psychotics has been adopted in cases where individuals may harm themselves or others
