L11 - Substance Use Flashcards
What are the two groups of substance disorders?
Substance Use Disorders
Substance induced disorders
What are the classes of drugs
- Alcohol
- Caffeine
- Cannabis
- Hallucinogens
- Inhalants
- Opioids
- Sedatives
- Anxiolytics
- Stimulants
- Tobacco
- Other
- Gambling….
Severity of disorder?
Depends on number of symptoms endorsed
mild - 2-3 symps
mod - 4-5
severe 6 or +
Intoxication?
Reversible substnace-specific syndrome, due to recent ingestion of a substance.
What does the clinical picture of intoxication depend on?
- substance
- dose
- route of administration
- duration/chronicity
- individual degree of tolerance
- time since last dose
- person’s expectaitons of substance effect
- contextual variables.
What is withdrawal?
substance specific syndrome problematic behavioural change due to stopping or reducing prolonged use.
physiological and cognitive components.
PCP, hallucinogens and inhalants dont have withdrawal.
substance induced mental disorder?
- potentially severe, usually temporary but sometimes persisting CNS syndromes
- occurs during or within 1 month of use.
Neuroadaptation?
underlying CNS changes that occur following repeated use such that person develops tolerance and/or withdrawal.
pharmacokinetic and pharmacodynamic
Name some stimulants
cocaine amphetamine methylphenidate rispiridone Caffeine
Generally, what do CNS stimlants do?
increase motor behaviour and elevate a person’s mood and level of alertness.
Cocaine?
derived from coca leaves/plant.
- potent local anaesthetic, constrictor of blood vessels and psychostimulant.
Blocks dopamine re-uptake
What is the mode of action for cocaine
Blocks dopamine reuptake
Cocaine decreases the discharge of neurons in ventral tegmental area and the nucleus acumbens
Cocaine potentiates the dopamine-induced decrease in discharge rate
D2 sites induce positive behavioural effects, reinforcement and movement effects
D1 permissive effect in behavioural expression
Effects of cocaine?
intense euphoria enhanced vigour gregariousness hypervigilance interpersonal sensitivity/ increased sexual responsivity alertness Talkativeness, anxiety, grandiosity increased tension anger stereotyped and repetitive behaviour impaired judgement
motor twitches due to facilitation of dopamine circuitry - parkinson-like
Some psychological effects of acute intoxication of cocaine?
confusion rambling speech headache transient ideas of reference tinnitus paranoid ideation auditory hallucinations in a clear sensorium tactile hallucinations extreme anger with threats or acting out of aggressive behaviour can occur.
What is the usage of cocaine usually like?
short half life = frequent dosing necessary
usage can be chronic or episodic (binges)
tolerance develops quickly.
most effective is injection
what is cocaine withdrawal like?
Intense and unpleasant feelings of lassitude and depression, often increased suicidal ideation or behaviour.
Mood changes, with depression, suicidal ideation, emotional lability, anhedonia, disturbance of attention and concentration
During sustained use weight loss, malnutrition, and impaired personal hygiene
Mode of action for amphetamine?
Dopamine agonist: releases dopamine and NA into the synapse and blocks the reuptake of dopamine, as well
(similar to cocaine in that it blocks reuptake)
Uses for amphetamine?
Some Uses:
Initially an asthma treatment
Study aid
Improvement of alertness and productivity Weight-loss aid
Why would increasing dopamine in ADHD be better?
adhd is associated with high levels of dopamine. flooding the synapse will desensitise the post synaptic receptor.
effectively decreases dopamine receptor function.
Side effects of amphetamine/dextroamphetamine?
Side effects: dry mouth, metallic taste, can pass thought the placenta, also in breast milk
Paradoxical effect: both increases attention span and has a calming effect
Mode of action for methylphenidate?
Increases release of noradrenaline and dopamine in the CNS and reticular activating system
Onset 30-60 mins, duration 4-6 hrs, metabolised by liver, excreted by kidneys
Paradoxical effect: both increases attention span and has a calming effect
Mode of action for respiridone?
Unclear, but probably related to its antagonism of dopamine and serotonin receptors
Peak plasma level in 1-2 hours, metabolism by the liver
Side effects: Dry mouth, stomatitis (infection of the mouth), taste alteration (but rare).
What is a ‘general stimulant’?
CAFFEINE!
Mode of action for caffeine?
Inhibits the enzyme the normally breaks down the second messenger cyclic AMP
Increase in cAMP leads to an increase in glucose production within cells, which makes more energy available and allows for higher rates of cellular activity
Antagonizes activity of adenosine
Produces behavioural sedation
inhibit the release of many neurotransmitters i.e. NA, DA, Ach, Glu, and GABA: thus increasing NT turnover
What systems does adenosine affect?
SYSTEM CNS Cardiovascular Renal Respiratory Gastrointestinal Metabolic
What effects does adensoine have?
Sedation Dilation of vessels Anti-diuresis Broncho-constriction Inhibition of acid Inhibition of lipolysis
What are some direct and desired effects of caffeine
relaxes smooth muscle; dilates vessels in body, constricts in
brain
alertness, speeds thought, decreases fatigue
withdrawal: headache, drowsiness, fatigue, negative mood
after placebo
What are some harmful effects of caffeine
caffeinism: anxiety, insomnia, mood change: tachycardia, hypertension
panic attacks may be exacerbated (4-5 cups)
may be harmful in pregnancy
Long term effects of caffeine?
No nutritional value Harmful to health including Cardiovascular system Osteoporosis Lower birth weights Adverse effects upon other medications Malaise No beneficial effects of habitual use
mode of action for nicotine?
Tobacco stimulates the cholinergic neurons in the CNS thus increasing heart rate, blood pressure, concentration, memory, and improving mood
medications to stop using tobacco?
bupropion (Zyban) 150mg po bid,
varenicline (Chantix) 1mg po bid
What are some CNS depressants?
Benzodiazepines
barbiturates
alcohol
z drugs
Barbiturates?
- produces sedation and sleep
- can also produce anaesthesia, coma and death
Mode of action for CNS depressants?
Activates the two cites on the GABA-a receptor
- sedative hypnotic site - alcohol & barbiturates (Cl- influx)
- antianxiety site - benzodiazepines (enhances binding effects of GABA)
harder to overdose on benzos as it depends on how much GABA is present - if you mix with alcohol, then easy to overdose.
in general, when the GABA receptor is excited, an influx of Cl- ions flow through to hyperpolarise the neuron
- there is a good picture on the slide*
What are CNS depressants also called
antianxiety agents and sedative hypnotics
What is the cumulative effect of hypnotic use?
Ref to page 455 of stahl text.
The half-lives of hypnotics can have an important impact on their tolerability and efficacy profiles.
(A) Hypnotics
with ultra-long half-lives (greater than
24 hours: for example, flurazepam and quazepam) can cause drug accumulation with chronic use. This can cause impairment that has been associated with increased risk of falls, particularly
in the elderly.
(B) Hypnotics with moderate half-lives (15–30 hours: estazolam, temazepam, most tricyclic antidepressants, mirtazapine, olanzapine) may not wear off until after the individual needs to awaken and thus may have “hangover” effects (sedation, memory problems).
(C) Hypnotics with ultra-short half-lives (1–3 hours: triazolam, zaleplon, zolpidem, melatonin, ramelteon) can wear off before the individual needs
to awaken and thus cause loss of
sleep maintenance.
(D) Hypnotics with half-lives that are short but not ultra-short (approximately 6 hours: zolpidem CR and perhaps low doses of trazodone or doxepin) may provide rapid onset of action and plasma levels above the minimally effective concentration only for the duration of a normal night’s sleep.
Adverse effect of benzo use?
Cognitive impairment, decreased motor skills, daytime sedation
Additive CNS depression (with ethanol, antihistamines, opioids)
Dependence
Behavioural disinhibition (paradoxical)
Anterograde amnesia
Abrupt withdrawal can result in panic attacks, rebound anxiety
Risk of foetal deformation (1st trimester)
Cog effects of long term benzo use?
- global cognitive impairment
- improvement after long term benzo users discontinued
benzos much worse than z drugs…
Solvent abuse?
Inhaling of aliphatic and aromatic hydrocarbons found in substances such as petrol, glue, paint thinners and spray paints.
Less common is inhaling halogenated hydrocarbons (found in cleaners, correction fluid and aerosol propellants) and other volatile compounds containing esters, keytones and glycols.
What are common inhalants
toluene, chroming, butane and petrol
May be a cumulative effect which does not manifest until 10 or more years following abuse
Mech of action for inhalants/solvents?
- thought to work in a similar way to alcohol, being that they are not mediated by a single transmitter.
- thought to dissolve myelin sheath surrounding neurons resulting in cell death
Toxicity of solvents?
- acute - cardiac arrhythmia, depression, delirium, respiratory failure
- chronic - damage to vital organs such as heart, lungs, brain, liver and kidneys.
What are psychotomimetics
these are another name for hallucinogens, as they mimic psychosis.
What are the main types of hallucinogen
Acetylcholine psychedelics
Norepinephrine (catecholaminergic) psychedelics (e.g.,
mescaline)
Serotonin psychedelics (e.g., lysergic acid diethylamide)
Psychedelic anaesthetics (e.g., PCP, ketamine)
Tetrahydrocannabinol (THC): active ingredient in marijuana
Anticholinergic agents?
- Hallucinogens
Scopolamine and atropine
obtained from belladonna, datura, and
mandrake
Mode of action for anticholinergic agents?
acts on PNS
What are the effects of anticholinergic agents?
act on pNS causing…
decreased sweating and salivation, increased body temperature, dilation of the pupils, blurring of vision, increasing the heart rate
at higher doses causes CNS effects including, delirium, confusion, sedation and amnesia
Catecholaminergic agents?
Mescaline, STP, MDA, MDMA (ecstasy), MMDA, DMA, myristin and elimicin
How do catecholaminergic drugs work
Psychedelic action probably as a consequence of their agonistic effect on post synaptic 5-HT2 receptors
Effects of catecholaminergic drugs?
time distortion, altered perception of colour, sound, and shapes, complex hallucinations, synaesthesia, dreaminess, depersonalisation, altered affect and somatic effects
What are designer drugs?
Chemical analogues of psychoactive substances
Have slightly different and often even more
powerful effects than the model drug
Not identical in structure to illegal substances so not covered by drug laws
mode of action for MDMA?
Releases reservoirs of serotonin in brain
More serotonin induces feelings of happiness
Effects begins in 20 min – 1 hour, Lasts 3 - 4 more hours
Takes 1 - 2 weeks to produce sufficient amount of serotonin to re-experience same feelings
Death by overdose is rare, but possible
Down Regulation-Serotonin receptor “retreat” into the cell membrane to avoid damage after excessive stimulation
Thus fewer receptors to respond to serotonin
What is MDMA?
Ecstasy
What are the side effects of mdma?
Increased heart rate Increased blood pressure Pupil dilation Muscular tension- jaw clenching Exhaustion Dry mouth & throat Nervousness Anti-fatigue effects Profuse sweating Numbness Dehydration Increased body temperature
How do most deaths from MDMA occur?
Dehydration and overheating
Long term effects of MDMA?
Anxiety/paranoia/depression especially in people with pre-existing mental disorders
Possible liver damage
Possible brain damage
Heart problems especially if one has pre-existing conditions
Some combination of dosage, frequency, & duration will destroy serotonin receptors
Does not cause Parkinson’s
Need more research on long-term effects
PATTERN of action for MDMA?
usually users are depressed due to serotonin depletion after use.
not physically dependent.
nerve damage can cause memory problems and increase depression
serotonergic drugs?
LSD, psilocybin, psilocin, DMT, bufotenine, ololiuqui, harmine
Effect can be divided into three phases: somatic, sensory and psychic
Physical effects of LSD?
Rise in heart rate & blood pressure Higher body temperature
Dizziness
Dilated pupils
Some sweating like amphetamines
Mental effects of LSD?
Intensified sensations
Synaesthesia (crossed sensations: seeing sound, hearing
colour, smelling shape)
Illusions
Delusions
Hallucinations (usually visual)
Altered mood
Impaired motivation, concentration and judgment
Distorted reasoning including increased gullibility
Flash backs
“Bad trips” (acute anxiety reactions) if in an unstable environment or mental state
What are the active ingreidents in magic mushrooms
psilocybin & psilocin
Effects:
Nausea before psychedelic effects
Visceral sensations
Changes in sight, hearing, taste, and touch Altered state of consciousness
Psychedlic anaesthetics?
PCP and ketamine
ketamine effects?
Effects: Mellow, colourful dreamlike intoxication Slurred speech Impaired muscular coordination Dizziness Hallucinations
marijuana effects?
Sedative, euphoriant and hallucinogenic properties
has its own receptor with its own agonist, anandamide
acute effects of marijuana?
physical lethargy
euphoria
stimulates appetite i.e. the ”munchies”
In some cases can cause
anhedonia
mild depression
anxiety or irritability (about one third of chronic users)
Usually one of the first drugs which young people experiment with
Higher doses of marijuana can do what?
- mimics other hallucinogens… causing bad trips etc..
- correlationally related to onset of psychotic disorders.
Adverse effects of marijuana
Interferes with cognitive function including short-term memory
Interferes with the operation of machinery (e.g. an automobile)
Contributes to psychological problems in adulthood
Elevates heart rate
Impairs lung structure and function
Therapetic actions of marijuana?
Reduces the nausea and loss of appetite associated with chemotherapy
Can reduce pain signaling (via THC)
Can be used to treat the discomfort of
AIDS
Can reduce the pressure increases in the eye associated with glaucoma
Cognitive effects of marijuana?
- temporary effects associated with withdrawal symptoms
- not clear whether there are long term irreversible effects.
regular use = poor functioning, though.
In which drugs are opiates usually found?
analgesics, anaesthetics, antidiarrheal drugs, and cough suppressants
What are some opioid analgeics?
heroine, morphine, naloxone, nalorphine, endorphin
What are opioid analgeics’ mode of action
Action mediated by the opiate receptors which have three types: mew, kappa and delta.
Nalorphin and naloxone?
NARCOTIC ANALGESIC
opiate antagonists that block the effects of morphine
Heroin?
NARCOTIC ANALGESIC
synthesised from morphine
penetrates BBB faster than morphine therefore producing rapid pain relief.
Endorphin
NARCOTIC ANALGESIC
peptide hormone that acts as a neurotransmitter and may be associated with feelings of pain and pleasure
mimicked by opioid drugs such as morphine, heroine, opium and codeine.
Morphine?
NARCOTIC ANALGESIC
acts on 3 opioid receptor classes - mu, delta, kappa
effects of long term opioid use?
Chronic users suffer no ill effects, provided they have continuing access to sufficient quantities.
With those users who experience chronic intoxication, there can appear bouts of depression.
Often associated with criminal behaviour, other drug offences and taking of other substances.
Effects of opioid withdrawal?
Euphoria, followed by drowsiness, slowed breathing, and often profound analgesia
At high doses respiration is completely suppressed and death follows
Withdrawal syndrome:
Can be extremely unpleasant: yawning, chills, muscle aches, vomiting, nausea, diarrhoea and insomnia (1-3 days)
Treatment of opiate use disorder?
CD treatment
support, education, skills building, psychiatric and
psychological treatment, NA
Medications
Methadone (opioid substitution)
Naltrexone
Buprenorphine (opioid substitution)
what are the drugs used to help with opiate use disorder?
Methadone (opioid substitution) - opioid blocker
Naltrexone - mu agonist
Buprenorphine (opioid substitution) - partial mu agonist with a ceiling effect - good for people who are highly motivated and do not need high doses
What drugs have been associated with brain damage or cog impairment
Amphetamines
MDMA (“ecstasy”): Serotonin neurons Methamphetamine: Dopamine neurons
Cocaine:
Blocks cerebral blood flow
Phencyclidine (PCP or “angel dust”): Blocks NMDA receptors
Alcohol
Benzodiazepines
What drugs have not be associated with long lasting brain damage?
LSD
Marijuana
Opiates
Prevention of substance use disorders?
Often aimed at adolescents
Utilize some or all of the following elements:
Enhancing self-esteem
Social skills training
Peer pressure resistance training
Parental involvement in school programs
Warning labels on alcohol bottles
Education regarding alcohol impairment
Testing for drugs and alcohol at school or work Correction of beliefs and expectations
Inoculation against mass media messages
Peer leadership
