Ruiz. THE SUBSTANCE HANDBOOK Flashcards
ODDS RATIO OF CHILDREN OF ALCOHOLICS TO BE ALCOHOLIC
4–5 times
role of aldehyde dehydrogenase in alcoholism
ALDH2*2 causes facial flushing, tachycardia, headache, hypotension with alcohol consumption and is therefore protective against alcoholism
which neurotransmitters are involved in alcoholism
D2 dopamine receptor(DR D2) and GABA are associated with alcoholism.
Serotonin transporter linked polymorphic region can also be involved receptors play central role in the reward process
percentage of genetic contribution to smoking initiation and persistence
50% initiation is genetically influenced. 70% of smoking continuation is genetically influenced
prevalence of allele of A1 RDD2
found in current smokers. Found in progressively increasing amounts in nonsmokers, past smokers, current smokers
mechanism of cocaine
cocaine causes blockade of dopamine reuptake and other monoamines resulting in accumulation of extracellular dopamine in the synaptic cleft
sounds likea cow
Mechanism of action of opioids
primarily act at mu opioid receptor
familial abuse of cannabis
mild heritability.
list limbic nuclei
amygdala
Hippocampus
Medial prefrontal cortex system
affinity of psychostimulants
–psychostimulants bind to all biologic amine transporters.
–Reenforcing potential is linked to dopamine but not serotonin or norepinephrine sites
what causes reinforcing effects of morphinelike opiates?
stimulation of mu opioid receptors is the main cause.
They’re widely distributed throughout the central nervous system
effects of ethanol on dopamine
–ethanol increases extracellular dopamine levels in the nucleus accumbens.
–Also affects calcium channel and potassium transport
effective opioid receptor antagonist on alcohol consumption
opioid receptor agonists increased ethanol self administration at low doses,
but decrease alcohol consumption at higher doses.
personality symptoms of potential addicts
sensation seeking
Delay discounting
Impulsivity
affective disorders and SUD
one third of comorbid individuals report that SUD preceded bipolar disorder
Major depressive disorder doubles odds of having SUD
schizophrenia and SUD
47% of schizophrenics meet lifetime diagnosis of substance abuse disorder
anxiety, PTSD and SUD
SUD much more common with anxiety and/or PTSD
attention deficit hyperactivity and SUD
20% of adults with SUD has ADHD.
Treatment of childhood ADHD with psychostimulant does not increased rates of SUD is adults
childhood adversity factors IN SUD
parental substance-abuse
Family violence Physical
Sexual abuse
Poverty
Multiple factors common! 4 family attachment
Poor school attachment
Involvement with drug using friends
adult alcoholism and stressful life events
Adults tend to use alcohol and drugs to mitigate pain in stressful life events,
but rarely are severe life stressors and independent major contributor
incidence of drug abuse in incarcerated people
in 2004 53% of state and 45% on the Federal inmates met DSM criteria for abuse or dependence
incidence of drug abuse at time of arrest
one quarter–one third of inmates were using illicit drugs at the time of their crime
incarcerated substance abusers by race
19% of white prisoners
21% Hispanic prisoners
23% a black prisoners
employment among substance abusers
17% unemployed
8% employed
Physicians and medical workers have historically higher rates of substance abuse
common comorbidities with substance abuse
depression
Antisocial personality disorder
General anxiety disorder
Mood disorders
HIV and substance use disorder
gay men traditionally had highest rate of HIV = 56%
IV drug users 11% of HIV
Recent years has seen declining in HIV in both groups
hepatitis C and substance abuse
peak incidence of hepatitis C was in the late 1990s
IVDA was most common cause
alcohol use by race
55% of all adults Americans her current alcohol user’s
21% report binge drinking
5% report heavy drinking
22% of whites report bbinge drinking
6% report heavy use
20% of Blacks report binge drinking
6% report heavy drinking
Native Americans report 23% binge drinking
12-1/2% heavy drinkers
percentage of Americans who have tried marijuana at least once
41% Americans have tried marijuana
rates of tobacco use
between 2002–20011 smoking declined from 26% to 22%
Smoking typically begins during adolescence
67% of eighth graders have tried smoking
rates of heroin and opioid use
- 1% of Americans have tried heroin
- 5% of 12 graders have used
cocaine use rates
approximately 1% hhave tried cocaine
Crack use is approximately 0.1%
blacks and White’s use approximately equal
Majority of cocaine hospitalizations were for chronic smoker’s
list most common club drugs
MDMA
GHB
Ketamine
methamphetamine rates
less than 1%
Rates of pharmacological stimulants
approximately 5% for nonmedical use of psychostimulants in K–12
7% of college students use them
rates of substance-abuse treatment
40% of treatment admissions for SUDwere not in labor force
30% of admissions were unemployed people
Majority of admissions were between 25 and 44 years old
70% men,
60% white,
25% black
What substances cause admission to treatment centers?
Alcohol 40%
Opiates, especially heroin 19%
Marijuana/hashish 16%
Cocaine 13%
Stimulants, especially methamphetamine 8%
40% at both alcohol and illicit drug
51% of opioids were self admits
14% were in criminal justice system
56% of marijuana users came to criminal justice
list dimensions of ASAM placement criteria
–Acute alcohol or drug intoxication or withdrawal potential.
–Vital medical considerations and complications
–Emotional behavioral or cognitive conditions
–Readiness to change
–Relapse continued use and continued problem potential
–Recovery environment
list levels of care based on dimensions of ASAM planning dimensions
level 0.5 early intervention
Level I outpatient treatment
Level II intensive outpatient treatment/partial hospitalization
Level III residential/intensive inpatient treatment
Level IV medically managed intensive inpatient treatment
Federal 5 drug tests– SAMHSA panel 1
amphetamine
Cannabinoids
Cocaine
Opioids
PCP
SAMHSA panel 2
barbiturates
Benzodiazepines
Methadone
Oxycodone
methylene dioxy methamphetamine (MDMA )
MDA
Alcohol
SAMHSA panel 3
LSD
Psilocybin
Ketamine
Other Club drugs
Other designer drugs
percent alcohol in various drinks
beer 3.2%–4.5%
wine 7 – 14%
Distilled beverages 40–75%
amount of alcohol needed to be legally drunk
4 drinks in an hour we will produce 0.08 g per 100 mL blood alcohol
biomarkers of alcohol use
gamma GT
ALT
AST
Carbohyydrate deficient transferrin
direct biomarkers for alcohol
ethyl glucuronide
Ethyl sulfate
in DSM 5, how many of how many criteria need to be met for diagnosis?
must meet 2 of the 11 criteria to diagnose SUD
changes from DSM-IV to DSM-V
–eliminating legal problems as criteria
–Adding cravings as a criteria
–Eliminated distinction between abuse and dependence
–Has separate criteria for each abusable substances
–Added caffeine withdrawal and can have his withdrawal
–Nicotine dependence is now nicotine use disorder
–Cocaine and amphetamines lumped in single stimulant use category
–Added severity codes mild, moderate, severe
–Added gambling disorder
how many criteria are needed in the severity codes in DSM-V
–mild equals 2–3 criteria
–Moderate = 4–5 criteria
–Severe = 6+ criteria
–early remission = >3 months
–Sustained remission = > 12 months
–Also’s for some diagnosis includes maintenance therapy or if patient is in a contained environment
ICD–10 dependence course modifiers
currently abstinent
Currently abstinent, in protected environment
Control dependence (methadone, nicotine gum etc.)
Currently abstinent, receiving adversive or blocking drugs e.g. naloxone disulfiram
Currently using actively
Continue issues Episodic use = dipsomania
number of people worldwide who consume alcoholic beverage
2 billion = one half of world population consume alcohol
–55% men
–34% women
30% of drinkers consumes 75% of all alcohol
highest and lowest countries for alcoholism
Hong Kong equals 4.5% alcoholism
Korea equals 22% alcoholic
statistics and US alcoholism
–87% of US adults have drank alcohol in their life
– 14% of adolescence male and female consume alcohol
–Highest drinking rate are young men 18–25 years old
Highest drinking rates
–Non-Hispanic whites
–Native Americans and Hispanics
–Non-Hispanic Caucasian
–College education usually doubles drinking rates
–5% of Americans meet criteria for alcohol abuse
–4% meet criteria for alcohol dependence
number of criteria needed for diagnosis of alcoholism under DSM-V
2 criteria are needed for diagnosis of substance use disorder under DSM-V
progression of alcohol behavior to the ages
early and mid 20s = daily heavy drinking frequent binge drinking.
–Produces euphoria and inhalation following first drinks
Early 30s = alcohol related psychosocial problems began to emerge, work absences, family conflicts, legal problems, accidents Frank loss of control over drinking worsening social and work problems, medical complications, often cognitive deficits
Early 40s = liver cirrhosis, chronic pancreatitis, emergency room visits, DVTs and trying to withdraw
absorption of alcohol
an empty stomach, 80% of alcohol is absorbed in duodenum and jejunum,
20% of alcohol is absorbed in stomach If consumable food because gastric emptying slowed
–stomach is main site of absorption
distribution of alcohol in the body
–poor solubility in fat
–Crosses all biologic membranes
–Women and elderly get drunk faster because of lower total body water, i.e. they reach a greater peak BAL with an equivalent dose of alcohol
alcohol dehydrogenase
ADH found in gastric mucosa
First-pass metabolism greatly determines alcohol toxicity is a determines bioavailability
First-pass metabolism is reduced and women and alcoholics due to decreased ADH activity
drugs that affect first-pass metabolism of alcohol
cimetidine, ranitidine, aspirin decrease gastric first-pass metabolism by inhibiting gastric ALDH aldehyde dehydrogenase in mitochondria
pharmacology of alcohol elimination
–90% eliminated as water and carbon dioxide
–1% transformed to ethyl gluconeride and eliminated in urine
–4% excreted unchanged in breath urine and sweat
–Averages about 1 drink per hour
effects of alcohol on neurotransmission–dopamine
alcohol enhances dopamine release by directly increasing fired rate of dopamine cells.
–Chronic alcohol exposure and withdrawal produced changes in dopaminergic transmission that are the opposite of acute effects of alcohol
effects of alcohol on neurotransmission–GABA
acts similar to benzodiazepine or barbiturates
effects of alcohol and neurotransmission –endorphins
alcohol administration stimulates hypothalamic symphysis and release of endogenous opioids
–such as beta endorphin and enkephalin
effects of alcohol on neurotransmission–serotonin
alcohol administration increases brain concentrations of serotonin (5-HT)
genetics of alcohol dependence
sevenfold increase in alcohol dependence in first-degree relatives of alcohol dependence persons
–However majority of alcohol dependence people do not have alcohol dependent first-degree relatives
chromosomal site of alcohol dependence
long arm of chromosome #4, where the ADH Gene cluster occurs.
Among African-Americans, significant linkage noted between alcohol dependence and chromosome 10
–Multiple other genes involved and they all interconnect with environment
evaluation questions for alcoholism
take complete drinking history
–Typical quantity and frequency of alcohol consumption
–Maximum number of drinks per drinking occasion
–Frequency of heavy drinking episodes
–History of alcohol-related problems
–Psychiatric symptoms–precipitation or exacerbation –History of medical complications
cage questions
cut down on drinking
Annoyed by people criticizing her drinking
Guilty about drinking
Eye-opener
–2 or greater suggests alcoholism
laboratory markers of alcoholism
carbohydrate deficient transferrin (CDT)
–Increase and despite heavy drinking
–Very specific
–Return to normal 1–2 weeks of abstinence
–Good indicator of relapse to alcohol
–Is only laboratory test approved by FDA for detection of heavy alcohol consumption Gamma glutamyl transpeptidase
–induced by alcohol consumption
–Falls by 50% within 2 weeks a sensation
–Normalization inhibited I alcoholic liver disease
–Also elevated in many nonalcoholic liver diseases
–Present in three fourths of alcoholics before evidence of liver disease
–More specific for alcoholic liver disease than CBT
LFTs
–SGPT/SGOT
–Nonspecific
–Ratio greater than 1.5 suggests alcohol damage
MCV
–Caused by folate deficiency
Alcohol breath test and blood alcohol level
–But alcohol greater than 1 50 mg/dL in patient showing no signs of intoxication is generally physiologic tolerance
treatment of alcohol withdrawal
social detoxification
–frequent reassurance
–Monitoring
–Generally outpatient Medical detoxification
–Use of agents acting on GABAergic transmitter
––Benzodiazepines our first choice
–––Diazepam and chlordiazepoxide are bests preventing seizures and DTs
––––Because they are long-acting
–administer thiamine 50–100 milligrams to prevent Wernicke-Korsakoff syndrome
medications used to treat alcoholism
–disulfiram
–Naltrexone
–Acamprosate
–Topiramate being studied
–Ondansetron being studied
treatment of anxiety and depression and alcoholism
buspirone his drug of choice for anxiety after detoxification.
–Treated with antidepressants as needed
concurrent use of substances with alcohol
13% of alcoholicS use substances
50% of SUD use alcohol
signs and symptoms of alcohol withdrawal–mild
signs and symptoms of autonomic hyperactivity
–Tachycardia
–Diaphoresis
–Tremor
–Nausea vomiting
–Insomnia –Anxiety Began 4-12 hours after last drink
–cheeks in 48 hours
–Subsided 4-5 days of sobriety
–Less severe symptoms last for a few weeks or up to 6 months
signs and symptoms of alcohol withdrawal–severe alcoholism
10% of withdrawals are severe
–Delirium, and/or grand mal seizures
–Delirium tremens occur 5% of the time
––Severe signs of autonomic hyperactivity
––Fluctuating level of consciousness and disorientation
–––(2-3 days after last drink
–Vivid hallucinations of auditory visual or tactile nature even and clear sensorium
–Seizures occur 5% of the time within 48 hours of sobriety
Predictors of complicated alcohol withdrawal
–Old age –Poor nutritional status
– Occurring medical or surgical conditions
–History of high tolerance alcohol
–History of previous DTs
alcohol-induced cognitive disorders
chronic alcohol drinking can result in severe folate and thiamine deficiency leading to severe neurocognitive problems
–Wernicke encephalopathy
––Confusion, disorientation ataxia, nystagmus and cane palsies
–Response to thiamine repletion. Repeated episodes of Wernicke encephalopathy can lead to persistent alcohol-induced amnestic disorder known is Korsakoff psychosis
–Confabulation caused by deficits and antegrade and retrograde memory
–Patient’s are unaware of their condition
4 known opioid receptors
–mu
–Sigma
–kappa
–SQ peptide
effects of mu receptors
mu receptors are preferentially activated by beta endorphin
–Responsible for classic morphinelike actions
––Analgesia
––Euphoria
––Cough suppression
––Respiratory suppression
––Pupillary constriction
––Constipation
effects of Sigma receptors
–anxiolytic
–Antidepressant like
–Pro convulsant effects
effects of kappa receptors
–analgesia
–Pro-depression
–Dysphoric effects
criteria under DSM-V for SUD
–neither tolerance nor withdrawal is necessary nor sufficient for the diagnosis of an opioid use disorder
–DSM-V merges diagnosis abuse and dependence
–criteria for opioid SUD is a fulfill 2 of 11 criteria
–More criteria means more severity
relatives speed of action of opioids by route of use
slowest
Oral Intranasal
Intramuscular
Subcutaneous
Intravenous
Inhalation (smoking)
Fastest
country with the largest licit production of opioids
India is a largest producer of licit opioids, and the highest use of illicit opium
demographics of cocaine use in USA
about 1% of Americans use cocaine
About 25% of these use crack cocaine
Total about 800,000 people with cocaine abuse or dependence
75% of cocaine users entering treatment are crack cocaine users
Higher usage with less education
Young smokers have 15 times higher cocaine use of than nonsmokers
chemical name for cocaine
benzoyl methyl ecgonine
drugs also in cocaine family
tropane family includes
–cocaine,
–atropine,
–scopolamine
primary neuro-pharmacologic effect of cocaine
blocks uptake of monoamines released into synapses of CNS
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pharmacology of cocaine
–lipophilic molecule
–Readily absorbent by mucous membranes and alveoli lining
–one third of oral or nasal dose absorbed
–95% of inhaled dose of freebase or crack bioavailable
–Readily penetrates blood-brain barrier
–Volume distribution is low
benzoylecgonine
metabolite of cocaine –Cardiotoxic
street cocaine
–rarely pure on street
–Adulterated with mannitol, lactose or glucose to add weight
–Adulterated with caffeine, lidocaine, amphetamines, quinine, heroin to add taste and additional CNS stimulation
–Usual street cocaine = 10%–50% pure
smoked cocaine effects
–any form of smoke cocaine is the most addictive, most rapid onset and most intense effect
–Can be 10 seconds to feel high
–High from smoking is faster than IV
–Often smoked with alcohol opioid to blunt undesirable effects and prolong high
–Coca ethylene = cardio toxic metabolite increases mortality
why is smoked crack cocaine so addictive?
–high lasts only 5–10 minutes
–High is followed by extremely anxious and depressed sensation in users immediately crave the euphoria they just felt
neurobiology of cocaine
–sometimes called disease of brains pleasure centers
–Affects dopamine
–acts on basal forebrain, including nucleus accumbens, and entire limbic system
–Impairs dopamine uptake, but also serotonin and norepinephrine
effects of cocaine on dominant and submissive animals
seem to have greater high in dominant animals and less effect on submissive animals
initial evaluation and management of cocaine intoxication
–withdrawal may not be prominent
–largely psychologic withdrawal
–Dysphoria, intense cravings
patterns of cocaine use
–severity withdrawal symptoms can be estimated from pattern use
–Chronicity of abuse tends to reflect disarray in the patient’s life
–Rarely find a “functioning cocaine user”
–With continued use, often less pleasure due to tolerance, and increased dysphoric effects and accumulation of adverse consequences
inpatient versus outpatient cocaine rehabilitation
usually outpatient
–No severe withdrawals
–Goal is return to normal life
–more convenient, especially for women with children
–inpatient therapy when there are multiple relapses or other Complications
pharmacologic management of cocaine use
–immunotherapies are being developed
––Include inactivated cholera B toxin
––may diminish euphoria
cocaine agonist therapy
modafinil has had some success but has abuse potential
relapse prevention of cocaine
disulfiram may be helpful in preventing cocaine relapse
N acetylcysteine may be useful
Antidepressants and anticonvulsants have not shown value
cocaine associated psychiatric disorders
–75% of cocaine users may have other psychiatric illness
–However cocaine symptoms may mimic other diseases
–Depression and anxiety disorders may drive reinforcing effects of cocaine and increased risk of relapse
–depression, dysthymia, anxiety, bipolar disorder are most common
–Up to 30% of cocaine user’s have residual ADHD and can give paradoxical relaxation similar to the stimulants
–Methylphenidate has been used for maintenance equivalent to methadone maintenance
––Most effects occur in patients with residual ADHD
–Acute, subacute, and chronic paranoia are common with cocaine use
–Cocaine delirium with or without psychosis features resolved in 3-5 days
–co–occurring alcoholism occurs in about 90% of cocaine abusers
medical complications of cocaine use
sudden cardiac death,
fatal intracranial hemorrhage,
malignant hyperthermia,
rhabdomyolysis,
renal failure have been documented with first-time use or chronic use
cardiovascular syndromes with cocaine use
cocaine affects release and uptake of epinephrine and norepinephrine causing a shift in the blood supply from the skin and the viscera into the skeletal musculature
increases oxygen levels and blood sugar levels
–Produces tachycardia with increased cardiac contractility and hypertension –Myocardial oxygen demand may outstrip supply
–Increases atherosclerotic coronary artery and renal artery disease
EKG changes with cocaine
atrial-ventricular nodal conduction block
–QT interval
–widening PVCs,
–ventricular tachycardia and asystole are common causes of death
presentation of cocaine users in the emergency room
–effects of violence
–Atypical, even bizarre chest pain
–Multiple other pathologies may develop
–Consider cocaine toxicity in young adult with chest pains or signs of congestive heart failure with or without other risk factors
pulmonary changes with cocaine–
–shortness of breath is second-most common cocaine related medical systems in ER
––Often related to cocaine inhalation
––Exacerbates asthma
–Can cause telltale disruption of the nasal septum, nasal cartilage, and hard or soft palate
crack lung syndrome
crack lung syndrome
–pneumonia type symptoms
–Shortness of breath
–Atypical chest pain
–High-temperature
–Negative or nonspecific abnormal chest x-ray
–May be related to talcum talcum or baking soda used to cut cocaine
neuropathology of cocaine
–global cerebral hypoxia
–Ischemia secondary to cardiopulmonary failure
–Hypertensive encephalopathy
–Intractable seizures
–Thromboembolic stroke
–Lobar hemorrhages
–Subarachnoid hemorrhages
–treatment of cocaine-induced seizures
benzodiazepines preferred
–Neuroleptics should be avoided due to seizure threshold lowering
neurologic effects of chronic cocaine abuse
chronic cocaine use can
–can cause dopamine disinhibition phenomena
–Increase release a prolactin (most common endocrine abnormality with cocaine)
–Extrapyramidal dysfunction including
––akathisia
––dystonias
––Choreiform movements
––bruxism
––severe typical movements and disordered gait (=crack dancing)
effects of cocaine on appetite
increase glucocorticoid response
–Inactivation of feeding center resulting in loss of primary drive to eat
–Severe loss of appetite and body weight
–Muscle wasting
effects of cocaine and sexuality
–something it may be an aphrodisiac
–Can produce spontaneous organism
–Chronic use results and loss of interest in sex (possibly due to hyperprolactinemia)
–Derangements in menstrual cycle Galactorrhea, amenorrhea, infertility
–Crack smoking isn’t independent predictor of HIV seropositivity
cocaine and pregnancy
crack babies are partially affected by poor nutrition, hygiene and neglect
–High rate a spontaneous abortion, higher than heroin because she hadn’t to be pain
active ingredient in cannabis
9 tetra hydro-cannabinol
epidemiology of cannabis
most common illicit drug
–41% of US population have tried it
–10% have used in the last year
–6% in past month
–2% use cannabis daily
–Similar in European countries
–Much lower but increasing rates in Third World countries
characteristics of cannabis users
male greater than female
–Most common use between 18 and 25 years old
–Highest initiation rates among 12-25-year-olds
–Self identified multiracial have highest rate of use
––Following African-Americans
––Followed by whites
––Followed by Hispanics (lowest rates)
sinsemilla
unfertilized flowers of female cannabis Plant
–7–15 percent THC versus 1-5% for whole Plant
hashish
–the resin of cannabis Plant, containing 10-20% THC
–hash oil is derived from concentrated resident extract–up to 60% THC
physiologic effects of cannabis use
–dry mouth
–Stimulated appetite
–anti-emetics effect at low dose –
–Vomiting at higher doses
–Increased resting heart rate
–Increase orthostatic hypotension
–Redness of the eyes caused by dilatation of small vessels
mental effects of cannabis use
impaired focus and divided attention
–short-term and episodic memory loss
–Decreased complex cognitive processing
–Some decrease in motor ability
–Sustained use may impair attention, memory
cannabis withdrawal syndrome
–anger and aggression
–Anxiety
–Depressed mood
–Irritability and restlessness
–Sleep difficulty and strange dreams
–Decrease appetite and weight loss
–Chills, headaches physical tension
–Sweating
–Stomach pain
–General physical discomforts
–Begins within 24 hours of cessation
–Peak some the first week
–Last 1-2 weeks
discuss cannabinoids
–90 different cannabinoids Known
–Excreted through Feces and Urine
–THC Is Highly Lipophilic, Therefore Stored in Fatty Tissues
––THC recruited from fatty tissues does not seem to produce intoxication
cannabinoid receptors
CB 1 and CB 2
–CB 1 is the most psychoactive and causes the most reinforcement
genetics of cannabis
heritable factors contributed 30%–80% of total variance in risk for cannabis use disorder
quantity of cannabis produced yearly
worldwide approximately 100,000 metric tons
comorbidities of cannabis use
–high rates of alcohol and nicotine dependence
–Associated with poor life satisfaction
–Higher rates of depression, anxiety, suicide attempts, conduct disorders
–Higher rates of most psychiatric disorders
cannabis and psychotic disorders
some evidence the cannabis can cause psychotic disorders and symptoms.
Evidence is not definitive
respiratory effects of cannabis
half of cannabis smokers also smoke tobacco
–Contains respiratory toxins similar to tobacco
–Could have more carcinogens and greater Tarr deposits in the lung than filtered cigarettes
–Cannabis smokers inhale deeply, hold the smoke longer than tobacco users
–Is a bronchodilator, which increases vulnerability to smoke
–Cannabis increases absorption of carbon monoxide
cannabidiol and cancer
–while THC seems to have cancer fostering properties, cannabidiols may have some tumor reducing effects in rodents
cannabis and pregnancy
up to 20% of women use cannabis during pregnancy
–Little evidence of major congenital abnormalities has been found
cannabis and cardiovascular
–primary effect is tachycardia that diminishes with tolerance
––No evidence of long-term cardiovascular problems in otherwise healthy users
brain function and cannabis
chronic cannabis produces changes in brain areas with higher cognitive functions
–Early initiation of cannabis produces some structural abnormalities
–Many acute effects reduced with tolerance
–Consistent effects observed on short-term memory, especially immediate memory, recall and retrieval
most common users of amphetamines
Military
––Because of long hours of sleep deprivation
––Military investigating modafinil as possible alternatives
Students
––Higher levels of alcohol, cannabis and, and cocaine use with amphetamine users and school
Athletes
––Evidence for performance enhancement is equivocal
––Thought to improve mood, aggression, self-confidence
––Deaths due to overheating due to peripheral vasoconstrictionresulted in amphetamines being the first drug block for Olympics
mechanism of action of amphetamines
amphetamines increased synaptic concentrations of the mono means dopamine, serotonin, and norepinephrine
types of amphetamine stimulants
–amphetamine
–Methamphetamine
–Methylphenidate
scope of amphetamine use worldwide
–55 million people worldwide use amphetamines regularly
––But only 21 million people use cocaine and opioids daily
–Methamphetamine is most available and most abused
–About 500 metric tons produced yearly
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comorbidities of amphetamine use disorder
–increased likelihood of psychiatric symptoms
–Increased drug use psychotic syndromes
–Increased previous suicide attempts and violent behavior problems
–Difficult to distinguish amphetamine psychosis from schizophrenia
–Treat amphetamine psychosis as with any other psychosis
–Methamphetamine associated with violent criminal behavior and recidivism
pharmacodynamic effects of amphetamines
–amphetamines have long duration of action
–Initial rush of euphoria––may last up to 12 hours
–Hyperalertness
–Increased energy
–Decreased appetite
–Intensified emotions
withdrawal effects of amphetamines
amphetamine withdrawal
–Insomnia
Restlessness
Hyperthermia
–Seizures
–Abuse and dependence
–Agitation
–Paranoia
–Mood disturbances
–Psychosis
–Cognitive impairment
amphetamines as drugs of abuse
–cognitive behavioral therapy and contingency management have value in reducing amphetamine use
–bupropion may have some value in amphetamine rehabilitation
–Modafinil may have some value, given that his stimulant like material
–no good pharmacotherapy for amphetamine use
epidemiology of sedative hypnotics–benzodiazepines
–benzodiazepine rarely first drug of abuse
–low rates of abuse
–Rarely primary drug of abuse
––Usually tied to marijuana, opioids or alcohol
–Peak use of benzodiazepines was in 1973
–Mostly replaced by Z drugs
–About 1% of population uses benzodiazepines for more than a year
–Long-term use more common among elderly, women, and people with chronic health problems
–20% of alcoholics also take benzos
–30% of psychiatric patient’s are prescribed benzodiazepines
–Anxiety disorder patient’s generally do not misuse benzodiazepines
comorbidities of sedative hypnotic drugs
–all are CNS depressants
–And higher doses slurred speech, ataxia, impaired gag reflex
–To therapeutic doses to adverse effects
–Side effects stronger in elderly patients
–No evidence of cleft palate when taken during pregnancy
–Benzodiazepine during pregnancy can lead to withdrawal syndrome in baby or floppy baby syndrome
–Barbiturates can produce major fetal malformations
sedative hypnotic abuse determinants
–barbiturates produce to greatest pleasant mood alterations
–Rapid onset, short duration benzodiazepines have greatest risk of abuse
–Alprazolam Produces the best high
–Tolerance to benzos and Barbies is well-established
tolerance to barbiturates and benzodiazepines
–temazepam and eszopiclone do not develop tolerance to hypnotic effect
––Low rebound insomnia
–Patient’s developed little or no tolerance to anti-anxiety effects of benzos and barbiturates
primary mediator of inhibition of neurotransmission in mammalian brain
GABA is mediator of inhibition
determinants of abuse in benzodiazepines and barbiturates
–benzodiazepines have moderate potential for abuse
––Lower the methyl Quaalude or barbiturates and older hypnotics
Most addictive
––Diazepam
––Lorazepam
––Alprazolam
––Triazolam
–Chlordiazepoxide and oxazepam are the least abuse potential
how are benzodiazepines metabolized in the liver?
benzodiazepines capitalized by cytochrome P 50 enzymes
–Therefore potential for drug–drug interactions
name some Z drugs
zopiclone
Eszopiclone
zolpidem
zaleplon
differences between Z drugs and benzodiazepines and barbiturates
–Z drugs do not produce marked changes in sleep architecture
but produce
––amnestic effects(less than benzos)
––anticonvulsant actions
––anxiolytic activity
––motor impairing effects
––muscle relaxant effects
half-life of Z drugs
half-life of Z drugs is 1–4 hours for varying drugs
Can be up to 7 hours in the elderly
determinants of abuse of Z drugs
–zolpidem is often abuse in the range of 100s of milligrams (therapeutic equals 10 mg daily)
–Use for anxiolytic, you for reck, or stimulant effects
–Effects can be additive with alcohol
–low tolerance developed with therapeutic doses
–Seizures can develop after high-dose abuse of Z drugs
discussed barbiturates
–uses anticonvulsants, sedative hypnotics, anesthetic agents
–Low therapeutic index, therefore frequent toxic reactions
–High risk of abuse and dependence
–Can have severe even lethal withdrawal
adverse effects of barbiturates
–nonselective, cannot separate anti-anxiety effects from other depressant effects
–Reduced slow-wave and REM sleep
–Produce sedation and disruption of motor coordination
–An elderly can produce paradoxical excitement
–Occasional exfoliative dermatitis and/or allergic reactions
–Cause of death is usually respiratory depression, respiratory acidosis, cerebral hypoxia and possibly pulmonary edema and renal failure
barbiturates induced drug tolerance of other drugs
–barbiturates induce cytochrome P4 50 enzymes and liver therefore may reduce plasma concentrations of the large number of drugs
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withdrawal effects of barbiturates
–barbiturate withdrawal can be severe even life-threatening
–Produced delirium and seizures
–Migraine patients receiving a talbutal risk developing withdrawal including seizures
gamma hydroxybutyrate
–gamma hydroxybutyrate = GHB
–Approved in US for treatment of cataplexy, excessive daytime sleepy
–Used in Europe for alcohol dependence and withdrawal
–Sometimes abused in nightclub settings with other club drugs
effects of GHB
–readily crosses brain blood barrier
–Produces sedation and sleep
–At higher doses produces anesthesia
–Abuse produces euphoria, disinhibition, increased libido
GHB has low therapeutic index
–Toxic doses produced, respiratory depression seizures bradycardia and death
pharmacology of GHB
–half-life of GHB = 20–40 minutes
–Difficult to detect in urine because a short half-life
–
Often rapid recovery from toxic dose
determine us of GHB abuse
tolerance to GHB
list common hallucinogens,
LST = lysergic acid diethylamide
Psilocybin
psilocin
DMT = dimethyl tryptamine
mescaline
DOM = dimethyloxy methyl amphetamine
Cannabis
Phencyclidine = PCP
MDMA = methylene dioxy methamphetamine
discuss LSD
–first synthesizing 1938
–Hoffman accidentally ingested some and had worlds first trip on bicycle ride home
–Seeds of morning glory contain lysergic acid derivatives, especially lysergic acid amide
––Commercial packed often have insecticides, fungicides etc.
–Used rarely more than once per week due to rapidly developing tolerance
–Is one of the most potent hallucinogens known
–discuss psilocin and psilocybin
occur naturally in a variety of mushrooms
–Mexican magic mushroom psilocybe mexicana
–Most product is produced sympathetically
–Related to ayahuasca
discuss mescaline
–present in peyote cactus lophophra
–grown in Northern Mexico and southwestern US
–Effect lasts 6-10 hours
acute effects of hallucinogen
–most acute effects of hallucinogens are very similar
–Different rate of onset, duration of action, absolute intensity
–First 4 hours of LSD are called pretrip
––Include dizziness, paresthesias, weakness, tremor, altered visual and hearing changes, mood changes, altered time sent, depersonalizations
– later visual alterations intensify
–Developed synesthesia = seeing smells, hearing colors
–Rapid mood changes can be extreme
–Later still, paranoia occurs. Dissipates 10-12 hours later
–Satiation is completely after event
–Memory for the events is quite clear afterwards
effects of chronic hallucinogen use–tolerance
–tolerance develops rapidly after repeated dosing and disappears rapidly with abstinence
mechanism of actions of hallucinogens
LSD and hallucinogens alter serotonin neurotransmission
–Many hallucinogens, including LSD, are structurally similar to serotonin
–
adverse reactions to hallucinogens
–hallucinating trip can be pleasant or unpleasant
–Individuals who value self-control do poorly
Adverse experiences during trip EEG being arrested may precipitate anxiety reactions
–Previous pleasurable traps give no immunity to adverse reaction
–Higher doses tend to give worse reactions
–Treated with benzodiazepines for anxiety reactions
–”Bad trip” is anxiety or panic reaction
–Depression and suicidal ideation can occur several days after LSD
–Differential diagnosis is between LSD psychosis and paranoid schizophrenia
––Auditory hallucinations suggest schizophrenia
–Therapeutic index of LSD is very high therefore generally safe,
treatment of acute hallucinogen crisis
–Treatment drug of choice = benzodiazepine
–Severe reactions can be controlled with Haldol
long-term adverse effects of hallucinogen usage
long-term use of hallucinogens
–No evidence of brain cell damage or teratogenic effects
Chronic effects
––Psychosis
––Depressive reactions
––Acting out
––paranoid states
––Flashbacks
––––Can occur even months after good or bad trip, last only a few seconds, but her frightening because of lack of control
Flashbacks can be initiated by SSRIs
–Flashbacks treated with SSRIs, psychotherapy, or benzos
Effects of PCP intoxication
At low doses, PCP resembles alcohol intoxication with getting euphoria
––Can produce anxiety, paranoia, emotional outbursts
Higher doses can lead to dysarthria, ataxia, increased deep tendon reflexes, decreased pain sensation, tachycardia, hypertension, altered perception
Is one of few drugs that can cause vertical nystagmus
Use of PCP
PCP is fairly cheap and is often used adulterated other substances
People often unaware that they were getting PCP
Usually smoked with marijuana
Occasionally inhaled or taken orally
Alternate Names for PCP
PCP is often called
–Angel dust
–Killer weed
–Ozone
–There is other names
