SECTI0N 2 PRINCIPLES OF ADDICTION MEDICINE Flashcards
percent of Americans using caffeine
87%
chemical name for caffeine
1, 3, 7 trimethyl xanthene
origin of caffeinated drinks
–tea from China
–Coffee from Ethiopia
–coca from South America
time to peak levels of caffeine after ingestion
30–45 minutes after ingestion
alcohol and caffeine
heavy use of alcohol is associated with heavy use of caffeine
caffeine and benzodiazepine
caffeine and benzodiazepines mutually antagonize each other
percent of deaths caused by tobacco
tobacco causes 10% of all deaths
nicotine absorption in respiratory and gastrointestinal systems
–absorbed by mucous membranes and nasal cavity
–Poorly absorbed in stomach, because of acidity
–Well absorbed in small intestines
nicotine and reproductive system
–Crosses placenta freely
–Concentration twice as high in breast milk is in blood
aspects of nicotine pharmacodynamics
half-life = 2 hours,
–steady-state in 6–8 hours
–smokeless tobacco produces slower rise in nicotine level
–Smokers tend to maintain consistent level of nicotine day-to-day
–Tolerance to nicotine increases as the day goes on
–Overnight abstinence allows considerable re sensitization of nicotine receptors
–Nicotine mostly metabolized and liver
–Metabolites = 14,
-women metabolize nicotine faster than man
–Estrogens increase rate of metabolism
racial differences in nicotine metabolism
–blacks obtain 30% more nicotine from cigarette
–Blacks clear nicotine and cotinine more slowly than whites
–Chinese get less nicotine per cigarette, smoke fewer cigarettes than Caucasians
–Chinese metabolized nicotine and cotinine more slowly than Caucasians or Hispanics
–Lung cancer rates highest in blacks and lowest in Chinese Americans
site of action of caffeine
caffeine acts on the adenosine receptor as it is structurally similar
tolerance to the effects of caffeine
tolerance to motor effects develops with chronic use of caffeine
–Caffeine antagonizes the sleep promoting effects of adenosine
half-life of nicotine
half-life of nicotine is 2 hours in the body
women and nicotine metabolism
women metabolize nicotine faster than man
–Estrogens promote faster metabolism of nicotine
–Pregnant women metabolize nicotine faster
cigarette smoking and OCPs
cigarette smoking and OCPs act synergistically to increase risk of stroke and premature myocardial infarctions
effects of nicotine at lower and high levels on cardiovascular system
–at low levels nicotine increase his blood pressure and heart rate and cardiac output
–Higher levels produces ganglionic stimulation and adrenal catecholamines
– at very high doses nicotine causes hypotension and bradycardia
psychoactive effects of nicotine
–primary CNS effects of nicotine is arousal
–promotes relaxation in stressful situations
–Enhances mood, attention and reaction time
–Improved performance in some tests (partially due to relief from withdrawal symptoms
women and nicotine replacement
–women benefit less from nicotine replacement than men
–Women more influenced by non-nicotine stimuli such as smell and taste
psychiatric comorbidities of smoking
–increase use and frequency among
–psychiatric patient’s and drug abusers
––Especially schizophrenia, depression and ADHD
––75% schizophrenics smoke
–40% of adults with ADHD are smokers
–Nicotine patches improved performance of ADHD patient’s
–Smoker’s experience fewer side effects from antipsychotic drugs
–Lifetime prevalence of depression among smokers = 60%
–Lifetime prevalence of depression and general population equals 17%
–Smokers with history of depression have more severe withdrawal syndromes, poor outcome and more likely to develop depression after withdrawal
relapse rate among smokers
–75% smokers want to stop
–33% of smokers try to stop each year
–<3% succeed in stopping long-term
–50% of smokers with major medical complications relapsed within a few weeks after hospitalization
withdrawal symptoms of nicotine
–irritability, frustration and/or anger –Anxiety, depression –Difficulty concentrating –Restlessness –Increase appetite –Impaired reaction time and attention
Peak at 1-2 days and diminishes over a few weeks
–Dysphoria, mild depression, and anhedonia may persist for months
–extinction of tobacco associated cues may take years
–Smokeless tobacco give similar symptoms
composition and toxicity of cigarette smoke
–tobacco smoke is composed of tar in particle phase and is responsible for most human morbidity and mortality
–volatile phase contains more than 500 gases compounds
––Nitrogen, carbon dioxide, carbon monoxide, ammonia, hydrogen cyanide, benzene
Particulate phase has 3500 different compounds
–Tar is composed of particulate matter minus is alkaloid and water content, contains many carcinogens
mortality and morbidity and smokers
–smokers averaged 14 years less of life than nonsmokers
–1 Pack of cigarettes costs $7 in medical care and lost productivity
–39,000 passive smoking deaths per year mostly from cardiovascular disease
history of marijuana
–in use for 12,000 years
–Probably started in Central Asia
–Brought to America’s in 1600s I English and Spanish
–Euphoric properties discovered in India about 2000 BC
–Recreational use began to surge in 1930s during prohibition
–American use ended in 1937 with marijuana tax act
therapeutic uses of marijuana products
–prevention of weight loss in AIDS patients –Pain management –Anti-nausea –glaucoma control –Control of movement disorders
marijuana and pain control
–CB 1 receptors played a role in regulating pain behavior
–CB 1 agonist produce analgesia at several sites of pain transmission
–CB 2 receptor is critical component of inflammatory pain
–THC may prevent opioid tolerance and dependence
–THC produces analgesia only at doses high enough to produce dysphoria
–THC is no more potent than commonly used opioid analgesia
–Low dose of THC will prevent tolerance and addiction to morphine
cannabis and glaucoma
–must be smoked frequently to depress intraocular pressure
–Cannabis alone will not lower pressure enough to prevent optic nerve damage
–Is no more effective than other glaucoma treatments
kinetics of cannabis
–most common Route is hand rolled joint = 0.5–1 g of cannabis gives 5–150 milligrams of THC
–2–3 milligrams THC needed to produce high and occasional user
–If taken with food, onset of psychoactive effects in about 1 hour
–THC can be deposited in fatty tissues for long periods after use
–Behavioral effects of THC are proportional to plasma concentration
psychomotor effects of cannabinoids
marijuana modifies
–Object distance and outlines leading to distortion
–decreases ability to discriminate shapes
–Decreases ability to make rapid critical judgments
–Slows reaction time and information processing
–Impairs perceptual motor coordination
–Short-term memory
–Impairs attention
–effects are dose-related
cognitive effects of cannabis
cognitive effects of cannabis
–Decreased cognition and memory
–All cognition and memory affected
–Effects not as great as chronic alcoholism
–Chronic heavy users have significantly lower educational achievement, income, social life, and health
effects of THC on CNS
–at low doses, a mixture of depression and stimulation
–At high doses predominantly CNS depression with hyperreflexia
dependence and cannabis
–about 9% chance of chronic users becoming dependent
–Develops with repeated exposure
–Characterized by lack of control of cannabis use and use despite adverse personal consequences
withdrawal effects from cannabis
withdrawal effects are generally opposite of those produced by marijuana –Insomnia –Anorexia –Anxiety –Irritability –Depression –Tremor
–Similar to tobacco in severity
–concurrent withdrawal from cannabis and nicotine produces worse withdrawal than individual drugs
–27% of cannabis users report use of cannabis to reduce or prevent withdrawal
–Clonidine will reduce withdrawal signs
toxicities/adverse effects of cannabis–psychiatric
–cannabis increase his risk of schizophrenia
–Increases schizophrenic symptoms
–Above effects increase if cannabis use early in adolescence
–Produces threefold increased risk of psychosis
major organ damages of cannabis
–respiratory system is main damage
–Contains same carcinogens as tobacco
–Can produce chronic cough, airway inflammation, and abnormal cell growth
cannabis effects on –liver –kidneys –endocrine –Reproductive
THC
–increases HIV infection
–Increase his heart rate
–Synergistic with alcohol in developing steatosis
–Altered pituitary hormones
–Not much effect on kidney
–Can induce galactorrhea
–Can disrupt female reproductive system
–Can contribute to low birth weight children
–accumulates and passes in breast milk
–Reduce in testosterone and sperm production
discuss hallucinogens
–produces alterations and thought, mood, perception
–Minimal autonomic side effects and cravings
–Failed to produce excessive stupor or central simulation
classical hallucinogens = serotonergic hallucinogens
––Indole alkylamines
––Phenyl alkyl amine
Designer drugs
history of hallucinogens
–mescaline in use for more than 5000 years
–LSD discovered in 1940
–LST = 1000 times more potent than mescaline
–LST similar structure to serotonin
–Hallucinogen = psycho mimetic
list psychomimetics
–LSD
–Mescaline (peyote cactus)
–DOM
–psilocybin
effects of MDMA
MDMA produces –Extroversion –Heightened mood –confidence and well-being –Dry mouth and increased thirst –Difficulty concentrating –Impaired balance –Dizziness –Jaw clenching –Lack of appetite –Restlessness –Moderate perceptual changes, primarily intensification of tactile visual and acoustic perception –No frank hallucinations
addiction potential of hallucinogens
classical hallucinogens do not contain amphetamine-like or cocaine like reinforcing properties
Exceptions are MDMA and MDA which have some addicting potential
toxicity of MDMA
MDMA
–Best that it hallucinogen
–Females are sensitive to psychotropic and physical effects
–males more sensitive to acute physiologic effects
–High-dose MDMA has risk of persistent cognitive impairments and disturbance of affect and personality
–In general, classical hallucinogens are free of toxicity
Noted MDMA is not a classic hallucinogen
discuss dissociatives
dissociatives
–Several heterogeneous chemicals which are antagonists to the N methyl aspartate receptor of the excitatory neurotransmitter glutamic acid in the brain
–Share common features with hallucinogens
–––But hallucinogens primarily affect 5 Ht 2 a instead of NMDA
Examples
–Phencyclidine, ketamine
–Dextromethorphan
–Nitrous oxide
Sub-anesthetic doses of phencyclidine and ketamine induced psychotomimetic state resembling schizophrenia
ketamine, PCP, and dextromethorphan
ketamine is used in general anesthesia
–Schedule 3
–Sometime used for prehospital analgesia and conscious sedation
–Especially useful in children
PCP
–No longer available commercially
–More potent than ketamine and longer-lasting
–More likely than ketamine to produce seizures
–Usually smoked
Dextromethorphan= DXM
–Most commonly abused over-the-counter drug
–Using large quantities for mental effects
–has low toxicity
discuss PCP
PCP = phencyclidine = angel dust = Hogg = Crystal = Chuck Norris
–Developed as intravenous anesthetic
–Produces symptoms of schizophrenia with delusions and hallucinations
–Blunted affect
Produces ambivalence and asociability
–Produces autistic-like effects
Similar to ketamine
discussed DXM
DXM= skittles
–synthesized in 1954 as opioid analgesic
–D isomer is antitussives and has less narcotic properties
–Does not produce respiratory depression or CNS depression
In very high doses produce his PCP like mental effects
Crash sometimes used in over 200 times recommended dose
–Often used by adolescence because of unavailability
––Highest frequency in 15–16-year-old
––most common was Coricidin HBP colds and cough tablets
pharmacodynamics of dissociatives
PCP half-life 7–46 hours
–Metabolizes and liver
–Excreted in urine
Ketamine
–Rapid onset, short duration
DXM readily absorbed from gut
–Peaks in 2 hours
effects of PCP, ketamine, other dissociatives
3 types of effects of dissociatives
A. Confusion, delirium, psychosis
B. Semicoma,,
C., coma With seizures
Long-term effects of PCP
–dysphoria
–Reduced memory and retention
–Apathy
–Irritability
effect of dextromethorphan abuse
dextromethorphan has serotonergic effects
–Increase since of this and release of serotonin
–Inhibits reuptake of serotonin
–Few side effects in therapeutic doses
Tacitly produced body rash, itching, nausea, vomiting
–Higher doses may produce dizziness, drowsiness, altered vision cardiovascular and CNS effects resembling PCP
–Euphoria or hallucinations began within 30 minutes of intoxicating dose
types of inhalants
volatile alkyl nitrates
––able nitrite
––butyl nitrite
Nitrous oxide
Solvents, fuels, anesthetics ––Toluene ––Xylene ––trichloroethene ––Tetrachloroethylene ––dichloroethylene ––Butane, isoprene ––ether ––Ketones
epidemiology of inhalants
–problems of inhalants most common among 12–17 murals
–Inhalant use is secondary only to alcohol, tobacco and marijuana
–Most common among non-Hispanic weight use
–Half abusers continue for 2 years
–growing problem in developing countries
–Often associated with other substance abuse disorders
–Often gateway drug
effects of aerosol inhalation
–often droplets
–Very rapid onset, user often falls down immediately
–Users sometimes become unconscious
–Rapid elimination usually via lungs
–metabolized inhalants contributed to liver toxicity
–Readily into brain
addiction liability of inhalants–backspace
the following have reinforcing parties
–Toluene
–Chloroform
–Nitrous oxide
Toxicity of inhalants
–cause respiratory depression
–Are neurotoxic
effects of inhalants on major organs
–Respiratory and eye irritation
–Coughing respiratory compromise
–Livers most important target for exposure to solvents
–Especially halogenated cut hydrocarbons
–Some kidney damage reported
–Benzene and vinyl chloride are known carcinogens
discuss pharmacology of anabolic androgenic steroids
–usually diverted licit medications
–female hormones rarely diverted
–Usually uses supraphysiologic doses
–Organ toxicity often reversible
anabolic androgenic steroids listed
testosterone
17 alpha L collated derivatives of testosterone
17 beta esterified derivatives of testosterone
Modified ring structure analogs
history of anabolic steroids
1930 = and I asked her own isolated from urine
1940s = testosterone synthesized
–1954 weightlifting champion Soviet coach in phone US coaches that members were taking testosterone
–1984 huge number of collegiate and amateur athlete’s using
regeneration performance and answers
substances are being developed there neither illegal nor band, but difficult to detect –Human growth hormone –DeHydro epi androsterone –Erythropoietin –Thyroxine
use and misuse of anabolic steroids
athletes use 10–20 times therapeutic dose
–Therapeutically used in women to treat metastatic breast cancer and bone
–methyltestosterone plus estrogen use to alleviate menopause symptoms
effects of anabolic steroids when misused
–can stunt growth
–Very few users actually have serious harm
–Most effects are reversible
–high rate of abnormal personality traits in bodybuilder’s
Score higher and paranoia, schizoid, antisocial, borderline, histrionic, narcissistic, Passive-aggressive personality profiles
serious effects of anabolic steroids
–usually reversible in 3 months after stopping
–Benefits usually remain
–Can cause “roid rage”
–About 3% develop hepatocellular adenomas–benign or malignant
–frenzied and violent behavior during cycle of high-dose anabolic steroid resemble hypomania or mania
––Talks faster, more energy, sleeps less
––Becomes impulsive
––Usually followed by depression
frequency of substance abuse in primary care
–20% of all direct admissions from primary care involve alcohol
–Illicit and prescription drug abuse up to 10% in primary care
–1 in 5 hospital admissions directionally relates to substance abuse
define SBI
Screening and Brief Interventions
–Time-limited, client center, designed to reduce substance abuse
–Average duration 5–20 minutes
–Emphasizes reduction rather than abstinence
–Not related to readiness to change
–Can work in pre-contemplators
screening questions for alcohol abuse and dependence
“do you sometimes drink beer, wine or other alcohol beverages?”
“How many times in the past year have you had 5 drinks in a day?”
men < 65 years old = 5 drinks
women and men >65 years = 4 drinks
define safe drinking
–5 drinks per day <65 years old
–14 drinks per week under 65 years old
–4/7 drinks per day/week over 65 years or female
defined at risk drinking
at risk drinking = exceeding safe limits, but abuse/dependence criteria not met
meta-analysis of SBI
–doesn’t work well for opioid abuse
–Otherwise, one of the highest ranking preventative services ever evaluated
–Results in significant reduction in heavy drinkers and alcohol consumed
–Effect lasts at least 4 years
–Equal for men and women
–Multiple encounters more effective than single
–Be I seems to reduce mortality by one third in population of heavy drinkers
alcohol in emergency room
alcohol abuse occurs in 5% of general emergency room admissions
And 50% trauma admissions
most young people mature out of hazardous drinking without intervention
alcohol in college students
40% of college students report binge drinking and prior 2 weeks
One third meet criteria for alcohol abuse
SPI effective in college students
pregnant women and drinking
2% of pregnant women engaged in binge drinking
–13% of nonpregnant women engaged in binge drinking
effects of alcohol on fetus
–7–14 standard drinks per week associated with developmental problems
–Moderate intellectual behavior deficits
Alcohol during first trimester associated with
–Low birthweight
–Decreased birth length
Alcohol drinks second and third trimesters can produce developmental delay
Alcohol is concentrated in breastmilk and can inhibit milk production
alcohol and trauma
alcohol is major risk factor for all categories of fatal and nonfatal injury
–Up to 70% life-threatening injuries about alcohol
Alcohol in older people
–10% of older people admitted to the hospital have alcohol
–Alcoholism is third most common psychiatric disorder among elderly
–One third of older alcoholics are late onset alcoholics
gamma glutamic transferase = GGT
GGT= will sensitive marker of alcohol abuse
–Increase in 75% of patients with alcohol dependence
–Elevated in 50% of patients hospitalized for alcohol related problems
–Elevated 30% of people who drink heavy amounts and have alcohol-related problems
But, is elevated with
–Fatty liver
–Obstructive liver disease
–Certain medications including anticonvulsants
–5 drinks per day ×2 weeks we’ll elevated GGT in most individuals
–GGT drops by 50% in 2 weeks
GGT drops to normal in 6-8 weeks
MCV is Marker for alcohol
–may take 4 months to return to normal
Nonalcohol related conditions can increase MCV –Chronic liver disease –Hypothyroidism –Folate deficiency –Megaloblastic disorder
CDT = carbohydrate deficient transferrin
–is more sensitive than GGT
AST/ALT and alcohol
if AST >ALT, likely to be alcoholic problem
if ALT >AST probably liver disease
correction factor for blood alcohol versus serum alcohol
serum alcohol levels will be higher than blood alcohol levels
Therefore 1.14/1.00 correction factor
testing for amphetamines
–amphetamines have D and L isomers
–D isomers have stronger CNS effects and more abuse potential
–CG/MS cannot distinguish D from L isomer
–Amphetamines have the most false positive screening tests
––Phenyl propyl alanine
––Pseudoephedrine
––Vicks nasal inhaler
––Appetite suppressants containing ephedrine and phentermine
what can cause false positive test for benzodiazepine?
tolmetin
sertraline
