Add Med Flashcards
What aspect of opiate addiction never shows tolerance?
Constipation
DATA 2000 approves writing of prescriptions by qualified physicians for which drugs?
Schedule III, IV, V
What are the four micro-skills involved with motivational interviewing?
OARS: Open ended questions Affirmations Reflective statements Summarization
What is the key part of the brain for “fight or flight” and stress circuits that is activated by withdrawal from ALL drugs of abuse?
Amygdala
At which receptor does buprenorphine have the most activity?
Mu
Federal regulations limit first dose of methadone in OTPs to what dose?
30 mg
What is the DEA schedule for buprenorphine?
Schedule III
Synthetic cathinones are derivatives of this plant
Catha edulis
For how long are Khat leaves effective in generating the relevant high
Cathinone is only found in the fresh leaves thus they can only be chewed for several days after harvesting
What medical problems have been associated with Khat chewing?
MI, dilated cardiomyopathy and duodenal ulcers
What is the only cathinone derivative approved for use in the U.S.?
Bupropion
What drug is known as “cat and Jeff”?
Methcathinone
What cathinone derivative was developed to tx chronic fatigue, lethargy and obesity before being withdrawn from the market due to dependency and abuse?
Pyrovalerone
What is MDPV?
Methylenedioxypyrovalerone
How are cathinones usually used?
Ingestion or insufflation
What is “bombing” with regard to cathinone use?
What is “keying”?
“Bombing” is a method of ingestion whereby mephedrone powder is wrapped in cigarette paper and swallowed.
“Keying” is the practice of dipping a key into powder and then insufflating. (there are 5-8 “keys” per gram)
What are the desired effects of synthetic cathinone use?
Energy
Empathy
Openness
Increased libido
What is the most common ED symptom associated with cathinone use?
Agitation ranging to severe psychosis
What is the physiological effect of the beta-ketone on the amino alkyl chain of synthetic cathinones
Increased polarity that causes decrease penetration of the blood brain barrier.
What are the statistically significant predictors of illicit buprenorphine use?
White ethnicity, intra-nasal inhalation of pharmaceutical opioids, sx of opioid dependance, and a greater number of illicit pharmaceutical opioids used in ones lifetime.
Gender, duration of illicit pharmaceutical opioid use and lifetime opioid abuse disorder had no relationship with the odds of illicit buprenorphine use.
What is the predominant motive of illicit buprenorphine use?
Self medication of withdrawal symptoms
What is the most common illicit drug used by pregnant women?
Marijuana
What is the effect of fetal exposure to marijuana?
Does not cause clinically important neonatal withdrawal signs but may have subtle effects on long term neurobehavioral outcomes.
What percentage of pregnant females report use of illicit drugs?
4.5%
What percent of pregnant females report first trimester binge or heavy drinking?
11.9%
Among neonates exposed to opiates in utero, what percent will develop withdrawal signs?
55-94%
Neurology-behavioral abnormalities frequently occur in neonates with IU cocaine exposure. What are these and when do they occur?
Irritability, hyperactivity, tremors, high pitched cry, excessive sucking– most frequently on the second or third postnatal day.
Third trimester use of what drug has been reported to cause continuous crying, irritability, jitteriness, restlessness, shivering, fever, tremors, hypertonia or rigidity, tachycardia, tachypnea, respiratory distress, poor feeding, sleep disturbance, hypoglycemia, seizures with onset hrs to days after birth with resolution in 1-2 weeks
SSRIs
Are methadone or buprenorphine approved for use in pregnancy?
Neither methadone nor buprenorphine are approved by FDA for use in pregnant females and both are FDA category C pregnancy drugs.
What is the MOTHER study?
Maternal Opioid Treatment Human Experimental Research study
What are the causes of variability of clinical presentation of NAS?
Varies with the opioid, maternal drug hx, maternal metabolism, net transfer across placenta, placental metabolism
The incidence and severity of NAS is greatest with which drug?
Methadone> heroin> buprenorphine
What correlates with lower risk for NAS?
Pre-term and lower gestational age. This may relate to developmental immaturity of the CNS, differences in total drug exposure or lower fat depos of drug.
What is a relative contraindication for the use of naloxone for the treatment of apnea or hypo ventilation during the transition period after birth?
Maternal use of opiates. Seizures have occurred that are not responsive to phenobarbital diazepam but only resolve with morphine!
Withdrawal signs in the newborn may mimic what other conditions?
Infection, hypoglycemia, hypocalcemia, hyperthyroidism, intracranial bleed, hypoxic- ischemic encephalopathy, hyper-viscosity syndrome.
What is the predominant tool used in the U.S. to measure/determine NAS?
The modified Neonatal Abstinence Scoring System. This assigns a score based on interval observations of 21 items relating to signs of neonatal withdrawal.
What is the bioavailability of buprenorphine?
Enteral=15%
Transbuccal=27.8%
Sublingual=51%
What is the volume of distribution of buprenorphine?
97-187 L
How is buprenorphine metabolized?
Buprenorphine undergoes n-dealkylation via p450 3A4 to form norbuprenorphine. Conjugates of buprenorphine and norbuprenorphine are primarily excreted in feces.
What is the elimination half life of buprenorphine?
37 hrs after sublingual administration. The elimination half life of norbuprenorphine is 34 hrs.
Why is there no opioid antagonism when buprenorphine/naloxone combinations are given SL?
Poor sublingual and enteral bioavailability of naloxone
Does buprenorphine indicate positive for opioids on a UDS?
No.
Which drug is most similar biochemically to methadone?
Propoxyphene (Darvon)
With increasing ETOH use what is the first and most sensitive liver enzyme to elevate?
GGT
What is the most reliable bio marker for recent ETOH use?
CDT (carbohydrate deficient transferrin) will detect ETOH use > 60 g ETOH/day. Has a high specificity and high sensitivity for recent alcohol use. Since it is unavailable at most hospitals and outpatient treatment settings, it is often recommended that clinicians use combinations of other approaches to assess for alcohol use. CDT is a biomarker for chronic alcohol intake of more than 60 g ethanol/day. It is based on the fact that an averaged daily consumption of more than 60g of alcohol (about 5 standard drinks) during the previous 2 weeks increases the percentage of transferrin that has deficient carbohydrate content. Data show that a 30% reduction in CDT is consistent with a substantial reduction in alcohol intake. A positive % CDT test result is 1.7% or higher and may change up or down with increased or decreased drinking.
Which assessment tool examines a persons resistance to treatment?
RAATE
What is varenicline?
Varenicline is a potent partial agonist at α6β2 nicotinic acetylcholine receptors and is FDA-approved for the treatment of Tobacco Use Disorder.
Prolonged substance-induced psychosis is common with chronic use of:
Methamphetamine
How is acamprosate cleared from the body?
Renally cleared
Which drugs are currently approved to treat alcohol dependence?
The first medication approved for the treatment of Alcohol Dependence was disulfiram in 1949, as an aversive medication. In 1994, oral naltrexone, an opioid antagonist that decreases the reinforcing effects of alcohol, was approved in a dosage of 50 mg/day. In 2004, acamprosate, (likely) a GABA receptor agonist and NMDA receptor modulator, was approved in a dosage of 666 mg three times a day (total dose of 1998 mg/day). In 2006, a monthly, long-acting, injectable naltrexone formulation of 380 mg/month was approved by the FDA.
What are the pharmacogenomics of alcoholism?
The primary pathway of ethanol metabolism involves oxidation by alcohol dehydrogenase (ADH) to acetaldehyde. The acetaldehyde is then further oxidized by aldehyde dehydrogenase (ALDH) to acetate, which is either excreted in the urine or reincorporated into intermediary metabolism as acetyl-CoA to begin fatty acid synthesis. Acetaldehyde buildup is toxic and causes flushing and palpitations. The ALDh2*2 allele has a prevalence of between 12% and 41% in East Asia. People who carry one copy of the inactive allele are strongly protected against alcoholism (odds ratio 0.5 to 0.12), and homozygotes are almost completely protected. (Hurley TD, Edenberg HJ. Genes encoding enzymes involved in ethanol metabolism. Alcohol Res 2012;334(3):339–344.)
What characterizes cannabis intoxication?
Tachycardia (not bradycardia), tachypnea, tremors, vasoconstriction, orthostatic hypotension, conjunctival injection, and appetite increase (not appetite suppression) are the physiological characteristics of cannabis intoxication.
Which neurotransmitter is activated during drug withdrawal and mediates behavioral, pituitary and *** responses to stress?
Corticotrophin Releasing Factor (CRF)
What is the strongest predictor of AA group attendance?
Severity of alcohol related problems. Per Project Match the more severe the problem and the less social support the more likely someone will attend.
32% referred by an AA member
47% referred by a facility or a professional
Religious involvement is a poor predictor of AA affiliation.
How long does it take for normal sleep to resume after stopping marijuana use?
4-6 weeks
What is the effect of alcohol at the NMDA receptor
Antagonism
Alcohol interacts with the serotonin (5-HT) receptor system at which receptor subtype?
5-HT3
What is the mechanism for ETOH/nicotine dependence as co- morbid conditions?
Additive effects on dopamine release in nucleus accumbens
What is the mechanism for most ETOH withdrawal manifestations
Up regulation of NMDA leading to neuronal hyper excitability.
What are the four opioid receptors?
Mu, kappa, delta, OFQ/N
Which brain regions mediate the pleasurable, positively reinforcing properties of opioids?
Ventral tegimental area and nucleus accumbens
What is reward salience?
“Wanting”
The negative reinforcement model postulates what state in the neural system of the addict?
Allostasis
When does methadone withdrawal peak?
Day 5-6
What is the mechanism for LAAM mediated torsades and sudden death?
Potassium channel blockade
What is LAAM?
Levo-alpha-acetylmethadol
What is the difference between methamphetamine induced psychosis and cocaine induced psychosis?
Meth has a longer half life than does cocaine and causes a psychosis lasting up to several weeks while cocaine induced psychosis lasts only up to several days
What neural pathway accounts for relapse in cocaine or amphetamine dependent patients?
Cingulate cortex to the nucleus accumbens
What is tapentadol
Tapentadol (brand names: Nucynta, Palexia and Tapal) is a centrally acting opioid analgesic of the benzenoid class with a dual mode of action as an agonist of the μ-opioid receptor and as a norepinephrine reuptake inhibitor. Its analgesic properties come into effect within thirty-two minutes of oral administration, and last for 4–6 hours.
What is the mechanism of action of nicotine
Nicotine binds to alpha4beta2 receptors in VTA of midbrain and leads to dopamine release in the ventral striatum/nucleus accumbens (presumably leading to the pleasurable effects).
Nicotine also inhibits the activity of MAO A and B leading to decreased breakdown of dopamine.
What is LAAM?
Closely related to methadone, the synthetic compound levo‐alpha‐acetyl‐methadol or LAAM (Brand name: ORLAMM®), has an even longer duration of action (from 48 to 72 hours) than methadone, permitting a reduction in frequency of use. In 1994, it was approved as a Schedule II treatment drug for narcotic addiction. Both methadone and LAAM have high abuse potential. Their acceptability as narcotic treatment drugs is predicated on their ability to substitute for heroin, the long duration of action, and their mode of oral administration.
What is the mechanism of action of ketamine?
Ketamine acts via competitive inhibition within the NMDA receptor complex
How long does a ketamine “trip” last
About 1 hour
What is the LD 50 for ketamine?
About 30x the intoxicating dose
What effect does GHB have on growth hormone?
GHB stimulates growth hormone release up to 16 fold in humans
What is the DEA schedule for GHB
Schedule III due to some legitimate uses
Which psycho analytic theoretician posited that drug use was a substitute for a heathy interaction with a parent figure?
Heinz Kohut
Which neurotransmitter system has decreased activity during alcohol withdrawal?
GABA…..also, it’s activity is increased during intoxication as it mediates some of ETOH’s depressive effects. Levels decrease during withdrawal.
What percentage of alcohol dependent individuals achieve permanent abstinence without formal tx?
20%
What are the top 4 causes of early death in ETOH dependent persons?
In order: heart disease, cancer, accidents, suicide
Which preparation of Cannabis has the highest concentration of THC
Hashish oil (30%)
Which part of the Cannabis plant has the lowest THC concentration?
Seeds and stems
What is sensemilla and what is the contained concentration of THC?
Buds and flowering tops; 8-24%
What is the amotivational syndrome?
Chronic amorivation due to chronic marijuana use that can persist even after abstinence.
What characterizes marijuana withdrawal syndrome?
Psychological, not physical, symptoms: craving, irritability, anxiety, depressed mood, insomnia
What effects does marijuana have in the endocrine and reproductive system?
Inhibits LH, prolactin, and GH but no effect on FSH. Decreases testosterone in males.
Can cause LBW infants. Highest consumption in women–>lowest BW infants.
Which acts on the vesicular monamine transporter system; cocaine or amphetamines?
Amphetamine
Which TCA has been studied most extensively as a treatment for cocaine dependence?
Desipramine…….but it may be most useful only in patients with co-occurring depression
What is contingency management therapy?
A highly structured incentive based therapy that has been successful for initiating abstinence and preventing relapse for stimulant dependent patients. It uses a system of privileges and nondrug reinforcers to counter and decrease behavior maintained by drug reinforcers.
What happens to brain glucose metabolism in early versus late cocaine withdrawal?
Early: glucose metabolism increases
Late: glucose metabolism decreases
What % of America’s prison population are estimated to have ETOH and drug abuse spectrum disorders?
70%
T or F
Alcohol and other drugs of abuse seem to cause medical problems in women at a younger age than men
True
What is the lifetime prevalence of co-occurring psychiatric disorders in women; in men, with ETOH abuse?
Women: 72%
Men: 57%
When major depression and ETOH dependence co-exist, the mood disorder is primary more often in women (2/3) versus men (1/3)
What is pseudoaddiction?
Drug seeking behavior that resembles a substance use disorder but is iatrogenically caused by inadequate pain treatment.
What is the lifetime incidence of substance use disorders in physicians?
8-15%. This is no higher than for other socioeconomically matched professionals
Which 2 medical specialities have the highest risk for participation in a physician health program?
ER and anesthesia
What percentage of states have PHPs?
All 50 states
What is the most frequently abused benzodiazepine?
Alprazolam (Xanax)
Does buprenorphine increase QTc?
Buprenorphine does not increase QTc!
Dextromethorphan is metabolized to what substance?
Dextrorphan; a weaker sigma opioid agonist and STRONGER NMDA antagonist than dextromethorphan.
What are the effects associated with DXM?
Significant serotenergic properties:
1- increase synthesis and release of serotonin;
2- inhibit re-uptake;
3- risk of serotonin syndrome
What is the major excitatory neurotransmitter in the CNS?
The amino acid L-glutamate
What is the primary CNS inhibitory neurotransmitter?
GABA
What happens to L-glutamate when benzodiazepines are reduced?
Increased activity of the glutamate system is seen. Rebound anxiety, increased muscle tone, sensory disturbances, tremors, and seizures can be related to the increased glutamate
Which centrally acting opioid has been associated with the development of serotonin syndrome and/or angioedema?
Tapentadol (Nucynta)–contraindicated in pts taking MAOIs.
Which p-gp inhibitors may increase the absorption of morphine by approximately 2-fold?
Quinidine, azithromycin, verapamil
What effect does CYP 3A4 inhibitors have on opioids?
Increase blood levels
How long for opioids to reach “steady state”?
3 days
What part of the brain is primarily involved with
analgesia?
Peri-aqueductal gray matter
Which portion of the brain is activated in withdrawal?
Locus ceruleus
What drug of abuse is legal within the Native American Church?
Mescaline/peyote; Ayahuasca
Which state has no Prescription Drug Monitoring Program (PDMP)?
Missouri
What is SBIRT?
Screening, Brief intervention, Referral to Treatment– is an evidence-based practice used to identify, reduce, and prevent problematic use, abuse, and dependence on alcohol and illicit drugs. The SBIRT model was incited by an Institute of Medicine recommendation that called for community-based screening for health risk behaviors, including substance use.
What % of neonates with in utero exposure to opioids will develop Neonatal Abstinence Syndrome?
50-81%
When does NAS have its onset?
1-72 hours
What characterizes Fetal Alcohol Syndrome?
Microcephaly, epicanthal folds, flat mid-face, smooth philtrum, low nasal bridge, small eye openings, short nose, thin upper lip, reduced intelligence
What is the mortality of ETOH withdrawal?
2%
What characterizes Korsakoffs psychosis
Antegrade amnesia
Confabulations
What is the mechanism of action of nicotine?
Nicotinic acetylcholine receptor agonist
What is the mechanism of action of Savinorin A?
Kappa opioid agonist
What are the components of the COWS (Clinical Opiate Withdrawal Scale)?
Pulse, sweating, restlessness, pupil size, bone/joint aches, runny nose/tearing, GI upset, tremor, yawning, anxiety/irritability, goose flesh.
Score items 1-5. Mild= 5-12; moderate= 13-24, severe over 36
Where is ETOH absorbed primarily
Duodenum
Each of the following drugs has an active metabolite except: 1- Methadone 2- Codeine 3- Heroin 4- Tramadol 5- Buprenorphine
Methadone
Horizontal nystagmus is associated with
PCP- esp in stage 1 intoxication
Have PDMPs been shown to reduce OD deaths
Not as yet
For which analyte is saliva drug testing not adequate or reliable?
THC
What is Truvada?
Pre-exposure prophylaxis for HIV
What is the brand name for oral naltrexone?
Revia
What are the four drugs currently approved to treat alcoholism?
Currently, there are four medications that have been approved by the Food and Drug Administration (FDA) for use in treating alcohol dependence: Disulfiram (Antabuse®), oral naltrexone (Revia®), acamprosate (Campral®), and an intramuscular (IM) once-a-month naltrexone injection (Vivitrol®)
What is the COMBINE study?
The largest known controlled pharmacotherapy clinical trial for treating alcohol dependence, i.e., the COMBINE study, which was supported by the National Institute on Alcohol Abuse and Alcoholism. This study evaluated the efficacy of specific pharmacotherapies, behavioral or psychosocial interventions, and their combinations for the treatment of alcoholism.
When major depression and alcoholism co-exist in women how often is the depression primary?
2/3 of the time
What factors increase the risk of a missed diagnosis of alcoholism in hospitalized patients?
Better education, higher income, private insurance, female
What is the lifetime prevalence of psychiatric co morbidity in females with alcohol abuse according to the National Comorbidity Survey (NCS)
NCS found a lifetime prevalence of other co-occurring psychiatric disorders to be 72% in women with alcohol abuse; 57% in men.
Methadone maintenance in pregnant females has been beneficial in which regards
Reduced fetal mortality Reduced fetal morbidity Reduced pregnancy related complications Reduced maternal mortality No known teratogenicity
What % of prison inmates are substance dependent at the time of their arrest?
65%
How does ADA treat drug abuse differently from ETOH abuse?
Current ETOH use, if associated with impairment that limits one or more major life activities, does not disqualify one from protection under ADA– on the job drinking is not protected. Individuals with drug addiction are protected from discrimination only if they are abstinent and engaged in rehabilitation or have completed it.
What is the most useful intervention shown to reliably reduce alcohol use among teens and college students
Raising the legal age to 21
What is the activity of ETOH at the NMDA receptor?
Antagonist at NMDA
What are the CAGE questions?
C-Have you ever felt you needed to Cut down on your drinking?
A-Have people Annoyed you by criticizing your drinking?
G-Have you ever felt Guilty about drinking?
E-Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?
What is the sensitivity and specificity of CAGE?
CAGE test scores ≥2 had a specificity of 76% and a sensitivity of 93% for the identification of excessive drinking and a specificity of 77% and a sensitivity of 91% for the identification of alcoholism.p
What are the FDA drug pregnancy categories?
Category A: Controlled studies show no risk or find no evidence of harm.
Category B: Animal studies show no risks, but there are no controlled studies on pregnant women.
Category C: Animal studies have shown risk to the fetus, there are no controlled studies in women, or studies in women and animals are not available.
Category D: There is positive evidence of potential fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (i.e. life threatening condition to mother).
Category X: Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk. The drug is contraindicated in women who are or may become pregnant.
What is one standard drink
14 grains or 0.6 oz of pure ETOH
What are three direct tests for use of ETOH
Ethyl glucuronide
Ethyl sulfate
Phosphatidylethanol
What is the endogenous cannabinoid neurolo-transmitter!
Anandamide
What is the endogenous neurotransmitter for hallucinogens and MDMA
Serotonin
What part of the brain is involved with anti-reward
Habenula
What part of the brain is involved with interception?
The insula.
A number of functional brain imaging studies have shown that the insular cortex is activated when drug abusers are exposed to environmental cues that trigger cravings.
Research published in 2007 has shown that cigarette smokers suffering damage to the insular cortex, from a stroke for instance, have their addiction to cigarettes practically eliminated.
The mnemonic “REDS” applies to what form of therapy?
Motivational interviewing:
R oll with resistance
E xpress empathy
D evelop discrepancy
S upport self-efficacy
What is the mission of Al-Anon
“Strength and hope for friends and families of problem drinkers”
With regard to smoking and ETOH use what happens to most users post-partum
Most return to pre-partum levels of use within 6-12 months.
What screening tool is validated for screening in pregnancy and post-partum?
The "four P's": Pregnancy Past Partner Parents
Which screening tool is validated for adolescents?
CRAFFT
What is the endogenous ligand active at the mu receptor?
Beta endorphins
What is the endogenous ligand active at the delta receptor?
Enkephalins
What is the endogenous ligand active at the kappa receptor?
Dynorphins
What percent of the vulnerability to addiction is attributable to genetic factors?
40-46%
What % of people with psychiatric disorder exhibit substance abuse disorders?
30%
What CB1 antagonist, initially approved in Europe for the treatment of obesity has seen it’s use limited by the onset of depressive sx with an incidence of suicide, which has prevented its approval in the U.S.?
Rimonabant
“Substance-Related Disorders” has been renamed to what in the DSM-5?
Substance-Related and Addictive Disorders”
What is the only non drug addiction included in the DSM-5 category “Substance-Related and Addictive Disorders”?
Gambling disorder
What are the determinants of incidence and severity of Neonatal Abstinence Syndrome?
1- NOT dose or duration of treatment;
2- AA allele is more severe than AG or GG allele SNP of Mu opioid receptor gene OPRM1;
3- Epigenetics: increased methylation at 3 sites of mu opioid receptor gene was associated with more severe NAS
What is the COMT SNP (val158met) associated with?
Increased heroin addiction and type 2 alcoholism–but findings not universally accepted
DSM-5 moved to what form of diagnosis
Nonaxial
What criterion was dropped and which one was added for DSM-5?
Legal problems was dropped
Craving was added
Which opiates cause seizures?
Meperidine (Demerol)
Propoxyphene (Darvon)
Pentazocin (Talwin)
Tramadol (Ultram)
Which drugs cause amphetamine false +
Trazadone Bupropion Selegeline Sertraline Chlorpromazine Labetalol Ranitidine
What drugs cause false + for PCP
Venlafexine
Dextromethorphan
Following ingestion of the same amount of ETOH what is the percentage difference in BAC between females and males?
Females have 20-25% higher BAC
Which CYP enzyme is involved in the metabolism of ETOH?
CYP2E1
What is the mechanism of action for naloxone and naltrexone with regard to reducing ETOH consumption?
ETOH increases the release of opioid peptides making opioid antagonists a mainstay in treating ETOH addiction
What is the lifetime prevalence of ETOH dependence?
13%
Type I Cloniger and type A Babor ETOH classifications are similar. What are those similarities?
1- Later onset ETOH related problems (>25 yo);
2- Fewer childhood behavior problems;
3- Relatively mild ETOH related issues with fewer hospitalizations;
4- Lower degree of novelty seeking coupled with a preference toward harm avoidance;
5- Less tendency to run in families
What factors increase the likelihood of developing dependence on benzodiazepines?
Female gender, advanced age, cognitive impairment, panic disorder, presence of suicidal thoughts as well as longer duration of treatment and use of higher doses
What is the most common subtype CYP enzyme involved in metabolism of benzos?
CYP 3A4
What is the mechanism of action for benzodiazepines?
They are direct GABA agonists. They do not activate the GABA receptor themselves but rather function by enhancing the binding of GABA to the receptor and thereby lead to an increased frequency of the opening of the central chloride channel.
What are the “Z” drugs and how do they differ from benzos in their mode of action
Zolpedem; zopione; eszopiclone and zakepon
Their amnestic effects are less pronounced and tolerance is less likely to develop
What are the common CYP 3A4 inhibitors?
All “avir” drugs; macrolide ABx; azole antifungals; nefazadone; fluoxetine; cimetidine; grapefruit juice
What are the common CYP inducers?
Rifampin; rifabutin; carbamazepine; phenobarbital; phenytoin; St. Johns wort
What is the half life of diazepam and the half life of its active metabolite?
Diazepam: 28-54 hours
Active metabolite: 30-100 hours
What is the DEA schedule for GHB
Schedule I; its approved formulation is III
What are the pro-drugs for GHB?
Gamma butyrolactone;
1,4 butanediol
GHB is both a precursor and degradation product of what inhibitory neurotransmitter?
GABA
Unlike GABA however GHB readily passes thru the BBB
What effect does GHB have on dopamine?
High concentrations—–>inhibit dopamine release
Low concentrations—-> stimulate dopamine release
What are the long term effects of GHB use?
Animal models suggest that GHB causes lasting deficits in memory and social interaction and increases in anxiety due to long term neuroadaptations in brain oxytocin systems
What is the ratio of blood to breath concentration of ETOH
2100:1
A breath level of 0.1 grams per 210 L is equivalent to a whole blood ETOH of 100 mg/dL
Which drug of abuse has the most frequent false + screens?
Amphetamines
Is Ritalin detected on confirmatory testing for amphetamine or methamphetamine?
No. Because methylphenidate is not metabolized to amphetamine or methamphetamine.
True or false; participation in a DTC ( Drug Treatment Court) is voluntary on the part of the offender
True
What is motivational interviewing?
MI is a non-coercive cognitive and experiential method whereby the therapist helps the patient explore and resolve ambivalence in order to increase internal motivation to change behavior.
What did the Epidemiologic Catchment Area study find?
Bipolar disorder was more strongly associated with substance use disorders (other than nicotine use disorders) than was schizophrenia.
What characterizes cognitive behavioral therapy?
Collaborative and non-paternalistic;
Highly structured;
Home work assignments;
Time limited (12-24 weeks);
Therapist is active and non-neutral
What percent of EAP referrals are self- referrals?
90%
What is the relative annual risk of death from heroin addiction?
6-20 fold
What is the usual daily dose of methadone?
60-100 mg daily
What are the contraindications for nicotine replacement therapy?
Pregnancy, unstable angina, nursing
What is the half life of nicotine?
2 hours
What drug has shown some efficacy as a pharmacotherapy for cannabis dependence?
Gabapentin
What is “pyramiding”?
Taking anabolic steroids in increasing doses in cycles alternating with drug-free periods
The use of transcranial magnetic stimulation has been studied for which addiction?
Stimulant addiction
What is a positive CAGE questionnaire?
Affirmative response to 2 questions —->7x more likely to be ETOH dependent
Which opioids are most likely to be diverted and used in cases of nonmedical use?
Oxycodone and hydrocodone
At what age should clinicians start implementing Alcohol Screening and Brief Interventions in adolescents?
9 years old
Untreated heroin dependence during pregnancy increases the risk for what problems?
Fetal growth retardation
Abruptio placenta
Preterm labor
Fetal death
When rotating from another opioid, the methadone equianalgesic dose should be reduced by how much?
80-90%
Individuals who are “almost gay” or “almost straight” tend to have higher rates of substance abuse disorders than do pure homosexuals
True
Which medication can be used to treat opioid dependence and alcohol dependence simultaneously?
Naltrexone
What does the CIWA-Ar assess?
Alcohol withdrawal severity
True/false
PDMPs reduce opioid overdose deaths
False
Based on CFR-42, what is the status of methadone and buprenorphine with regard to listing in the ODMP
They are not listed
How should pregnant females on methadone or buprenorphine be managed?
Pregnant opioid addicted women maintained on methadone or buprenorphine should continue their dose and NOT taper due to high relapse rates. It is common to need dose increases with methadone, but NOT buprenorphine in the 2nd and 3rd trimesters. In HIV+ women, breast feeding is encouraged with either methadone or buprenorphine.
What are the differences between the “LOT” benzodiazepines and diazepam?
Diazepam has a longer half-life with active metabolites and is actively metabolized via microsomal oxidation. The LOT benzodiazepines are metabolized by glucuronidation conjugation which is more rapid with inactive metabolites.
How long can the disruption of sleep patterns persist following cessation of alcohol use?
18 months
Bipolar disorder is more likely to increase the risk of developing a substance abuse disorder during adolescence if it occurs during childhood rather than adolescence.
T or F
False
What type of hallucinations are associated with MDA and MDMA?
Auditory NOT visual
What is “telescoping”?
Rapid acceleration of use
What approach to treatment of amphetamine addiction has been supported by several clinical trials?
Agonist substitute with a stimulant plus naltrexone
What part of the brain is involved in chronic alcoholism or dependence?
Core of the NA
What are the relative contraindications for Antabuse?
CAD, active liver disease, hx of psychotic reaction, impaired renal function
T or F
Buprenorphine for opioid addiction is less effective than methadone for treatment retention m
True
What is “stacking”?
Using several types of anabolic steroids simultaneously
What is the mechanism of action of bupropion?
Reuptake inhibitor of dopamine in nucleus accumbens and of norepinephrine in locus ceruleus. Also acts as weak antagonist of alpha4 beta2 nicotinic receptors
What is the FDA drug schedule for anabolic steroids?
Schedule III
What is the difference in effect on the chloride channel between benzodiazepines and barbiturates?
Benzodiazepines increase the frequency of opening of the chloride channel while barbiturates increase the duration of opening.
What are the most frequently abused benzodiazepines?
Alprazolam> clonazepam> lorazepam > diazepam
Where do benzodiazepines and barbiturates bind on the GABA receptor?
Benzodiazepines bind at the alpha and gamma subunits while barbiturates bind only the alpha subunit.
What is the FDA drug schedule for anabolic steroids?
Schedule III
What is the difference in effect on the chloride channel between benzodiazepines and barbiturates?
Benzodiazepines increase the frequency of opening of the chloride channel while barbiturates increase the duration of opening.
What are the most frequently abused benzodiazepines?
Alprazolam> clonazepam> lorazepam > diazepam
Where do benzodiazepines and barbiturates bind on the GABA receptor?
Benzodiazepines bind at the alpha and gamma subunits while barbiturates bind only the alpha subunit.
What is the protocol for non-opioid treatment of opioid withdrawal?
Clonidine 0.2 mg 3x daily or lofexidine 0.2 mg BID for 10 days for heroin and 14 days for methadone.
What is the role for beta blockers in treatment of ETOH withdrawal?
Improvement in VS; reduction in craving
What percentage of women who use THC develop galactorrhea and what is the mechanism?
20% develop galactorrhea which results from THC causing decrease in prolactin.
What is the effect of THC on FSH?
No effect
Which hormones are inhibited by THC?
Prolactin, LH and GH
Smoke “ice” amphetamine causes euphoria that lasts how long?
12-24 hours
What is the “K hole”
State of helplessness and lack of coordination associated with ketamine intoxication
What is the effect of nicotine withdrawal on heart rate?
Bradycardia
What might be the effect of suddenly stopping opioids with regard to psychosis?
Opioids have antipsychotic properties and suddenly stopping them may precipitate psychosis.
What is the relative annual risk of death due to heroin addicts?
6-20 fold increase
What does the ASAM Patient Placement Criteria (PPC) strive to do?
Match patients according to fixed levels of care
What is contingency management therapy
An incentive based therapy that has been shown successful for initiating abstinence and preventing relapse. It uses a system of privileges and no drug reinforcers to counter and decrease behavior maintained by drug reinforcers.
Benzodiazepine metabolism is via which hepatic cytochrome enzymes?
CYP450 3A4
T or F
Barbiturates induce their own metabolism
True; this leads to tolerance
What is the effect of benzodiazepines on memory and learning?
Impaired learning and anterograde amnesia
What is the floppy baby syndrome?
Low Apgar, poor sucking, hypotonia, poor reflexes, apnea.
What is the half life of diazepam? What is the half life if it’s metabolite?
Diazepam half life = 28-54 hours
Metabolite half life = 30-100 hours
What pharmacokinetic property of benzodiazepines increase risk for abuse?
Rapidity of onset is associated with euphoria and higher addiction liability.
What is the effect of GHB on brain dopamine?
High concentrations of GHB inhibit dopamine release while low concentrations enhance dopamine release. This leads to the coma followed by sudden awakening phenomenon seen following GHB use
Which genes encode for the mu, kappa, and delta opioid receptors?
OPRM1, OPRK1, OPRD1 respectively
What are the genes that encode the endogenous opioid receptors?
POMC—–>beta endorphin
PENK1—->enkephalins
PDYN—–>dynorphins
What is the primary active metabolite of morphine?
Morphine-6-glucuronide (M6G)
How is hydromorphone (Dilaudid) excreted?
Renally
What is CRAFT?
Community Reinforcement and Family Training– used to encourage drinkers to enter therapy and reduce drinking by eliciting support of concerned significant others and to enhance satisfaction with life among members of the patient’s social network.
What does the Harrison Act dictate?
No prescribing of opioids for maintenance (other than methadone or buprenorphine)
What percent of substance use disorder patients in the U.S. receive residential treatment?
10%
The federal Anabolic Steroids Control Act of 2004 placed testosterone and related compounds in what DEA class?
III
What drug is taken by anabolic steroid users to ameliorate testicular atrophy?
HCG
What drug mitigates gynecomastia effects of AAS?
Tamoxifen
What % AAS users develop acne?
50%
What are “bath salts”?
Synthetic analogues of cathinone.
What is the “rate hypothesis”?
Those who use IV and smoked cocaine are more likely to become dependent related to the faster rate of drug delivery to the brain.
Amphetamine is a metabolite of what drug?
Methamphetamine
Why must stimulants be used cautiously with TCAs?
TCAs block reuptake of NE
What is the rim art cell type in the nucleus accumbens?
The GABA containing medium spiny neuron which receives direct synaptic contacts from both dopamine and glutamate inputs.
What are the 3 most popular constituents of bath salts?
Mephedrone
Methylone
MDPV (3,4 methylenedioxypyrovalerone)
What is the mechanism for mephedrone and methylone? MDPV??
Exert amphetamine-like actions on transporters for dopamine, NE and serotonin thereby stimulating nonexocytotic release of these neurotransmitters.
MDPV is structurally distinct from other cathinones and produces a cocaine-like blockade of transporters for D and NE.
What is the site of action of caffeine?
Adenosine receptor
What is mechanism of action of caffeine?
Caffeine is structurally similar to adenosine and acts as a competitive inhibitor at A1 and A2 thus producing effects opposite to those of adenosine.
What is the effect of smoking on caffeine half-life?
Smoking reduces caffeine half life by as much as 50%
Caffeine a half life is increased by oral contraceptives and in the later stages pregnancy
Has caffeine tolerance been demonstrated?
Yes, but complete tolerance does not occur at low daily doses. High daily doses produce “complete” tolerance only to some but not all effects: sleep disruption, diuresis, parotid gland salivation, inc metabolic rate, inc plasma NE and E and inc plasma renin activity.
What is the lethal dose of caffeine?
5-10 grams
What is the hallmark of caffeine withdrawal?
Headache
When is onset for caffeine withdrawal?
12-24 hours after last. Lasts 2-9 days.
What is the heritable link between caffeine use and smoking and ETOH?
28-41% of the heritable effects of caffeine are shared with ETOH and smoking
What is the association between caffeine consumption and Parkinson’s?
Increased consumption
—>reduced risk for Parkinson’s
Also reduced risk for T2 DM and chronic liver disease.
How does DSM-V consider caffeine use disorder
DSM-V considers caffeine use disorder as a “condition for further research”.
What is the primary cellular site of action of caffeine?
The adenosine receptor
What are the bio markers for nicotine use?
Blood, salivary, plasma cotinine;
Expired breath CO;
Blood CO-HgB;
Plasma or salivary thiocyanate
Smoking during pregnancy increases the RR of having a low birth weight infant by how much?
Two-fold
What must be monitored in pts being given naltrexone for alcoholism?
LFTs
When should acamprosate be used?
Reduces protracted withdrawal by targeting glutamate receptor.
Is disulfiram effective for relapse?
No
What is the triad of Wernikes encephalopathy?
Ocular disturbances–29% are nystagmus and lateral rectus palsy;
AMS;
Ataxia
What is Korsakoff’s syndrome?
Antegrade amnesia; and one of: -aphasia -apraxia -agnosia -deficit in executive function
How does National Institute on Alcohol Abuse and Alcoholism define heavy drinking?
Men: >4 drinks per day or >14 drinks per week
Women: >3 drinks/day or > 7 drinks per week
What is a standard drink?
12 oz beer;
5 oz wine;
1.5 oz 80 proof spirits
What medical complications are associated with heavy drinking?
Hypertension, increased risk of stroke, hypercoagulability, decreased cerebral blood flow
What % of the American public believes in God or a universal spirt?
95%
What are the five A’s for brief smoking cessation intervention?
Ask, Advise, Assess, Assist, Arrange
Which part of the brain is responsible for producing the drive mechanism to seek out drugs
Basolateral amygdala
Which law describes circumstances in which information about a substance abuse pts treatment may be disclosed and used with and w/ pt consent?
42 CFR Part 2
How long will alcohol metabolites EtG or ethyl sulfate be detectable in urine?
5-7 days
How do DTCs work?
They employ a series of incentives and sanctions to induce treatment compliance and lifestyle changes in criminal defendants
Participation in DTCs find most financial savings as a result of what phenomenon?
Decreased recidivism
Do the classic hallucinogens (LSD, DMT, psilocybin) induce either physical dependence or withdrawal?
No. Users very rarely meet most of the ICD-10 or DSM-V criteria for substance use disorder
What are the only clinically significant long term after effects due to hallucinogens?
Flashbacks-occurring in 1-10%
What is the primary site of action for hallucinogens?
5-HT2A receptor. Stimulation of this receptor leads to increased cortical glutamate levels.
Do the entactogens mediate thru the dopaminergic system?
The psychoactive effects of the entactogens are mediated by potent synaptic release as well as reuptake blockade of serotonin that in turn results in increased intrasynaptic serotonin levels.
What is the mode of action if Savinorin
Agonist at kappa opioid receptor.
What is the duration of action for the hallucinations and mood changes associated with salvinorin?
30 minutes to 2 hours; when smoked it can produce a rapid and intense hallucinatory effect of 10-15 min duration.
What hallucinogen with dissociative properties has been used as an anti-addiction drug?
Ibogaine
Where is the highest density of CB1 receptors?
Cerebellum, basal ganglia, hippocampus, cerebral cortex
Why is respiratory depression uncommon/unlikely in THC users?
CB1 receptors are in low density in brainstem
How do synthetic cannabinoids compare with cannabis?
5x greater affinity for CB1 receptor;
10x greater affinity for CB2 receptor;
2-3x more likely to cause sympathomimetic effects;
5x more likely to cause hallucinations
What drug acts as an anti-craving agent with regard to marijuana?
Lofexidine
What is the addictive potential of:
Tobacco
ETOH
Cocaine
Cannabis
Tobacco 67%
ETOH 23%
Cocaine 21%
Cannabis 9%
What is the difference between hallucinations due to marijuana and sczophrenia?
Cannabis: visual>auditory hallucinations
Szchophrenia: auditory>visual hallucinations
What concentration of THC can be achieved in butane hash oil (BHO)?
100%
What is nabiximols?
Generic name for an oral mucosal spray containing THC and cannabidiol-approved for use in Canada, the UK and Europe
What is the primary role for CB2 receptors?
CB2 receptors exist in the periphery and affect the immune system and immune responses.
What is the lifetime prevalence of substance use in the general population?
8-12%
Which drugs are more likely to be abused by psychiatrists?
Benzodiazepines
Cocaine use is highest amongst which medical specialty?
Emergency medicine
What is the most common illegal drug used by physicians in training?
Cannabis
What is the strongest predictor of substance use disorder in both the general population and the population of physicians?
Family hx
What is the typical period of drug monitoring for substance use disorders in physicians?
5 years
What has been the outcome of physicians who participate in PHPs with regard to abstinence?
Continuous abstinence in nearly 80% followed for 5 years or more
What is the equianalgesic dose of morphine of 0.4 mg buprenorphine?
0.4 mg buprenorphine = 10 mg morphine
What is the volume of distribution of ETOH?
Men: 0.68 L/ Kg
Women: 0.55 L/Kg
What is “proof” (re ETOH)
% by volume x 2
What is the mechanism for ETOH saliva testing?
Color change through a reaction involving alcohol dehydrogenase.
What are the usual urine bio markets for ETOH consumption?
Ethyl glucuronide and ethyl sulfate. Ethyl sulfate is more specific as bacteria in urine can alter EtG levels
Which amphetamine and methamphetamine isomers are available as Schedule II drugs and for what indications?
d-isomer; ADD, ADHD, narcolepsy, and learning disorders associated with FAS.
Will methylphenidate turn the urine test for amphetamine +?
Methylphenidate does not contain, and is not metabolized to, amphetamine or methamphetamine.
Compare length of cocaine withdrawal with methamphetamine withdrawal
Cocaine: 1-2 days
Meth: several days
If stimulant tx is withheld from adolescents with ADHD they have increased chance of developing what?
Stimulant addiction
What is Nabilone?
An analogue of dronabinol under brand name “Cesamet”. FDA approved as Schedule II in 2006.
What is Sativex?
Mouth spray for MS patients contains THC and cannabidiol, marketed in Canada and Europe.
What is the difference between Cannabis sativa and Cannabis indica?
Indica contains 5x more THC and 4x less THC
What % users of Cannabis experience intense anxiety and panic
20-30%
What is the past year usage of marijuana in the U.S.?
12%
What % of those who experiment with marijuana will become addicted?
9%. This goes up to 1 in 6 who begin as teenagers and 25-59% of those who smoke daily.
What are the ASAM criteria assessment dimensions?
1- Acute intoxication and/or withdrawal potential;
2- Biomedical conditions and complications;
3- Emotional, behavioral, or cognitive conditions;
4- Readiness to change;
5- Relapse, continued use, or continued problem potential;
6- Recovery environment
How many levels of care does ASAM conceptualize?
Five
What is the effect attributed to kudzu?
Kudzu has been shown to reduce beer consumption and increase the number of sips taken to finish a beer.
What has the effect of transcutaneous electrical acupoint stimulation been?
TEAS is effective in both detoxification and anti craving for opioid addiction
Which receptors are stimulated by the classic hallucinogens?
5HT2A agonists or partial agonists—->serotonergic
What is HPPD?
Hallucinogen persisting perception disorder– persisting flashbacks that are constant. Usually resolved within 1-2 years. Can be triggered by other substance use
What is the mechanism of dissociatives?
NMDA antagonists
Which screening tools for alcohol are validated for older adults?
MAST-G; (Michigan Alcohol Screening Test-geriatric)
SMAST; (Short MAST)
AUDIT (Alcohol Use Disorders Identification Test)
What are the side effects of carbamazepine (often used in pain management)?
Dizziness, hyponatremia, severe neutropenia, somnolence
What topical has shown promise for HIV related neuropathy pain?
8% topical capsaicin
What is the utility of network therapy?
Network therapy is for abusers who cannot set limits. CRAFT is a form of network therapy.
What is CRAFT?
Community Reinforcement and Family Training.
What is the “therapeutic community”?
The philosophical foundation of the modern TC is personal responsibility for one’s behavior and the belief that change is fully possible if the individual exerts the personal effort to follow the teachings of the program.
What is the typical duration of treatment in the therapeutic community?
12-18 months
What are the hallmarks of the Daytop TC model?
Self determination
Individual responsibility
Self change
What are the four categories of benzodiazepine discontinuation?
Symptom recurrence or relapse;
Rebound;
Pseudo withdrawal;
True withdrawal
When do benzo withdrawal symptoms peak?
Long acting benzos: onset 5 days, peak 1-9 days
Short acting benzos: onset 24 hours, peak 1-5 days
When using the tapering method for long term benzo users, how quickly should the dose be reduced?
Dose decreased should not exceed 5 mg of diazepam equivalents per week. This rate should be cut in half during the last 25% of the taper.
Can clonidine be used for benzo withdrawal?
No
Can buspirone be used to treat benzo withdrawal?
Buspirone is an anxiolytic that is not cross tolerant with other sedative-hypnotics and should not be used to treat benzo withdrawal.
What percent of college students report drinking daily?
4%
What % of college students meet criteria for an ETOH use disorder?
18-20%
T or F
For both college and high school males and females involvement in athletics is associated with more frequent ETOH drinking
T
Students in team sports report higher drinking and binge drinking rates than students in individual sports.
What are the risk factors for heavy drinking in college students?
Male gender;
Caucasian;
Involved in athletics;
Membership in Greek system
Which drug is considered a first line agent in the treatment of gambling disorder?
Naltrexone
What agent, acting via increasing glutamatergic tone in the NA may be helpful for gambling disorder by reducing reward-seeking behavior?
NAC
Which form of psychotherapy maybe useful in treating gambling disorder?
CBT
T or F
Suicidal ideation and attempts are common in gambling disorder and must be assessed at each clinical session.
T
What % of alcohol dependent patients relapse within 3 months of detoxification?
50%
What is the significance of a CIWA-R less than or equal to 9?
Suggests pharmacotherapy may not be required
What tool matches patients to an appropriate intensity of services for detoxification?
ASAM PPC-2R
What condition in heavy drinkers is associated with and may be causative of pancreatitis?
Hypertriglyceridemia
What is “holiday heart”?
Rhythm disturbances, particularly SVTs, can occur as a consequence of ETOH use or withdrawal.
What % of liver transplant recipients return to drinking?
22% in first year
Which electrolyte deficiency may be unmasked when dextrose is given to malnourished people with heavy ETOH use?
Severe hypophosphatemia. Must replete magnesium in order for correction
When do ETOH withdrawal symptoms begin?
6-48 hours after last drink
T or F
Injection drug users often have false positive RPR
True
Chronic skin infections in IVDAs may lead to ??
Amyloidosis and nephrotic syndrome
What is a common renal complication of injection drug use?
Nephropathy, primarily due to HIV infection
Chronic cognitive deficits can be seen in users of which drugs of abuse (other than ETOH)?
Cocaine
Sedatives (barbs)
Toluene
Polyarteritis nodosa has been associated with which drug of abuse?
Amphetamines
Osteomalacia from vitamin D deficiency has been associated with which drug of abuse?
Barbiturates
What is the primary manifestation of NAS?
Seizures;
Seizures;
Seizures;
Seizures
Which drugs of abuse have been associated with cleft lip/palate in neonates?
Benzodiazepines
Is coronary calcification correlated with incident coronary atherosclerosis in heavy ETOH users?
No
What is the neurobiology of toluene sniffing
Toluene significantly inhibits the N-Methyl-D-aspartic acid (NMDA) subtype of glutamate-activated ion channels.
What is the incidence of acute MI in pts presenting with cocaine associated chest pain?
0.7%-6%
What form of cardiac hypertrophy is common in methamphetamine users?
Concentric hypertrophy
What are the purported effects in atherogenesis of CB1 versus CB2 stimulation?
CB1 is proatherogenic; CB2 is antiatherogenic.
What role does nutritional status play in the development of alcohol related cardiomyopathy?
Development of cardiomyopathy is independent if nutritional status
Who is at greatest risk for alcohol related liver disease; men or women?
Women
How much alcohol does one have to drink to develop cirrhosis?
Reversible fatty liver at be observed after a single heavy drinking episode but progression to more advanced liver disease usually requires regular intake of more than 40 g/day for >10 years.
Which of the alcohol drug therapies is safe to use in the face of alcohol related liver disease?
Acamprosate does not accumulate in severe liver disease;
Disulfiram is contraindicated in ALD due to hepatotoxicity;
Naltrexone is associated with dose dependent hepatotoxicity (usually at supra therapeutic doses of 399 mg/ day or more )
Which drug may reduce mortality in alcoholic hepatitis?
Pentoxifylline (especially those with hepato
What % of liver transplant recipients transplanted for ALD resume drinking?
30-50%
What is the mot common means if transmission of hepatitis B world wide
Mother-to-child
Is methadone maintenance an absolute contraindication to liver transplantation?
No
What is heroin nephropathy?
A secondary cause of focal and segmental glomerulosclerosis often assoc with hypertension and progression to ESRD
What is the mechanism producing acidosis in toluene intoxication?
Increased production of hippuric acid
What percentage of pancreatitis cases are due to ETOH?
39% only. ETOH is the most common etiology in men (59%) but only 28% in women.
What type of carcinogen is ETOH
ETOH is not a complete carcinogen; it is a co-carcinigen
What is the most common cause of non-anion gap acidosis in alcoholics?
Diarrhea
Use of which drug may result in the development of polyarteritis nodosa?
Amphetamines
What are the most common bacterial contaminants of illicit drugs?
Bacillus and Clostridium sp
What is “crack lung”?
A self-limited eosinophilic hypersensitivity pneumonitis
What % of cocaine U.S. Is contaminated with levamisole?
70%
What has levamisole contaminated cocaine caused?
Anti-neutrophil cytoplasmic antibody mediated vasculitis.
What effects do amphetamines have in the immune system?
Decrease CD4 and increase in immunosuppressive cytokines
What is hepato-pulmonary syndrome?
Affects 15-30% pts with cirrhosis. Consists of portal hypertension, intrapulmonary microvascular vasodilation, and increased A-A gradient with hypoxia in pts with cirrhosis. Liver transplant reverses HPS.
Opioid related pulmonary vein construction and increased pulmonary capillary permeability with resultant pulmonary edema and broncho- construction are due to what opioid effect?
Histamine release
What pulmonary effect has been associated with intra-nasal heroin use?
Hypersensitivity pneumonitis
What metabolic derangement is common in alcoholics with cirrhosis?
Chronic respiratory alkalosis. May be due to the respiratory stimulant effect of poorly cleared progesterone and estradiol on the CNS.
What percent of cirrhotics will have hepato-pulmonary syndrome?
15-30%
What effect does rifampin have on methadone levels?
Reduces methadone levels!
What is the leading cause of death in cirrhosis?
Infection
What is the effect on methadone blood levels of protease inhibitors?
Significant decrease in blood levels
What is the effect of atazanavir on buorenorphine levels?
Increase in buprenorphine levels with concomitant sedation or change in mental status.
Which HIV drugs decrease methadone blood levels?
Ritonavir Nelfinavir Lopinavir Nevirapine Efavirenz
Which HIV drugs have their blood levels decreased by methadone?
Stavudine
Didanosine
What is the effect of HAART in buprenorphine levels?
No effect
A pattern of sleep related, irregular respirations associated with chronic opioid therapy is know as what?
Ataxic breathing or Biot respirations
What is the mode of action for caffeine?
Blocks adenosine at A1 and A2A
What do stimulants do o sleep latency
Increase sleep latency
What is normal “sleep need”?
3-10 hrs per 24 hours
What percent of fatal car crashes involve ETOH? Cocaine?
30%; 25%
What is the so-called “spectrum of alcohol use”?
At risk drinkers: 14 or more per wk or 4 or more in a given day for men 7/wk, 3/day women
harmful drinkers:
dependent drinkers
Conventional screening systems such as CAGE, TWEAK and AUDIT do not identify which level of drinking behavior?
At risk drinkers
What are the six (6) elements of the brief intervention?
"FRAMES" Feedback; Responsibility; Advice; Menu of strategies; Empathy; Self-efficacy
What is the incidence of substance abuse during pregnancy?
ETOH: 9.4%
MJ: 9-15%
Opioids: 2%
Cocaine: 1-10%
How should methadone dose be adjusted in 3rd trimester?
Must be increased due to larger maternal plasma volume, decrease plasma protein binding, increased tissue binding, increased methadone metabolism, increased maternal methadone clearance.
What is the most common ill effect of opioid abuse in pregnancy?
IUGR
What are the effects on the children of women prescribed opioids for treatment of pain with steady-state concentrations of opioids?
No increase in pregnancy complications;deliver normal weight/length infants.
Is cannabis teratogenic?
No
What is the utility of disulfiram during pregnancy?
Contraindicated
What is the incidence of pre-term labor associated with opioid use? Cocaine use?
29-41%; 6%
Maternal tobacco use is linked to what disorder?
SIDS
What percent of AA members are female
35%
What characteristics are predictive of AA affiliation?
Male gender; More serious alcohol problems; Greater commitment to abstinence; More social support to stop drinking; Stress and LACK of support from significant other; Fewer psychological problems; More avoidant coping style
What therapies did Project Match assess?
12 Step facilitation (TSF);
Motivational enhancement therapy (MET);
Cognitive behavioral therapy (CBT)
What is the mechanism for opioid related reward?
One critical step in opioids producing reward is by binding GABA-ergic inter neurons to disinhibit dopamine production in the limbus reward system.
What brain regions are activated by erotic visual stimuli?
Right insulation and claustrum (somatosensory processing and penile erection;
Hypothalamus and striatum (areas of D transmission);
Anterior cingulate gyrus (repetitive behavior)
Among men who have sex with men what psych comorbidity is common?
Depression
What pharmacotherapy has been proposed for sexual addiction?
SSRIs
What is the lifetime estimate for some form of disordered gambling?
5.45%
What % of disordered gamblers are women?
32%. Also disordered gambling seems to progress more quickly to a pathological state in woman than in men- a phenomenon known as telescoping.
How do brief interventions differ from traditional treatments?
Traditional treatments aim for abstinence while BI simply aims for harm reduction
What is the T-ACE screen?
Screen for women of child bearing age based on CAGE questions:
T (Tolerance): how many drinks does it take to make you feel high?
A
C
E
A score of 2 or more is pos. T= 2 points
What is the TWEAK screening assessment?
Screen for women of child bearing age. T (tolerance) W (worry) E (eye opener) A (amnesia) K (kut down)
W and T are both 2 points. Positive assessment is 2 points!
What is the ADAPT program?
This is the U.S. Air Forces program; Alcohol and Drug Abuse Prevention.
What is the ASAP program?
This is the U.S. army’s program; Army Substance Abuse Program.
What is the SARP program
This is the U.S. Navy program; Substance Abuse Rehabilitation Programs
What is SACC program?
This is the Marine Corps program; Substance Abuse Counseling Centers
What tool does the military employ as part of its Pre Deployment Health Assessment?
AUDIT-C (Alcohol Use Disorders Identification Test-C
What % of veterans of Afghanistan/Iraq with PTSD have comorbidity SUD?
20%
Which commonly used drug is most likely to be missed on oral fluid tests?
Marijuana due to the fact that it is present at lower concentrations than other drugs of abuse
What alternative treating matrix is most closely correlated with blood testing?
Oral fluid as it is in equilibrium with blood
What period of time can oral fluid testing identify drug use?
12-24 hours
What test represents the highest analytical standard for drug testing?
LC-MS/MS
Which is more common regarding on site testing; false positives or false negatives?
False negatives are more common
What is the time delay for drugs to appear in hair that is long enough to snip off at the scalp?
One week
How long a period does the typical 1.5 inch hair specimen cover?
90 days
Which drug of abuse accumulates in hair at very low concentrations thus making repeated use necessary for adequate detection in hair
Cannabis
Is there a difference in accumulation of drugs in AA hair versus Caucasian hair?
No
Which form of drug testing is prospective as opposed to retrospective?
Sweat testing
How long can ethyl sulfate or EtG, ETOH metabolites be found in urine?
5-7 days
What are common confounders ( false positive ) for EtG in urine
Alcohol containing hand sanitizer or mouthwash
Why is naloxone included in the sublingual firm of buprenorphine (suboxone)?
Because naloxone is poorly absorbed orally and its presence discourages IV use.
What is Actiq?
The lozenge form of fentanyl
The use of Visine eye drops into urine can cause a false negative result for what drug of abuse?
THC. The benzalkonium chloride and borate buffer interfere with the immunoassay.
What are the three components of informed consent?
Knowledge
Competency
Voluntary acceptance
At what age is it usually deemed that adolescents have the ability to understand informed consent?
14 years of age
What is “Part 2”?
Describes the circumstances in which information about a substance abuse patient’s treatment may be disclosed and used with and w/o the patients consent
Who falls under 42 CFR Part 2?
Any individual or entity that is Federally assisted and holds itself out as providing alcohol or drug abuse diagnosis, treatment or referral for treatment. Practitioners holding DEA license would fall under this.
Is inhalant withdrawal recognized in DSM-V?
No
What is the most likely neurobiology at play for inhalants?
GABA enhancement; NMDA antagonism
What is the difference in neurobiology between hallucinogens and dissociatives?
Hallucinogens affect 5-HT2A receptors and dissociatives affect NMDA receptors
What are the typical dissociatives?
PCP Ketamine Dizocilpine (MK801) Dextromethorphan Nitrous oxide
What is the mode of action of nitrous oxide?
NMDA antagonism
PCP effects model the symptoms of which mental disorder?
Schizophrenia
What is the metabolism of Dextromethorphan?
DXM is metabolized to dextrorphan which is an NMDA antagonist
What genetic polymorphism is involved in the metabolism of DXM?
Rapid metabolizers have a plasma half life of about 3.4 hours; slow metabolizers (10-15% of the population) have half lives exceeding 24 hours.
Increased serum levels of brain-derived neurotrophic factor are found in chronic users of which dissociative agent?
Ketamine
How does dextrorphan (DXO) differ from Dextromethorphan (DXM)?
DXO is a stronger NMDA antagonist and is relatively inactive at mu, kappa and delta opioid receptors.
DXM abuse may be associated with deficiency of what co-vitamin?
Folate
What potential effect of ketamine has shown promise in psychiatry?
Anti-depression
Why is it that nitrous oxide should be described as a dissociative agent
In low anesthetic concentrations it produces dissociative effects and it produces “Olney” retrosplenial cortex lesions
The use of which hallucinogen has been successful in treating PTSD?
MDMA
Which hallucinogen is considered the sacrament for the Native American Church in the U.S. and Canada?
Peyote cactus (containing mescaline)
What is the most widely used hallucinogenic drug?
LSD
What is the active metabolite of psilocybin?
Psilocin; thus psilocybin is really a pro-drug
What is the phenomenon known as kindling?
KINDLING due to substance withdrawal refers to the neurological condition which results from repeated withdrawal episodes from sedative hypnotic drugs such as alcohol or benzodiazepines. Each withdrawal leads to more severe withdrawal symptoms than the previous withdrawal syndrome. Individuals who have had more withdrawal episodes are at increased risk of very severe withdrawal symptoms up to and including seizures.
According to USPSTF for which entities is there insufficient evidence to recommend routine use of SBI?
Alcohol misuse among children and adolescents and for illicit and prescription based drug misuse. However NIAAA and NIDA do endorse SBI for these interventions.
What are the 5-As of SBI?
Ask (screen and assess risk) Advise Assess (readiness) Assist Arrange
What are the NIAAA maximum drinking limits for adults?
Healthy men = 65 yo —–4/day, 65 yo:
What is the withdrawal syndrome associated with Salvinorin?
There is no addiction or withdrawal syndrome associated with Salvinorum
Serious complications have been reported when MDMA is combined with which drugs?
Anti-retrovirals
What is the primary site of action for the indolealkylamine and phenylalkylamine hallucinogens?
5-HT2A receptor
What are the enactogenic phenylalkylamines?
MDA
MDMA
MDE
LSD has been proposed in the treatment of what neurological disorder?
Cluster headache
What is the most widely used hallucinogen?
LSD
How long do the psychological effects of LSD last?
6-12 hours
What is the most consistent neurological finding associated with LSD use?
Hyper-reflexia
Which hallucinogen does not induce tolerance in humans?
DMT
What are the constituents of ayahuasca?
DMT plus an MAO inhibitor
What is the typical dose of acamprosate?
Two, 333 mg tabs, 3X per day
What are the “numbers to treat” data with regard to acamprosate or naltrexone treated patients returning to any drinking?
12; 20
What is the NTT for naltrexone prevention of return to heavy drinking?
12
In head to head trials how does acamprosate compare with naltrexone?
No statistical difference re improvement in ETOH consumption.
Which meds, used “off label” show efficacy in improving some consumption outcomes?
Moderate support for topiramate and nalmefene;
Limited evidence for valproic acid
Are health outcomes improved with medications for AUDs?
Insufficient direct evidence
What is the endogenous precursor of testosterone, estrogen and progesterone?
DHEA (dehydroepiandrosterine)
What is the mode of action of Stadol (butorphanol)?
Kappa partial agonist/Mu antagonist
What is the mode of action of Nubain (nalbuphine)?
Kappa agonist/ Mu antagonist
What is the incidence of acne in users if anabolic-androgen steroids (AAS)?
50%
What is “stacking”?
“Stacking” is the use of combinations of multiple drugs at the same time
What is “cycling”?
“cycling” is the use of steroid combinations for weeks to months with abstinent rest periods before resumption of a different steroid or steroid combination in order to “avoid tolerance”
What is “pyramiding”?
“pyramiding” involved starting with a low dose and gradually increasing the dose until peak levels are achieved a number of weeks before a competition and then tapering so the urine will be drug free when tested.
What % of AAS users experience testicular atrophy?
45%
What % AAS users experience gynecomastia?
50%
What ocular thromboembolic disease may occur in AAS users?
Branch retinal vein occlusion
How is AAS use disorder coded under DSM-V?
“Other substance use disorder”
Is methamphetamine legally available in the US?
Yes. Desoxyn
What is Frotteurism?
Frotteurism is a paraphilic interest in rubbing against a non-consenting person for sexual pleasure.
What is the metabolism of ETOH?
ETOH–>Acetaldehyde–>Acetate
ETOH is broken down in the liver by alcohol dehydrogenase to Acetaldehyde which is then converted by Acetaldehyde dehydrogenase to harmless acetic acid. Disulfiram blocks Acetaldehyde dehydrogenase
Does disulfiram reduce craving for ETOH
No.
What are the 6 elements of FRAMES?
Feedback Responsibility Advice Menu of strategies Empathy Self-efficacy
What is FRAMES?
FRAMES captures the essence of the interventions commonly tested under the terms brief intervention and motivational interviewing
What are the CRAFFT questions?
1-Have you ever ridden in a CAR with someone including yourself who was high or has been using ETOH or drugs?
2-Do you ever use drugs or ETOH to RELAX?
3-Do you ever use drugs or ETOH while ALONE
4-Do you ever FORGET things you did?
5-Have your FAMILY or FRIENDS said you should cut down?
6-Gotten into TROUBLE using drugs or alcohol?
How is the CRAFFT screen scored?
1 point for each positive response. A score of 2 indicates a high risk for having a drug or alcohol disorder.
What is the mechanism of action of Rimonabant?
Rimonabant is a selective blocker of the CB1 cannabinoid receptor. Developed as an anorectic anti-obesity drug. Withdrawn from market due to psych side effects.
What will change from DSM IV to DSM V for substance use disorders as a plus for diagnosing adolescents?
The distinction between drug abuse and dependence is dropped.
Which GABA receptor subunits mediate the sedative hypnotic effects of benzodiazepines?
Alpha 1
The use of which drug has efficacy to treat cocaine addiction supported by more than one controlled clinical trial?
Disulfiram
When does tolerance to LSD effects occur in daily users?
3-4 days
What is the rate of significant GI problems as a result of prostaglandin therapy?
10%
Safrole is a precursor for the manufacture of what drug of abuse?
MDMA
What % of the US population have used marijuana?
43%
What % of Americans favor marijuana legalization?
58%
If a patient is medically stable but suffers from both an addiction disorder and an eating disorder, which should be treated first?
The addition disorder should be treated first.
What is a hematological side effect of pregabalin?
Thrombocytopenia
T or F
Family therapy is the most effective treatment for substance use disorder in adolescents
True
What is the risk for smoking based on genetics?
60%
The Alcohol Use Disorders Identification Test (AUDIT) is a well validated screen including which parameters?
Quantity of ETOH use
Frequently of use
Binge drinking
Consequences of drinking
But NOT reasons for drinking
What maternal and fetal morbidities have been associated with methamphetamine use in pregnancy?
Gestational hypertension Pre-eclampsia Intra-uterine fetal death Abruptio placenta Pre-term birth Neonatal death Infant death
What is the time course for methamphetamine withdrawal?
Two phases:
Phase 1 lasts 7-10 days
Phase 2 lasts additional 2 weeks
Characterized by increase in sleeping and appetite with an early cluster of depression symptoms including fatigue, anhedonia, and dysphoria.
Define “binge drinking”
5 or more drinks on the same occasion
What group has the highest rate of binge drinking?
American Indians and Alaska Natives (30.2%)
What is the Synar Amendment
The Synar Amendment to the Alcohol Drug Abuse and Mental Health Administration Act of 1992 requires states to enact and enforce laws prohibiting the sale or distribution of tobacco products to anyone under the age of 18.
Does methadone have an active metabolite?
No
What does PDMP stand for?
Prescription Drug Monitoring Program
Which screening tool is helpful for primary care screening where time is limited?
AUDIT-C.
The military also uses AUDIT-C as part of their pre-deployment screening.
What is MAST-G and SMAST-G
Michigan Alcoholism Screening Test-Geriatric (and Short, or SMAST). These were developed specifically for older adults. MAST-G was the first major elderly-specific alcoholism
screen with items unique to older problem drinkers.
MAST-G has 24 items
SMAST-G has 10 items
What are the rates of co-occurring psychiatric illnesses in older adults with substance use disorders?
21-66%
What is a standard drink?
12 oz beer
1.5 oz distilled spirits
5 oz wine
4 oz sherry or liquor
How does substance abuse treatment differ in older persons versus younger?
Better outcomes;
More likely to complete treatment;
What is the NIAAA recommendation regarding ETOH consumption for those over age 65?
No more than one standard drink per day; no more than 7 per week.
Older males should not consume more than 4 standard drinks on any drinking day.
How is “at risk drinking” defined for persons older than 65?
More than 1 drink per day or 7 per week
What was the MOTHER project?
Maternal Opioid Treatment: Human Experimental Research project/ a multi-center randomized controlled trial comparing Buprenorphine with methadone for the treatment of opioid dependent pregnant patients
What effect does tobacco smoking have on inflammatory bowel disease?
Smoking increases the risk for Chrons but decrease the risk for, and severity of, UC.
Bath salt ingestion has been associated with what effect on uric acid?
Hyperuricemia
Polyarteritis nodosa has been associated with Hepatitis B infection and which drug of abuse?
Amphetamines
What test confirms thiamine deficiency?
Erythrocyte transketolase
Meconium drug screening/testing reflects maternal drug use from what time frame?
2nd trimester forward
What is the mortality associated with DTs?
15%
What is CIWA-Ar?
Clinical Institute Withdrawal Assessment of Alcohol, Revised.
1- Nausea/Vomiting: 0-7 2- Tremors: 0-7 3- Anxiety: 0-7 4- Agitation: 0-7 5- Paroxysmal sweating 6- Orientation/AMS 7- Tactile disturbances 8- Auditory disturbances 9- Visual 10- Headache
15 severe
Which isoenzynes mediates conversation of codeine to morphine?
2D6
Which region of the brain mediates withdrawal?
Locus ceruleus
Describe Tramadol
Tramadol is a pro-drug that must be converted to the M1 metabolite. It’s a weak mu. Increases serotonin release and thus possible serotonin syndrome. Causes seizures both in taking and in withdrawal.
What is the half life of methadone?
24-100 hours
How long for methadone to reach steady state?
4-5 days
What is the minimal desirable blood level for methadone?
200 ng/mL
Where is buprenorphine derived from?
Thebaine
What is the mechanism of action of clonidine in the treatment of opioid withdrawal?
Clonidine acts in the locus ceruleus to decrease NE; thus decreases autonomia. But does not do much for myalgias/arthralgias
Compare naltrexone to naloxone
Naltrexone has a longer half-life (av= 4 hrs); Active metabolite (6 beta-naltrexol, mean half life= 13 hours); Greater affinity for kappa receptor.
50 mg naltrexone will block the pharmacological effects of 25 mg IV heroin for up to 24 hrs
Name 2 alpha adrenergic non-opioid agonists used to treat autonomic symptoms during opioid withdrawal.
Clonidine; lofexidine
Lofexidine has less hypotension than does clonidine.
What is the dose of clonidine to treat symptoms of nor-adrenergic hyperactivity?
0.1 to 0.2 mg clonidine every 4 hours, up to 1.2 mg per 24 hrs with careful BP monitoring
Why has LAAM been withdrawn?
Torsades de pointe
What is the ratio of buprenorphine to naloxone in Suboxone?
4:1
How is methadone metabolized?
Hepatic via CYP 450 3A4 enzymes
What are the two most studied and best characterized endocannabinoids?
Anandamide and 2-arachidonalglycerol (2-AG)
Which endogenous neurotransmitters are affected by benzodiazepines and GHB
Benzodiazepines—>GABA A
GHB—–> GABA B
What is the volume of distribution for nicotine?
180 L
What is the half-life of nicotine?
2 hours
What is the metabolism of nicotine?
Metabolized to cotinine in brain, liver and lung via CYP 2A6.
Chinese have slower CYP 2A6 alleles.
Which gender metabolizes nicotine faster?
Female
What are the bio markers for nicotine replacement modalities?
Anabasine, anatabine
How long does plasma cotinine persist?
Up to 7 days
What cotinine level indicates smoking?
> 14 ng/mL;
100 ng/mL indicates 1/2 pack per day use
What CO level indicates smoking within past 8-12 hours?
10 ppm CO
Smoking accelerates metabolism of drugs metabolized by which CYP?
1A2
What characterizes nicotine withdrawal?
Craving, irritability, anger, anxiety, depression, difficulty concentrating, restlessness, increased appetite. Symptoms reach max intensity 24-48 hrs after cessation.
Which nicotine receptors are responsible for dependence?
Alpha-4 beta-2
What mediates nicotine withdrawal?
Alpha-5 containing nAChRs in the habenula produce nicotine’s aversive effects and the somatic symptoms of withdrawal.
What are the pregnancy related smoking risks?
Double the risk for LBW infant;
30% inc risk for spontaneous abortion and peri and neonatal mortality.
The effect of smoking in LBW is influenced by the metabolic genes CYP 1A1 and GSTT1.
What is the half life of cotinine?
18-30 hours and reflects exposure over 2-3 days
Which marker can distinguish abstinent tobacco users who are using NRT from those still using tobacco?
Anabasine
What is the mechanism of action of varenicline?
Partial agonist/antagonist that selectively binds to the alpha-4 beta- nicotinic acetylcholine receptor.
It acts to block both nicotine from binding to the receptor (antagonist effect) and stimulate (agonist effect) receptor mediated activity leading to the release of dopamine which reduces craving and nicotine withdrawal symptoms.
What are the most frequent adverse effects of varenicline?
Nausea; vivid dreams Neuropsychiatric effects (suicidal thoughts and aggressive or erratic behavior)
What is the only absolute contraindication to varenicline?
Allergy
What is the effect of adding pharmacotherapy to a behavioral intervention in smoking cessation?
Doubles abstinence rates
What are the drug-drug interactions between varenicline and bupropion for smoking cessation?
There are none as they have different mechanisms of action
Which is more efficacious;bupropion or varenicline?
Varenicline is but it is not superior to NRT
What are the adverse effects of topiramate used for alcohol use disorder?
Parenthesis, taste perversion, anorexia, difficulty with concentration/attention, nervousness, dizziness, pruritus, psychomotor slowing, weight loss
Which medications show the best results in alcohol use disorder?
Acamprosate and naltrexone but neither is superior
What is the availability of injectable naltrexone and acamprosate in the VA system?
These are non-formulary for the VA system
What are the averse effects of acamprosate?
Anxiety, diarrhea, vomiting
What are the adverse effects of naltrexone?
Dizziness, nausea, vomiting
