2-18 Drug Tolerance / Abuse / Dependence Flashcards
What are the top 3 ILLICT drugs used among persons 12 and older?
Marijuana
Psychotherapeutics
Cocaine
Name 7 categories of drugs of abuse (and provide some examples):
Which drug is the most addictive?
Psychomotor stimulants (cocaine, amphetamines)
Opiates and Opioids (heroin-MOST ADDICTIVE, morphine, codeine, oxycodone, hydromorphine)
Cannabinoids (marijuana)
Alcohol
Sedatives (barbiturates, benzodiazepines)
Nicotine
Hallucinogens (LSD, mescaline “club drugs”
DSM-V criteria for Substance Use Disorder include the following symptoms (7), within ______ (#) months:
Which symptom is the marker of physiological dependence?
How many symptoms would indicate…
“Mild” substance use disorder?
“Moderate” substance use disorder?
“Severe” substance use disorder?
DSM-V criteria for Substance Use Disorder include the following symptoms, within 12 months:
Tolerance
Withdrawl *marker for physiological dependence*
Use of larger amounts than intended
Persistent desire, inability to control use
Excessive time spent obtaining, using and recovering
Normal activities given up or reduced
Use despite knowledge of problem drugs cause, unable to cut back
How many symptoms would indicate…
“Mild” substance use disorder? 2-3
“Moderate” substance use disorder? 4-5
“Severe” substance use disorder? 5+
When do WITHDRAWAL signs and symptoms emerge?
Can signs/sx be reversed? If so, how?
When do WITHDRAWAL signs and symptoms emerge?
When use of the drug is stopped
Can signs/sx be reversed?
Yes, reversed when drug is administered again
What are the two ways to define drug tolerance?
Drug tolerance:
Decreased effect with repeated use of the drug (effect vs duration of use graph)
Need to use more drug to have the same effect (RIGHT shift in dose-effect curve)
The _____________ system is the major target of addictive drugs,
it originates in ____ (location) and projects to nucleus _____, and _____, _____ (two other areas in the brain).
Which pathway is activated by all drugs of dependence?
Activation of this pathway results in the release of
____ [neurotransmitter]?
The MESOLIMBIC DOPAMINE SYSTEM is the major target of addictive drugs,
it originates in VENTRAL TEGMENTAL AREA (VTA) and projects to NUCLEUS ACCUMBENS and AMYGDALA and PREFRONTAL CORTEX
Which pathway is activated by all drugs of dependence?
VTA-NUCLEUS ACCUMBENS PATHWAY
Activation of this pathway results in the release of
DOPAMINE
What inhibitory interneurons act on dopaminergic neurons in the VTA?
GABA-ergic inhibitory interneurons
What are the two different ways in which an individual could experience withdrawal?
- due to natural decay of drug/agonist half-life (agonist is out of circulation and no longer stimulating its specific receptors)
- presence of an antagonist with a higher affinity for the same receptor as the drug
Cocaine is derived from _____ plant cultivated in South America
Historically, it has been used as a powerful CNS stimulant and appetite suppressant, and now used for what type of surgery?
Cocaine is derived from Erythxylon cocoa plant cultivated in South America
Historically, it has been used as a powerful CNS stimulant and appetite suppressant, and now used for what type of surgery? nasal and lacrimal duct surgery
Cocaine MOA:
Cocaine works by _____ [stimulating/inhibiting] the action of ________ transporters at the ___[pre/post] synaptic terminal, which leads to what type of neurotransmitter change within the synaptic cleft?
Cocaine works by INHIBITING the action of DOPAMINE TRANSPORTERS at the PRESYNAPTIC terminal –> INCREASE of DOPAMINE within the cleft (mostly @ nucleus accumbens)
Amphetamines are synthetic _________
MOA: AMPHETAMINES work by _____ [stimulating/inhibiting] the action of ________ transporters inside the ___[pre/post] synaptic terminal. This [increases/decreases] the free levels of _____ (neurotransmitter).
What subsequent change does this cause (think of other transporters..)
Amphetamines are SYNTHETIC PHENYLETHYLAMINE
MOA: AMPHETAMINES work by INHIBITING the action of VESICULAR MONOAMINE TRANSPORTER 2 (VMAT2) inside the PRE-SYNAPTIC TERMINAL. This INCREASES the free levels of cytoplasmic DOPAMINE by preventing filling of the synaptic vesicles –> reversal of DAT direction and INCREASE of DOPAMINE concentration within the synpaic cleft.
Cocaine and amphetamine mimicks what types of behavioral and physiological effects of our nervous system?
What are the acute effects of psychostimulants (11)?
Cocaine and amphetamine mimicks what types of behavioral and physiological effects of our nervous system?
sympathomimetic, mimicking the effects of the sympathetic nervous system
Acute effects of psychostimulants:
Rush (orgasmic)
Euphoria / arousal (feeling of well-being)
INC energy
Feelings of competency
DEC feelings of fatigue/boredom
DEC appetite
INC heart rate
INC blood pressure
INC temperature
INC bronchodilation
INC pupillary dilation
Pharmacokinetics of Cocaine:
What does onset, magnitude/potency and duration depend on?
If I was a coke addict and wanted to get my cocaine peak levels within 15 seconds, what should be my route of choice?
Half-life:
Acute effects last less than ____ minutes
How does do these parameters contribute to its use?
Pharmacokinetics of Cocaine:
RAPIDLY ABSORBED IN THE BRAIN & SHORT-ACTING
What does onset, magnitude/potency and duration depend on?
ROUTE OF ADMINISTRATION
If I was a coke addict and wanted to get my cocaine peak levels within 15 seconds, what should be my route of choice?
TAKEN IV OR SMOKED
Half-life: 40-80 minutes –> req. repeated administration
Acute effects last less than 30 minutes –> binge use!
Where and how is cocaine metabolized?
[name the enzyme/s and any metabolites, are they active?]
If someone wanted to monitor/check if I have consumed cocaine, how can it be monitored and what tests could be done? ..what is being measured?
What if I am trying to avoid someone finding out I’ve used cocaine- how long will it remain detectable?
Metabolism of cocaine: Cocaine is metabolized in the LIVER by cholinesterases into benzoylecgonin (inactive compound) and ecgonine methy ester
MONITORED:
biological fluids (saliva, blood, urine, milk) and hair.
MEASURED:
Urine test measures benzoylecgnonine, remains detectable 36 hours - 8 days.
cocaine metabolites could also be measured in saliva, hair and breast milk
I get real crazy after a long night studying psych, and go to the club. I snort some cocaine and have some drankks…
How does cocaine in the presence of ethanol change?
How does this change the effects of cocaine (3)?
How does cocaine in the presence of ethanol change?
Cocaine in the presence of ethanol is TRANSESTRIFIED -into cocaethylene
How does this change the effects of cocaine (3)?
INC euphoria and longer duration of action than cocaine alone
Cocaethylene is MORE CARDIOTOXIC than cocaine alone, could lead to cardiac arrest
Long term use of psychostimulants could result in (5):
Sensitization OR tolerance
Impairment of neurocognitive functions (visuomotor performance, attention, verbal memory)
Increased risk of developing rare autoimmune or connective tissue dieases such as lupus, Goodpasture’s syndrome, Stevens-Johnsons Syndrome
INC risk of infections (viral heptatitis, HIV)
controversial: physical dependence
What are signs and symptoms of psychostimulant overdose? (12)
Which one of the signs/sx is the culprit that can be fatal in case of overdose?
Hyperactivity
Sweating
Dilated pupils
Agitation/tremor
Tachycardia/chest pain
*CARDIAC ARRYTHMIAS*
Hypertension
Hyperpyrexia
Stereotypical behavior such as pacing, nail-biting
Seizures / coma
Paranoia / tactile hallucinations
Confusion
(other: chills, N/V, wt loss, muscle weakness)
Death can occur due to cardiac arrythmias! (Also, secondary to MI, cerebrovascular accident, seizures or respiratory depression)
When does withdrawal to psychostimulants occur?
What are sign/sx someone is experiencing psychostimulant withdrawl? (11)
Withdrawl peaks at 2-4 days
Anxiety
Agitaiton
Insomnia / hypersomnia
Nightmares
Fatigue
Depression
Headaches
Sweating (note- also a sx of overdose!)
Muscle cramps
Hunger / cravings
Erectile dysfunction
Detection of use (3 big categories)-
Signs/symtoms and urine tests are two ways to detect cocaine use, what are some (6) indirect indicators of cocaine use?
Detection of Use:
- Observe for signs and symptoms
- Urine tests (2-4 days..so annoyed)
* (recall: measures cocaine metabolite benzoylecgnonine)*
3. Indirect indicators - AIDS, hepatitits, track marks, abscesses, bacterial endocarditis, chronic respiratory symptoms
SHORT TERM treatment of Cocaine withdrawal:
What are 2 treatments that can be used for acute withdrawal?
- MOA*
- what would be the benefit of using one over the other*
Bromocriptine - dopamine agonist
ameliorates dopamine deficiency state of cocaine withdrawal
Benzodiazepines (lorazepam) - enhances effects of GABA
in patients with severe agitation and sleep disturbance
LONG TERM treatment of cocaine withdrawal:
Is there effective treatment for long-term addiction?
No FDA approved pharmacological therapies
Cognitive-behavior therapies could be tried…
two components:
- Functional analysis - identify patient’s thoughts, feelings and circumstances before and after the cocaine use to udnerstand reson for using cocaine
- Skills training - help cocaine users cope with intrapersonal and interpersonal problems
Opium is derived from extracts of juice of the opium poppy _____
Examples (2) of opiods derived directly from opium
Example of a (2) semi-synthetic opioid
Example of (1) synthetic opioid
Opium is derived from extracts of juice of the opium poppy PAPAVER SOMNIFERUM
Examples (2) of opiods derived directly from opium:
Morphine and codeine
Example of a (2) semi-synthetic opioid:
Heroin, hydromorphone
Example of (1) synthetic opioid:
Fentanyl
What receptors do opioids exert its pharmacodynamic effects (3)?
Which receptor do opioids exert its dependence producing properties?
What is the MOA of opioids in the CNS, specifically?
Opiods exert their pharmacodynamic effects through:
mu, delta and kappa receptors
the _dependence producing properties_ of opioids are mediated through the mu receptors
MOA: opioids cause disinhibition of mesolimbic dopaminergic sys -
By binding the mu R on GABA-interneuros in the VTA, opioids act as agonist and inhibit the inhibitory action of GABA neurons –> disinhibition of the dopaminergic system
What are the different patterns of opioid abuse? (5)
Oral (prescription drugs)
Intravenous
subcutaneous (“skin popping”)
smoking
snorting (become more prevalent because of fear of AIDS)
Opioid Patterns of Use:
Heroins’ effects last about _____ hours.
The average addict uses heroin _____ X per day.
Tolerance and physical dependce develop____ [slow/gradual/fast]. How does this affect the use of heroin, in terms of frequency and quantity?
Opioid Patterns of Use:
Heroins’ effects last about 3-5 hours.
The average addict uses heroin 2-4 X per day.
Tolerance and physical dependce develop gradually, leading to both frequency and quantity of drug consumed.
What are the signs of opioid overdose? (6)
Which are the top two signs that can lead to death?
Signs of Opioid Overdose:
Unconsciousness
MIOSIS (pinpoint pupils)
Hypotension
Bradycardia
*Respiratory depression*
*Pulmonary edema*
Respiratory depression and pulmonary edema are the two leading causes of death in an opioid overdose
Heroin is a PRO-DRUG that is rapidly converted into ________ [metabolite] by ________ [what enzyme], present in blood, brain and most tissue.
This metabolite is further metabolized to _______ [metabolite] which contributes to the duration of the effect of heroin.
Heroin is a PRO-DRUG that is rapidly converted into 6- monoacetylmorphine by esterases present in blood, brain and most tissue.
This metabolite is further metabolized to morphine, which contributes to the duration of the effect of heroin.
Pharmacokinetics of Heroin:
What is meant by opioids exhibiting “cross-tolerance” ?
Withdrawal begins _____ hours after last dose, peaks at _____ days and is mostly over by _______ days, yet lingering symptoms called the _____________syndrome, can persist for months and are associated with relapse.
Pharmacokinetics of Heroin:
Cross-tolerance = tolerance to one opioid is usually associated with tolerance to other opioids
Withdrawal begins 12 hours after last dose, peaks at 5-7 days and is mostly over by 1.5-3 days; yet lingering symptoms called the Protracted Abstinence Syndrome, can persist for months and are associated with relapse.
Withdrawal of opioids can be profoundly PAINFUL and even could be life-threatening..what are some symptoms associated with opioid withdrawal (15). Which are SPECIFIC to opioid withdrawal? (5)
Anxiety
Dysphoria
Craving and drug-seeking
Sleep disturbances
N/V
Diarrhea
Lacrimation
Rhinorrhea
Yawning
Piloerection/gooseflesh (cold turkey)
Sweating, chills
Mydriasis (excessive pupil dilation)
Cramps
Hyperpyrexia
involuntary movements “kicking the habit”
*Opioid specific symptoms: lacrimation, rhinorrhea, yawning, piloerection/gooseflesh, involuntary movement
What are the different methods to treat opioid addiction? (3)
What are two challenges to treatment of opioid addiction?
- Self-help groups such as Narcotics Anonymous
- Inpatietn detoxification facilities/residentials
- Pharmacotherapy
CHALLENGES
- *Individual therapy rare largely due to sociodemographic characteristics of users*
- *Dependence on prescription opioids presents a new challenge for treatment*
What are the goals of pharmacotherapy? (5)
- Cure of withdrawal or overdose
- Improve the holding power of outpatient treatment
- to reduce drug cravings
- to create a window of opportunity during which patients can receive psycho-social intervention to decrease the risk of relapse
- to serve as short or long-term maintenance againts for patients who can’t function without them but can lead productive lives with them
Treatment approaches of opioid overdose and withdrawal syndrome:
Treatment of opioid OVERDOSE with: _________, type of receptor
Treatment of opioid DEPENDENCE with:________, type of receptor
Treatment of opioid WITHDRAWAL with:_______, type of receptor
OR _______, type of receptor
Treatment approaches of opioid overdose and withdrawal syndrome:
Treatment of opioid OVERDOSE with naloxone, u-opioid R antagonist
Treatment of opioid DEPENDENCE with: Naltrexone [Vivitrol], u-opioid R antagoinst
Treatment of opioid WITHDRAWAL with: Methadone, u-opioid R agonist
OR buprenorphine, partial u-opioid R agonist
Naloxone [Narcan, Nalone] is used for opioid overdose,
Is a u-opioid competitive antagonist with ____ [low/high] affinity and____ [low/high] half-life
Acts within _____ minutes, and duration of action is_____, which is ________ [shorter than/same as/longer than] heroin. Due to this, what is important to do while treating individuals with opioid overdose?
Naloxone [Narcan, Nalone] is used for opioid overdose,
Is a u-opioid competitive antagonist with HIGH AFFINITY and SHORT HALF-LIFE
Acts within 2 minutes, and duration of action is ~45 minutes, which is MUCH SHORTER THAN HEROIN.
Due to this, what is important to do while treating individuals with opioid overdose?
Should be kept under observation for the duration of the opioid drug’s effects to determine if additional antagonist treatment is needed (ie - heroin can occupy the opiod receptors again when action of Naloxone is over)
Nalterxone [Vivitrol], is used to treat opioid dependence
Is a u-opioid antagonist with ____ [short/long] half-life
Absorbed _____ [IV/oral/transdermal…]
_____ [low/high] receptor affinity
What effect does Nalterxone have on the effects of heroin?
When should this drug be avoided?
Nalterxone [Vivitrol], is used to treat opioid dependence
Is a u-opioid antagonist with LONG half-life
Absorbed ORALLY
HIGH receptor affinity
What effect does Nalterxone have on the effects of heroin? heroin is no longer rewarding
When should this drug be avoided? AVOID IN PT WITH LIVER FAILURE
Methadone, is one of the drugs used for opioid withdrawal
it is a u-receptor agonist with _____ [short/long] half-life of _____ [time]
Administered _____
Lasts about _______
What does methadone therapy accomplish?
What is a draw back of using Methadone? (2)
Methadone, is one of the drugs used for opioid withdrawal
it is a u-receptor agonist with LONG half-life of 15-60 hours!
Administered orally
Lasts about 24 hours
What does methadone therapy accomplish? Prevents withdrawal symptoms and cravings due to its long half life (will out compete heroin at receptor sites), and has cross-tolerance with other opioids
What is a draw back of using Methadone? it is only dispensed at federally licenced clinics and requires almost daily clinci visits even for individuals with long-term success
Buprenorphine [suboxone] is also a drug used for opiod withdrawal
it is a partial U-opiod receptor agonist
_____ [low/med/high] affinity for receptors and dissociates ___ [slowly/quickly] –> long acting
HIGH affinity for receptors and dissociates SLOWLY –> long acting
why is buprenorphine formulated with naloxone [suboxone] in a 4:1 ratio?
What could occur if buprenorphine is initiated prior to the onset of acute withdrawal signs?
Buprenorphine was abused, thus when sold in combo, it will result in withdrawal symptoms due to the presence of Naloxone (u-opioid receptor antagonist), thus less likely for someone to abuse treatment.
If buprenorphine is initiated prior to the onset of acute withdrawal signs, it may lead to abrupt withdrawal syndrome due to displacement of full agonist (ie - heroin), for u-opioid receptor by buprenorphine
What is the active constituent of cannabinoids?
Delta-9-tetrahydrocannabinol (THC)
What is the mechanism of action of cannabinoids?
THC i_nhibits GABAergic interneurons_ by acting on CB1 receptors –> inhibiting the inhibitor–> INC DOPAMINE release @ nucleus accumbens
cannabinoids cause disinhibition of mesolimbic DA system
What are the acute effects of Marijuana? (8)
Sedation / relaxation
Mood alteration, sense of well-being
Altered perception and time estimation
Impaired judgment, memory and concentration
INC heart rate
Dry mouth
INC appetite “munchies” (due to drop of sugar levels and also stimulation of cannabinoid R in the hypothalamus)
Injection of the conjunctiva“red eyes” (due to decreased pressure in the eyes and increased blood pressure)
What are the adverse effects of marijuana use? (6 “groups”)
Panic, delirium, paranoia,
Amotivation syndrome, inattention, poor judgement, distractibility leading to accidents and misbehavior
Tolerance occurs but physical dependence remians controversial
Personality cahnges and cognitive deficits (loss of short-term memory)
GATEWAY to other drug abuse
Criminal or workplace sanctions
What is used to treat the following syndromes of marijuana abuse:
Anxiety and panic –>
Delirium and paranoia –>
Dependence –>
Is there any pharmacotherapies for marijuana abuse?
What is used to treat the following syndromes of marijuana abuse:
Anxiety and panic –> anxiolytics
Delirium and paranoia –> antipsychotics
Dependence –> CBT
Is there any pharmacotherapies for marijuana abuse? NO but discovery of CB1 R and development of an antagonist is promising
Why is alcohol misuse a big issue?
Excessive alcohol consumption costs the US billions of dollars annually and millions of dollars on individuals due to speciality services, medical consequences, lost present and future earnings, accidents and criminal justice system.
How much is alcohol misuse related to genetics vs envrionment?
~ 50% of the risk is attributed to genetics, yet many individuals may not even have family history and thus misuse is a result of environmental factors
Type A Alcohol Dependence:
What percentage of alcoholics are Type A?
Onset?
Familial alcohol-dependency?
Disease progression rate:
Alcohol dependence?
Environmental influence?
Relation to criminality?
Response to treatment?
Type A Alcohol Dependence:
75% of alcoholics are Type A
Onset: LATE >25 y/o
Familial alcohol-dependency: FEW
Disease progression rate: SLOW
Alcohol dependence: milder form
Environmental influence: IMPORTANT
Relation to criminality? minimal
Response to treatment? better response than Type B
Type B Alcohol Dependence:
Onset? EARLY
Familial alcohol-dependency?
Disease progression rate?
Alcohol dependence?
Environmental influence?
Relation to criminality?
Response to treatment?
What other pychiatric disorder is frequently present?
Type B Alcohol Dependence:
Onset? EARLY (less than 25 y/o)
Familial alcohol-dependency? PATERNAL type B alcohol depend.
Disease progression rate: quicker
Alcohol dependence? MORE SEVERE FORM
Environmental influence? minimal
Relation to criminality? FREQUENT
Response to treatment? not as good as Type A
What other pychiatric disorder is frequently present? personality disorder
Chronic alcohol dependce could result in primary and secondary diseases.
What are primary diseases associated with chronic use? (6)
What are secondary diseases associated with chronic use? (6)
What are primary diseases associated with chronic use? alcohol poisoning, alcoholic heart disease (CARDIOMYOPATHY), alcoholic gastritis, alcoholic liver cirrhosis, alcoholic nerve disease (polyneuropathy), alcoholic psychoses
What are secondary diseases associated with chronic use? (6) Cancer (lip, mouth, pharynx, esophagus, larynx, liver stomach), diabetes, GI disease, heart disease (HTN, stroke), liver disease, pancreatitis (acute. chronic)
What effect does acute alcohol have on dopamine and opioid systems in the brain?
DOPAMINE SYSTEM: Alcohol indirectly INC DA levels in the mesocorticolimbic system –> positively reinforcing effects (probaly of alcohol)
OPIOID: alcohol can indirectly INC dopamine by activating the
mesocorticolimbic system
Acutely, alcohol ____ [INC/DEC] the effects of GABA, the major ____ [inhibitory/excitatory] NT in the brain
Leads to feelings of (2):
Chornic exposure of alcohol leads to a ____ [INC/DEC] in the levels of GABA-ergic receptors
INC the effects of GABA, the major INHIBITORY NT in the brain
–> feelings of relaxation and sedation
Chornic exposure of alcohol leads to a DECREASE in the levels of GABA-ergic receptors
Acutely, alcohol intake ____ [INC/DEC] the effects of glutamate, the major ____ [inhibitory/excitatory] NT in the brain
Leads to feelings of (2):
Chronic exposure to alcohol leads to an ___ [down/up] regulation of NMDA receptors
What effect does this have on a person? (2)
Acutely, alcohol intake DEC the effects of glutamate, the major EXCITATORY NT in the brain
–> decreased anxiety and increased sedation
Chronic exposure to alcohol leads to an UPregulation of NMDA receptors
Leads to tolerance and dependence
balances the acute alcohol effects
SUDDEN reduction in chronic alcohol intake leads to ____ [over/under]activation of NMDA system?
What effect does this have acutely (2)? Post-actuely (2)?
SUDDEN reduction in chronic alcohol intake leads to OVERactivation of NMDA system?
Acutely –> dysphoria, hallucinations
Post-Acute –> sleep and mood disturbances
What are the 4 stages of Treatment of Alcohol Dependence?
- Identification
- Detoxification/Withdrawal
- Rehabilitation
- Adherence
What is used to relieve IMMEDIATE symptoms of withdrawal?
What would be a good alternative for patients with cirrhosis?
Relieve immediate symptoms of withdrawal with benzodiazepines, which are indirect agonist for GABA receptors
Benzos with LONG half-lifes (diazepam/valium) have less chance of recurrent withdrawal
Lorazepam/Ativan has a short half life but it is NOT metabolized by the liver, so good for patients with cirrhosis
What are the 4 stages of alcohol withdrawal- symptoms, time frame?
Which stage can be most life threatening?
6-36 hours after last drink –> Minor Withdrawal
- CNS hyperactivity, HYPERAROUSAL*
- Mild anxiety, H/A, sweating, palpitations, GI upset, insomnia, nausea*
6-48 hours after last drink –> Seizures
**CAN BE MOST LIFE THREATENING**
3% of chronic alcoholics can develop tonic-clonic seizures, some develop status epilepticus (seizures withouth regaining consciousness for 30 minutes)
12-48 hours after last drink –> Alcoholic Hallucinations
visual, auditory or TACTILE
48-96 hours after last drink, can last 5 days –> Delirium Tremens
___ % of alcohol withdrawal leads to delirium tremens, and mortality can be up to ____ when left untreated.
Sx (5)
Treatment:
5% of alcohol withdrawal leads to delirium tremens, and mortality can be up to 35 % when left untreated.
Sx: confusion, disorientation, hallucinations, uncontrollable tremors of extremities, severe autonomic instability (fever, tachy, HTN, diaphoresis)
Treatment: Long half-life benzos (diazepam, lorazepam), and pharmacotherapy is symptomatic and supportive
What are the 3 approved pharmacotherapeis for alcohol DEPENDENCE?
Disulfiram- alcohol aversion therapy
Naltrexone- long-acting opioid antagonist
Acamprostate- restores balance between neural excitation and inhibition (mechanism unknown)
*DNA*
Alcohol (ADH)–> acetaldehyde (ALDH)–> acetate
High levels of acetaldehyde leads to (5):
How does disulfiram act as alcohol aversion therapy? (MOA, symptoms and increased risk for..?)
Does disulfiram increase abstinence?
High levels of acetaldehyde leads to (5): nausea, dizziness, H/A, hypotension, vomiting
Disulfiram inhibits aldehyde dehydrogenase (ALDH) that leads to increased high levels of acetaldehyde when taken with alcohol
–> decreases desire to drink alcohol but does not increase abstinence
INC risk for hepatotoxicity
Naltrexone
MOA
When should Naltrexone be avoided? (2)
What drug should you not take with Naltrexone?
Naltrexone
MOA: anatgonist of opioid receptors, blocks release of DA from nucleus accumbens –> REDUCES alcohol cravings
When should Naltrexone be avoided? Liver disease, or patients dependent on opioids (can percipitate actute withdrawal syndrome)
What drug should you not take with Naltrexone? DO not take with DIsulfiram (both hepatotoxic)
Acamprosate
MOA:
Overall effect:
Minor side effects:
Contraindicated:
Acamprosate
MOA: UNKNOWN
Overall effect: decreases excitatory glutamate NT and increases GABA-ergic activity
Minor side effects: Diarrhea, allergic reactions, irregular heartbeats
Contraindicated: severe renal disease, dose adjustments in patients with moderate renal disease (when creatinine clearance 30-50 mL/min)
What are the therapeutic uses of benzodiazepines (5)
Bezodiazepines are INDIRECT AGONIST of the GABA receptors
Used for:
Severe anxiety, panic attacks and phobias
Insomnia
Muscular disorders- effective muscle relaxants
Alcohol withdrawal
Epilepsy (anticonvulsant)
What are the Benzo withdrawal symptoms? (6)
Withdrawal management?
Anxiety, agitaiton
INC sensitivity to light and sound
Muscle cramps
Sleep disturbances
Dizziness
Mycolonic jerks
Withdrawal managemetn: treat with diazepam, benzos with a long-half life, gradually tapering off the drug ove a period of months
Nicotine:
Is a selective agonist for…? MOA
Treatment for nicotine (4).
How does the non-nicotine medicine work?
ONE OF THE MOST ADDICTIVE DRUGS
Selective agonist of the nicotininc acetylcholine receptor (nAChR), –> simualtes dopaminergic neurons in the VTA and increases teh release of dopamine in the nucleus accumbens
Treatment:
Nicotine patches, nasal spray, nicotine lozenge
Varenicline [chantrix] = non-nicotonic medication, partial agonist that binds subunits of nicotine ACh receptors. Because it stimulates the receptors, it relieves cravings and withdrawal symptoms during abstinence from smoking. Binds to the nACh receptors with GREATER AFFINITY than nicotine –> reduces the pharmacologic reward from cigarette smoking
What is the moleculear target of hallucinogens such as LSD and mescaline…where?
Symptoms of hallucinogen use? (5)
Treatment: (2) for nonpsychotic agitation and for servere agitation
Molecular target: 5-HT2A in the CORTEX
Symptoms: changes in sensation, illusions, hallucinations, creation of fantasies or living nightmares (called mind-beinding drugs)
Treatment:
For non-psychotic agitation- antianxiety drugs (diazepam)
For severe agitation - use antipsychotic drugs
