Drugs of Abuse Flashcards
Psychomotor stimulants
Cocaine, amphetamines
Opiates and opioids
Heroin, morphine, codeine, oxycodone, hydromorphone
Cannabinoids
Marijuana
Sedatives
Barbituates, benzodiazepines
Hallucinogens
LSD, mescaline “club drugs”
Three signs of dependence
Abuse
Craving
Legal Problems
Criteria (within 12 months) for Substance Use Disorder by DSM-V
Tolerance Withdrawal Use of larger amounts than intended Persistent desire Inability to control use Excessive time spent Normal activities given up Use despite knowledge of problems drug cause
Mild Substance Use Disorder
2-3 symptoms
Moderate Substance use disorder
4-5 symptoms
Severe substance use disorder
5+ symptoms
Withdrawal
A marker of physiological dependence
Signs and symptoms emerge when use of the drug is stopped, or are reversed when drug is administered again
Drug Tolerance
Decreased effect with repeated use of the drug
Need to use more drug to have the same effect
Where does the mesolimbic dopamine system originate
The VTA
Where does the mesolimbic dopmaine system project to
The nucleus accumbens
The amygdala
The prefrontal cortex
what happens when the VTA nucleus accumbens is activated by drugs of dependence
Release of dopamine
The shorter amount of time between injection of drug and delivery of the compound to brain, the ___ “high” somebody feels
more
What are the two ways to get withdrawal?
1) Give an antagonist
2) Let the drug naturally decay
No longer binding the receptor
What are some medical uses of cocaine?
1) stimulant of CNS
2) Freud used to treat depression
3) appetite suppressant (obesity)
4) topical anesthetic (historically- eye/nasal surgery, currently nasal/lacrimal duct surgery)
Cocaine MOA
Cocaine inhibits the dopamine transporter on the presynaptic terminal > causes levels of dopamine in the synaptic cleft to increase (particularly in the nucleus accumbens)
Amphetamine MOA
Amphetamines inhibit the VMAT2 (vesicular monoamine transporter 2)
DA not placed in presynaptic vesicles, high levels of dopamine in cell, travel reversely through the dopamine transporter (DAT) > causes increased levels of dopamine in the presynaptic cleft (particularly nucleus accumbens)
Historical uses for amphetamines
Treat asthma, narcolepsy, obesity
What is amphetamine?
synthetic phenylethylamine
Acute effects of psychostimulants (cocaine, amphetamines)
Rush Euphoria and arousal Increased energy Feelings of competency Decreased feelings of fatigue/boredom Decreases appetite Increased HR, BP, temp
Onset, magnitude (potency), and duration depend on____
route of administration (smoked, injected, inhaled)
If taken IV, cocaine reaches peak in ___
15 seconds
What is the half-life of cocaine?
40-80 mins
Where is cocaine metabolized?
Liver (cholinesterases)
What is cocaine metabolized into?
Benzoylecgonine
can be monitored in biological fluids
How long can you detect cocaine in the urine?
up to 8 days after use
Cocaine in the presence of ethanol makes what compound
Cocaethylene
What are the characteristics of cocaethlyene?
Produces more euphoria
Long duration of action than cocaine
What is the risk of cocaetylene?
More cardiotoxic
Can cause cardiac arrest
What are the consequences of long term use of psychostimulants?
Sensitization
Tolerance
Impairment of neurocognitive functions
Increased risk of autoimmune/connective tissue diseases (lupus, goodpasture, SJS)
Overdose signs and symptoms of psychostimulants
Hyperactivity Sweating Dilated pupils Agitation/tremor Tachycardia/chest pain Cardiac Arrhythmia******* Hypertension Hyperpyrexia Stereotypical behavior Seizures/coma Paranoia/tactiel hallucinations
Withdrawal signs and symptoms of psychostimulants
Anxiety and agitation Insomnia and hypersomnia Fatigue and depression Sweating Muscle cramps Hunger Erectile dysfunction
Treatment of cocaine withdrawal (acute withdrawal=symptomatic treatment)
Bromocriptine (dopamine agonist)
Benzodiazepines (in pts with severe agitation and sleep disturbance)
Treatment of long term cocaine addiction
No FDA approved pharma Rx
Cognitive Behavioral Therapes (functional analysis, skills training)
Development of vaccine against cocaine?
What is opium derived from?
Extracts of juice of the opium poppy, Papaver somniferum
Opioid MOA
Inhibit the GABAergic interneurons by binding u receptors > double inhibition > elevated DA levels in nucleus accumbens
Opioid potential routes of adminitration
Oral
IV
Snorting
Smoking
Subcutaneous ("skin popping")How long do Heroin’s effects last?
3-5 hours
Average addict uses ___ times/day?
2-4
Signs of Opioid Overdose
Unconsciouness Miosis Hypotension Bradycardia Respiratory depression*** Pulmonary edema****
Opioid cross tolerance
Tolerance to one opioid is usually associated with tolerance to other opioids
Metabolism of Heroin (why it is so addictive!)
Metabolized to 6-monoacetylmorphine > metabolized to morphine (2 drugs in one!)
When does Heroin withdrawal begin?
12 hours after last dose
When does Heroin withdrawal peak?
1 1/2 - 3 days
When does Heroin withdrawal finish?
Usually over by 5-7 days
Heroin and protract abstinence syndrome
Lingering symptoms of withdrawal can persist for months and are associated with relapse
Can Heroin withdrawal be life threatening?
YES! also very painful
Opioid withdrawal symptoms
Anxiety and dysphoria Craving and drug-seeking Sleep disturbance Nausea, vomiting, diarrhea Lacrimation* Rhinorrhea* Yawning* Piloerection* Sweating Mydriasis Cramps Hyperpyrexia (high fever) Involuntary movement*
*specific to heroin withdrawal
Treatment of opioid addiction
Self-help groups Inpatient detox Individual therapy Prescription opioids Pharmacotherapy
Goals of pharmacotherapy
Cure of withdrawal or overdose
Create window of opportunity for pt to receive psycho-social intervention
Treatment of Opioid Overdose
Naloxone
MOA of Nalaxone
u-opioid competitive antagonist with very high affinity but short half-life
Individuals treated for overdose with Nalaxone must be____-
Kept under observation for duration of the opioids drug’s effects
Treatment of Opioid Dependence
Naltrexone
MOA of Naltrexone
u-opioid antagonist with long half-life
heroin self-administration no longer rewarding
What is Naltrexone FDA approved for?
Opioid dependence
Alcohol dependence
Contraindication for Naltrexone
Avoid in pts with liver failure
Treatment with Methadone
for opioid
Prevents withdrawal symptoms and cravings, has a cross tolerance with other opioids
Only dispensed in federally licensed clinics (daily visits)
MOA of methadone
u-opioid receptor agonist with long half life
Treatment with Buprenorphine (for opioid)
Given in formulation with nalaxone, has high affinity for receptors and dissociates slowly
Take Sublingually
What happens when Buprenorphine is misused intravenously
Will result in withdrawal symptoms (due to presence of Naloxone)
What happens if buprenorphine is initiated prior to onset of acute withdrawal signs
Can leads to abrupt withdrawal syndrome
Active constituent of marijuana
THD (delta-9-tetrahydrocannabinol)
MOA of THC
Inhibits GABAergic interneurons by binding the CB1 receptors >stimulation of DA release in nucleus accumbens
Acute effects of marijuana
sedation, relaxation Mood alteration Altered perception and time estimation impaired judgement, memory, and concentration Increase heart rate, dry mouth Increased appetite Injection of the conjunctiva
Adverse effects of marijuana use
Panic, delirium, paranoia, poor judgement, tolerance, personality chances, gateway to other drug abuse
Treatment of marijuana abuse is symptomatic
Anxiolytics
Antipsychotics
Cognitive behavioral therapy
Characteristics of Type A Alcohol Dependence
Late onset (>25) Few familial Milder form Environmental influence Minimal criminality
Characteristics of Type B Alcohol Dependence
Early onset (
Primary diseases associated with chronic alcohol use
Alcohol poisoning Alcoholic heart disease Alcoholic gastritis Alcoholic liver cirrhosis Alcoholic nerve disease Alcoholic psychoses
Secondary diseases associated with chronic alcohol us
Cancer (lip, mouth, pharynx, esophagus, larynx, liver, stomach) Diabetes GI disease Heart disease Liver disease Pancreatitis
Effects of alcohol on neural circuits
Indirectly increasing dopamine levels in mesocorticolimbic system
Indirect activation of opioid receptors
Increases effect of GABA > (decreased GABA receptors)
Inhibits the effects of glutamate (>upregulation of NMDA receptors)
Treatment stages of alcohol dependence
- identification (CAGE)
- detoxication/withdrawal
- Rehab
- Aftercare
Treating symptoms of alcohol withdrawal
Benzidiazepines (indirect agonist of GABA)
Diazepams (long half-life)
Lorazepam (shorter half-life)
Which drug is preferable to treat alcohol withdrawal in a patient with cirrhosis?
Lorazepam
Minor alcohol withdrawal symptoms
6-36 hrs after
CNS hyperactivity
anxiety, headache, sweating, palpitations, GI upset, insomnia, nausea
Seizures from alcohol withdrawal
6-48 hours after
tonic-clonic seizures (3%)
status epilecticus
life threatening
Alcoholic hallucinations
12-48 hours after
Visual, auditory, tactile
Delirium tremens
49-96 hours after (can last 5 days)
Withdrawal from long-term alcohol consumption or benzodiazepine withdrawal
Symptoms of delirium tremens
Confusion, hallucinations, tremors of extremities, fever, tachycardia, HTN, diaphoresis
Treatment of delirium tremens
Benzodiazepines with long half-life (diazepam, lorazepam)
FDA approved therapies for alcohol dependence
Disulfiram
Naltrexone
Acamprosate
Disulfiram
Alcohol aversion therapy
inhibit ALDH > increased levels of acetaldehyde > nausea, dizziness, headache, hypotension, vomiting
Risk of disulfiram
Hepatotoxicity
Does not increase abstinence
Which genetic variant of the ALDH enzyme to asians have which protects against alcohol dependence?
ALDH2*2
Naltrexone
Long acting opioid antagonist
Blocks release of dopamine from nucleus accumbens
Reduces alcohol cravings
Avoid naltrexone in which types of patients?
pts taking disulfiram
pts dependent on opioids
Acamprosate
Restores balance between neuronal excitation and inhibition (mechanism unknown)
-decreases glutamate, increases GABA
Side effects of acamprosate
Diarrhea, allergic reactions, irregular heart beats
Contraindication of acamprosate
Severe renal disease
dose adjust in patients with moderate renal disease
What is the BEST drug on the market for treating alcohol dependence?
Acamprosate (80% success)
Therapeutic use of benzodiazepines
severe anxiety, panic attacks, phobias
insomnia, muscular disorders, alcohol withdrawal, epilepsy
MOA of benzodiazepines
indirect agonist of GABA receptor
Benzodiazepine Withdrawal symptoms
anxiety, agitation Increased sensitivity to light/sound Muscle cramps sleep disturbance dizziness Myoclonic jerks
Treatment of benzodiazepine withdrawal
diazepam
long half-life–gradually taper off the drug
Nicotine
selective agonist of the nicotinic acetylcholine receptor > stimulates dopaminergic neurons in VTA, increases DA release in nucleus accumbens
Treatment of nicotine addiction
Nicotine patches, nasal spray, nicotine lozengem varenicline (chantix)
Varenicline (Chantix)
Non-nicotine medication
Partial agonist that binds subunits of nicotine Ach receptors
Relieves cravings and withdrawal symptoms
Binds with greater affinity than nicotine
Symptoms of hallucinogens
Changes of sensation, illusions, hallucinations, create fantasies, living nightmares
Do hallucinogens induce dependence or addiction?
NO!
Molecular target of hallucinogens
Serotonin receptors (5-HT2A in cortex)
Treatment for non-psychotic agitation (due to hallucinogens)
anti-anxiety drugs (diazepam)
Treatment for severe agitation (due to hallucinogens)
Anti-psychotic drugs
