Drugs of Abuse Flashcards
Substance Abuse Disorder
What are the 3 critical components?
Abuse
Craving
Legal problems
What are the criteria of Substance Abuse Disorder?
- Tolerance
- Withdrawal
- Using larger amounts than intended
- Persistent desire and inability to control use
- Excess time spent
- Normal activities reduced or given up
- Unable to cut back
Mild 2-3
Moderate 4-5
Severe >5
What is tolerance?
Decreased effect with repeated use of the drug
Need to use more drug to have the same effect
What is withdrawal?
Signs and symptoms that emerge when use of drug is stopped
Symptoms subside when drug is administered again
What is the major neuronal circuit involved in drug abuse? Where does it project to?
Mesolimbic dopamine system in the VTA, projecting to the nucleus accumbens, amygdala, and prefrontal cortex
What are two mechanisms (generally) by which you can produce withdrawal syndrome?
Stop taking the drug
Give an antagonist to the drug
Cocaine
MOA
Inhibits dopamine transporter on the presynaptic membrane, preventing reuptake of dopamine
Levels of dopamine in the synaptic cleft increase, mostly in nucleus accumbens
Amphetamines
MOA
Inhibits VMAT2, preventing dopamine from being packaged into vesicles in the axon terminal
Dopamine levels increase in the cytoplasm and eventually the dopamine reuptake transporter will reverse its transport of DA from inside –> outside cell into the synapse
What are the acute effects of Psychostimulants (Cocaine, Amphetamines)?
Rush High confidence Decreased fatigue and boredom Decreased appetite Increased HR, BP, temp
Cocaine
Half life
40-80 minutes
Cocaine
Metabolism
Metabolized in liver into an inactive compound, which can be detected in urine, saliva, hair, and milk for 8 days after use
What happens if you take cocaine with alcohol?
Cocaine will be transesterified, leading to cocaethylene
Cocaethylene causes more euphoria, but a higher cardiotoxic risk
Long Term Consequences of Cocaine/Amphetamine use
Sensitization or Tolerance
Impaired neurocognitive functions
Increased risk of autoimmune diseases
Signs of Cocaine Overdose
Hyperactivity Sweating Dilated pupils Agitation Tremor Tachycardia Chest pain Cardiac arrhythmia (deadly) HTN Seizures/coma Paranoia
Signs of Cocaine Withdrawal
Anxiety and agitation Insomnia or Hypersomnia Fatigue Sweating Muscle cramp Hunger ED
How should Acute Cocaine Withdrawal be treated?
Bromocriptine (dopamine agonist)
Benzodiazepines
How should long term addiction to cocaine be treated?
Cognitive Behavioral Therapy
List the Opioid Drugs of abuse
Morphine
Codeine
Heroin
Oxycodone
Opioids
MOA
Inhibit GABAergic neurons by blocking mew receptors
Since GABA normally inhibits release of dopamine, opioids increase the release of dopamine in the nucleus accumbens
Signs of Opioid Overdose
Unconsciousness Miosis Hypotension Bradycardia Respiratory Depression Pulmonary edema
Describe the metabolism of heroin
Heroin is a prodrug that is converted to 6-monoacetylmorphine by esterases, which is then metabolized to morphine, which contributes to heroin’s duration of effect
Opioid Withdrawal Symptoms
Lacrimation Rhinorrhea Yawning Piloerecetion/gooseflesh Involuntary movement Anxiety Craving Sleep disturbance Nausea, vomit, diarrhea Sweat Mydriasis Cramps
What is the primary treatment for opioid overdose?
Naloxone
Naloxone
MOA
Mew opioid competitive antagonist with a high affinity for mew receptors
Fast acting, Short half life
What is the primary treatment for opioid dependence?
Naltrexone
Naltrexone
MOA
Mew opioid antagonist with long half life
What are two drugs used in withdrawal syndrome and maintenance from opioid addiction?
Methadone
Buprenorphine
Methadone
MOA
Mew-opioid receptor agonist with long half life
Prevents withdrawal symptoms, but does not cause addiction due to its long half life
Buprenorphine
MOA
Partial mew-opioid receptor agonist
How is buprenorphine misused by patients?
On its own, could be crushed and injected to cause a high.
It is often combined with naloxone in pills, so patients crush and dissolve it, then inject it IV to get a high. This causes withdrawal symptoms due to presence of Naloxone.
Cannabinoids
What is the active compound in marijuana?
THC (Delta-9-tetrahydrocannabinol)
Cannabinoids
What is the MOA?
THC inhibits GABAergic interneurons, causing disinhibition of the mesolimbic DA system
Increases dopamine in nucleus accumbens
Acute Effects of Marijuana
Sedation, relaxation Mood alteration, sense of wellbeing Altered perception Impaired judgment, memory, concentration Increased HR, dry mouth Increased appetite Red eyes
Adverse Effects of Marijuana
Panic, delirium Amotivational syndrome Tolerance Personality changes Cognitive deficits (loss of ST memory) Gateway to other drugs
Treatment of Marijuana Abuse
Symptomatic
Anxiolytics for anxiety and panic
Antipsychotics for delirium and paranoia
Cognitive behavioral therapy
Alcohol
Type A Alcohol Dependence (Onset, Progression, etc)
- Late onset (over 25yo)
- Few familial EtOH dependency
- Slower progression
- Lower criminality
- Important environmental influence
Alcohol
Type B Alcohol Dependence (Onset, Progression, etc)
-Early onset (
Diseases caused by Chronic Alcohol Use
Alcohol poisoning Cardiomyopathy Gastritis Liver cirrhosis Polyneuropathy Psychosis cancer Diabetes HTN Stroke Pancreatitis
Alcohol
How does it affect GABA and glutamate?
Increases effects of GABA
Inhibits effects of Glutamate
Leads to upregulation of NMDA receptors in brain
Alcohol withdrawal after chronic intake may result in sudden death. How?
NMDA receptor upregulation in the brain from excess alcohol intake –> stop drinking –> more glutamate present –> NMDA overactivation
Treatment Stages of Alcohol Dependence (1-4)
- Identification
- Detox/Withdrawal
- Rehab
- Aftercare
What drug class is given to prevent alcohol withdrawal symptoms?
Benzodiazepines with long 1/2 life, like diazepam and Iorazepam
Symptoms of Alcohol Withdrawal
Anxiety, sweating, palpitations, GI upset, insomnia, nausea
Seizures (within first 3 days)
Hallucinations
Delirium tremens (tremor, confusion, fever, tachycardia, HTN, diaphoresis)
What drug is used in Alcohol Aversion Therapy?
Disulfram
Disulfram MOA
Inhibits acetaldehyde dehydrogenase, leading to increased levels of acetaldehyde when drinking.
Acetaldehyde makes pt feel sick, so they will hopefully become more averse to drinking.
What drug may be used to decrease alcohol cravings?
Naltrexone
Naltrexone
MOA
Antagonist of opioid receptors
Blocks release of DA from nucleus accumbens
Why should Naltrexone and Disulfram not be used together?
Both are potential hepatotoxins
What drug can restore the balance between neuronal excitation and inhibition in alcoholics?
Acamprosate
Acamprosate
Contraindications and Adverse Effects
AEs: diarrhea
Contraind: severe renal disease
Benzodiazepines
MOA
Indirect agonists of GABA A receptors
Benzodiazepine Withdrawal symptoms and management
Symptoms: Anxiety, agitation, photo and phonosensitivity, muscle cramps, sleep disturbance, dizzy
Withdrawal Mgmt: Diazepam
Nicotine
MOA
Nicotinic Ach receptor antagonists
Stimulates neurons in the VTA and increases dopamine in the nucleus accumbens
Best Treatment for Nicotine Addiction
Varenicline (Chantix)
-partial nicotinic agonist that decreases cravings and nicotine withdrawal syndrome
Hallucinogens (LSD, mescaline)
MOA and Symptoms
Activate 5HT 2A receptors in cortex
Changes in sensation, illusions, hallucinations
Do NOT induce dependence or addiction
