Drugs of Abuse Flashcards

1
Q

Substance Abuse Disorder

What are the 3 critical components?

A

Abuse

Craving

Legal problems

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2
Q

What are the criteria of Substance Abuse Disorder?

A
  • 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

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3
Q

What is tolerance?

A

Decreased effect with repeated use of the drug

Need to use more drug to have the same effect

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4
Q

What is withdrawal?

A

Signs and symptoms that emerge when use of drug is stopped

Symptoms subside when drug is administered again

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5
Q

What is the major neuronal circuit involved in drug abuse? Where does it project to?

A

Mesolimbic dopamine system in the VTA, projecting to the nucleus accumbens, amygdala, and prefrontal cortex

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6
Q

What are two mechanisms (generally) by which you can produce withdrawal syndrome?

A

Stop taking the drug

Give an antagonist to the drug

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7
Q

Cocaine

MOA

A

Inhibits dopamine transporter on the presynaptic membrane, preventing reuptake of dopamine

Levels of dopamine in the synaptic cleft increase, mostly in nucleus accumbens

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8
Q

Amphetamines

MOA

A

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

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9
Q

What are the acute effects of Psychostimulants (Cocaine, Amphetamines)?

A
Rush
High confidence
Decreased fatigue and boredom
Decreased appetite
Increased HR, BP, temp
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10
Q

Cocaine

Half life

A

40-80 minutes

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11
Q

Cocaine

Metabolism

A

Metabolized in liver into an inactive compound, which can be detected in urine, saliva, hair, and milk for 8 days after use

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12
Q

What happens if you take cocaine with alcohol?

A

Cocaine will be transesterified, leading to cocaethylene

Cocaethylene causes more euphoria, but a higher cardiotoxic risk

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13
Q

Long Term Consequences of Cocaine/Amphetamine use

A

Sensitization or Tolerance

Impaired neurocognitive functions

Increased risk of autoimmune diseases

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14
Q

Signs of Cocaine Overdose

A
Hyperactivity
Sweating
Dilated pupils
Agitation
Tremor
Tachycardia
Chest pain
Cardiac arrhythmia (deadly)
HTN
Seizures/coma
Paranoia
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15
Q

Signs of Cocaine Withdrawal

A
Anxiety and agitation
Insomnia or Hypersomnia
Fatigue
Sweating
Muscle cramp
Hunger
ED
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16
Q

How should Acute Cocaine Withdrawal be treated?

A

Bromocriptine (dopamine agonist)

Benzodiazepines

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17
Q

How should long term addiction to cocaine be treated?

A

Cognitive Behavioral Therapy

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18
Q

List the Opioid Drugs of abuse

A

Morphine
Codeine
Heroin
Oxycodone

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19
Q

Opioids

MOA

A

Inhibit GABAergic neurons by blocking mew receptors

Since GABA normally inhibits release of dopamine, opioids increase the release of dopamine in the nucleus accumbens

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20
Q

Signs of Opioid Overdose

A
Unconsciousness
Miosis
Hypotension
Bradycardia
Respiratory Depression
Pulmonary edema
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21
Q

Describe the metabolism of heroin

A

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

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22
Q

Opioid Withdrawal Symptoms

A
Lacrimation
Rhinorrhea
Yawning
Piloerecetion/gooseflesh
Involuntary movement
Anxiety
Craving
Sleep disturbance
Nausea, vomit, diarrhea
Sweat
Mydriasis
Cramps
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23
Q

What is the primary treatment for opioid overdose?

24
Q

Naloxone

MOA

A

Mew opioid competitive antagonist with a high affinity for mew receptors

Fast acting, Short half life

25
What is the primary treatment for opioid dependence?
Naltrexone
26
Naltrexone | MOA
Mew opioid antagonist with long half life
27
What are two drugs used in withdrawal syndrome and maintenance from opioid addiction?
Methadone Buprenorphine
28
Methadone | MOA
Mew-opioid receptor agonist with long half life Prevents withdrawal symptoms, but does not cause addiction due to its long half life
29
Buprenorphine | MOA
Partial mew-opioid receptor agonist
30
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.
31
Cannabinoids | What is the active compound in marijuana?
THC (Delta-9-tetrahydrocannabinol)
32
Cannabinoids | What is the MOA?
THC inhibits GABAergic interneurons, causing disinhibition of the mesolimbic DA system Increases dopamine in nucleus accumbens
33
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 ```
34
Adverse Effects of Marijuana
``` Panic, delirium Amotivational syndrome Tolerance Personality changes Cognitive deficits (loss of ST memory) Gateway to other drugs ```
35
Treatment of Marijuana Abuse
Symptomatic Anxiolytics for anxiety and panic Antipsychotics for delirium and paranoia Cognitive behavioral therapy
36
Alcohol | Type A Alcohol Dependence (Onset, Progression, etc)
- Late onset (over 25yo) - Few familial EtOH dependency - Slower progression - Lower criminality - Important environmental influence
37
Alcohol | Type B Alcohol Dependence (Onset, Progression, etc)
-Early onset (
38
Diseases caused by Chronic Alcohol Use
``` Alcohol poisoning Cardiomyopathy Gastritis Liver cirrhosis Polyneuropathy Psychosis cancer Diabetes HTN Stroke Pancreatitis ```
39
Alcohol | How does it affect GABA and glutamate?
Increases effects of GABA Inhibits effects of Glutamate Leads to upregulation of NMDA receptors in brain
40
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
41
Treatment Stages of Alcohol Dependence (1-4)
1. Identification 2. Detox/Withdrawal 3. Rehab 4. Aftercare
42
What drug class is given to prevent alcohol withdrawal symptoms?
Benzodiazepines with long 1/2 life, like diazepam and Iorazepam
43
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)
44
What drug is used in Alcohol Aversion Therapy?
Disulfram
45
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.
46
What drug may be used to decrease alcohol cravings?
Naltrexone
47
Naltrexone | MOA
Antagonist of opioid receptors Blocks release of DA from nucleus accumbens
48
Why should Naltrexone and Disulfram not be used together?
Both are potential hepatotoxins
49
What drug can restore the balance between neuronal excitation and inhibition in alcoholics?
Acamprosate
50
Acamprosate | Contraindications and Adverse Effects
AEs: diarrhea Contraind: severe renal disease
51
Benzodiazepines | MOA
Indirect agonists of GABA A receptors
52
Benzodiazepine Withdrawal symptoms and management
Symptoms: Anxiety, agitation, photo and phonosensitivity, muscle cramps, sleep disturbance, dizzy Withdrawal Mgmt: Diazepam
53
Nicotine | MOA
Nicotinic Ach receptor antagonists Stimulates neurons in the VTA and increases dopamine in the nucleus accumbens
54
Best Treatment for Nicotine Addiction
Varenicline (Chantix) | -partial nicotinic agonist that decreases cravings and nicotine withdrawal syndrome
55
Hallucinogens (LSD, mescaline) | MOA and Symptoms
Activate 5HT 2A receptors in cortex Changes in sensation, illusions, hallucinations Do NOT induce dependence or addiction