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Pharmacology > Drugs of Abuse > Flashcards

Drugs of Abuse Flashcards

1
Q

Abuse

A

Excessive self-administration of any substance for nonmedical purposes

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2
Q

Addiction

A

Use of substance that alter perception & cause a sensation of reward & euphoria

  • Impaired control over drug use
  • Compulsive use
  • Continued use despite harm
  • Craving
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3
Q

Dependence

A

State of adaptation manifested by drug class specific withdrawal syndromes

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4
Q

Withdrawal syndrome

A

physiological & behavioral changes directly related to sudden cessation or reduction in use of drug to which the body has become adapted to.

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5
Q

Causes of Withdrawal syndrome

A
  • Abrupt cessation
  • Rapid dose reduction
  • Antagonist administration
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6
Q

Tolerance

A

State of adaptation in which exposure to drug induces changes that result in a diminution of 1/more of the drug effects over time

  • Can occur to both the desired & undesired effects of drugs
  • May develop at different rates for different effects
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7
Q

Mechanism of Addiction

A

Activation of the Mesolimbic Dopamine pathway

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8
Q

Classes of Drugs of abuse based on how Dopamine levels are increased

A
  1. Inc DA release indirectly by inhibiting GABA neurons that act as local inhibitory interneurons
    - Opioids, cannabinoids, Benzos & ethanol
  2. Directly stimulate dopaminergic neurons
    - Nicotine & ethanol
  3. Block or reverse DAT
    - Cocaine, amphetamines & MDMA
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9
Q

Classes of Drugs of Abuse

A
  • CNS depressants
  • Psychostimulants
  • Nicotine
  • Opioids
  • Marijuana
  • Psychedelic agents
  • Inhalants
  • Anabolic steroids
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10
Q

CNS Depressants (Classes/ names)

A
  1. Ethanol
  2. Benzos
  3. Barbituates
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11
Q

Why is ethanol classified as a CNS depressant?

A

its initial effects are perceived as stimulation due to the suppression of inhibitory systems BUT it eventually produces Sedation & Sleep

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12
Q

MOA of Ethanol

A

Affects:

  • GABAa receptors
  • Kir3/ GIRK channels
  • Adenosine reuptake
  • Glycine receptors
  • NMDA receptors
  • 5HT3 receptors (vomiting)
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13
Q

How does Alcohol/Ethanol increase DA?

A

Ethanol causes release of Endorphins from the Endorphinergic neurons –> Activates u-receptors –> Inhibits GABAergic interneurons –> Inc DA release

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14
Q

Drugs used to treat Alcohol addiction

A
  1. Disulfiram
  2. Naltrexone
  3. Acamprosate
  4. Topiramate (NOT FDA approved)
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15
Q

Disulfiram

A

Inhibits Aldehyde dehydrogenase
- Creates an aversion to drinking because if ethanol is consumed w/ disulfiram the aldehyde accumulates –> Nausea, headache, flushing & hypotension

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16
Q

Naltrexone

A

Opioid antagonist- blocks activation of u-receptors –> Dec DA release
- Reduce the craving for alcohol & dec. relapse to heavy drinking

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17
Q

Acamprosate

A

Unclear mechanism - Blocks Hyper-glutamatergic state in alcoholic brain

NMDA receptor antagonist - Prevent relapse drinking

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18
Q

Topiramate

A
  • Inc GABA function
  • Antagonize Glutamate receptors

May reduce cravings
NOT FDA approved

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19
Q

Alcohol Withdrawal Syndrome

A
  • Tremor
  • Nausea
  • Sweating
  • Agitation
  • Anxiety
  • Hallucinations
  • Generalized seizures (24-48hrs)
  • Delirium tremens (48-72hrs) - 5-15% mortality
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20
Q

Treatment of Alcohol Withdrawal

A

Long-term Benzos - Diazepam & Chlordiazepoxide (DOC)

Intermediate-acting Benzos - Lorazepam & Oxazepam (DOC in elderly & pts. w/ liver failure)

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21
Q

Benzodiazepine Withdrawal Syndrome

A
  • Tremors
  • Anxiety
  • Perceptual disturbances
  • Dysphoria
  • Psychosis
  • Seizures

(Life-threatening)

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22
Q

Benzo Withdrawal Syndrome Management

A

If pt. is on a short-acting benzo –> Switch to long-acting (DIAZEPAM) –> Gradually reduce dose

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23
Q

Barbiturates Abuse

A

Similar to that of Benzos

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24
Q

Psychostimulants (Class/ names_

A
  1. Methylxanthines
    - Caffeine, Theophylline & Theobromine
  2. Cocaine
  3. Amphetamines
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25
Q

Methylxanthine MOA

A

Blocks presynaptic Adenosine receptors –> Inc. NE release

Normally, activation of Adenosine receptors inhibits NE release

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26
Q

CNS Effects of Methylxanthines

A 
100-200 mg
- Dec fatigue
- Inc mental alertness
1.5g
- Anxiety
- Tremors
2-5g
- Spinal cord stimulation
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27
Q

Methylxanthines Tolerance & Withdrawal

A

Tolerance- rapidly develop
Withdrawal - Fatigue & sedation
Addiction- Rare

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28
Q

Cocaine DEA classification

A

Schedule 2 (due to its abuse potential)

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29
Q

MOA of Cocaine

A

Inhibits DA, NE & 5TH reuptake (prolonged dopaminergic effect –> Intense euphoria)

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30
Q

Cocaine CNS Actiosn

A
  • Stimulated cortex & brainstem
  • Inc mental awareness
  • Feeling of well-being & Euphoria
  • Paranoia (repeated doses)
  • Tremor & convulsions –> Resp. & Vasomotor depression (High doses)
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31
Q

Cocaine SNS Actions

A
  • Tachycardia
  • HTN
  • Mydriasis
  • Diaphoresis

These are due to the adrenergic stimulation by NE

32
Q

Cocaine addiction Treatment

A
  • Antidepressants

- Dopamine agonists

33
Q

Cocaine Withdrawal Syndrome

A
  • Dysphoria
  • Depression
  • Sleepiness
  • Fatigue
  • Cocaine craving
  • Bradycardia

Withdrawal is generally mild and symptoms are treated are they appear.

34
Q

DEA Classification of Amphetamine

A

Schedule 2

35
Q

MOA of Amphetamines

A

Taken into neurons by Biogenic Amine Transporters –> Interferes w/ VMAT –> Deplete synaptic vessels –> Inc in cytoplasmic levels of DA & other transmitter amines –>Reversal of DAT –> DA release into synapse

  • Inc catecholamine levels
  • Weak MAOI
  • Direct catecholaminergic agonists in brain
36
Q

Actions of Amphetamines

A

CNS (DA release)

  • Behavioral effects similar to cocaine
  • Inc alertness & insomnia
  • Depressed appetite
  • Psychosis & convulsion (high does)

SNS
- Activate receptors through NE release

37
Q

Uses of Amphetamines

A

Amphetamine + Methylphenidate

  • Attention Deficit Syndrome
  • Narcolepsy
38
Q

Amphetamine Withdrawal Symptoms & Treatment

A
  • Inc appetite
  • Sleepiness
  • Exhaustion
  • Mental depression

Tx = Antidepressants

39
Q

MOA of Nicotine

A

Full Nicotine receptor agonists
Ventral tegmental area (VTA) nicotinic receptors are expressed on DA neurons

Nicotine excites neurons –> DA release

40
Q

Actions of Nicotine

A

CNS
LOW DOSE - Ganglionic stimulation by depolarization
- Euphoria & relaxation
- Improves attention, learning, problem solving & reaction time
- Restlessness

HIGH DOSE - Ganglionic blockade

  • Central Resp. paralysis
  • Severe hypotension (medullary paralysis)
  • Appetite suppressant
41
Q

Treatment of Nicotine Addiction

A
  1. Nicotine replacement therapy
    - Transdermal patch, gum, nasal spray, vapor inhaler or lozenge for buccal absorption
  2. Sustained-release Bupropion
    - MOA unclear
  3. Varenicline
    - Partial Nicotinic receptor agonist in the CNS
    - Dec reward of smoking
42
Q

Nicotine Withdrawal Syndrome

A
  • Irritability
  • Sleeplessness
  • Anxiety
  • Dec concentration
  • Inc appetite/ weight gain

Withdrawal is mild but relapse is very common

43
Q

Opioids (names)

A
  • Heroin
  • Morphine
  • Codeine
  • Oxycodone
44
Q

Opioid Intoxication

A
  • Euphoria
  • Resp & CNS depression
  • Dec gag reflex
  • “Pinpoint pupils”
  • Seizures
  • Dec GI motility
45
Q

Opioid Withdrawal Syndrome

A
  • Dysphoria
  • Lacrimation
  • Rhinorrhea
  • Yawning
  • Stomach cramps, nausea & diarrhea
  • Dilated pupils
  • Sweating
  • Piloerection

Unpleasant but not life-threatening

46
Q

Opioid Tolerance & Dependence

A

Strong tolerance & dependence

addiction to heroin (& other short-acting opioids) produces behavioral disruptions & is usually incompatible w/ a productive life

47
Q

MOA for Treating Opioid Withdrawal Syndrome

A
  1. Detoxification w/ Opioid agonists
    - METHADONE or BUPRENORPHINE
    - Illicit agent replaced w/ long-acting opioid and then the dose is slowly reduced
  2. Detoxification w/ Opioid antagonist
    - NALTREXONE (antagonist w/ high affinity for u-receptor)
    - Used after detox in pts. that really wants to remain opioid-free
    - Will NOT satisfy craving or relieve withdrawal symptoms
48
Q

Marijuana (smoking)

A

61 different cannabinoids release

- Δ9-tetrahydrocannabinol

49
Q

MOA of Marijuana

A

Cannabinoid receptors = CB1 (GABAergic neurons in VTA of Brain) & CB2 (Immune cells)
- G-protein-linked receptors coupled to Gi

THC binds to CB1 –> Dec GABA –> No inhibition of dopaminergic neurons –> Inc DA release

50
Q

Actions of Marijuana

A
  • Euphoria –> Drowsiness & Relaxation
  • Conjunctival injection
  • Affects short-term memory & mental activity
  • Impaired judgement
  • Perception of slowed time
  • Social withdrawal
  • Impairs highly skilled motor activity
  • Stimulate appetite
  • Xerostomia
  • Visual hallucination & delusion
  • Enhancement of sensory activity
  • Toxic psychosis (HIGH DOSE)
51
Q

Withdrawal syndrome of Marijuana

A
  • Irritability
  • Anxiety
  • Depression
  • Insomnia
  • Restlessness
  • Dec appetite
52
Q

Tolerance & Dependence of Marijuana

A

Mild

53
Q

FDA-approved Cannabinoids for medical use (names)

A
  1. Nabilone (Synthetic THC derivative)
  2. Dronabinol (Synthetic form of THC)
  3. Cannabidiol (CBD)
54
Q

Medical uses of Marijuana

A

Dronabinol & Nabilone

  • Nausea & vomiting associated w/ cancer chemotherapy in pts. who failed to respond to conventional antiemetic treatments
  • Anorexia associated w/ weight loss in pts. w/ AIDS (DRONABINOL ONLY)

CBD
- seizures associated w/ Lennox-Gastaut syndrome, Dravet syndrome or Tuberous sclerosis complex

55
Q

Psychedelic agents (names)

A

LSD-like drugs

  1. LSD
  2. Mescaline
  3. Psilocybin
  4. Phencyclidine
  5. MDMA
56
Q

Psychedelic agents (names)

A

LSD-like drugs

  1. LSD
  2. Mescaline
  3. Psilocybin
  4. Phencyclidine
  5. MDMA
57
Q

What features are affected by Psychedelics?

A
  • Thought
  • Perception
  • Mood

Does NOT cause marked psychomotor stimulation or depression

58
Q

MOA of LSD

A

5HT2 receptor agonist –> Hallucinogenic effects

59
Q

CFs of LSD use

A

Combination of Somatic (Sympathomimetic effects) & Psychomimetic symptoms

  • Mydriasis
  • HTN
  • Tachycardia
  • Flushing
  • Sweating
  • Tremors
  • Piloerection
  • Perceptual distortion
  • Depersonalization
  • Anxiety & Paranoia
  • Flashbacks
60
Q

LSD Dependence & Withdrawal

A

NO addiction or withdrawal

61
Q

Adverse effects of LSD

A

“Bad trips”

Severe agitation – Tx is Diazepam

62
Q

MOA of Phencyclidine (PCP)

A

Dissociative anesthetic

Blocks NE & DA reuptake

  • Cholinergic & Anticholinergic effects
  • Nicotinic effects
  • Opioid receptor actions

Non-competitive antagonist of NMDA receptors
- Dissociative properties

63
Q

CFs of PCP

A
  • Violent or bizarre behavior
  • Psychosis
  • Delirium
  • Seizures
  • Impulsivity
  • Tachycardia
  • HTN
  • Diaphoresis
  • Miosis
  • Anesthesia
  • Analgesia
  • NYSTAGMUS (important diagnostic clue)
64
Q

PCP treatment

A

NO antidote

Extreme violence & seizures
- Sedation w/ parenteral Benzos

65
Q

MDMA “Ecstasy” MOA

A

Causes release of Biogenic amines —> Inc 5HT conc in synaptic cleft

66
Q

MDMA CFs

A 
Feelings of empathy & intimacy
- Euphoria
- Hallucinations
- Disinhibition
- Hyperactivity
- Inc thirst
- Social withdrawal
- Distorted sensory & time perception
- Mydriasis
- Bruxism - teeth grinding/clenching
NO Intellectual impairment
67
Q

Life-threatening effects of MDMA

A
  • HTN
  • Tachycardia
  • Hyperthermia
  • Hyponatremia
  • Serotonin syndrome
68
Q

Withdrawal Syndrome of MDMA

A
  • Depression (lasting several weeks)
  • Fatigue
  • Appetite changes
  • Difficulty concentrating
  • Anxiety
69
Q

Inhalants (Classes/ Names)

A
  1. Nitrous Oxide
  2. Volatile organic solvents
    - Gasoline, paint thinners, lighter fluid, glue & degreasers
  3. Organic nitrates
    - Amyl nitrate & Butyl nitrate
70
Q

Nitrous oxide

A

34% N2O + O2

  • Euphoria
  • Analgesics –>
  • Loss of consciousness

100% N20

  • Asphyxia –>
  • Death
71
Q

Volatile Organic Solvents

A
  • Sense of exhilaration & light-headedness
  • Implicated in cancer, cardiotoxicity, neuropathies & hepatotoxicity

(Gasoline, lighter fluid, glue, paint thinner & degreaser)

72
Q

Organic Nitrites

A

Amyl nitrite & Butyl nitrite
- Enhance Erection

NOT addictive

73
Q

Anabolic Steroids

A

Inc muscle mass

74
Q

Opioid overdose treatment

A

Naloxone

Overdose usually results in death

75
Q

Naloxone vs Naltrexone

A

Naloxone
- Overdose

Naltrexone
- Withdrawal treatment

Pharmacology (16 decks)

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