Drugs of Abuse Flashcards
(75 cards)
1
Q
Abuse
A
Excessive self-administration of any substance for nonmedical purposes
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
3
Q
Dependence
A
State of adaptation manifested by drug class specific withdrawal syndromes
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.
5
Q
Causes of Withdrawal syndrome
A
- Abrupt cessation
- Rapid dose reduction
- Antagonist administration
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
7
Q
Mechanism of Addiction
A
Activation of the Mesolimbic Dopamine pathway
8
Q
Classes of Drugs of abuse based on how Dopamine levels are increased
A
- Inc DA release indirectly by inhibiting GABA neurons that act as local inhibitory interneurons
- Opioids, cannabinoids, Benzos & ethanol - Directly stimulate dopaminergic neurons
- Nicotine & ethanol - Block or reverse DAT
- Cocaine, amphetamines & MDMA
9
Q
Classes of Drugs of Abuse
A
- CNS depressants
- Psychostimulants
- Nicotine
- Opioids
- Marijuana
- Psychedelic agents
- Inhalants
- Anabolic steroids
10
Q
CNS Depressants (Classes/ names)
A
- Ethanol
- Benzos
- Barbituates
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
12
Q
MOA of Ethanol
A
Affects:
- GABAa receptors
- Kir3/ GIRK channels
- Adenosine reuptake
- Glycine receptors
- NMDA receptors
- 5HT3 receptors (vomiting)
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
14
Q
Drugs used to treat Alcohol addiction
A
- Disulfiram
- Naltrexone
- Acamprosate
- Topiramate (NOT FDA approved)
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
16
Q
Naltrexone
A
Opioid antagonist- blocks activation of u-receptors –> Dec DA release
- Reduce the craving for alcohol & dec. relapse to heavy drinking
17
Q
Acamprosate
A
Unclear mechanism - Blocks Hyper-glutamatergic state in alcoholic brain
NMDA receptor antagonist - Prevent relapse drinking
18
Q
Topiramate
A
- Inc GABA function
- Antagonize Glutamate receptors
May reduce cravings
NOT FDA approved
19
Q
Alcohol Withdrawal Syndrome
A
- Tremor
- Nausea
- Sweating
- Agitation
- Anxiety
- Hallucinations
- Generalized seizures (24-48hrs)
- Delirium tremens (48-72hrs) - 5-15% mortality
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)
21
Q
Benzodiazepine Withdrawal Syndrome
A
- Tremors
- Anxiety
- Perceptual disturbances
- Dysphoria
- Psychosis
- Seizures
(Life-threatening)
22
Q
Benzo Withdrawal Syndrome Management
A
If pt. is on a short-acting benzo –> Switch to long-acting (DIAZEPAM) –> Gradually reduce dose
23
Q
Barbiturates Abuse
A
Similar to that of Benzos
24
Q
Psychostimulants (Class/ names_
A
- Methylxanthines
- Caffeine, Theophylline & Theobromine - Cocaine
- Amphetamines
25
Methylxanthine MOA
Blocks presynaptic Adenosine receptors --> Inc. NE release
| Normally, activation of Adenosine receptors inhibits NE release
26
CNS Effects of Methylxanthines
```
100-200 mg
- Dec fatigue
- Inc mental alertness
1.5g
- Anxiety
- Tremors
2-5g
- Spinal cord stimulation
```
27
Methylxanthines Tolerance & Withdrawal
Tolerance- rapidly develop
Withdrawal - Fatigue & sedation
Addiction- Rare
28
Cocaine DEA classification
Schedule 2 (due to its abuse potential)
29
MOA of Cocaine
Inhibits DA, NE & 5TH reuptake (prolonged dopaminergic effect --> Intense euphoria)
30
Cocaine CNS Actiosn
- Stimulated cortex & brainstem
- Inc mental awareness
- Feeling of well-being & Euphoria
- Paranoia (repeated doses)
- Tremor & convulsions --> Resp. & Vasomotor depression (High doses)
31
Cocaine SNS Actions
- Tachycardia
- HTN
- Mydriasis
- Diaphoresis
These are due to the adrenergic stimulation by NE
32
Cocaine addiction Treatment
- Antidepressants
| - Dopamine agonists
33
Cocaine Withdrawal Syndrome
- Dysphoria
- Depression
- Sleepiness
- Fatigue
- Cocaine craving
- Bradycardia
Withdrawal is generally mild and symptoms are treated are they appear.
34
DEA Classification of Amphetamine
Schedule 2
35
MOA of Amphetamines
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
Actions of Amphetamines
CNS (DA release)
- Behavioral effects similar to cocaine
- Inc alertness & insomnia
- Depressed appetite
- Psychosis & convulsion (high does)
SNS
- Activate receptors through NE release
37
Uses of Amphetamines
Amphetamine + Methylphenidate
- Attention Deficit Syndrome
- Narcolepsy
38
Amphetamine Withdrawal Symptoms & Treatment
- Inc appetite
- Sleepiness
- Exhaustion
- Mental depression
Tx = Antidepressants
39
MOA of Nicotine
Full Nicotine receptor agonists
Ventral tegmental area (VTA) nicotinic receptors are expressed on DA neurons
Nicotine excites neurons --> DA release
40
Actions of Nicotine
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
Treatment of Nicotine Addiction
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
Nicotine Withdrawal Syndrome
- Irritability
- Sleeplessness
- Anxiety
- Dec concentration
- Inc appetite/ weight gain
Withdrawal is mild but relapse is very common
43
Opioids (names)
- Heroin
- Morphine
- Codeine
- Oxycodone
44
Opioid Intoxication
- Euphoria
- Resp & CNS depression
- Dec gag reflex
- "Pinpoint pupils"
- Seizures
- Dec GI motility
45
Opioid Withdrawal Syndrome
- Dysphoria
- Lacrimation
- Rhinorrhea
- Yawning
- Stomach cramps, nausea & diarrhea
- Dilated pupils
- Sweating
- Piloerection
Unpleasant but not life-threatening
46
Opioid Tolerance & Dependence
Strong tolerance & dependence
addiction to heroin (& other short-acting opioids) produces behavioral disruptions & is usually incompatible w/ a productive life
47
MOA for Treating Opioid Withdrawal Syndrome
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
Marijuana (smoking)
61 different cannabinoids release
| - Δ9-tetrahydrocannabinol
49
MOA of Marijuana
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
Actions of Marijuana
- 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
Withdrawal syndrome of Marijuana
- Irritability
- Anxiety
- Depression
- Insomnia
- Restlessness
- Dec appetite
52
Tolerance & Dependence of Marijuana
Mild
53
FDA-approved Cannabinoids for medical use (names)
1. Nabilone (Synthetic THC derivative)
2. Dronabinol (Synthetic form of THC)
3. Cannabidiol (CBD)
54
Medical uses of Marijuana
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
Psychedelic agents (names)
LSD-like drugs
1. LSD
2. Mescaline
3. Psilocybin
4. Phencyclidine
5. MDMA
56
Psychedelic agents (names)
LSD-like drugs
1. LSD
2. Mescaline
3. Psilocybin
4. Phencyclidine
5. MDMA
57
What features are affected by Psychedelics?
- Thought
- Perception
- Mood
Does NOT cause marked psychomotor stimulation or depression
58
MOA of LSD
5HT2 receptor agonist --> Hallucinogenic effects
59
CFs of LSD use
Combination of Somatic (Sympathomimetic effects) & Psychomimetic symptoms
- Mydriasis
- HTN
- Tachycardia
- Flushing
- Sweating
- Tremors
- Piloerection
- Perceptual distortion
- Depersonalization
- Anxiety & Paranoia
- Flashbacks
60
LSD Dependence & Withdrawal
NO addiction or withdrawal
61
Adverse effects of LSD
"Bad trips"
Severe agitation -- Tx is Diazepam
62
MOA of Phencyclidine (PCP)
Dissociative anesthetic
Blocks NE & DA reuptake
- Cholinergic & Anticholinergic effects
- Nicotinic effects
- Opioid receptor actions
Non-competitive antagonist of NMDA receptors
- Dissociative properties
63
CFs of PCP
- Violent or bizarre behavior
- Psychosis
- Delirium
- Seizures
- Impulsivity
- Tachycardia
- HTN
- Diaphoresis
- Miosis
- Anesthesia
- Analgesia
- NYSTAGMUS (important diagnostic clue)
64
PCP treatment
NO antidote
Extreme violence & seizures
- Sedation w/ parenteral Benzos
65
MDMA "Ecstasy" MOA
Causes release of Biogenic amines ---> Inc 5HT conc in synaptic cleft
66
MDMA CFs
```
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
Life-threatening effects of MDMA
- HTN
- Tachycardia
- Hyperthermia
- Hyponatremia
- Serotonin syndrome
68
Withdrawal Syndrome of MDMA
- Depression (lasting several weeks)
- Fatigue
- Appetite changes
- Difficulty concentrating
- Anxiety
69
Inhalants (Classes/ Names)
1. Nitrous Oxide
2. Volatile organic solvents
- Gasoline, paint thinners, lighter fluid, glue & degreasers
3. Organic nitrates
- Amyl nitrate & Butyl nitrate
70
Nitrous oxide
34% N2O + O2
- Euphoria
- Analgesics -->
- Loss of consciousness
100% N20
- Asphyxia -->
- Death
71
Volatile Organic Solvents
- Sense of exhilaration & light-headedness
- Implicated in cancer, cardiotoxicity, neuropathies & hepatotoxicity
(Gasoline, lighter fluid, glue, paint thinner & degreaser)
72
Organic Nitrites
Amyl nitrite & Butyl nitrite
- Enhance Erection
NOT addictive
73
Anabolic Steroids
Inc muscle mass
74
Opioid overdose treatment
Naloxone
Overdose usually results in death
75
Naloxone vs Naltrexone
Naloxone
- Overdose
Naltrexone
- Withdrawal treatment
