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Pharmacology (Winter) > Drugs of Abuse (Part 2) > Flashcards

Drugs of Abuse (Part 2) Flashcards

1
Q

What are the stimulant drugs?

A
  • Cocaine
  • Methamphetamine
  • MDMA (ecstasy)
  • Nicotine
  • Hallucinogens & Dissociative Drugs
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2
Q

Which stimulant drugs structually resemble dopamine & epinephrine?

A
  • Cocaine
  • Methamphetamine
  • MDMA (ecstasy)
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3
Q

Where is Cocaine derived from?

A

coca plant

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4
Q

What is the mech of action of Cocaine?

A
  • Blocks reuptake of dopamine
  • Also blocks reuptake of norepinephrine and serotonin
  • Elevates reward system
  • (therefore) Using only ONCE can make someone want to use it again and again
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5
Q

Where is Methamphetamine produced from?

A

pseudoephedrine and other over-the-counter medicines

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6
Q

What is the mech of action of Methamphetamine?

A
  • Blocks dopamine reuptake, but also increases dopamine release
  • Much higher levels of synaptic dopamine than cocaine!!
  • Blocks uptake of norepinephrine and serotonin
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7
Q

What does Meth have that’s diff from Cocaine?

A

Blocks dopamine reuptake (LIKE COCAINE), but ALSO increases dopamine release

Much higher levels of synaptic dopamine than cocaine

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8
Q

What are the Pharmacokinetics of Cocaine?

A
  • Usually snorted, smoked, or injected
  • Half life is 1 hr
  • 95% is metabolized in liver (CYP2D6), 5% is excreted unchanged in urine
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9
Q

What are the Pharamacokinetics of Meth?

A
  • Usually smoked, snorted, or injected
  • Half life is 12 hrs
  • 40% is excreted unchanged in urine, the rest is metabolized in the liver to active metabolites (amphetamine)
  • Euphoria disappears before drug concentration drops, so users take more to try to maintain the high
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10
Q

What are the short term effects of cocaine & meth?

A

Dopamine effects: (last 3 @ higher doses)
- Euphoria
- Aggressive behaviour (violence)
- Psychosis (paranoia, hallucinations, etc.)
- Psychomotor agitation (can’t sit still)

Norepinephrine effects:
- Energetic, talkative
- Hyperawareness; Fight or flight

Serotonin effects:
- Mood, loss of appetite, less need for sleep

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11
Q

What can cocaine result in?

A
  • increase sympathetic output & catecholamines can cause ischemia & then infraction resulting in death
  • decrease Na transport can cause arrhythmias resulting in death
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12
Q

What are the long term effects of cocaine & meth?

A

The brain
- Dopamine, norepinephrine, serotonin are depleted
- Excitatory glutamate neurons blunted (particularly in the nucleus accumbens)
- Stress pathways are more sensitive
– Stress leads to more drug seeking behaviour
- Reduced activity in prefrontal cortex
– Poor decision-making, consequences not understood
- Reduced brain glucose metabolism

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13
Q

What are the long term effects of meth (in addition to the ones that are with cocaine & meth)?

A
  • Methamphetamine psychosis
  • Severe structural and functional changes in areas associated with emotion and memory
    – Possibly permanent (longer than 14 months after abstinence)
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14
Q

What are the long term effects of cocaine & meth?

A
  • Skin sores (crawling insects)
  • Weight loss
  • Organ toxicity
  • Fever

(Dental problems)

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15
Q

What are Cocaine & Meth withdrawal?

A
  • Increased appetite (b/c these drugs are suppressing their appetite)
  • Chills, fatigue
  • Anxiety, depression, insomnia
  • Muscle aches
  • Tremors
  • Meth withdrawal lasts longer (usually at least 3 weeks)
  • Antidepressants, antipsychotics, dopamine agonists (D2 receptors) are currently being investigated as treatment options
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16
Q

What is MDMA (Ecstasy)?

A
  • N-methyl-3,4 methylenedioxymethamphetamine
  • Structurally similar to amphetamines, but also similar to hallucinogen mescaline
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17
Q

What is the mech of action of MDMA (Ecstasy)?

A
  • Blocks reuptake of serotonin and norepinephrine
  • WEAKLY blocks reuptake of dopamine (less association with addiction)
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18
Q

What is the route of admin of MDMA?

A
  • Oral tablet or capsule
  • 45 min to feel effects, high usually lasts 3-4 hours
  • Half life 5-7 hours
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19
Q

What is the metabolism of MDMA?

A
  • Metabolized in liver by CYP2D6 (like cocaine)
  • However, other enzymes are involved and they are saturated at relatively low concentrations
    – Small changes in dosage can greatly increase the risk of toxicity.
  • ELIMINATION IS SLOW
  • 40 hours for 95% of the drug to be cleared
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20
Q

What are the short term effects of MDMA?

A
  • Well-being, stimulation, distortions in time and sensory perception, and enhance enjoyment from sensory experiences
  • Increases empathy

called the empathetic drug

Serotonin effects:
- Mood-elevation, empathy

Norepinephrine effects:
- Energetic, talkative
- Hyperawareness; Fight or flight

Dopamine effects:
- Euphoria

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21
Q

What can MDMA cause?

A

Amphetamine-like side effects on other organs (mostly b/c increase NE)

Overdose can cause:
- Hypertension
- Faintness
- Panic attacks
- Seizures
- Loss of consciousness

  • *Hyperthermia- deadly in warm environments (#1 risk)
22
Q

What are the long term effects of MDMA?

A

Serotonin is depleted leading to negative psychological effects for several days after use
–> Depression, sleep disturbances, etc.

  • Dental problems
  • Lack of appetite
23
Q

What happens with heavy use of MDMA?

A
  • Serotonin neurons become damaged
  • Decreased brain activity
24
Q

What is Nicotine?

A

Active ingredient in tobacco

25
Q

What is the mech of action of Nicotine?

A
  • Binds nicotinic acetylcholine receptors (are ion channel receptors)
  • Mimics acetylcholine, causes cell depolarization
  • Activates adrenal gland to release epinephrine
  • Activates nicotinic receptors on dopaminergic neurons in the reward pathway
  • Transient surge in endorphins that causes a brief, weak euphoria
26
Q

What are the Pharmacokinetics of Nicotine?

A
  • Half life is 1 hr
  • Dissipates quickly along with positive feelings, driving frequent using
  • 70% of nicotine is metabolized to cotinine
  • Cotinine
    – Long half life (20-30 hrs)
    – Some brain effects (decreases anxiety, enhances memory)
27
Q

What are the short term effects of nicotine & smoking?

A
  • “Kick”
  • Appetite suppression
  • Short term memory enhancement
  • Irritability, dizziness, abnormal dreams
  • Increased heart rate and blood pressure
  • Muscle tremors/pain
  • Bronchospasms
  • Nausea, diarrhea, dry mouth
28
Q

What is the long term effects of Nicotine?

A

The prefrontal cortex is altered
- In young people this might be permanent (b/c prefrontal cortex is still developing until 20)

  • Difficulty paying attention
  • Decision making
  • Impulse control
29
Q

How is nicotine addition treated?

A

Nicotine withdrawal
- Irritability, cravings, cognitive deficits, sleep disturbances, increased appetite

Nicotine replacement therapy
- Patch, chewing gum, etc.
- Varenicline
– Blocks specific nicotinic receptors in the mesolimbic system
– No rewarding feelings when smoking

30
Q

What are the Classic Hallucinogens?

A
  • LSD (d-lysergic acid diethylamide, aka: acid)
  • Psilocybin (mushrooms)
  • Peyote (mescaline)
31
Q

What are the Dissociative Drugs?

A

PCP

32
Q

What is the Classic Hallucinogens mech. of action?

A
  • Activate 5-HT2 serotonin receptors
  • 5-HT activation increases glutamate pathways
  • At high doses, modest influence on dopamine pathways

Not entirely clear how this causes hallucinations

33
Q

What is the route of admin. of LSD?

A
  • Paper soaked in LSD, placed on the tongue
  • Tablets or diluted in drinks
34
Q

What are the Pharmacokinetics of LSD?

A

Most potent hallucinogen

  • Rapidly metabolized in the liver to inactive metabolites
  • Effects last up to 12 hours (b/c brain chemistry is altered)
    (even though the drug isn’t in system it still has effects)
35
Q

Which hallucinogen is the MOST potent?

A

LSD

36
Q

What are the Pharmacokinetics of Psilocybin (mushrooms)?

A

Mushrooms- dried or raw, steeped in tea

  • Significant hallucinations up to 1hr
  • Effects last up to 8 hours
  • Dephosphorylated to active metabolite PSILOCIN
  • 80% of psilocin is glucuronidated and excreted in the urine
  • Remainder is metabolized in liver
37
Q

What are the short term effects of Hallucinogens?

A

Profound distortions in a person’s perceptions of reality
- See images, hear sounds, and feel sensations that don’t exist

Emotions swing widely

Autonomic system is activated
- Increased heart rate
- Increased blood pressure

38
Q

What are the 2 diff. effects of Hallucinogens characterized as?

A

“Good trip”
- Mentally stimulating and feelings of a heightened understanding

“Bad trip”
- Terrifying thoughts and nightmarish feelings of anxiety and despair that include feelings of losing control, insanity, or death

39
Q

Which Hallucinogen are BAD trips more common in? & what does it also cause?

A

LSD

b/c LSD is MOST potent

LSD also causes “flashbacks” that occur up to years after taking the drug

40
Q

What is general about the effects of Hallucinogens?

A

Generally NO evidence of organ toxicity

However, extreme LSD use can lead to long-term psychosis

41
Q

What is Phencyclidine (PCP)?

A

Dissociative anesthetic and analgesic

42
Q

What is the mech. of action for Phencyclidine (PCP)?

A
  • HIGHEST AFFINITY: inhibits NMDA receptors (glutamate ion channels)
  • Inhibits dopamine, norepinephrine, and serotonin reuptake (risk of addiction)
  • Increases dopamine and norepinephrine production
  • LOWEST AFFINITY: activates opioid receptors
43
Q

What is the route of admin. for PCP?

A

Can be SMOKED, snorted, ingested, or injected

44
Q

What are the Pharmacokinetics of PCP?

A
  • 90% metabolized by oxidative hydroxylation in liver
  • Effects last 6-24 hours (lasts v. long)

PCP is fat soluble and effects can linger in people with more body fat
- up to 48 hours or come and go over days (as its released from body fat)

45
Q

What are the short term effects of PCP at LOW doses?

A
  • Alternate between lethargy and fearful agitation
  • Violent behaviour
  • Nystagmus (involuntary eye movements)
  • Tachycardia
  • Hypertension
  • Drunk/euphoric
  • Analgesia
46
Q

What are the short term effects of PCP at MODERATE - HIGH doses?

A
  • Acute schizophrenia: psychosis, hallucinations, paranoid delusions
  • Cardiac arrythmias
  • Coma
47
Q

Why does Acute Schizophrenia occur due to PCP at MODERATE - HIGH doses?

A

b/c of the NMDA receptor inhibition

48
Q

What are the long term effects of PCP?

A
  • Prolonged psychosis that may develop into schizophrenia
  • Flashbacks (like LSD; even years later)
  • Persistent speech problems
  • Severe depression
  • *Significant likelihood of self-inflicted trauma due to violent behaviour combined with analgesic effects of drug (they don’t feel pain so are more likely to injure themselves)
49
Q

Which drugs cause the greatest euphoria (most addictive)?

A
  • Opioids
  • ~Alcohol
  • Cocaine
  • Meth
  • Nicotine
  • PCP
50
Q

Which drugs cause nasty withdrawal symptoms?

A
  • Opioids
  • Alcohol
  • Cocaine
  • Meth
51
Q

Which drugs cause permanent neuronal damage or death?

A
  • Inhalants
  • Cocaine
  • Meth
  • MDMA
  • ~Nicotine
52
Q

Which drugs cause organ toxicity?

A
  • Opioids
  • Alcohol
  • Inhalants
  • Cocaine
  • Meth
  • MDMA
  • Nicotine

Pharmacology (Winter) (23 decks)

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