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Pharmacology > Ch 32: Drugs of Abuse > Flashcards

Ch 32: Drugs of Abuse Flashcards

1
Q

Mesolimbic Dopamine System

A

“reward pathway”
- a dopaminergic pathway in the brain
Note:
(this pathway connects the ventral segmental area in the midbrain to the ventral striatum of the basal ganglia in the forebrain?

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2
Q

THC withdrawal

A
  • mild & short lived: restlessness, irritability, mild agitation, insomnia, nausea, cramping

other cannabinoids:

  • Dronabinol: FDA approved
  • Nabilone: chronic pain management
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3
Q

What’s opiate tolerance?

A

initially:
activation of the mu receptor lead to inhibition of less cAMP

Now:
up regulation of AC, increased cAMP activates cAMP response element bending protein (CREB)

  • also during withdrawal the nucleus accumbens start producing dynorphin (kappa agonist)
    it gets released onto the VTA
    & reduces its DA release
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4
Q

physical dependence

A

“dependence”
- caused by chronic use of a tolerance-forming drug

(higher dose used, the greater the duration of use)
can cause severe withdrawal syndromes

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5
Q

Nucleus accumbens

A

promotes satiety (5-HT) and desire (DA)

may increase DA and reduce 5-HT in addiction

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6
Q

Prefrontal cortex

A

conscious component

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7
Q

DMT

A

Dimethyltryptamine (similar to 5-HT)

- hallucinogenic

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8
Q

Nicotine

A
  • drug that act through ion channels

- act through nicotinergic cholinergic receptors

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9
Q

Psilocybin

A

similar to LSD & mescaline

- from psilocybin mushrooms

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10
Q

Sniffing

A

inhalation from an open container

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11
Q
  1. Impact DA transport
A
  • prevent DA re-uptake (increasing DA at VTA targets)
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12
Q

physiological dependence

A

“addiction”

  • the emotional and mental processes that’s associated with the development of and recovery from a substance use disorder/process addiction
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13
Q

THC effects

A
  • presynaptic inhibition at THC receptors

- THC receptors will inhibit the release of GABA onto the VTA DA- secreting neuron

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14
Q

Huffing

A

soaking a cloth in the “stuff” prior to inhalation

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15
Q

cocaine:

A

blocks DA uptake (especially in nucleus accumbens) leads to reward effects

can be abolished in mice w/ cocaine-insensitive DA transporter

has local anesthetic effect: Blocks NA+ channels
block NE uptake
leads to increased intracranial hemorrhage, stroke, MI, seizures

note: constricts Blood Vessels (nasal damage)

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16
Q

Alcohol

A
  • drug that act through ion channels
  • effect GABA-A, Adenosine re-uptake, glycine receptor, NMDA receptor, 5-HT3 receptor
  • dependence (6-12 hrs after cessation of heavy drinking)
      • tremors, nausea, sweating, agitation, anxiety
  • cause visual, tactile, auditory hallucinations
  • seizures or delirium tremors (5-15% mortality)
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17
Q

Bagging

A

breathing in and out of a bad it is in

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18
Q

Ecstacy (MDMA)

A
  • methylene-dioxymethamphetamine
  • related to amphetamines
  • cause feelings of intimacy & empathy, used in psychotherapy
  • Raves

– may permanently deplete 5-HT (selective for serotonin transporter mechanism)

– acute effects: hyperthermia, dehydration, autonomic, hyperactivity, change in mental status, seizures

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19
Q

How do drugs of abuse activate the mesolimbic system?

A
  1. activate receptors that couple to GIO.
  2. activate receptors
  3. Impact DA transport
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20
Q

abuse is

A

“wanting together high”

21
Q

Misuse is

A

“taking too much”

- taking more than what was prescribed

22
Q

Mu opioid Drugs

A
  • Morphine, heroine (diacetylmorphine, quickly metabolized to morphine)
  • Codeine, oxycodone, meperidine (esp. in health care professionals)
  • strong tolerant & dependence
  • Withdrawal (dysphoria, nausea, vomiting, muscle aches, lacrimation, rhinorrhea (runny nose), mydriasis (dilated pupils), piloerection, sweating, diarrhea, yawning, fever
23
Q

Inhalants

A

recreational exposure to nitrates, ketones, or hydrocarbons of volatile containers

(can cause white matter lesions in the CNS)

sniffing
huffing
bagging

(prevalent in children & youths)

24
Q

Opiates

A
  • knockout mice lacking mu receptor
  • do not knock. out sigma or kappa
  • do not show signs of dependence, analgesia or reward
  • show dramatic tolerance effects to opiate addiction
  • do not show physiologic effects (respiratory depression)
25
Q

what causes addiction?

A
  • feelings of euphoria & active reward systems
  • repeating doses (can lead to tolerance)
  • if drug can no longer be accessed, you’ll get withdrawal symptoms = DEPENDENCE

ADDICTION = when one keeps using a drug despite negative consequences
(compulsively seek/ wanting without liking)

NOT ALL USERS BECOME ABUSERS
1/6 COCAINE USERS BECOME ADDICTS

26
Q
  1. activate receptors that couple to GIO.
A
  • mostly at GABA receptors, causing hyperpolarization, and disinhibition (more DA release)
27
Q

Tetrahydrocannabinol (THC)

A
  • euphoria, relaxation
  • well-being
  • grandiosity
  • altered perception
  • dose dependent visual distortions (drowsiness, diminished, coordination, memory impairment)
  • increased appetite
  • reduced nausea
  • decreased intraoccqular pressure
  • relief from chronic pain
28
Q

systemic administration of most drug abuse

A

leads to the VTA bursting with DA

29
Q

LSD

A

Acts at 5-HT-2a receptors

  • created by Albert Hoffmann
  • from Ergot of Rye (1939)
    • ergot produces lysergic acid
30
Q

what causes a person to relapse?

A

re-exposure to the drug
stress
go back to a context that recalls prior drug use

31
Q

LSD (Lysergic Acid Diethylamide)

A
  • causes hallucinations
  • DO NOT CAUSE DEPENDENCE/ ADDICTION
  • do not increase DA release in mesolimbic structures & are NOT REWARDING
32
Q

Class I drugs

A
  • opioids (mu opioid receptor)
  • Cannabinoids (cannabinoid receptor)
  • Gamma Hydroxy Butyric Acid (GHB) (GABA-b)
  • LSD, Mescaline, psilocybin (5-HT 2a receptor)
33
Q

alcohol treatment?

A
  • Benzos to deal w/ anxiety and agitation

- be supportive

34
Q

Hippocampus

A

involved in memory production

it is a “good memory” of that drug participation

35
Q

Mescalines

A

from peyote cactus

  • used by native Americans & native Mexican American in rituals
  • similar to LSD actions = hallucinogenic, etc.
36
Q

Drugs that inhibit amine transport

A

cocaine
amphetamines
MDMA

37
Q

why abuse drugs?

A 
alter consciousness
build body
escape
pleasure
prevent withdrawal effects
38
Q

disinhibition

A
  • when VTA is inhibited from releasing DA
  • Opiates can act at mu opioid receptors (MOR) and prevent GABA release (normally inhibits DA neurons from firing) by inhibiting Ca2+ influx or by increasing K+ conductance, & inhibiting GABA release
39
Q

Amphetamines

A
  • synthetic sympathomimetics that cause release of amines (dopamine, norepinephrine)
  • inhibit storage by inhibiting vesicular monoamine transported (VMAT)
  • increase in catecholamines
  • increase arousal and reduce sleep
  • DA increases to induce reward
  • psychoses, hallucinations, & anorexic effects
40
Q

drug abuse tragedies

A

illicit use for non-medical purposes

41
Q

Amygala

A

adds an agreeable/disagreeable nature to an event

may add to the “it was good” nature of drug participation

42
Q

GHB effects

A
  • acts as GABA-b receptors on both pre-synaptic cell and VTA DA-secreting neurons
  • the presynaptic GABA neurons are more sensitive to GHB = overall effect seems to be in favor of disinhibition of the pre-synaptic cell release of GABA
43
Q

Ergotism

A
  • convulsive ergotism includes: shakiness, tremor, convulsions, hallucination
  • (witchcraft??) –> Salem witch trials?
44
Q

Ketamine & PCP

A
  • drug that act through ion channels
  • develop as general anesthetics (induce anesthesia)
  • act as NMDA receptors
  • neither are addictive, BUT can be psychedelics
  • chronic use can lead to schizophrenia-like psychosis

PCP –> “angel dust”

Ketamine –> “special K”

(both are white, crystalline powders, can be sold as liquid, capsules, pills, and can be snorted, ingested, injected, and smoked)

45
Q

Ventral Tegmental Area (VTA) protects to:

A

Nucleus accumbens
Amygala
Hippocampus
Prefrontal cortex

(mostly DA/dopamine releasing neurons)

46
Q
  1. activate receptors
A
  • open ion channels to cause disinhibition or excitation (more DA release)
47
Q

what happens when VTA start releasing DA?

A
  • once DA is released, it starts bursting onto other sites

- leads to an “award” (press a lever so it can happen again)

48
Q

Cocaine

A
  • from Erythroxylon coca in Andes
    • water soluble (in hydrochloride form)
      injected or absorbed in mucosa

– when heated in alkaline solution= becomes free base
can be smoked

49
Q

Benzodiazepines

A
  • drug that act through ion channels
  • act at GABA-a receptors
  • withdrawal effects last just a few days

Pharmacology (17 decks)

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