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Pharmacology II > Drugs of Abuse > Flashcards

Drugs of Abuse Flashcards

1
Q

Addiction is characterized by what? (3)

A
  1. Compulsive behavior
  2. Reinforcing behavior (rewarding/pleasurable)
  3. Loss of control
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2
Q

How do behavioral abnormalities of addiction develop? how long do they last?

A

Develop progressively during repeated exposure

Can persist for months/years after discontinuation of drug

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3
Q

3 steps of addiction

A
  1. Repeated exposure which alters gene expression in certain brain areas
  2. Altered expression mediates altered neural function
  3. Result - behavioral changes
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4
Q

Which reward pathway does addiction affect?

A

reward pathway

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5
Q

MOA of the reward pathway? (areas and neurons involved)

A 
Noradrenergic neurons (locus ceruleus) send info of novelty and arousal to dopaminergic neurons in ventral tegmental area (VTA)
VTA projects to nucleus accumbens (NAc) and cortex
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6
Q

Multiple inputs modify signaling in the ________ pathway and modulate which perception?

A

Mesolimbic dopamine pathway

Perception of pleasure

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7
Q

VTA output is modulated by what? and which functions are these involved in? (3)

A
  1. Glutamatergic input from prefrontal cortex - executive function and cognitive control
  2. Excitatory input from amygdala signals - stress and anxiety
  3. Glutamatergic input from hippocampus - memory
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8
Q

Which receptors are decreased with addiction?

A

Dopamine D2 receptors

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9
Q

Do all drugs lead to dependence and are they all addictive?

A

No

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10
Q

What is dependence?

A

Development of adaptive responses that lead to symptoms of withdrawal (abstinence syndrome) when drug is discontinued. This drives repeated exposure to avoid withdrawal

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11
Q

4 short-term effects of drugs and their withdrawal symptoms?

A
  1. Loss of inhibition - Irritability, tremor
  2. Reduction in anxiety - Anxiety
  3. Sedation - Sleep disturbances
  4. Decreased motor coordination - Seizures
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12
Q

3 main types of tolerance?

A

Acquired tolerance
Cross-tolerance
Reverse-tolerance

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13
Q

3 types of acquired tolerance?

A

Pharmacokinetic tolerance
Pharmacodynamic tolerance
Behavioural tolerance

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14
Q

5 types of drugs of abuse

A 
Stimulants
Hallucinogens
Cannabinoids
Opioid Analgesics
Sedative-Hypnotics
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15
Q

3 stimulant drugs?

A

Cocaine
Amphetamines
MDMA

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16
Q

Form of administration of cocaine is important in determining what? (3)

A

Intensity of effects
Abuse liability
Toxicity

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17
Q

4 types of cocaine administration?

A

Oral
Inhaled
Injected
Smoked

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18
Q

Is cocaine addictive? Especially in which form?

A

Yes

smoke-able free-base form (crack)

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19
Q

Cocaine mainly blocks what?

2 others mechanisms it blocks and physical effects?

A

Reuptake of monoamines
Blockade of DA reuptake in the CNS related to rewarding effects
Others:
1. Reuptake of norepinephrine in sympathetic nervous system : Increased pressure, tachycardia
2. Blocks sodium channels : arrhythmias

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20
Q

4 toxicities of cocaine?

A

Psychosis
CV complications
Hepatotoxicity
Convulsions

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21
Q

Cocaine increases _____, ______ and ______

Cocaine decreases _______ by inducing _______. This leads to ______

A

HR, BP, Myocardial oxygen demand
Oxygen supply by inducing coronary vasoconstriction
This leads to Myocardial Ischemia

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22
Q

What is the major CV complication observed in cocaine use?

A

Myocardial ischemia

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23
Q

Which route of cocaine administration increases plasma concentration the fastest? slowest?

A

IV

Oral

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24
Q

Which two cocaine administration cause quick intoxication?

A

IV

Smoked

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25
Q

How does cocaine affect glucose metabolism? Where in the brain does this mainly happen and which functions are affected?

A

It decreases glucose metabolism

Frontal lobes - Planning, abstract thinking and impulse behavior regulation

26
Q

3 amphetamine administration forms?

A

Orally
IV
Smoked

27
Q

MOA of amphetamines?

A

Transported like dopamine
Transported into cell, inhibits vesicular monoamine transporter (VMAT)
Increases dopamine in presynaptic terminal

28
Q

Physiological actions of amphetamines? (5)

A
  1. Fight-or-flight response
  2. Alertness
  3. Anxiety, apprehension, panic
  4. Potent effects on DA
  5. Behavioral stereotypy (meaningless repetition of a single activity)
29
Q

Drug that is structurally similar to amphetamines and DA?

A

Metamphetamine

30
Q

Is meth addictive? What does it look, smell and taste like?

A

Yes

White, odorless, bitter tasting crystalline powder

31
Q

Is meth more or less potent than amphetamine? Longer or shorter duration?

A

More

Longer

32
Q

MOA of meth?

A

Blocks DA re-uptake and increases DA release

33
Q

MOA of MDMA? (3)

A

Block 5-HT transporter
Causes release of biogenic amines - reverses transporters
Long-term depletion of intracellular 5-HT

34
Q

Acute toxic effects of MDMA? (2)

Long-term? (2)

A

Acute : hyperthermia, dehydration

Long : Neurotoxicity, cognitive impairment

35
Q

What is a syndrome that can occur if combining MDMA with other drugs that increase serotonin levels?
What are the many symptoms? (10)

A

Serotonin syndrome

  1. Agitation
  2. Diarrhea
  3. Fast HR
  4. Hallucinations
  5. Increased body temp
  6. Loss of coordination
  7. Nausea
  8. Overactive reflexes
  9. Rapid changes in BP
  10. Vomiting
36
Q

Cannabinoids interact with ____ receptor

A

CB1

37
Q

MOA of cannabinoids?

A

Inhibiting release of GABA, which causes disinhibition of dopamine neurons

38
Q

5 effects of cannabinoids?

A 
Euphoria
Relaxation
Increase appetite
Prevent nausea
Lower intraocular pressure
39
Q

How does CB1 distribution change with age?

A

Decreases

40
Q

Designer Marijuana :
Other name for it?
What does it contain and their effect? (2)

A

Spice, K2
Contains synthetic cannabinoids the potently activate CB1 receptors
Contains other unknown compounds, constantly changing

41
Q

5 opioid analgesics?

A 
Morphine
Heroin
Oxycodone
Meperidine
Fentanyl
42
Q

Opioids work on which receptor in which region?

What does this do?

A

u k delta opioid receptors (Gi/o couple GPCR)
VTA
Activation of u opioid receptors selectively expressed on GABA neurons results in disinhibition of DA neurons and euphoria

43
Q

When opioids act on GABA neurons in the VTA, what the affects on neurotransmission?

A

Efflux of K+
Hyperpolarization
Difficulty of neuron to fire

44
Q

Dependence on opioids leads to which syndrome and what are the symptoms? (7)

A

Abstinence syndrome

Yawning, sweating, weakness, nausea/vomiting, tremors, muscle jerks

45
Q

How do you treat opioid withdrawal? Why is it more efficient?

A

Replacement with pharmacological equivalent agent

-Doesn’t reach “high” or “withdrawal symptom” levels (peaks arent as fast or as high)

46
Q

What drug precipitates opioid withdrawal and abstinence syndrome?

A

Naloxone - opioid receptor antagonist

47
Q

Example of a partial agonist in the treatment of addiction?

A

Buprenorphine

48
Q

What is the MOA of buprenorphine?

A

Competes with morphine, binds with more affinity on the opioid receptor and decreases cAMP levels.
Prevents lower affinity full agonists (morphine) from binding

49
Q

What causes opioid withdrawal symptoms

A

Large increase in cAMP production following discontinuation of opioid agonist or administration of antagonist

50
Q

3 sedative hypnotics

Do they produce tolerance and/or dependence aka withdrawal symptoms?

A

Barbiturates
Benzodiazepines
Ethanol

Yes both

51
Q

Sedative hypnotics relieve ____ and ____

A

stress

anxiety

52
Q

Higher doses of sedative hypnotics produce what state? What is this called

A

Sleep-like state

Hypnosis

53
Q

5 Hallucinogens

A 
LSD
Mescaline
Psilocybin
PCP
Ketamine
54
Q

Hallucinogens alter _______ and distort ______

A

Consciousness

Perceptions

55
Q

Hallucinogens are also called ______

A

psychomimetics

56
Q

Do hallucinogens induce addiction?

A

No

57
Q

Do hallucinogens stimulate DA release?

A

No

58
Q

MOA of LSD?

Half-life?

A

Acts as agonist at 5-HT2A receptors
Modulates glutamate-mediated sensory, perceptual, affective and cognitive processes (compete with serotonin, increases glutamate release)

Half-life : 2,5-4 hr with inactive metabolites

59
Q

What areas of the CNS does LSD act (2)

A

Deep cortical layers

Cortical layer V

60
Q

PCP and Ketamine cause _____ state and _____

Chronic exposure leads to long-lasting ______

A

Dissociative, hallucinations

Psychosis

61
Q

MOA of PCP and Ketamines?

A

Bind to NMDA-receptors as non-competitive antagonist

Affects glutamate-mediated cortical neuron signaling

Pharmacology II (21 decks)

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