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Medsci 204 > Drugs of Abuse > Flashcards

Drugs of Abuse Flashcards

1
Q

What does abuse liability mean?

A

Likelihood of whether the drug could be addicting.

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2
Q

What does the reward pathway involve?

A

Dopamine, beginning in the substantia nigra -> nucleus accumbens -> BRAIN

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3
Q

Mesolimbic pathway involves which structures?

A

Ventral tegmental area (Substantia nigra)
Nucleus accumbens (in basal ganglia)
Amygdala
Hippocampus

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4
Q

What is the consequence of repeated administration?

A

If you take the drug a lot, you can develop tolerance and thus have to take more to get the same therapeutic effect. Become physically dependent.

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5
Q

What are the probable mechanisms behind tolerance?

A
  • receptor desensitization

- reduction in receptor numbers

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6
Q

What happens with physical dependence?

A

Neurons adapt to the presence of the drug. Removal/reduction of the drug can cause withdrawal syndrome.

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7
Q

What are 5 classifications of drugs that can be abused?

A
  • CNS depressants (opioids, sedative hypnotics)
  • Psychomotor stimulants (nicotine, caffeine, meth)
  • Hallucinogens (LSD)
  • Cannabis (marijuana)
  • Solvents and aerosols (NO, Toluene)
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8
Q

What potency does alcohol have and what does this mean?

A

Low potency, so large dose required for desired effect -> toxicity

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9
Q

Does alcohol distribute through water quickly?

A

Yes. Women have smaller body water weight and so can be drunk quicker.

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10
Q

What is the mechanism of action of alcohol?

A

Binds to subunit of GABAa receptor -> enhanced activity of inhibitory transmittor -> CNS depressant effects.

Decreases activity of glutamate receptors (NMDA), preventing Ca ions entering cell (which normally activates the cell).

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11
Q

NMDA receptors are found where? What does this mean in terms of alcohol effects?

A

Found in neural centres involved in memory (hippocampus) and so can cause memory impairment.

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12
Q

How much alcohol is absorbed via hepatic circulation and stomach?

A

Hepatic - 80%

Stomach - 20%

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13
Q

How long does it take for alcohol to reach the brain?

A

5 minutes

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14
Q

When does blood alcohol reach peak concentration?

A

30 - 90 minutes

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15
Q

Does alcohol readily cross the BBB and placental barriers?

A

Yes.

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16
Q

How much of alcohol is metabolised?

A

About 90%

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17
Q

What is the first metabolic step of alcohol metabolism?

A

Alcohol -> acetaldehyde by alcohol dehydrogenase (ADH)

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18
Q

What is the rate limiting step of alcohol metabolism?

A

Alcohol -> acetaldehyde by ADH

Enzyme is quickly saturated at very low alcohol concn’s which limits the rate of metabolism.

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19
Q

What is the constant rate of metabolism?

A

About 7.5g/hour

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20
Q

What is the 2nd metabolic step of alcohol metabolism?

A

Acetaldehyde rapidly metabolised by ALDH into acetate. Acetaldehyde is very toxic, so if ALDH is inhibited, very toxic!!

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21
Q

Which variant of ALDH is found in some asian populations?

A

ALDH(2.2)

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22
Q

What inhibits ALDH as an aversive agent in people with alcohol dependence?

A

Disulfiram. Helps to reduce alcohol addiction by stimulating vomiting, headaches, etc.

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23
Q

What is withdrawal characterised by?

A

CNS hyperactivity

24
Q

Cannabis comes in what forms?

A

Marijuana, Kief, Hashish, Hash oil, Resin

25
Q

What is the active agent in Cannabis?

A

Tetrahydrocannabinol (THC)

26
Q

Where are CB1 and CB2 receptors located?

A

CB1 - brain and peripheral tissue (MOST EFFECT)

CB2 - immune cells (linked to G-proteins)

27
Q

What do cannabinoids do?

A

Facilitate activity of brain reward centre.

28
Q

What does a low dose and high dose do?

A 
Low = mix of stimulatory and depressant effects
High = mainly depressant
29
Q

Is THC lipophilic?

A

Yes.

30
Q

How is THC metabolised?

A

In liver by CYP450 enzymes

31
Q

What is the major metabolite of THC?

A

11-carboxy-THC (inactive) but high concentrations.

32
Q

What is the minor metabolite of THC?

A

11-hydroxy-THC (active) but low concentrations.

33
Q

What is the therapeutic potential of cannabinoids?

A

Help to prevent glaucoma, epilepsy, etc.

34
Q

Can cannabinoids reduce sperm count and testosterone?

A

Yes.

35
Q

What are 2 synthetic cannabinoids that were available in NZ?

A

JWH-018 and JWH-073. These act as agonists at the CB1 and CB2 receptors.

36
Q

Amphetamine is what type of drug?

A

Psychostimulant

37
Q

Increases concentrations of which neurotransmitters?

A

Dopamine, NA and serotonin through:

  1. Increased release from storage sites
  2. Inhibition of re-uptake
38
Q

How are amphetamines eliminated?

A

CYP450 in the liver, excreted via kidneys.

39
Q

What is the half life of amphetamine?

A

12-36 hours

40
Q

What is the half life of methamphetamine?

A

8-17 hours

41
Q

What is the crash phase caused by in meth users?

A

Decreased DA supply. Lasts 1-4 days.

42
Q

What are the 4 classifications of acute toxicity in the body from meth?

A
  • CNS
  • Neuropsychiatric
  • CV
  • skeletal muscles
43
Q

Opioids are from what plant?

A

Opium poppy

44
Q

What are the general effects of opioids?

A 
Analgesia
Sedation
Depression of respiration
Pupillary constriction
Nausea
GI symptoms
45
Q

What is a substitute treatment for those who were on opioids?

A

Methadone

46
Q

What is the mechanism of opioid action?

A

Inhibits adenylate cyclase, decreaes cAMP levels. cAMP would normally activate PKA which would activate many proteins.

47
Q

Where are opioid receptors found?

A

Throughout the body.

48
Q

What is a partial agonist of opioid?

A

Buprenorphine

49
Q

What are 2 antagonists of opioid?

A

Naloxone and Naltrexone

50
Q

opioids predominantly target which opioid receptor?

A

u receptor (endorphin)

51
Q

What are the 3 receptor types?

A

u (endorphin)
k (dynorphin)
delta (enkephalin)

52
Q

All opioids undergo what type of metabolism?

A

Hepatic metabolism.

53
Q

Does morphine have high or low bioavailability?

A

Low.

54
Q

What does morphine undergo in the liver?

A

Gluronidation.

Active metabolite (morphine-6-glucuronide) is excreted via kidneys.

55
Q

Half life of morphine?

A

2-3 hours

56
Q

Opioid withdrawal depends on what?

A

The half-life of the opioid drug.

57
Q

Most physical symptoms of withdrawal settle after how many days?

A

5-7 days.

Medsci 204 (18 decks)

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