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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
What is the active agent in Cannabis?
Tetrahydrocannabinol (THC)
26
Where are CB1 and CB2 receptors located?
CB1 - brain and peripheral tissue (MOST EFFECT) | CB2 - immune cells (linked to G-proteins)
27
What do cannabinoids do?
Facilitate activity of brain reward centre.
28
What does a low dose and high dose do?
``` Low = mix of stimulatory and depressant effects High = mainly depressant ```
29
Is THC lipophilic?
Yes.
30
How is THC metabolised?
In liver by CYP450 enzymes
31
What is the major metabolite of THC?
11-carboxy-THC (inactive) but high concentrations.
32
What is the minor metabolite of THC?
11-hydroxy-THC (active) but low concentrations.
33
What is the therapeutic potential of cannabinoids?
Help to prevent glaucoma, epilepsy, etc.
34
Can cannabinoids reduce sperm count and testosterone?
Yes.
35
What are 2 synthetic cannabinoids that were available in NZ?
JWH-018 and JWH-073. These act as agonists at the CB1 and CB2 receptors.
36
Amphetamine is what type of drug?
Psychostimulant
37
Increases concentrations of which neurotransmitters?
Dopamine, NA and serotonin through: 1. Increased release from storage sites 2. Inhibition of re-uptake
38
How are amphetamines eliminated?
CYP450 in the liver, excreted via kidneys.
39
What is the half life of amphetamine?
12-36 hours
40
What is the half life of methamphetamine?
8-17 hours
41
What is the crash phase caused by in meth users?
Decreased DA supply. Lasts 1-4 days.
42
What are the 4 classifications of acute toxicity in the body from meth?
- CNS - Neuropsychiatric - CV - skeletal muscles
43
Opioids are from what plant?
Opium poppy
44
What are the general effects of opioids?
``` Analgesia Sedation Depression of respiration Pupillary constriction Nausea GI symptoms ```
45
What is a substitute treatment for those who were on opioids?
Methadone
46
What is the mechanism of opioid action?
Inhibits adenylate cyclase, decreaes cAMP levels. cAMP would normally activate PKA which would activate many proteins.
47
Where are opioid receptors found?
Throughout the body.
48
What is a partial agonist of opioid?
Buprenorphine
49
What are 2 antagonists of opioid?
Naloxone and Naltrexone
50
opioids predominantly target which opioid receptor?
u receptor (endorphin)
51
What are the 3 receptor types?
u (endorphin) k (dynorphin) delta (enkephalin)
52
All opioids undergo what type of metabolism?
Hepatic metabolism.
53
Does morphine have high or low bioavailability?
Low.
54
What does morphine undergo in the liver?
Gluronidation. Active metabolite (morphine-6-glucuronide) is excreted via kidneys.
55
Half life of morphine?
2-3 hours
56
Opioid withdrawal depends on what?
The half-life of the opioid drug.
57
Most physical symptoms of withdrawal settle after how many days?
5-7 days.

Medsci 204 (18 decks)

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