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PHAR0002 > Drugs Of Abuse 1 (Lecture 19) > Flashcards

Drugs Of Abuse 1 (Lecture 19) Flashcards

1
Q

Why is there a high risk of dependence for cocaine (particularly crack)?

A

Because it is a potent but short-acting stimulant

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2
Q

Who first produced MDMA?

A

Merck in 1912

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3
Q

What was MDMA initially used for?

A

An adjunct for psychotherapy in the 1970s
Used recreationally from 1980s - emerged / popularised by the rave scene

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4
Q

Stimulants affect the transmission of which NTs?

A

Serotonin
Noradrenaline
Dopamine

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5
Q

What is the mechanism of action of stimulants?

A

Stimulants increase serotonergic, noradrenergic & dopaminergic transmission through 2 mechanisms:

  1. Major mechanism - inhibit transmitter removal
    - block SERT, NAT & DAT re-uptake transporters
  2. Minor mechanism - reverse transportation
    - drug molecule itself is taken up by the transporter, substituting for K+ ions
    - extra transmitter released via reverse transport through the transporter
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6
Q

What is MDMA as a class of drug?

A

A synthetic amphetamine derivative

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7
Q

What is cocaine hydrochloride isolated from?

A

(It is the active ingredient) isolated from coca leaves (erythroxylaceae)

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8
Q

What is an example of a clinically used amphetamine?

A

Adderall for ADHD

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9
Q

What are the medical uses of cocaine?

A

Highly effective LA - used for nose, mouth & throat surgeries
(Lidocaine is a derivative of cocaine)

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10
Q

What is the meaning of substance abuse?

A

Compulsive & continuous use despite adverse effects

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11
Q

What is the meaning of addiction?

A

State of psychological / physical dependence (or both) on the use of alcohol or drugs

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12
Q

What are the functional / subjective effects of inhalants?

A

Euphoria / lightheadedness (brief)

Increase HR & body temp

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13
Q

What are the functional / subjective effects of hallucinogens?

A

Altered perspective

Introspection

Panic / paranoia

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14
Q

What are the functional / subjective effects of dissociative anaesthetics? (E.g. ketamine, PCP)

A

Sedation
Hallucinations
Dissociation from reality
Slowed breathing & increased BP

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15
Q

What are (5) functional / subjective effects of CNS depressants (e.g. benzodiazepines, barbiturates) ?

A

Euphoria
Drowsiness
Confusion / memory loss
Slowed breathing
Lowered BP

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16
Q

What are the functional / subjective effects of cannabinoids?

A

Euphoria
Relaxation / sedation
Increased HR & appetite

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17
Q

What are the 5 environmental factors of drug abuse?

A

Chaotic home & abuse
Parental use & attitudes
Peer influences
Community attitudes
Low academic achievement

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18
Q

What are the biological / genetic factors of drug abuse?

A

Genetics
Gender
Mental disorders

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19
Q

What are the 7 drug categories?

A
  1. CNS depressants
  2. CNS stimulants
  3. Hallucinogens
  4. Dissociative anaesthetics
  5. Narcotic analgesics
  6. Cannabinoids
  7. Inhalants
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20
Q

What are the 5 categories in the spectrum of drug use?

A

Non-use

Beneficial use - use that can have positive health, social / spiritual effects (eg. Taking prescribed medication / ceremonial or religious use of tobacco)

Lower-risk use - has minimal impact to an individual, their close ones & others (eg. Drinking according to guidelines)

Higher-risk use - has harmful impact to an individual, their close ones & others (eg. Using illegal drugs, binge drinking)

Addiction - substance use disorder - medical condition affecting the brain involving compulsive & continuous use despite negative impacts

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21
Q

What are the 4 stages of drug use?

A
  1. Experimental - early stages, peers, choice
  2. Recreational - non-addictive,
  3. Dependent - addicts, disrupted lifestyle
  4. Abstinent (post-use)
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22
Q

What are 3 common CNS stimulants?

A
  1. Cocaine (hydrochloride)
  2. Amphetamines (speed)
  3. MDMA (3,4-methylenedioxymethamphetamine)
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23
Q

What are CNS stimulants structurally very similar to?

A

Monoamine molecules

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24
Q

MDMA is currently in clinical trials with which conditions?

A

PTSD
Alcoholism

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25
Q

What are the functional / subjective effects of narcotic analgesics?

A

Euphoria
Pain relief
Sedation
Slowed breathing & HR

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26
Q

What are the functional / subjective effects of CNS stimulants?

A

Stimulation / hyperactivity
Euphoria
Agitation / paranoia
Increased HR & BP

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27
Q

Give 4 examples of narcotic analgesics

A

Opium
Heroin
Fentanyl
OxyContin

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28
Q

What are 3 examples of inhalants?

A

Nitrous oxide
Amyl nitrite
Lighter gas / household aerosols

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29
Q

What are 5 examples of hallucinogenic drugs?

A

LSD
Mescaline (from peyote & San Pedro cacti)
DMT (from ayahuasca, synthetic)
Psilocybin
MDMA

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30
Q

What are examples of dissociative anaesthetics?

A

ketamine
PCP

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31
Q

What are examples of CNS stimulants?

A

Cocaine
Amphetamine / methamphetamine
Nicotine
MDMA

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32
Q

What are examples of CNS depressants? (5)

A

Alcohol
Barbiturates (e.g. phenobarbital)
Anxiolytics (e.g. Diazepram, fluoxetine)
GHB
Rohypnol

33
Q

What are 2 examples of cannabinoids?

A

Cannabis sativa
Synthetic cannabinoids

34
Q

What are amphetamines a class of?

A

Naturally occurring (ephedrine & cathinone) and synthetic alkaloid stimulants

35
Q

How is cocaine typically consumed?

A

Snorted
Smoked (crack / freebase forms)

36
Q

What are examples of narcotic analgesics? (4)

A
  1. Opium
  2. Heroin
  3. Fentanyl
  4. OxyContin
37
Q

What are 3 examples of CNS stimulants?

A
  1. Cocaine
  2. Amphetamines
  3. MDMA
38
Q

What are 2 examples of CNS depressants?

A
  1. Benzodiazepines - e.g. Diazepam (Valium)
  2. Barbiturates - e.g. Phenobarbital
39
Q

Give 2 examples of dissociative anaesthetics

A
  1. Ketamine
  2. PCP
40
Q

Give examples of inhalants (3)

A
  1. Nitrous oxide
  2. Lighter gas / household aerosols
  3. Amyl nitrite
41
Q

What are 3 examples of hallucinogens?

A
  1. LSD
  2. Psilocybin (magic mushrooms)
  3. Ayahuasca
42
Q

The Cannabis sativa plant contains >100 unique compounds called…

A

Phytocannabinoids (pCBs)

43
Q

What are the psychoactive / medicinal effects of Cannabis thought to result from?

A

The combined effects of multiple pCBs on multiple targets (CNS and the body)

44
Q

What are the majority of effects of Cannabis due to?

45
Q

What do differences in potency of different cannabis strains / methods of preparation result from?

A

THC and CBD concentrations and their ratio

46
Q

How do THC & CBD (from cannabis) affect the endocannabinoid system?

A

They work predominantly by modulating endocannabinoid (eCB signalling) via the CB1 receptor

Endocannabinoids AEA (anandamide) & 2-AG act as retrograde neuromodulators and are endogenous ligands for CB1R (type of pre-synaptic heteroceptor / GPCR, widely expressed in the CNS & elsewhere)

47
Q

What is the CB2R receptor?

A

The main endocannabinoid receptor in the periphery
(Less relevant for psychoactive effects of cannabis)

48
Q

How does THC affect the endocannabinoid system?

A
  • THC is a partial agonist of CB1 (and CB2) receptors
  • disrupts endogenous retrograde signalling process by interfere in with anandamide & 2-AG (endogenous ligands for CB1R)
  • this alters glutamatergic & GABAergic signalling throughout the brain and modulates release of neuromodulatory transmitters (particularly dopamine)
  • this causes wide-ranging effects - combination of excitation & inhibition
49
Q

Why is THC not a particularly good therapeutic drug?

A

THC > CB1R not functionally selective - implications for dose / side effects

50
Q

What can be said about commercial CBD products?

A

(Mainly) the doses are far too low to have an effect - effectively an expensive & fashionable placebo

51
Q

What effect can CBD have on THC and what is this implication of this?

A

CBD thought to reduce some of the psychotomimetic effects of THC

Inc THC & dec CBD in modern cannabis is driving increased incidence of psychosis (causes hallucinations & delusions)

52
Q

What is CBD’s effect on CB1R (receptors)?

A

Negative allosteric modulator at CB1R

—> reduces binding & activity of AEA, 2-AG and / or THC

53
Q

How does CBD potentiate AEA (anandamide) signalling?

A

Inhibits FAAH-mediated breakdown of anandamide

54
Q

CBD and targets

A

There are many targets for CBD, but it has low affinity / potency for most of them

55
Q

When was LSD synthesised?

A

1938 - by Alex Hoffman

56
Q

When was LSD discovered to be a highly potent hallucinogen?

57
Q

When was LSD marketed as a clinical medication for psychiatric indications?

58
Q

When was LSD extensively used in psychotherapy research?

A

1950s / early 1960s

59
Q

When was the recreational use of LSD popularised?

A

Early - mid 1960s

60
Q

When was LSD made illegal in the USA?

61
Q

What happens to psilocybin when orally ingested by mammals?

A

It’s converted to the hallucinogen psilocin

62
Q

What has psilocybin recently been in clinical trials for?

A

Depression
Anxiety
(Drug) dependence

63
Q

What is ayahuasca ?

A

A hallucinogen used by the indigenous peoples of Amazonian jungle

64
Q

What is ayahuasca ‘tea’ made from?

A
  1. Bark of Banisteriopsis caapi
  2. Leaves of Psychotria viridis - contains potent & rapid hallucinogen DMT (N,N-dimethyltryptamine)
65
Q

Why is ayahuasca made with both (DMT-containing) leaves of P. viridis and B. caapi?

A

Orally consumed DMT is broken down by MAO-A (monoamine oxidase - A) in the periphery - so little / no effect will occur if taken alone

B.caapi contains harmala alkaloids which inhibit MAO-A and allow DMT to reach the brain

66
Q

All hallucinogens are agonists of which receptor?

A

5-HT2A (crucial for psychoactive effects)

67
Q

What are the perceptual abnormalities (caused by hallucinogens) due to?

A

Impairment of sensory (sensorimotor) gating - the filtering of irrelevant auditory / visual / olfactory stimuli to prevent overload of cortical processing

(This is thought to break down in schizophrenia)

68
Q

What is sensorimotor gating controlled by?

A

The interaction of serotonin and dopamine signalling, particularly in the thalamus & cortex

Serotonin signalling via 5-HT2A (and 5-HT1A / 2C to a lesser extent) is crucial for gating process

69
Q

Impaired sensorimotor gating is thought to be a part of the pathophysiology of which condition?

A

Schizophrenia

70
Q

What are hallucinogens sometimes called?

A

Psychotomimetics

(Sometimes thought to, temporarily, mimic the process of psychosis)

71
Q

What 5 drugs are approved and in regular medical use?

A
  1. Cocaine hydrochloride
  2. Morphine
  3. Amphetamine
  4. Cannabis
  5. Ketamine
72
Q

What is the approved and medical use of COCAINE HYDROCHLORIDE ?

A

Local anaesthesia during surgery

73
Q

What is the approved and medical use of MORPHINE

A

Emergency analgesia and acute / chronic pain

74
Q

What is the approved and medical use of AMPHETAMINE

A

ADHD (Adderall component)

75
Q

What is the approved and medical use of CANNABIS

A

Childhood epilepsy, multiple sclerosis

76
Q

What is the approved and medical use of KETAMINE

A

Surgical anaesthesia

77
Q

What 3 drugs are under clinical investigation? And for what?

A

Psilocybin
MDMA
Ketamine

Depression, anxiety, PTSD

78
Q

What 2 drugs have no known medical use?

A

Alcohol
Nicotine

79
Q

Give examples of cannabinoids (2)

A
  1. Cannabis sativa
  2. Synthetic cannabinoids

PHAR0002 (20 decks)

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