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Pharmacology (MPAS) > Lecture 14: Drugs of abuse > Flashcards

Lecture 14: Drugs of abuse Flashcards

1
Q

What is recreational drug use?

A

Use of a pharmacologically active agent (drug) for purposes other than its intended medicinal or other purpose.

Use of a substance/drug to get “high” or be in an mentally altered state

Psychoactive substances

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2
Q

Misuse vs abuse

A

Misuse: person taking drug to alleviate symptom but the drug they are taking doesn’t do that

Abuse: looking for drugs with main intention of getting high, not what drug is actually used for

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3
Q

Characteristics of addiction

A

Inability to consistently Abstain

Impairment in Behavioral control

Craving; or increased “hunger” for drugs or rewarding experiences;

Diminished recognition of significant problems with one’s behaviors and
interpersonal relationships; and

A dysfunctional Emotional response

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4
Q

How do addictive drugs cause addiction?

A

Activation of the mesolimbic dopamine system

Three classes: Gio protein-coupled receptors

Ionotropic receptors

Dopamine transporters

See figure

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5
Q

How do class I addictive drugs work?

A

Gio protein-coupled receptors

Block GPCRs responsible for recognizing GABA (inhibitory neurotransmitter)

With less GABA effect, neurons fire more easily = euphoria

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6
Q

How do class II addictive drugs work?

A

Ionotropic receptors

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7
Q

How do class III addictive drugs work?

A

Dopamine transporters

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8
Q

What is dependence? How is it influenced by withdrawal?

A

the state at which the user functions normally only when taking the drug

Withdrawal symptoms re-enforce dependence and are a response of the body to less drug

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9
Q

Physiological dependence example

A

withdrawal of alcohol from an alcoholic; life

threatening

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10
Q

Psychological dependence example

A

It implies addiction and pertains to desirable properties or “the high”
repeated crack cocaine use

drug seeking habits in spite of risks

repeated dosing related need to keep the “high”

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11
Q

What pathways play a role in cravings to use drugs again?

A

Dopaminergic pathways

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12
Q

Opioids and pathways for dependence

A

thought to have separate neurochemical pathways for physiological dependence versus psychological dependence

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13
Q

What is tolerance?

A

a state at which there is no longer the desired response to the drug

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14
Q

What is the progressive model of tolerance?

A

To achieve the desired response, more drug is required

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15
Q

Is tolerance addiction?

A

No, development of tolerance is not necessarily addiction

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16
Q

Tolerance to drug effect vs drug lethality

A

These two types of tolerance can differ and thus affect therapeutic index

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17
Q

What is reverse tolerance?

A

sensitization

can persist for years e.g. cocaine and
amphetamines

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18
Q

Impairing effects of a drug based on drug concentration

A

Impairing effects of a drug can be greater during rise to maximal concentration that in comparison on the downward slope: e.g. ethanol

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19
Q

What is functional tolerance?

A

aka pharmacodynamic tolerance

Change in post synapses of CNS

Desensitization of receptors (short)

Down regulation of receptors/signalling pathways (long_

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20
Q

What type of drugs cause functional tolerance

A

Psychoactive drugs

Hormones

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21
Q

Examples of post-synaptic receptors

A

G-protein

Ionotropic

Extrasynaptic proteins

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22
Q

What is cross tolerance in functional tolerance?

A

What hen multiple drugs affect the same receptor, tolerance to one drug may cause tolerance to another, different drug that acts on the same receptor

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23
Q

What is metabolic tolerance?

A

aka pharmacokinetic tolerance

Adaptation of the metabolic “machinery” to repeated exposure to a drug

Similar to drug resistance mechanisms

Enzyme induction

Drug metabolism (CYP P450, glucuronidation)

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24
Q

Cross tolerance in metabolic tolerance

A

If the enzyme affected by one drug also metabolizes other drugs, the metabolism of the other drugs can be affected

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25
Q

What is withdrawal?

A

a maladaptive behavioral change, with physiological and cognitive concomitants

Occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance

See figure

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26
Q

What is a person in withdrawal likely to do?

A

person is likely to take the substance to relieve or to avoid those symptoms

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27
Q

In what drugs are physiological signs of withdrawal obvious?

A

Alcohol

Hypnotics

Anxiolytics

Opioids

Sedatives

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28
Q

For what drugs are the physiological signs of withdrawal less obvious?

A

Amphetamines

Nicotine

Cocaine

Cannabis

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29
Q

Flow chart of events leading to addiction

A

See figure

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30
Q

What causes addiction?

A

Behavioural, environmental and biological factors

Similar to diabetes, cancer and heart disease

Using a drug may be a choice, but the effects (addiction) are not

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31
Q

Benefits of treating addiction as a disease?

A

Removes stigma

Standardization of diagnosis and therapy

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32
Q

Emergency department stats

A

See figure

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33
Q

Drug use among people in drug treatment by region of the world

A

See figure

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34
Q

People who inject drugs and HIV prevalence

A

High PWID, high HIV: south west africa, eastern and south-eastern europe

High PWID, low HIV: North america, central asia, Oceania

Low PWID, low HIV: africa, south asia, latin america, western and and central europe

See figure

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35
Q

Risk of different drugs

A

Most dangerous: opioids

36
Q

How to diagnose abuse

A

DSM-V (questionnaire) - see figure

Laboratory testing

37
Q

What can laboratory testing look for?

A

Indicates recent use

Not related to frequency or intensity (drugs can be stored in the body)

Monitor compliance

Determine extent of damage (ex: alcoholic lier disease)

Epidemiology (info for the future)

38
Q

Drawback with laboratory tests to diagnose abuse

A

It is a targeted detection, so you can’t detect a drug for which you don’t have a test

Not related to frequency or intensity

39
Q

Recreational drug classes

A

Alcohols

Cannabinoids

Cocaine

Amphetamine-like

Opioids

Sedative hypnotics

Hallucinogens

Antidepressants

Antipsychotics

Inhalants

Other: e.g. GHB, DMMA

40
Q

What is a natural opioid?

A

Morphine

41
Q

Natural vs synthetic opioid structure

A

See figure

42
Q

Continum of opiates and opioids

A

Natural: opiates

Synthetic: opioids

See figure

43
Q

Considerations with source of drug

A

Prescription vs street market

44
Q

Considerations with scheduled drugs

A

Legal vs illegal highs

45
Q

What are the endogenous opioids?

A

Enkephalins

Endorphins

Dynorphins (peptides)

46
Q

Why are opioids used as recreational drugs?

A

Euphoric affect

47
Q

Examples of opioids

A

Morphine

Heroin

Codeine

Dextromethorphan

Oxycodone

Hydromorphone

Fentanyl

Meperidine

Acetylfentanyl (designer drug)

48
Q

How is an opioid chosen?

A

Route of administration

Availability

Duration of high

Potency

Side effects

49
Q

Clinical use of opioids

A

Most efficacious analgesic drugs available

50
Q

Side effects of opioids

A

Respiratory depression

Variable euphoric affect

Dependence

Prominent affect on GI tract

Miosis

51
Q

How do opioids differ?

A

They are similar in pharmacology but differ in:

Duration of action

Oral availability

Relative potency

Adverse side effect profile

52
Q

What is the potency of opioids related to?

A

Binding affinity for mu, kappa and delta receptors

Most are selective for mu receptor (exception: pentazocine)

Full vs mixed agonist

53
Q

Desirable effects of opioids

A

Analgesia

Euphoria

Sedation

Relief of anxiety

Depress cough reflex

54
Q

Undesirable effects of opioids

A

Dysphoria

dizziness

nausea

Vomiting

Constipation

Biliary tract spasm

Urinary retention

Withdrawal

Respiratory depression

55
Q

What are common autopsy findings with opioid overdose?

A

Pulmonary congestion and frothing of mouth;

witnesses often comment that deceased was heavily snoring prior to death: blockade of respiratory centres to pCO2

56
Q

Routes of administration of opioids

A

Oral:readily absorbed

IV

IM

Smoked

Intranasal

Transdermal: ++lipophilicity

57
Q

What does lipophilicity of an opioid determine?

A

distribution and CNS levels

Higher lipophilicity drugs are better given transdermally

58
Q

What does prolonged affect of opioids cause?

A

accumulation of drug/formation of active metabolites

59
Q

What happens during first pass metabolism of opioids?

A

Glucuronidaton (liver) and renal elimination

Also undergo enterohepatic recycling

60
Q

Mitigation strategies against opioid diversion and misuse

A

Screening tools to ID patients with substance use disorder

Use data from the prescription drug monitoring program (ID doctor shopping)

Use of urine drug screening (provides info on drug use not reported by patients)

Doctor-patient agreement adherence (personal contract)

61
Q

Carfentanil in MB

A

Rise in overdose related deaths (4 deaths/week, now 1/month)

Post mortem blood conc of carfentanil: 0.03 to 13 ng/ml

Reports indicate accidental overdoses

Active abuse is on the rise (blotters)

62
Q

What is naloxone?

A

Emergency antidote to opioid OD

63
Q

Characteristics of naloxone?

A

Different admin routes lead to different concentrations in the blood

Hard to know how much to give to patient

See figure

64
Q

Which part of the world has the highest cannabis usage?

A

Australia

Canada

France

Nigeria

See figure

65
Q

Use of illicit drugs in youths (12-17)

A

Cannabis is most popular, followed by psychotherapeutics, followed by inhalants and hallucinogens

See figure

66
Q

Variable effects of cannabis

A

Dysphoria (unease or dissatisfaction) to hallucination

67
Q

Dependence and tolerance in cannabis use

A

1 in 9 first time users become dependent

Tolerance with chronic use

68
Q

What is the major psychoactive constituent in cannabis?

A

THC

69
Q

Route of administration of cannabis

A

Oral or smoked

70
Q

What is CB1 linked to?

A

MAP kinase /adenylyl cyclase/K-channel-linked

71
Q

What are the endogenous cannabinoids?

A

anadamide and 2-arachidonyl glycerol

72
Q

Active ingredient in cannabis

A

Delta-9-tetrahydrocannabinol (THC)

73
Q

Amount of THC in leaves, hashih and oil extract

A

Leaves: 2-5%

Hasish: 5-15%

Oil extract: >20%

74
Q

CNS effects of cannabis

A

Euphoria

Lack of concentration

Motor function impairment (reaction time): driving under the influence

Impairment can persist after the perceived high has dissipated

Impaired attention, memory and learning

Users at heightened anxious state (CB1 in amygdala)

paranoia

75
Q

CVS effects of cannabis

A

Increased HR

Decreased BP (vasodilation)

76
Q

Respiratory effects of cannabis

A

Decreased RR

Bronchodilation

Lung damage (smoking)

77
Q

Drug interactions with cannabis

A

Use with cocaine and amphetamines may lead to increased hypertension, tachycardia and possible
cardiotoxicity

Additive effect with CNS depressants (impaired driving enhanced with alcohol)

78
Q

Cannabis PK (smoking)

A

rapid onset (minutes)

18-50% bioavailability

dynamics: # puffs, duration and volume of inhalation, hold

79
Q

Cannabis PK (oral)

A

Slower onset (1-5 hours)

6-18% bioavailability

1st pass effect

80
Q

Lipophilicity of THC

A

THC is lipophilic and undergoes enterohepatic circulation

81
Q

Urinary THC half life

A

Urinary t1/2 of 11-carboxy-THC (as glucuronide)

3 days in chronic user

82
Q

Issues with legalization of cannabis

A

Danger to kids (acute toxicity through edibles)

Harmful effects

DUI

83
Q

Rates of paediatric marijuana calls in colorado (legalized marijuana) vs rest of US

A

Much higher in colorado

See figure

84
Q

Harmful effects of marijuana

A

Short term: impaired short erm memory, impaired motor coordination, altered judgement (risk of sexual behaviours), paranoia and psychosis (high doses)

Long term: addiction, altered brain development, poor educational outcome, cognitive impairment, diminished life satisfaction and achievement, symptoms of chronic bronchitis, risk of chronic psychosis disorders in persons with predisposition

85
Q

Marijuana and DUI’s

A

Volume of distribution in body is variable

Amount of THC in blood does not always correlate with behaviour

86
Q

What are acceptable limits of THC in blood?

A

2-5 ng/ml

Pharmacology (MPAS) (19 decks)

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