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Pharmacology - Fall > Lecture 13 - Addiction & Drugs of Abuse > Flashcards

Lecture 13 - Addiction & Drugs of Abuse Flashcards

1
Q

What are the 5 characteristics of addiction?

A
  • ABCDE
    1) Inability to consistently abstain
    2) Impairment in behavioural control
    3) Craving
    4) Diminished recognition of significant problem’s w/ one’s behaviours and interpersonal relationships
    5) Dysfunctional emotional response
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2
Q

What is the diagnostic criteria for opioid use disorder?

A

Problematic pattern of opioid use leading to clinically significant impairment or distress, as manifested by at least 2 of the 11 criteria, occurring w/in a 12 month period

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3
Q

What is the criteria for mild, moderate, or severe opioid use disorder?

A
  • Mild = presence of 2-3 symptoms
  • Moderate = presence of 4-5 symptoms
  • Severe = present of 6 or more symptoms
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4
Q

What are the 11 symptoms of opioid use disorder?

A

1) Taken in larger amounts or over a longer period than was intended
2) Persistent desire or unsuccessful efforts to cut down or control opioid use
3) Lots of time spent in activities necessary to obtain or use the opioid and recover from the effects
4) Craving
5) Failure to fulfill major obligations
6) Continued use despite problems caused or exacerbated by the effects of opioids
7) Important activities given up or reduced b/c of opioid use
8) Recurrent use in situations where it is physically hazardous
9) Continued use despite knowledge of a persistent or recurrent physical/psychological problem
10) Tolerance
11) Withdrawal

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5
Q

What is the definition of tolerance?

A

1) Need for markedly increased amounts of opioids to achieve intoxication or desired effect
2) Markedly diminished effect w/ continued use of the same amount of opioid

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6
Q

When is the criteria for tolerance not met?

A

When the px is taking opioids solely under appropriate medical supervision

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7
Q

When is the criteria for withdrawal not met?

A

When the px is taking opioids solely under appropriate medical supervision

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8
Q

What is the purpose of harm reduction?

A

Attempts to decrease harmful consequences of illicit drug use to the individual, family, community, & society

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9
Q

What are the goals of the harm reduction program?

A

Reduce illicit opioid use, needle sharing, criminal activity, and mortality associated w/ addiction

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10
Q

What are the pharmacological options for opioid use disorder?

A
  • Methadone

- Buprenorphine/naloxone or buprenoprhine alone

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11
Q

Is methadone structurally related to opiates?

A

No

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12
Q

Is methadone an agonist or antagonist and for which receptor?

A
  • Agonist for Mu(u) opioid receptor

- NMDA antagonist

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13
Q

What are the uses of methadone?

A

Analgesia and withdrawal management in opioid dependent individuals

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14
Q

What is the duration of action for methadone and what does this mean for dosing?

A
  • Long duration

- Once daily dosing

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15
Q

Can methadone cause tolerance?

A

Not normally

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16
Q

How long does it take to reach peak plasma level for methadone, and why is it good to know this?

A
  • 2-4 hours

- When a patient is overdosing, it will likely be when it is peaking and you will see symptoms during this time period

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17
Q

How long does it take to reach steady state w/ methadone?

A

5-7 days

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18
Q

What is the half-life of methadone?

A

22 hours, but can be 15-40 hours

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19
Q

With therapeutic doses of methadone, how long can withdrawal symptoms be suppressed for?

A

24-36 hours

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20
Q

What is methadone metabolized by?

A

CYP 3A4

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21
Q

Methadone is a weak inhibitor of which CYP enzyme?

A

2D6

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22
Q

How is methadone excreted?

A

As an unchanged drug and as metabolites in urine and feces

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23
Q

Amount of methadone excreted in urine _____ as pH decreases

A

Increases

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24
Q

What are common persistent adverse effects of methadone?

A
  • Constipation
  • Dental (dry mouth)
  • Insomnia
  • Neuroendocrine
  • Sexual changes
  • Sweating
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25
Q

What are common adverse effects of methadone that a px can develop tolerance to?

A
  • Drowsiness
  • Nausea
  • Psychoactive effects
  • Weight gain
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26
Q

What effect does methadone have on QT interval?

A

With high doses, can prolong QT interval

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27
Q

What is considered a QT interval that is too long?

A
  • Males = 450

- Females = 470

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28
Q

What should be done when methadone is given with a drug that is a CYP 3A4 inducer or inhibitor?

A

Monitor for signs of toxicity or withdrawal and adjust dose accordingly

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29
Q

What is the starting dose of methadone?

A

10-30 mg; 10-20 mg if patient is high risk

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30
Q

When and by how much should methadone dosing be increased?

A

Increase by 5-10 mg every 3-5 days as tolerated

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31
Q

Why should prescriptions w/ automatic methadone dosing increases be avoided?

A

If a px misses a dose, they may not be tolerant to the previous dose so an increase will harm them

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32
Q

What is the usual therapeutic dose of methadone?

A

50-120 mg

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33
Q

What are some withdrawal signs and symptoms?

A
  • Agitation
  • Sweating
  • Intense anxiety/depression
  • Insomnia
  • Cravings
  • Tachycardia
  • Chills
  • Muscle aches
  • Abdominal cramping/diarrhea
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34
Q

What are some overdose signs and symptoms?

A
  • Sedation
  • Lack of coordination
  • Respiratory depression
  • Cardiac arrest
  • Sweating
  • Pinpoint pupils
  • Death
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35
Q

When should you consider split dosing?

A
  • Rapid metabolizers

- Pregnancy

36
Q

What are signs that a patient is a rapid metabolizer?

A
  • Drowsy in afternoon but withdrawal in evening

- Measure methadone peak and trough (over 2 = rapid metabolizer)

37
Q

How is methadone dosing usually split?

A

Heavier in the morning and a smaller take-home dose

38
Q

How does pregnancy affect methadone metabolism?

A
  • Metabolism changes in 3rd trimester

- May require dose increase and/or split dosing

39
Q

____ is standard of care for pregnant women dependent on opioids

A

Methadone

40
Q

What effects can opioid withdrawal have during pregnancy?

A

Fetal complications or stillbirth

41
Q

When does opioid overdose most often occur?

A

When patients are using other sedating drugs

42
Q

How is opioid overdose treated?

A

Naloxone for a minimum of 24 hours w/ additional 12 hours of monitoring

43
Q

Is buprenorphine an agonist or antagonist and at which receptor?

A
  • Partial Mu-opioid agonist

- Very high affinity and slow dissociation from receptor

44
Q

Is naloxone an agonist or antagonist and at which receptor?

A

Pure opioid antagonist

45
Q

How is buprenorphine/naloxone administered?

A

Sublingual (under tongue)

46
Q

What will happen when someone is administered buprenorphine?

A
  • Will go into withdrawal

- When going from a full agonist to a partial agonist, px will feel sluggish

47
Q

When does buprenorphine reach peak levels?

A

1-4 hours

48
Q

What is the max dose of buprenorphine in Canada?

A

24 mg/day

49
Q

What is buprenorphine metabolized by?

A

CYP 3A4 and glucuronidation

50
Q

What occurs when BZDs and buprenorphine are used in combination?

A

Additive respiratory depression w/ no plateau

51
Q

Is methadone or buprenorphine considered safer in overdose?

A

Buprenorphine

52
Q

What is recreational drug use?

A
  • Use of a pharmacologically active drug for purposes other than its intended medicinal or other purpose
  • Use of a substance/drug to get “high” or be in a mentally altered state
53
Q

What is the difference between drug misuse and drug abuse?

A
  • Drug misuse - taking a drug that you think is for a certain condition when it actually isn’t
  • Drug abuse - purposely taking a drug to get euphoric effects
54
Q

Which system and which receptors are activated during addictive drug use?

A
  • Mesolimbic dopamine system

- Receptors = Gio protein-coupled receptors, ionotropic receptors, and dopamine transporter

55
Q

What is dependence?

A

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

56
Q

Is physiological or psychological dependence more serious?

A

Physiological

57
Q

What is thought to play a role in cravings for opioids?

A

Affects on the dopaminergic pathways

58
Q

Do opioids have separate or the same neurochemical pathways for physiological vs. psychological dependence?

A

Separate

59
Q

Does tolerance always mean addiction?

A

No

60
Q

How long does it take for tolerance to be lost?

A

10-14 days

61
Q

What is reverse tolerance?

A

Sensitization

62
Q

Which drugs can cause reverse tolerance?

A

Cocaine and amphetamines

63
Q

When are impairing effects of a drug greater?

A

During rise to maximal concentration, as opposed to on the downward slope

64
Q

What occurs to neurons during functional tolerance?

A
  • Changes in post synapses of CNS (stimulatory and inhibitory pathways)
  • Exposure to psychoactive drugs and cause desensitization of receptors or down regulation of receptors/signaling pathways
65
Q

What is another name for functional tolerance?

A

Pharmacodynamic tolerance

66
Q

What is another name for metabolic tolerance?

A

Pharmacokinetic tolerance

67
Q

What occurs during metabolic tolerance and what is it similar to?

A
  • Adaptation of metabolic “machinery” to repeated exposure to drug
  • Similar to drug resistance mechanisms
68
Q

What must occur for withdrawal to take place?

A

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

69
Q

Is withdrawal a permanent consequence?

A

No, the body will get used to no drug eventually

70
Q

What role does laboratory testing play in diagnosis of abuse?

A

Doesn’t help w/ diagnosis, but gives info about how the px is using the drug (ex: if they took the drug weeks ago, but are still excreting it now); can also determine extent of damage

71
Q

What is the difference between opiates and opioids and what are examples of each?

A
  • Opiates are naturally occurring or semi-synthetic (ex: morphine, heroin)
  • Opioids are completely synthetic (ex: fentanyl)
72
Q

What determines the potency of opioids?

A

Binding affinity to Mu, Kappa, and Delta receptors

73
Q

Most opioids are selective for ___ receptors, except ___

A

Mu; pentazocine

74
Q

What are desirable effects of opioids?

A
  • Analgesia
  • Euphoria
  • Sedation
  • Relief of anxiety
  • Depress cough reflex
75
Q

What are common autopsy findings associated w/ opioid overdose?

A
  • Pulmonary congestion and frothing of mouth
  • Heavily snoring prior to death
  • Blockade of respiratory centres to CO2
76
Q

What is the general effect of opioid toxicity on the respiratory, CV, and GI centres?

A

Depresses systems and functions

77
Q

What are cannabinoids?

A

All drugs that have similar pharmacological properties as cannabis

78
Q

Can cannabis produce tolerance?

A

Yes

79
Q

___ is the major psychoactive constituent of cannabis

A

THC

80
Q

What is the mechanism of action of cannabis?

A

Cannabinoid receptors CB1 and CB2

81
Q

What are the CNS effects of cannabis?

A
  • Euphoria
  • Lack of concentration, attention, and memory
  • Motor function impairment
  • Heightened anxious state
  • Paranoia
82
Q

What are the cardiovascular effects of cannabis?

A

Increased heart rate and decreased blood pressure from vasodilation

83
Q

What are the respiratory effects of cannabis?

A
  • Decreased respiratory rate
  • Bronchodilation
  • Lung damage from smoking
84
Q

What are the drug interactions w/ cannabis?

A
  • Use w/ cocaine and amphetamines may lead to increased hypertension, tachycardia, and possible cardiotoxicity
  • Additive effect w/ CNS depressants
85
Q

What is the onset and bioavailability from smoking cannabis?

A
  • Rapid onset, minutes

- 18-50% bioavailability

86
Q

THC is ___philic and undergoes _____ circulation

A

Lipophilic; enterohepatic

87
Q

What are the acceptable limits of THC blood concentration?

A

2-5 ng/mL

Pharmacology - Fall (15 decks)

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