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Pharmacology > Lecture 13 - Drugs of Abuse > Flashcards

Lecture 13 - Drugs of Abuse Flashcards

1
Q

Define 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 altered mental state
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2
Q

List some recreational drug classes

A 
Alcohols
Cannabinoids
Cocaine
Amphetamine-like
Opioids
Sedative hypnotics
Hallucinogens
Antidepressants
Antipsychotics
Inhalants
GHB, DMMA
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3
Q

Define tolerance

A

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

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4
Q

Describe the Progressive model

A

To achieve the desired response, more drug is required

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5
Q

Tolerance typically lost in?

A

10-14 days

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6
Q

What is reverse tolerance?

A

sensitization - can resist for years (ex. cocaine and amphetamines)

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7
Q

Functional tolerance also referred to as?

A

pharmacodynamic tolerance

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8
Q

Describe functional tolerance

A
  • change in the post synapses of the CNS
  • stimulatory and inhibitory pathways
  • exposure to psychoactive drugs (could also means hormones)
  • desensitization of receptors (short)
  • down regulation receptors/signaling pathways (long)
  • cross tolerance
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9
Q

List the post-synapse receptors

A

G-protein
Ionotropic
Extrasynaptic proteins

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10
Q

Metabolic tolerance is also referred to as?

A

pharmacokinetic tolerance

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11
Q

What is metabolic tolerance?

A
  • adaptation of the metabolic “machinery” to repeated exposure to a drug
  • similar to drug resistance mechanisms
  • enzyme induction
  • drug metabolism:
    • CYP P450 system
    • Glucuronidation
  • cross tolerance: drugs metabolized similarly
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12
Q

What is cross tolerance?

A

drugs metabolized similarly

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13
Q

What is withdrawal?

A

-a maladaptive behavioural change, with physiological and cognitive concomitants, that occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance

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14
Q

What happens after a person develops the unpleasant withdrawal symptoms?

A

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

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15
Q

There are physiological signs available of withdrawal symptoms for?

A 
alcohol
hypnotics
anxiolytics
opioids
sedatives
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16
Q

There are less obvious signs available of withdrawal symptoms for?

A

amphetamines
nicotine
cocaine
cannabis

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17
Q

Define dependence

A

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

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18
Q

How do withdrawal symptoms and dependence work?

A

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

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19
Q

Physiological dependence

A

withdrawl of alcohol from an alcoholic - life threatening

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20
Q

Psychological dependence

A

repeated crack cocaine use - drug seeking habits in spite of risks, repeated dosing related to keep the high
-it implies addiction and pertains to desirable properties or the high

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21
Q

Affects on _____ pathways though to play a role in crave to use the drug again

A

dopaminergic

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22
Q

What is addiction characterized by?

A
  • Inability to consistently abstain
  • Impairment in behavioural control
  • Cravings or increased “hunger” for drugs or rewarding experiences
  • Diminished recognition of significant problems with one’s behaviours and interpersonal relationships
  • A dysfunctional emotional response
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23
Q

Good data in Canada on recreational drug use is _____

A

lacking

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24
Q

What do you need to consider when discussing recreational use?

A
  • recreational drug use is country-dependent
  • rationalizing risk
  • source of drug (prescription versus street market)
  • scheduled drugs (legal versus illegal highs)
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25
Q

Synthetic opioids?

A

Sufentanyl
Carfentanil
Fentanyl

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26
Q

Semi-synthetic opioids?

A

Heroin

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27
Q

Plant Extracts Opiates?

A

Opioids

Morphine

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28
Q

Endogenous opioids?

A

Enkephalins
Endorphins
Dynorphins (peptides)

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29
Q

Why are opioids used recreationally?

A

Euphoric affect associated with recreational use

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30
Q

Examples of opioids

A 
Morphine
Heroin
Codeine
Dextromethorphan
Oxycodone
Hydromorphone
Fentanyl
Meperidine
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31
Q

What are designer drugs?

A

acetylfentanyl
furanylfentanyl
carfentanil

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32
Q

What contributes to an abuser’s drug of choice?

A
  • route of administration
  • availability
  • duration of high
  • potency
  • side effects
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33
Q

_____ are the most efficacious analgesic drugs available

A

Opioids

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34
Q

Opioids also produce??

A
  • Respiratory depression
  • Variable euphoric affect (the high)
  • Dependence
  • Prominent affect on GI tract
  • Miosis
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35
Q

Opioids are similar in pharmacology but differ in: ?

A
  • Duration of action
  • Oral availability
  • Relative potency
  • Adverse side effect profile
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36
Q

Potency related to binding affinity: ??

A

mu, kappa, delta

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37
Q

Most opioids are selective for ___ receptor

A

mu

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38
Q

Desirable effects of opioids?

A 
Analgesia
Euphoria
Sedation
Relief of anxiety
Depress cough reflex
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39
Q

Undesirable effects of opioids?

A 
Dysphoria (dizziness, nausea)
Vomiting
Constipation
Biliary tract spasm
Urinary retention
Withdrawal
Respiratory depression
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40
Q

What is the common autopsy finding associated 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

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41
Q

Admin routes for opioids?

A
  • Oral: readily absorbed
  • IV
  • IM
  • Smoked
  • Intranasal
  • Transdermal: increased lipophilicity
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42
Q

Opioids have a prolonged affect

A

accumulation of drug/formation of active metabolites

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43
Q

First pass metabolism of opioids

A

glucuronidation (liver) and renal elimination

*also enterohepatic re-circulation

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44
Q

Opioid Toxicity:

CNS

A
  • convulsions (delta receptor dependent and targeted to hippocampal pyramidal cells)
  • meperidine metabolism to normeperidine
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45
Q

Opioid Toxicity:

Respiratory (brain stem)

A
  • depression of rate, volume & exchange

- decreased respiratory responsiveness

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46
Q

Opioid Toxicity:

Cardiovascular

A
  • orthostatic hypotension
  • stroke
  • ECG abnormalities
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47
Q

Opioid Toxicity:

GI

A
  • decreased motility
  • intestinal obstruction
  • increased biliary tract pressure
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48
Q

Chronology of Opioid Abstinence Syndrome:

8-12 hrs

A
  • lacrimation
  • perspiration
  • yawning
  • rhinorrhea
49
Q

Chronology of Opioid Abstinence Syndrome:

12-14 hrs

A
  • irritability
  • piloerection
  • restlessness
  • weaknesses
  • mydriasisT
  • remor
  • anorexia
50
Q

Chronology of Opioid Abstinence Syndrome:

48-72 hrs

A
  • increased irritability
  • insomnia
  • marked anorexia
  • sneezing
  • hyperthermia
  • hyperpnea
  • aching muscles
  • increased heart rate
  • hypertension
  • hot and cold flashes
  • nausea & vomiting
  • piloerection
  • abdominal cramps
51
Q

How long is the opioid abstinence syndrome duration?

A

7-10 days

52
Q

Cannabinoids includes?

A
  • cannabis
  • medical “pot”
  • dronabinol
  • encompasses all drugs that have similar pharmacological properties as cannabis
53
Q

Is marijuana addictive?

A

yes

*see slide 28

54
Q

Variable effects of cannabis

A

dysphoria to hallucination

55
Q

1 in _ first time users become dependent

A

9

56
Q

Major psychoactive constituent in cannabis leaves?

A

1-5% THC

57
Q

Cannabis has ____ with chronic use

A

tolerance

58
Q

Can take cannabis ?

A

oral or smoked

59
Q

Mechanism of action of cannabis?

A

Cannabinoid receptors: CB1, CB2

60
Q

Endogenous cannabinoids?

A

anandamide and 2-arachidonyl glycerol

61
Q

CB1: ??

A

MAP kinase / adenylyl cyclase / K-channel-linked

62
Q

Active ingredient in cannabis?

A

delta-9-tetrahydrocannabinol, THC

63
Q

Cannabis leaves are ____%

A

2-5

64
Q

Sinsemilla cannabis ___%

A

35

65
Q

Hashish cannabis ___%

A

5-15

66
Q

High potency cannabis oil up to __%

A

98

67
Q

Cannabis:

CNS Effects

A
  • euphoria
  • lack of concentration
  • motor function impairment (rxn 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
68
Q

Cannabis:

CV Effects

A
  • increased HR

- decreased BP (vasodilation)

69
Q

Cannabis:

respiratory effects

A
  • decreased respiratory rate
  • bronchodilation
  • lung damage (smoking)
70
Q

Cannabis:

drug interactions

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)
71
Q

Smoking of cannabis

A
  • rapid onset (minutes) 18-50% bioavailability

- smoking dynamics: # puffs, duration and volume inhalation, hold

72
Q

Oral cannabis

A
  • slower onset (1-5 hr)
  • 6-18% bioavailability
  • 1st pass effet (liver)
73
Q

THC is _____

A

lipophilic

74
Q

THC undergoes _____ circulation

A

enterohepatic

75
Q

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

A

3 days in chronic users

76
Q

Cannabis PK follows a ____ curve

A

hysteresis

*slide 36

77
Q

__mg is a legal dose of cannabis

A

10

78
Q

What are spice products?

A

cannabinoids that are structurally related to cannabis

*not pharmacologically equivalent to THC

79
Q

Desirable effects of cocaine

A
  • locomotor stimulation
  • euphoria
  • elevation of mood
  • increased energy
  • alertness, sociability
  • confidence
  • sexual arousal
  • decreased need for food
80
Q

Undesirable effects of cocaine

A
  • dysphoria
  • irritability
  • drug craving
  • paranoia
  • assaultive behaviour
  • hallucinations
  • hyperthermia
  • psychosis
  • death
81
Q

Cocaine is a _____

A

stimulant (inhibits reuptake of NE, DA, and serotonin)

82
Q

DA

A
  • localized to striatum (reward and control of motivation)

- some side effects: hyperthermia

83
Q

NE

A

adrenergic (tachycardia)

84
Q

5-HT

A

dysphoria

depression and craving seen in withdrawal

85
Q

Route of admin for cocaine

A

hydrochloride salt versus free base (crack)

86
Q

Purity of cocaine HCl

A

20-95%

87
Q

Purity of crack cocaine

A

20-80%

88
Q

Smoking cocaine produces similar effects as IV

A

Peak effect and cocaine blood level

  • 5 min after IV
  • 7 min after smoking (bioavailability 32-77%)
  • 20 min after intranasal (dose dependent?)
89
Q

t1/2 of intranasal cocaine

A

27 min

90
Q

t1/2 of IV cocaine

A

15 min

91
Q

t1/2 of smoking cocaine

A

17 min

92
Q

Cutters of cocaine

A 
Lidocaine
Hydroxyzine
Phenacetin
Levamisole
Sugars
Caffeine
93
Q

Cocaine duration of action

A

short half life 10-30 mins and this leads to binge use for hours or days

94
Q

Cocaine:

______ to euphoric effects but also ____ to psychomotor effects

A

tolerance

sensitization

95
Q

Cocaine:

binge to crash

A

depletion of NE, DA

96
Q

Cocaine:

repeated dosing

A

diminished effect or kindling

97
Q

Cocaine:

withdrawl

A

fatigue, irritability,, loss of sexual desire, muscle pain, etc.

98
Q

Cocaine:

high doses and chronic use lead to?

A

toxic symptoms, including anxiety, insomnia, irritability, paranoia, suspiciousness (toxic paranoid psychosis)

99
Q

Co-Abuse:

Speedball

A

cocaine & heroin

100
Q

Co-Abuse:

Tick

A

cocaine & phencyclidine

101
Q

Co-Abuse:

Turbo

A

cocaine & marijuana

102
Q

What happens with acute cocaine intoxication?

A
  • Increased muscular activity & vasoconstriction (hyperthermia)
  • Pronounced CNS stimulation (psychosis, grand-map convulsions, coma)
  • Cardiovascular overstimulation (vasoconstriction, ventricular arrhythmia, myocardial infarction)
  • Respiratory dysfunction (Chenyn-stoke breathing, respiratory paralysis)
103
Q

What happens with chronic use of cocaine?

A
  • Excited delirium (sudden collapse, DIC, renal failure, rhabdomyolysis)
  • Death can occur in spite of appropriate medical intervention (1-12 hr)
  • Upregulation of kappa receptors in amygdala
104
Q

Chronic use of cocaine leads to?

A
  • Malnutrition
  • Psychiatric disturbance (violent protective behaviour, hyperkinetic behaviour, distorted perception)
  • Rhinitis (nasal septum perforation)
  • Shortness of breath
  • Cold sweats
  • Cardiovascular toxicity (tachycardia, vessel rupture, MI; stroke, tolerance to cardiovascular affects does not occur during a cocaine run)
105
Q

Amphetamine and Methamphetamine are ______

A

stimulants (promote synthesis and release of DA, serotonin and NE)

106
Q

Rx names of amphetamine?

A

Adderall, Benzedrine, Dexedrine

107
Q

Clandestine names of methamphetamine?

A

crank, crystal, speed, ice 2, rock candy

108
Q

Rx name of methamphetamine?

A

Desoxyn

109
Q

Toxicity symptoms of amphetamine and methamphetamine?

A
  • Parasitosis
  • Meth mouth
  • Cardiac toxicity, endocarditis, aortic dissection, dilated cardiomyopathy, aneurisms
110
Q

Half life of amphetamine?

A

7 - 34 hours

111
Q

Half life of methamphetamine?

A

12 - 34 hours

112
Q

Route of admin of amphetamine and methamphetamine?

A

oral
intranasal
smoked
intravenous

113
Q

Mechanism of action for amphetamine and methamphetamine?

A
  • Increase synaptic levels of DA, 5-HT, NE
  • Displace DA from nerve terminals storage vesicles
  • Substrate for 5-HT, DA, and NE transporters lead to transmitter release
  • Reduce accumulation in synaptic vesicles (affect proton gradient)
114
Q

Other drugs metabolized to amphetamine and methamphetamine?

A
  • selegeline
  • faprofazone
  • benphetamine
115
Q

What does ecstasy do?

A
  • increases serotonin, DA, and NA release

- inhibits serotonin transporters, neurotoxic to serotonin neurons

116
Q

Positive effects of ecstasy?

A

empathy
well-being
reduced anxiety

117
Q

Adverse effects of ecstasy?

A 
hyperthermia
dehydration
increased blood pressure
depression
risk of serotonin syndrome
118
Q

Amphetamine-like substances are known as ??

A

“bath salts”

119
Q

Effects of bath salts include ??

A
  • paranoia and violent behaviour
  • hallucinations
  • delusions
  • suicidal thoughts
  • seizures
  • panic attacks
  • chest pain
  • nausea and vomiting
  • increased heart rate
  • increased blood pressure
  • increased body temperature
  • rhabdomyolysis (skeletal muscle tissue breakdown)
  • multiple organ failure
  • coma
  • death

Pharmacology (21 decks)

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