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Drugs of Abuse Flashcards

1
Q

What is recreational drug use?

A

Use of a pharmacologically active agent for purposes other than it’s intended medicinal or other purpose.
Psychoactive substances

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2
Q

What are the recreational drug classes?

A

Cannabinoids, Cocaine, Amphetamine-like, Opioids and sedative hypnotics

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3
Q

What is tolerance?

A

A state at which there is no longer the desired response to a drug. More drug will be required to achieve the same response.
Not necessarily addiction.

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4
Q

How high can tolerance potentially be?

A

200 fold

Diazepam, methamphetamine

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5
Q

How long until tolerance is typically lost?

A

10-14 days

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6
Q

What is reverse tolerance?

A

Sensitization. A tolerant person takes a break, and then when they start again they won’t be able to take as much as they were before.

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7
Q

When are the impairing effects of a drug greater?

A

During rise to maximal concentration in comparison to downward slope

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8
Q

What is functional tolerance (pharmacodynamic tolerance)?

A

Change in the post synapses of the CNS due to exposure to psychoactive drugs (or hormones)

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9
Q

What are the short and long term effects of functional tolerance?

A

Short (few days): desensitization of receptors (from something like phosphorylation)
Long (few weeks): down or up regulation of receptors/signalling pathways

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10
Q

What is functional cross tolerance?

A

When 2 drugs work on the same receptor, if tolerance occurs to one, it will most likely occur to the other.

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11
Q

What is metabolic tolerance (pharmacokinetic tolerance)?

A

The adaptation of metabolic “machinery” to repeated exposure to a drug (similar to drug resistance)
Enzyme induction, drug metabolism (CYP P450, Glucuronidation)
Different from inherent susceptibility (polymorphisms)

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12
Q

What is metabolic cross tolerance?

A

When 2 drugs are metabolized similarly tolerance to one can cause tolerance in the other

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13
Q

What is withdrawal?

A

An unpleasant maladaptive behavioural change that occurs when blood tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance (symptoms vary between classes of drugs)

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14
Q

Which drugs have physiological withdrawal symptoms?

A

Alcohol, hypnotics, anxiolytics, opioids and sedatives

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15
Q

What is dependence?

A

The state at which the user functions normally only when taking the drug
Reinforced by withdrawal symptoms

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16
Q

What is an example of physiological dependence?

A

An alcoholic’s withdrawal from alcohol (CNS depression) can be life-threatening

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17
Q

What is an example of psychological dependence?

A

Repeated cocaine use, they will continue drug seeking habits in spite of risks and repeated dosing needed to keep the “high”

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18
Q

What pathway can play a role in drug cravings?

A

Dopaminergic pathway

Separate neruochemical pathways for physiological vs psychological dependence

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19
Q

What is addiction characterized by?

A

Inability to consistently Abstain, impairment in Behavioural control, Craving, Diminished recognition of significant problems with one’s behaviours and interpersonal relationships and a dysfunctional Emotional response

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20
Q

What are opiates?

A

Plant extracts and semi-synthetics derived from the poppy

Morphine, heroine

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21
Q

What are opioids?

A

The umbrella term for opiates and synthetics like fentanyl.

Be aware of the source of the drug.

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22
Q

What are some examples of endogenous opioids?

A

Enkephalins, endorphins, dynorphins

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23
Q

What are some desirable effects of opioids?

A

Analgesia, euphoria, sedation, anxiety relief, depression of cough reflex

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24
Q

Which receptors do opioids bind to?

A

Mu, kappa, delta
Most are selective for mu
Pentazocine works on kappa

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25
What are some undesirable effects of opioids?
Dysphoria (dizziness, nausea), vomiting, constipation, urinary retention, withdrawal, respiratory depression
26
What are some symptoms associated with overdose?
Pulmonary congestion, frothing of the mouth, snoring heavily prior to death, blockade of respiratory centres (pneumonia patients at risk)
27
What the routes of administration for opioids?
Oral, IV, IM, Smoked (more immediate high than oral), Intranasal, Transdermal (more lipophilicity)
28
What is the prolonged affect of opioids due to?
Accumulation of drug/formation of active metabolites
29
Which polymorphism can affect opioid metabolism?
Morphine 6-glucuronide is active, morphine 3-glucuronide is not
30
What are some symptoms of opioid toxicity?
Convulsions, meperidine metabolism to normeperidine, decreased respiration, orthostatic hypotension, stroke, ECG abnormalities, intestinal obstruction
31
How long will opioid abstinence syndrome last?
7-10 days
32
What occurs in 8-12 hours of opioid abstinence?
Lacrimation, respiration, yawning, rhinorrhea
33
What occurs in 12-14 hours of opioid abstinence?
Irritability, restlessness, mydriasis, anorexia, piloerection, weaknesses
34
What occurs in 48-72 hours of opioid abstinence?
Sneezing, hyperthermia, aching muscles, insomnia, hypertension, abdominal cramps
35
What is acetyl fentanyl?
An opioid analgesic that is not recognized for medical use (follows controlled analogue rules) 5-15 times more potent than heroin
36
What is included in the cannabinoids?
Cannabis, medical "pot: and dronabinol | All drugs that have similar pharmacological properties as cannabis
37
What is the mechanism of action of cannabis?
The active ingredient (THC) works on the cannabinoid receptors (CB1, CB2) to give variable effects from dysphoria to hallucination
38
What kind of receptor is CB1?
CB1 is an MAP kinase, adenylyl cyclase, K channel linked receptor
39
What occurs with chronic cannabis use?
Tolerance | 1 in 9 first time users become dependent ( risk during teen years)
40
What are some of the effects of cannabis use?
Motor function impairment which can persist after high has dissipated (reaction time), lack of concentration, paranoia, lung damage, decreased blood pressure, decreased respiration, impaired attention, memory and learning
41
What are the drug interactions with cannabis?
Cocaine and amphetamines causing increased hypertension, tachycardia, cardiotoxicity Additive effect with CNS depressants
42
What are the dynamics of smoking cannabis for pharmacokinetics?
Number of puffs, duration and volume inhalation and hold | Rapid onset, lots of bioavailability
43
What are the pharmacokinetics of oral cannabis?
Slower onset (1-5 hours), less bioavailability, 1st pass effect
44
What are the pharmacokinetics of cannabis?
Lipophillic, undergoes enterohepatic circulation Half life is 3 days in chronic users Hysteresis (levels in blood quickly decline, difficult to say that someone is impaired)
45
What are the desirable effects of cocaine?
Locomotor stimulation, sexual arousal, increased energy, decreased need for food, elevation of mood, confidence
46
What are the undesirable effects of cocaine?
irritability, drug craving, paranoia, assaultive behaviour, hyperthermia, hallucination, psychosis
47
How does cocaine work?
Inhibits the reuptake of norepinephrine (tachycardia), dopamine and serotonin (dysphoria, depression)
48
How is cocaine administered?
As a hydrochloride salt or as a free base (crack) cut with lidocain, sugars, caffeine, hydroxyzine
49
How does the route of administration of cocaine effect peak effect times?
5 minutes after IV 7 minutes after smoking 20 minutes after intranasal (may be dose dependent)
50
What is the duration of action of cocaine?
10-30 minutes, leading to binge use for hours or days
51
What happens after repeated dosing of cocaine?
Tolerance to euphoric effect but also sensitization to psychomotor effects. A crash can occur due to depletion of norepinephrine and dopamine
52
What are some symptoms of cocaine withdrawal?
Fatigue, irritability, loss of sexual desire, muscle pain
53
What is the cycle of cocaine use?
Binge, crash, withdrawal | Correlates with the rise and fall of synaptic dopamine levels
54
What are the symptoms of acute cocaine intoxication?
Hyperthermia (increased muscular activity and vasoconstriction), psychosis, grand-mal convulsions, coma, (pronounced CNS stimulation), vasocontriction, arrhythmia, MI (cardiovascular overstimulation), respiratory dysfunction
55
What are the effects of cocaine overdose/chronic use?
Excited delirium, sudden collapse, renal failure, rabdomyolysis Upregulation of kappa receptors in the amygdala Death can incur in spite of appropriate medical intervention
56
What are the effects of chronic cocaine use?
Malnutrition, distorted perception, hyperkinetic and violent, protective behaviour, rhinitis, shortness of breath, cold sweats, cardiovascular toxicity (tachycardia, MI, stroke)
57
How does ecstasy work?
Increases serotonin, dopamine and norepinephrine release | Inhibits serotonin transporters, neurotoxic to serotonin neurons
58
What are the positive effects of ecstasy?
Empathy, well-being, reduced anxiety
59
What are the adverse effects of ecstasy?
Hyperthermia, dehydration, hypertension, depression, risk of serotonin syndrome
60
Which enantiomer of ecstasy is more neurotoxic?
S-enantiomer. | Most that you get comes as an enantiomer
61
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 two of the 11 criteria occurring within a 12 month period Mild has 2-3, moderate has 4-5, severe has 6 or more
62
What are the symptoms of opioid use disorder?
Opioids taken in larger amounts or longer period than intended Persistent desire or unsuccessful efforts to cut down or control Lots of time spent trying to obtain, use or recover from opioid effects Craving, strong desire or urge to use opioids Use results in failure to fulfill major role obligations Continued use despite problems Tolerance and/or withdrawal
63
What is the harm reduction philosophy?
Decrease the harmful consequences of illicit drug use to the individual, family, community and society. Decrease illicit opioid use, needle sharing, criminal activity and mortality
64
Which drugs are used to help with opioid use disorder?
Methdone, buprenorphine/naloxone or buprenorphine alone
65
What is methadone?
A synthetic opioid that isn't structurally related to opiates that works as an agonist at the mu-opioid receptorand a NMDA antagonist
66
What is methadone used for?
Analgesia and withdrawal management in opioid dependent individuals Once daily dosing
67
What does methadone cause?
Blocks the euphoria from heroin and other opioids and do not impair psychomotor performance Stop tolerance effects (NMDA) Sold on street for those who are junk sick (low lethal dose)
68
When are the peak plasma levels of methadone?
Detected in 30 minutes | Peak in 2-4 hours (drowsiness, CNS depression) this is when you can die from the dose
69
How long does it take for methdone to reach a steady state?
5-7 days to reach a steady state with repeated dosing (watch out in case of accumulation leading to OD) Withdrawal will be suppressed for 24-36 hours
70
How can polymorphisms cause drug interactions with methadone?
Polymorphisms can cause drug interactions with ciprofloxacin
71
How is methdone excreted?
Both unchanged and as metabolites in the urine and feces. | Amount excreted in urine increases as pH decreases
72
What are some persistent adverse effects of methadone?
QT interval prolongation | Constipation, dental, insomnia, neuroendocrine, sexual changes and sweating
73
What are the some adverse effects that you develop tolerance to from methadone?
Drowsiness, nausea, psychoactive effects and weight gain
74
What is recommended for patients on high doses of methadone?
ECG | Male QT will be higher than 400?, females 470
75
On which CYP enzyme do drug interactions with methadone occur?
CYP P450 3A4 Pharmacokinetic (inhibition/induction) Pharmacodynamic with benzodiazepines (similar side effect profile) MUST TAPER BENZOS
76
What is the dosing for methadone?
10-30 mg to start (10-20 mg in high risk) Increase by 5-10 mg every 3-5 days as tolerated Once above 60-80 mg, you can increase by 10 mg every 1-2 weeks
77
What are some signs and symptoms of withdrawal?
Agitation, sweating, chills, insomnia, diarrhea, abdominal cramping, tachycardia, nausea/vomiting, intense anxiety
78
What are some signs and symptoms of overdose?
Sedation, lack of coordination, respiratory depression, pinpoint pupils, cardiac arrest, sweating
79
What must be done about methadone in patients who are rapid metabolizers?
Those who are drowsy in the afternoon but are in withdrawal by the evening (measure peak:trough ration-should be 2) Consider BID dosing
80
How does methadone dosing change in pregnancy?
Metabolism changes in 3rd trimester May require a dose increase and/or split dosing Baby may experience withdrawal after birth
81
How is methadone overdose treated?
Occurs with cocurrent use of sedating drugs | Treat with naloxone for minimum 24 hours (IV or hourly bolus) with another 12 hours of monitoring
82
What is buprenorphine? What is naloxone?
Buprenorphine is a partial mu-opioid agonist that is absorbed sublingually. (Need to be in withdrawal to begin) Naloxone is a pure opioid antagonist that is injected.
83
How does buprenorphine work?
Will displace morphine, methadone and other full agonists from the mu-opioid receptors Slow dissociation from receptor, low intrinsic activity Antagonist at kappa opioid receptor Will cause precipitated withdrawal
84
What is the onset of action, peak effect and duration of action of buprenorphine?
30-60 minutes onset of action, peak in 1-4 hours | Duration is dose-dependent (higher dose is longer duration of action)
85
What are the drug interactions with buprenorphine?
Interacts with 3A4 inducers/inhibitors, other sedating drugs Additive respiratory depression with benzos Makes pain management difficult with full opioid agonists
86
What makes buprenorphine better than methadone?
Safer in overdose than methdone, less side effects, less withdrawal on discontinuation

Pharmacology 2 (23 decks)

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