Lecture 13 - Drugs of Abuse Flashcards Preview

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Flashcards in Lecture 13 - Drugs of Abuse Deck (119)
1

Define recreational drug use

-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

2

List some recreational drug classes

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

3

Define tolerance

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

4

Describe the Progressive model

To achieve the desired response, more drug is required

5

Tolerance typically lost in?

10-14 days

6

What is reverse tolerance?

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

7

Functional tolerance also referred to as?

pharmacodynamic tolerance

8

Describe functional tolerance

-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

9

List the post-synapse receptors

G-protein
Ionotropic
Extrasynaptic proteins

10

Metabolic tolerance is also referred to as?

pharmacokinetic tolerance

11

What is metabolic tolerance?

-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

12

What is cross tolerance?

drugs metabolized similarly

13

What is withdrawal?

-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

14

What happens after a person develops the unpleasant withdrawal symptoms?

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

15

There are physiological signs available of withdrawal symptoms for?

alcohol
hypnotics
anxiolytics
opioids
sedatives

16

There are less obvious signs available of withdrawal symptoms for?

amphetamines
nicotine
cocaine
cannabis

17

Define dependence

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

18

How do withdrawal symptoms and dependence work?

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

19

Physiological dependence

withdrawl of alcohol from an alcoholic - life threatening

20

Psychological dependence

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

21

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

dopaminergic

22

What is addiction characterized by?

-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

23

Good data in Canada on recreational drug use is _____

lacking

24

What do you need to consider when discussing recreational use?

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

25

Synthetic opioids?

Sufentanyl
Carfentanil
Fentanyl

26

Semi-synthetic opioids?

Heroin

27

Plant Extracts Opiates?

Opioids
Morphine

28

Endogenous opioids?

Enkephalins
Endorphins
Dynorphins (peptides)

29

Why are opioids used recreationally?

Euphoric affect associated with recreational use

30

Examples of opioids

Morphine
Heroin
Codeine
Dextromethorphan
Oxycodone
Hydromorphone
Fentanyl
Meperidine

31

What are designer drugs?

acetylfentanyl
furanylfentanyl
carfentanil

32

What contributes to an abuser's drug of choice?

-route of administration
-availability
-duration of high
-potency
-side effects

33

_____ are the most efficacious analgesic drugs available

Opioids

34

Opioids also produce??

-Respiratory depression
-Variable euphoric affect (the high)
-Dependence
-Prominent affect on GI tract
-Miosis

35

Opioids are similar in pharmacology but differ in: ?

-Duration of action
-Oral availability
-Relative potency
-Adverse side effect profile

36

Potency related to binding affinity: ??

mu, kappa, delta

37

Most opioids are selective for ___ receptor

mu

38

Desirable effects of opioids?

Analgesia
Euphoria
Sedation
Relief of anxiety
Depress cough reflex

39

Undesirable effects of opioids?

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

40

What is the common autopsy finding associated with opioid overdose?

-pulmonary congestion and frothing of mouth
-witnesses often comment that deceased was heavily snoring prior to death: blockade of respiratory centres to PCO2

41

Admin routes for opioids?

-Oral: readily absorbed
-IV
-IM
-Smoked
-Intranasal
-Transdermal: increased lipophilicity

42

Opioids have a prolonged affect

accumulation of drug/formation of active metabolites

43

First pass metabolism of opioids

glucuronidation (liver) and renal elimination

*also enterohepatic re-circulation

44

Opioid Toxicity:
CNS

-convulsions (delta receptor dependent and targeted to hippocampal pyramidal cells)
-meperidine metabolism to normeperidine

45

Opioid Toxicity:
Respiratory (brain stem)

-depression of rate, volume & exchange
-decreased respiratory responsiveness

46

Opioid Toxicity:
Cardiovascular

-orthostatic hypotension
-stroke
-ECG abnormalities

47

Opioid Toxicity:
GI

-decreased motility
-intestinal obstruction
-increased biliary tract pressure

48

Chronology of Opioid Abstinence Syndrome:
8-12 hrs

-lacrimation
-perspiration
-yawning
-rhinorrhea

49

Chronology of Opioid Abstinence Syndrome:
12-14 hrs

-irritability
-piloerection
-restlessness
-weaknesses
-mydriasisT
-remor
-anorexia

50

Chronology of Opioid Abstinence Syndrome:
48-72 hrs

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

51

How long is the opioid abstinence syndrome duration?

7-10 days

52

Cannabinoids includes?

-cannabis
-medical "pot"
-dronabinol
*encompasses all drugs that have similar pharmacological properties as cannabis

53

Is marijuana addictive?

yes
*see slide 28

54

Variable effects of cannabis

dysphoria to hallucination

55

1 in _ first time users become dependent

9

56

Major psychoactive constituent in cannabis leaves?

1-5% THC

57

Cannabis has ____ with chronic use

tolerance

58

Can take cannabis ?

oral or smoked

59

Mechanism of action of cannabis?

Cannabinoid receptors: CB1, CB2

60

Endogenous cannabinoids?

anandamide and 2-arachidonyl glycerol

61

CB1: ??

MAP kinase / adenylyl cyclase / K-channel-linked

62

Active ingredient in cannabis?

delta-9-tetrahydrocannabinol, THC

63

Cannabis leaves are ____%

2-5

64

Sinsemilla cannabis ___%

35

65

Hashish cannabis ___%

5-15

66

High potency cannabis oil up to __%

98

67

Cannabis:
CNS Effects

-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

Cannabis:
CV Effects

-increased HR
-decreased BP (vasodilation)

69

Cannabis:
respiratory effects

-decreased respiratory rate
-bronchodilation
-lung damage (smoking)

70

Cannabis:
drug interactions

-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

Smoking of cannabis

-rapid onset (minutes) 18-50% bioavailability
-smoking dynamics: # puffs, duration and volume inhalation, hold

72

Oral cannabis

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

73

THC is _____

lipophilic

74

THC undergoes _____ circulation

enterohepatic

75

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

3 days in chronic users

76

Cannabis PK follows a ____ curve

hysteresis
*slide 36

77

__mg is a legal dose of cannabis

10

78

What are spice products?

cannabinoids that are structurally related to cannabis
*not pharmacologically equivalent to THC

79

Desirable effects of cocaine

-locomotor stimulation
-euphoria
-elevation of mood
-increased energy
-alertness, sociability
-confidence
-sexual arousal
-decreased need for food

80

Undesirable effects of cocaine

-dysphoria
-irritability
-drug craving
-paranoia
-assaultive behaviour
-hallucinations
-hyperthermia
-psychosis
-death

81

Cocaine is a _____

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

82

DA

-localized to striatum (reward and control of motivation)
-some side effects: hyperthermia

83

NE

adrenergic (tachycardia)

84

5-HT

dysphoria
depression and craving seen in withdrawal

85

Route of admin for cocaine

hydrochloride salt versus free base (crack)

86

Purity of cocaine HCl

20-95%

87

Purity of crack cocaine

20-80%

88

Smoking cocaine produces similar effects as IV

Peak effect and cocaine blood level
-5 min after IV
-7 min after smoking (bioavailability 32-77%)
-20 min after intranasal (dose dependent?)

89

t1/2 of intranasal cocaine

27 min

90

t1/2 of IV cocaine

15 min

91

t1/2 of smoking cocaine

17 min

92

Cutters of cocaine

Lidocaine
Hydroxyzine
Phenacetin
Levamisole
Sugars
Caffeine

93

Cocaine duration of action

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

94

Cocaine:
______ to euphoric effects but also ____ to psychomotor effects

tolerance
sensitization

95

Cocaine:
binge to crash

depletion of NE, DA

96

Cocaine:
repeated dosing

diminished effect or kindling

97

Cocaine:
withdrawl

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

98

Cocaine:
high doses and chronic use lead to?

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

99

Co-Abuse:
Speedball

cocaine & heroin

100

Co-Abuse:
Tick

cocaine & phencyclidine

101

Co-Abuse:
Turbo

cocaine & marijuana

102

What happens with acute cocaine intoxication?

-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

What happens with chronic use of cocaine?

-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

Chronic use of cocaine leads to?

-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

Amphetamine and Methamphetamine are ______

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

106

Rx names of amphetamine?

Adderall, Benzedrine, Dexedrine

107

Clandestine names of methamphetamine?

crank, crystal, speed, ice 2, rock candy

108

Rx name of methamphetamine?

Desoxyn

109

Toxicity symptoms of amphetamine and methamphetamine?

-Parasitosis
-Meth mouth
-Cardiac toxicity, endocarditis, aortic dissection, dilated cardiomyopathy, aneurisms

110

Half life of amphetamine?

7 - 34 hours

111

Half life of methamphetamine?

12 - 34 hours

112

Route of admin of amphetamine and methamphetamine?

oral
intranasal
smoked
intravenous

113

Mechanism of action for amphetamine and methamphetamine?

-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

Other drugs metabolized to amphetamine and methamphetamine?

-selegeline
-faprofazone
-benphetamine

115

What does ecstasy do?

-increases serotonin, DA, and NA release
-inhibits serotonin transporters, neurotoxic to serotonin neurons

116

Positive effects of ecstasy?

empathy
well-being
reduced anxiety

117

Adverse effects of ecstasy?

hyperthermia
dehydration
increased blood pressure
depression
risk of serotonin syndrome

118

Amphetamine-like substances are known as ??

"bath salts"

119

Effects of bath salts include ??

-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