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
2
Q
List some recreational drug classes
A
Alcohols Cannabinoids Cocaine Amphetamine-like Opioids Sedative hypnotics Hallucinogens Antidepressants Antipsychotics Inhalants GHB, DMMA
3
Q
Define tolerance
A
Tolerance is a state at which there is no longer the desired response to the drug
4
Q
Describe the Progressive model
A
To achieve the desired response, more drug is required
5
Q
Tolerance typically lost in?
A
10-14 days
6
Q
What is reverse tolerance?
A
sensitization - can resist for years (ex. cocaine and amphetamines)
7
Q
Functional tolerance also referred to as?
A
pharmacodynamic tolerance
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
9
Q
List the post-synapse receptors
A
G-protein
Ionotropic
Extrasynaptic proteins
10
Q
Metabolic tolerance is also referred to as?
A
pharmacokinetic tolerance
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
12
Q
What is cross tolerance?
A
drugs metabolized similarly
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
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
15
Q
There are physiological signs available of withdrawal symptoms for?
A
alcohol hypnotics anxiolytics opioids sedatives
16
Q
There are less obvious signs available of withdrawal symptoms for?
A
amphetamines
nicotine
cocaine
cannabis
17
Q
Define dependence
A
The state at which the user functions normally only when taking the drug
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
19
Q
Physiological dependence
A
withdrawl of alcohol from an alcoholic - life threatening
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
21
Q
Affects on _____ pathways though to play a role in crave to use the drug again
A
dopaminergic
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
23
Q
Good data in Canada on recreational drug use is _____
A
lacking
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)
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
