Module 03 Flashcards
(256 cards)
1
Q
Sedative-hypnotic agents
A
CNS depressants
2
Q
Magnitude of CNS depression
A
determines what effect the agent produces
3
Q
Low Dose of CNS depression
A
- anti-anxiety
- sedation
- hypnosis (sleep)
- general anesthesia
4
Q
Anti-anxiety drugs
A
used to treat anxiety disorders, such as generalized anxiety disorder and obsessive compulsive disorder
5
Q
Sedation drugs
A
used to relieve anxiety, decrease activity, moderate excitement, and calm the individual
6
Q
Hypnosis (sleep) drugs
A
used to produce drowsiness and aid in the onset and maintenance of sleep
7
Q
General anesthesia drugs
A
used to induce general anesthesia - state of unconsiousness with an absence of pain sensation
8
Q
What is the major excitatory neurotransmitter?
A
Glutamate
9
Q
Mechanism of action of sedative-hypnotics
A
- when a person is anxious or having trouble sleeping, some therapies aim to depress overall brain activity by reducing glutamate-induced nerve firing
- this is accomplished by increasing inhibitory signalling in the brain
10
Q
drug classes
A
a group of drugs that have the same mechanism of action and similar pharmacological properties
11
Q
CNS Excitation Controlled by Comparing Neuronal Activity With Sedative-Hypnotics
A
inhibitory signals from GABA neurons increase with most sedative-hypnotics, resulting in decreased glutamate nerve firing
12
Q
CNS Excitation Controlled by Comparing Neuronal Activity Without Sedative-Hypnotics:
A
- most brain activity involves excitatory neurons
- these neurons release neruotransmitter glutamate
- neurons “fire” when the excitatory inputs exceed inhibitory inputs
13
Q
GABA
A
primary inhibitory neurotransmitter in the CNS
14
Q
GABA signalling
A
- GABA causes inhibition by binding to and selectively opening chloride channels
- allows chloride ions to flow into the cell when signalled to open
- when GABA binds to and opens the chloride channel, chloride ions flow into the postsynaptic neuron
- the influx of chloride ions makes it harder for the postsynaptic neuron to transmit incoming messages to other neurons, thereby depressing CNS neuronal signalling
15
Q
When is the chloride channel closed?
A
when there is nothing bound to the GABA binding site
16
Q
When is the chloride channel open?
A
when a drug (such as a sedative-hypnotic) bind to the GABA binding site, the channel opens and allows an influx of chloride ions into the neuron
17
Q
Sedative-hypnotics and chloride channel
A
1most sedative-hypnotics modulate the chloride ion channel in the brain and spinal cord
- BUT each bind to a different site on the chloride channel
2. results in an increase in synaptic inhibition and thus a dampening of neuronal responses
18
Q
What do sedative-hypnotic drugs do to GABA?
A
ENHANCE THE INHIBITORY EFFECT OF GABA
19
Q
Benzodiazepines
A
are among the most widely prescribed drugs in the world (5-10% of Canadians being prescribed)
20
Q
Routes of Administration of Benzodiazepines
A
usually capsule or tablet, some are available for intravenous or intranasal use
21
Q
Mechanism of Action of Benzodiazepines
A
activation of benzodiazepine receptor increases frequency of the opening of the chloride channel
22
Q
Therapeutic Effects of Benzodiazepines
A
have minimal suppression of REM-type sleep
23
Q
Lethality of Benzodiazepines
A
one of the drugs most commonly involved in overdose
- BUT have a very high therapeutic index and therefore a wide margin of safety which means that deaths from overdose are very rare
24
Q
Deaths from Benzodiazepines occur when…
A
- ingestion of enormous doses
- rapid intravenous injection of a large dose
- when taken in combination with other sedating drugs (alcohol)
25
Antidote for Benzodiazepines
Flumazenil
26
Flumazenil
reverse Benzodiazepines effects in the event of an overdose
- contains a benzodiazepine receptor antagonist that blocks the effects of benzodiazepines
27
Adverse Effects of Benzodiazepine Short-Term Use:
affect the CNS, lungs and motor coordination
28
Adverse Effects of Benzodiazepine Short-Term Use: CNS
1. drowsiness
2. lethargy
3. fatigue
3. impairment of thinking and memory
***what is considered an adverse effect depends on the targeted therapeutic effect
- if the therapeutic goal is anti-anxiety, drowsiness may be an adverse effect
- however it would be considered a therapeutic effect if the goal is sedation
29
Adverse Effects of Benzodiazepine Short-Term Use: Breathing (Lungs)
respiratory depression has been observed following rapid intravenous administration of benzodiazepines
30
Adverse Effects of Benzodiazepine Short-Term Use: Motor Coordination
1. moderate doses can impair motor coordination and driving
2. patients taking these during the day should refrain from driving or operating dangerous machinery
3. these responses are exaggerated as the dose is increased
31
Adverse Effects of Benzodiazepine Long-Term Use:
Vary between individuals
- some individuals can take large amounts of benzos for long periods of time without any major evidence of intoxication
- others will demonstrate the symptoms of chronic sedative-hypnotic intoxication
32
Adverse Effects of Benzodiazepine Long-Term Use: Symptoms
1. impaired thinking
2. poor memory and judgement
3. disorientation
4. incoordination
5. slurred speech
33
Adverse Effects of Benzodiazepine Use: Pregnanct/Chestfeeding
1. benzodiazepines cross the placenta and distribute into the fetus
- if they are administered in the first trimester, they result in small but significant risk for fetal abnormalities
2. they are secreted into the milk, exposing nursing infants to therapeutic or toxic doses of the drug, and can result in sedation or death
34
Adverse Effects of Benzodiazepine Use: Older Adults
1. benzodiazepines can produce cognitive dysfunction in older adults
2. benzodiazepines are metabolized slower in older adults often leading to over-sedation, falls and injury
35
Benzodiazepines: Misuse Potential
weaker reinforcing properties than other drugs
36
Benzodiazepines: Inherent Harmfulness
low, as it does not depress respiration at therapeutic doses and does not often lead to death on its own
37
Benzodiazepines: Tolerance
1. Tolerance can develop to the sedative effects and impairments of coordination
- the anxiolytic effect (less common) or the euphoric effects (occasionally)
2. the magnitude of tolerance that develops to benzodiazepines does not produce clinical concerns
38
Benzodiazepine and Cross-Tolerance
a high degree of cross-tolerance occurs among benzodiazepines and other sedative-hypnotic drugs (barbiturates and alcohol)
- they all modulate the chloride channel in the CNS
39
Anxiolytic
a drug or other intervention that reduces anxiety
40
Benzodiazepines: Withdrawal
mild but distinct withdrawal can occur after therapeutic use, exhibiting anxiety, headache and insomnia
41
Benzodiazepines: Withdrawal after chronic use (1 year or more)
1. agitation
2. paranoia
3. seizures
4. delirium
42
Benzodiazepines: Addiction
1. may develop in some individuals, but not all
2. depends on a multitude of factors including genetics and the environment
43
Benzodiazepines in Sport
Reduce an athletes anxiety
- increase CNS depression in a dose-dependent manner
- at low doses, they act as anti-anxiety agents
44
Barbiturates
can be long-acting (1-2 days), short-acting (3-8 hours), and ultra-short acting (20 minutes)
- have been replaced by safer, more effective sedative-hypnotics
45
Routes of Administration of Barbiturates
Administered differently depending on what they are used to treat
1. epilepsy - administered orally
2. anesthesia - administered intravenously
46
Mechanism of Action of Barbiturates
Activation of the barbiturate receptor increases duration of the opening of chloride channel
- demonstrate full spectrum of dose-dependent CNS depression
47
Therapeutic Use of Barbiturates
In low doses, usually result in beneficial effects of tranquility and relaxation
- will also induce sleep if dose is sufficient
48
Therapeutic Use of Ultra-short and Short-acting Barbiturates
are used to induce anesthesia
49
Therapeutic Use for Long-acting Barbiturates
used as anti-epileptics
50
Lethality of Barbiturates
1. low therapeutic index and potential for lethality
2. lethality due to depression of respiration is common - especially when combined with alcohol
3. lethal dose varies between individuals
4. death can also occur with barbiturate withdrawal
***NO ANTIDOTE
51
Adverse Effects of Barbiturate Short-Term Use
1. low doses, result in mild euphoria and reduced interest in one’s surroundings
2. dizziness and mild impairment of motor coordination (fine motor dexterity)
3. pleasurable state of intoxication and euphoria as dose of drug increases
4. high doses, depress cardiovascular system, slowing the heart and lowering BP
52
Adverse Effects of Barbiturate Long-Term Use
1. chronic inebriation
2. memory, judgement and thinking are all impaired
3. hostility and mood swings, including depression
53
Potential for Misuse: Barbiturates
1. POM is equal to or greater than alcohol (should be avoided)
- the pleasurable effects give a significant degree of reinforcement
- sometimes injected to obtain a “rush effect”
54
Inherent Harmfulness of Barbiturates
very high due to risk of death from respiratory depression or from withdrawal
55
Cross-tolerance of Barbiturates
a high degree of cross-tolerance occurs between barbiturates and other sedatives (ex. benzodiazepines)
56
Withdrawal of Barbiturates
1. occurs after discontinuation of chronic use
2. must be withdrawn slowly under medical supervision
57
Initial symptoms of barbiturate withdrawal
1. tremors
2. anxiety
3. weakness
4. insomnia
5. postural hypotension (form of low BP in which a person’s BP falls when suddenly standing up or stretching)
58
Postural Hypotension
form of low BP in which a person’s BP falls when suddenly standing up or stretching
59
Progressive symptoms of barbiturate withdrawl
1. seizures
2. delirium
3. visual hallucinations
4. high body temperature
60
Addiction of Barbiturates
1. can result from regular use, irrespective of dose
2. crave the drug and a feeling of panic may occur if they cannot get adequate supply
- craving often persists long after use has stopped
61
Barbs vs. Benzos - MOA
Benzos: increase frequency of opening of chloride channels
Barbs: increase duration of opening of chloride channels
62
Benzos Summary
- very high therapeutic index
- minimal suppression of REM sleep
- decreased aggression, skeletal muscle relaxation
- have an antidote (flumazenil)
63
Barbs Summary
- low therapeutic index
- supress REM sleep
- cause doese-dependent respiratory and cardiovascular depression
- lethality common (especially with alcohol)
- no antidote
64
Is withdrawal more common in Benzos or Barbs?
Barbs
65
Benzodiazepine-like drugs
zopiclone and zolpidem
66
Zopiclone and Zolpidem
1. class of sedative-hypnotics used to treat anxiety or difficulty sleeping
2. more sedative effects as compared to anxiolytic effects
3. should be used with caution in older adults
67
Barbiturate-like drugs MOA
1. bind to a subset of the GABA receptors and cause sedation
2. bind to the chloride ion channel in a similar location to the benzos
3. these drugs increase chloride channel opening induced by GABA
68
Advantage of Benzodiazepine-like drugs
they disturb sleep patterns (REM sleep) even less than benzodiazepines
69
Buspirone (Buspar)
1. used in generalized anxiety states
2. may have an advantage in that it does not have additive effects with other sedative-hypnotic drugs
3. may be prescribed instead of a benzo or benzo-like drug when the individual is already taking other CNS depressant drugs
70
Buspirone MOA
does not act on the GABA receptor, but rather at the serotonin receptor
71
Which one of the statements listed correctly applies to sedative-hypnotics?
Zopiclone, a benzo-like drugs, is a GABA receptor agonist which has minimal effects on sleep patterns
72
Which one of the options listed is a pharmacological property of the benzodiazepines?
tolerance occurs to the sedative and hypnotic effects of the benzodiazepines
73
Alcohol
CNS depressant that works by slowing down brain function and neural activity
74
Ethanol
only safe type of alcohol that can be consumed
- one of three most used non-medical drugs in Canada (along with caffeine and nicotine)
- produced more health problems and deaths than all illicit drugs combined
75
Why is alcohol (ethanol) a major problem?
readily available and permissive attitudes of society
76
Absorption of Alcohol
ethanol is absorbed rapidly from the stomach (where 20% is absorbed) and the upper small intestine (80%)
77
How long does it take for max blood alcohol conc. from the last drink
30-90 minutes
78
What is overall absorption rate of ethanol effected by?
1. stomach-emptying time, or time required for alcohol to reach the SI
2. ethanol concentration in the GI tract
3. presence of food
79
Distribution of Alcohol
Ethanol distributes throughout the total body water and readily gains access to the brain
- can also readily transfer across the placenta and distribute throughout a developing fetus
80
4 Main steps of alcohol metabolism
1. Alcohol Dehydrogenase
2. MEOS
3. Aldehyde Dehydrogenase
4. Acetate
81
Step 1 of Alcohol Metabolism: Alcohol Dehydrogenase
ethanol is converted to acetylaldehyde by the enzyme alcohol dehydrogenase (ADH)
- Rate-limiting step
82
Rate-limiting step of alcohol metabolism
the speed of this conversion typically sets the pace for the rest of metabolism
- Alcohol Dehydrogenase
83
Step 2 of Alcohol Metabolism: Microsomal Ethanol Oxidizing System (MEOS)
1. part of the cytochrome P450 system
2. breaks down ethanol to acetylaldehyde, especially at high doses when ADH is at full capacity (saturated)
84
When is MEOS induced?
pathway of ethanol metabolism that is induced when BAC is 0.1% or greater
85
Step 3 of Alcohol Metabolism: Aldehyde Dehydrogenase
acetylaldehyde is then converted to acetate by aldehyde dehydrogenase (ALDH) - in the liver
86
Step 4 of Alcohol Metabolism: Acetate
Acetate (acetic acid) is further metabolized by a number of tissues into CO2 and H20
- or used to form acetyl CoA
87
Genetic Variability in Ethanol Metabolism
there are genetic variants in the gene that codes for ADH and ALDH
- some people rapidly convert alcohol to acetaldehyde, causing an accumulation of acetaldehyde in the body (causes unpleasant side effects - protects against alcoholism)
88
Rate of Ethanol Metabolism
occurs at a constant rate irrespective of BAC
- a constant amount of alcohol is metabolized each hour
ex. body rate of ethanol metabolism is about 120 mg ethanol/kg body weight/hour
89
What does ethanol metabolism occur at a constant rate?
Because ADH becomes rate-limiting, or saturated
90
Excretion of Alcohol
1. Over 95% of ethanol in the body is eliminated by biotransformation - mostly in liver
2. Remaining 5% is excreted in breath, urine and sweat
91
What is alcohol primarily metabolized by?
The enzyme alcohol dehydrogenase (ADH)
- alcohol converted to alcohol dehydrogenase
92
What causes the symptoms of a hangover?
The build-up of acetaldehyde
93
Medical uses of ethanol
1. alcohol sponge applied topically to treat fever
2. skin disinfectant
3. antidote in treatment of methanol (wood alcohol) poisoning
4. hand sanitizer
- since the SARS epidemic occurred
94
CNS effects of ethanol
CNS effects of ethanol are proportional to the BAC
95
BAC 0.05-0.1% Clinical Effect
1. sedation
2. subjective "high"
3. slower reaction times
96
BAC 0.1-0.2% Clinical Effect
1. impaired motor function
2. slurred speech
3. ataxia
97
BAC 0.2-0.3% Clinical Effect
1. Emesis
2. Stupor
98
BAC 0.3-0.4% Clinical Effect
Coma
99
BAC >0.4% Clinical Effect
1. respiratory depression
2. death
100
BAC and driving
new drivers and drivers under 22, a zero tolerance BAC applies
101
BAC and driving - provincial offence
BAC of 0.05%
102
BAC and driving - criminal offence
BAC of 0.08%
103
Mechanism of Action of Alcohol
Binds to chloride ion channel and augments GABA-mediated neuronal inhibition
- different binding site than other GABA agonists
104
Why does alcohol have a reinforcing effect?
The interaction of alcohol with chloride ion channels on dopaminergic receptors in reward areas of brain
105
Effects of Short-Term Use of Alcohol
alcohol also effects other system and organs such as cardiovascular system, the stomach and the liver
106
Cardiovascular Effects of Alcohol - Low Doses (1-3 drinks)
Can create vasodilation (flushing) of the vessels to the skin, resulting in a feeling of warmth
107
Cardiovascular Effects of Alcohol - High Doses (>5 drinks)
Depress the cardiovascular system
- can lead to alterations in normal rhythm of the heart
108
Stomach Effects of Alcohol - Low Doses (1-3 drinks)
Increased gastric secretion
109
Stomach Effects of Alcohol - High Doses (>5 drinks)
1. Irritate the lining of the stomach, causing inflammation and erosion (gastritis)
- this condition causes vomiting and abdominal pain
2. Ulcers may be aggravatesd, often leading to a serious gastrointestinal bleed
110
Liver Effects of Alcohol - Low Doses (1-3 drinks)
Does not appear to have significant adverse effects on liver
111
Liver Effects of Alcohol - High Doses (>5 drinks)
Alcohol binge will inhibit glucose production and in association with fasting, can lead to hypoglycermia (low blood sugar)
112
Short-Term High-Dose Alcohol Use
Binge-drinking
113
Adverse Effects of Binge-drinking
1. Memory loss
2. Psychiatric effects
3. Overdose
114
Memory loss from binge-drinking
Individual does not remember events while under the influence
- can be frightening and may result in the individual seeking help
115
Psychiatric effects of binge-drinking
1. Heavy drinking often leads to depression, irritability and over-sedation
2. Negative mood states in concert with impaired judgement and impulsiveness may lead to self-harm or acts of violence
116
Overdose from binge-drinking
Respiratory depression, coma and death
- many comatose drinkers die each year after aspirating their own vomit
117
Adverse Effects of Chronic High-Dose Alcohol Use
1. CNS
2. Cardiovascular
3. Liver
118
Adverse Effects of Chronic High-Dose Alcohol Use on CNS
Many neurological and mental disorders are associated with chronic alcohol misuse
- alcohol damages axons of neurons within the brain, resulting in fewer connections between neurons
- Alcohol Dementia
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Alcohol Dementia
Decrease in cognitive functioning affecting memory, judgement and thinking
120
Adverse Effects of Chronic High-Dose Alcohol Use - Cardiovascular
1. Alcoholic cardiomyopathy (destruction of or poor heart muscle)
2. Increased incidence of hypertension and stoke
121
Adverse Effects of Chronic High-Dose Alcohol Use - Liver
1.Leads to alcohol liver disease
- a major cause of hospitalizations and deaths in NA
2. Can be reversible with alcohol abstinence at early stages, but at later stages it is irreversible and liver function is severely impaired
122
Effects of Alcohol Use During Pregnancy
1. teratogenic effects in the embryo/fetus
2. can manifest postnatally as Fetal Alcohol Spectrum Disorder (FASD)
3. there is not a safe dose of ethanol in pregnancy, so alcohol abstinence is recommended
123
Fetal Alcohol Spectrum Disorder (FASD)
a group of conditions that can occur in a person whose mother drank alcohol during pregnancy
124
2 Types of Drug-Drug Interactions:
1. Alcohol Use During Drug Therapy
2. Chronic Alcohol Use Before Drug Therapy
125
Alcohol Use During Drug Therapy
Effects of having a drug + ethanol at same time
- additive or synergistic effect on CNS depression
- inhibition of metabolism of certain drugs (ex. sedative-hypnotics)
126
Chronic Alcohol Use Before Drug Therapy:
Effects of chronically drinking alcohol but abstaining during drug therapy
- only occurs if there is no existing ethanol-induced liver injury
- increases activity of metabolizing enzymes in liver, resulting in increased metabolism of certain drugs (ex. sedative-hypnotics)
127
Potential for Misuse of Alcohol
Ethanol has significant reinforcing properties
- results in moderate misuse potential
- the ease of availability and social and legal acceptance contributes to ethanol’s misuse potential
128
Inherent Harmfulness of Alcohol
1. Moderate - less than methanol
2. Death can occur from high dose acute ethanol ingestion
3. Chronic ingestion can have long-term effects on health
129
Tolerance of Alcohol
Does occur to chronic consumption
- Individuals can develop tolerance more rapidly to the ethanol-induced impairment of performance of a task when they perform that task repeatedly under the influence (ex. driving)
130
Cross-Tolerance of Alcohol
Ethanol and...
1. Sedative-hypnotics
2. General anesthetics
131
Cross-tolerance of ethanol and sedative-hypnotics
a higher dose of a sedative-hypnotic drug is required for desired therapeutic effect
132
Cross-tolerance of ethanol and general anesthetics
a higher dose of anesthetic agent is required for surgical anesthesia in someone who has developed tolerance to alcohol (require more for surgery yes)
133
Withdrawal of Alcohol
1. Produces compensatory excitation of the CNS (ex. arousal, stimulation)
2. In severe cases, delirium tremens (DTs) may occur, which can involve convulsions, coma and possibly death
134
Addiction to Alcohol
1. Acompulsive desire to seek, obtain and drink ethanol exists
2. Most powerful factor in chronic use of ethanol, contributing to SUD
135
Treatment of Alcohol Withdrawal
1. Initial therapy of alcohol withdrawal syndrome is to maintain fluid and electrolyte balance and prevent seizures
2. More severe case, can be treated by oral administration of diazepam (a benzo)
136
Drugs Used to Treat Alcohol Use Disorder
Alcohol-deterrent or alcohol-sensitizing drugs
ex. Naltrexone
137
Naltrexone
1. An opioid antagonist
2. effective in the treatment of alcohol addiction
- diminishes the craving for ethanol, and assists in maintenance of abstinence
- blocks the activation of dopaminergic reward pathways in the brain
138
Which step of alcohol metabolism is considered rate-limiting?
Conversion of alcohol to acetaldehyde by alcohol dehydrogenase
139
Cannabis
refers to the drug-containing forms of the help plant (Cannabis sativa), which is an herbaceous plant
- contain 60 chemical compounds (cannabinoids (CB))
140
What is the most potent psychoactive agent in cannabis?
I-trans-delta-9-tetrahydrocannabinol (THC)
- accounts for most psychoactive effects
141
What year was cannabis considered a narcotic?
1920s
142
Narcotic
a drug that affects behaviour or mood, consumed for non-medial reasons
143
What year did Canada change the law for some varieties of Cannabis (THC) to be used?
1997
- must obtain a specific license to grow though
144
What year was recreational use of Cannabis legalized in Washington?
2012
145
What year was recreational use of Cannabis legalized in Canada?
2018
146
Classifications of Cannabis
1. Pharmacological
2. Legal
146
Pharmacological use of Cannabis
Classified as a CNS depressant, euphoriant, and hallucinogen (only at high doses hallucination occurs)
147
Administration of Cannabis
1. Typically smoked or inhaled
2. Extracts containing concentrated cannabinoids can be administered through vaping or oral consumption (edibles)
148
Vaping
inhalation of aerosolized extracts, usually containing other chemicals that have been heated via and electronic device (ex. e-cigarette)
149
Mechanism of Action of Cannabis
1. THC binds to Type I Cannabinoid Receptors (CB1) in brain and spinal cord
2. Anandamide is an endogenous ligand for CB receptors
3. when the CB1 receptor is activated by anandamide on THC, it inhibits the release of excitatory neurotransmitters
- causes reduction in cognitive function and CNS depressant effects
150
Anandamine
retrograde transmitter
1. released from the postsynaptic neuron and influences the presynaptic neuron (opposite as usual)
2. bind to CB1 receptors on presynaptic cleft
3. binding inhibits the release of excitatory neurotransmitters (glutamate) into synaptic cleft
4. causes depression of the CNS
***Cannabis works the same
151
2 Types of Cannabinoid Receptors
1. CB1 Receptors
2. CB2 Receptors
152
CB1 Receptors
1. found in the brain, more than any other receptor
2. THC is not a very effective agonist, but since a large number of receptors exist, it does produce a response
153
CB1 Receptors in the cerebral cortex
1. mediate distortions of time, colour, sound and taste
2. mediate decrease in cognitive function and concentration
154
CB1 receptors in hippocampus
may account for changes in memory and learning
155
Why do cannabinoids not depress respiration?
Cause no CB1 receptors are present in the brain stem
- this explains why it is not a lethal drug
156
CB2 Receptors
1. only found outside the CNS
2. do not appear to be involved in psychoactive effects of THC, but may be involved in inflammation
3. binding of THC to CB2 receptors in lymphocytes is thought to be responsible for immunosuppressive properties of THC
157
Absorption of THC
commonly inhaled or ingested - method of administration influences its absorption
158
Absorption of THC - Inhaled
1. rapid and onset of action is immediate
2. effects last 3-4 hours
159
Absorption of THC - Ingested
1. slow and incomplete
2. onset of action is delayed 30-60 minutes
3. effects last less than inhalation
160
Distribution of THC
1. rapidly distributes throughout the body to tissues with high blood perfusion such as the lung, heart, brain and liver
2. also rapidly crosses the placenta
3. highly lipid soluble and will be stored in adipose tissues over time
***much slower following oral ingestion given the slow absorption
161
Metabolism of THC
Metabolized slowly
- metabolites of THC can be measured in drug tests, so those consuming cannabis chronically may test positive for the metabolites weeks after use has stopped
162
Excretion of THC
half-life of approximately 30 hours
- elimination of THC from adipose tissue may take longer
163
Effects of Short-Term Cannabis Use
primarily observed in the CNS, cardiovascular system, and GI tract
164
Early effects of short-term cannabis use on CNS:
- relaxation and drowsiness
- feeling of well-being and euphoria
- impaired motor coordination
- increased appetite
165
Effects of cannabis as you increase dose on CNS
- pseuco-hallucinations (person knows it is a hallucination)
- running together of senses
- imapired judgement and coordination
***some cases a toxic psychotic reaction may occur
166
Effects of Short-Term Cannabis Use on Cardiovascular System
- increased HR
- increase BF to the extremities
- postural hypotension
167
Effects of Short-Term Cannabis Use on GI Tract
- increased appetite
- dryness of mouth and throat
168
Effects of Short-Term Cannabis Use on Males
reduction of sex drive in males, as THC may reduce testosterone
169
Effects of Short-Term Cannabis Use on Females
disruption of ovarian cycle in females
170
THC and Driving
motor coordination, tracking, perception and vigilance are all impaired under the influence of THC = can interfere with safe functioning of a vehicle
171
Psychological effects of long-term cannabis use - occasional low-dose
no harmful effects
172
Psychological effects of long-term cannabis use - high dose
- loss of short-term memory
- lack of concentration
- loss of ability in abstract thinking
- loss of ambition and emotional flatness
- amotivational syndrome
173
Amotivational Sydrome
appears upon cessation of drug use, represents chronic intoxication
174
Permanent psychological effects of long-term cannabis use
structural changes occur in the brain that may be associated with impairment of memory and learning
175
Cardiovascular effects of long-term cannabis use
- usually reversible
- changes in BP are not serious
- increase in HR can be a potential problem for those with heart disease
176
Respiratory effects of long-term cannabis use
- bronchitis
- asthma
- sore throat
- chronic irritation of and damage to membranes of respiratory tract
- increased risk of lung cancer and COPD
177
Smoking cannabis
1. Can be damaging cause of higher concentrations of tars and carcinogens present in cannabis smoke compared to tobacco
2. Inhaled deeply and held in the lungs to maximize absorption of THC and other CBs (also enhances tars and carcinogens absorbed)
178
Fertility effects on males with long-term cannabis sue
decreased sperm count
179
Fertility effects on females with long-term cannabis sue
1. Cause follicle stimulating hormone and luteinizing hormones to be reduced
2. Cycles can potentially occur without ovulation (no release of egg from ovary)
180
Effects of long-term use of cannabis with pregnancy
1. THC freely crosses placenta
2. can cause developmental delays leading to cognitive deficits, impulsiveness and inattention and hyperactivity
- drug should be avoided in pregnancy
181
Vaping Cannabis:
associated with respiratory risks
- e-cigarette or vaping produce use-associated lung injury (EVALI) - public health crisis
182
Medical Uses of Cannabis
use of cannabis for relief of many symptoms that have not responded to conventional medical treatments
ex. prescribed for prevention of nausea and vomiting associated with anticancer drugs
183
What drugs are less toxic than THC?
drugs that bind to CB1 and CB2 receptors
- derivatives of THC
184
Challenge with medical use of cannabis
must separate beneficial effects (ex. analgesia) from the psychotropic effects
185
Analgesia
a loss of sensation of pain due to interruption of NS pathways between sense organs and the brain
186
Potential for Misuse of Cannabis
low to moderate as euphoria and reinforcement are less compared to other drugs (ex. cocaine)
187
Inherent Harmfulness of Cannabis
low, especially with an infrequent use
188
Greatest concern with cannabis
1. automobile accidents
2. accidental exposure of cannabis to children and lung effects associated with smoking and vaping
189
what does a tolerance of Cannabis occur to
1. psychoactive properties of the THC
2. effects of the cardiovascular system
3. impairment of performance and cognitive function
190
Withdrawal of Cannabis symptoms
- sleep disturbances
- irritability
- loss of appetite
- nervousness
- mild agitatation
- upset stomach
- sweating
191
Addiction to Cannabis
1. persistent craving
2. risk of addiction is more evidence in those use use cannabis to control psychological stress
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The mechanism of action of cannabis is best described as?
Cannabis binds to CB1 receptors on presynaptic neuronal membranes in the brain
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Which receptor does THC bind to?
Cannabinoid (CB)
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Opiods
class of drugs naturally found within the opium poppy plant (Papaver somniferum)
- been used for millennia, most are analgesics and have high misuse potential and OUD
- produces morphine and codeine through purified substance
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Morphine
One of most useful drugs known to pharmacologists
- BUT it is known for causing **opioid use disorder (OUD)**
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Endogenous Opioids
1. Not administered drugs
2. Opioids made in the body that bind to opioid receptors and exert analgesic effects
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Function of Endogenous Opioids
1. Affect the perception of pain and emotional response to pain
2. Influence mood and are associated with reward pathways in the brain
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3 families of endogenous opioids
1. Enkephalins
2. Dynorphins
3. Beta-endorphins (endorphins)
***when you exercise, your body releases endorphins
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Natural Opioids
Not made by the human body, but are derived from the opium poppy plant
- Includes Morphine and Codeine
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Morphine
1. Binds directly to opioid receptors
2. Used clinically to treat severe acute and chronic pain
3. 10x more potent than codeine
4. can cause euphoria
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Codeine
Converted to morphine in the body by liver enzymes
- Tylenol 3 contains codeine
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Tylenol 3
A combination of codeine and acetaminophen and caffeine
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Semi-Synthetic Opioids
Slightly altered versions of morphine that are chemically changed to obtain different pharmacological properties (ex. potency, duration of action, distribution)
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Examples of Semi-Synthetic Opioids
1. Hydromorphine
2. Diacetylmorhpine (Heroin)
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Hydromorphine
clinically used for analgesia
- 5 times more potent than morphine
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Diacetylmorphine (Heroin)
uUsed as part of injectable opioid agonist therapy (iOAT) to manage OUD
- most often synthesized for illicit use
- 2-5 times more potent than morphine
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Synthetic Opioids
Not derived from morphine, but are chemically synthesized to bind to the opioid receptor
- may be designed to elicit similar responses to morphine (ex. analgesia, euphoria)
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Examples of Synthetic Opioids
1. Fentanyl and related compounds
2. Loperamide
3. Methadone
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Fentanyl and related compounds
1. Designed for treatment of severe acute and chronic pain
2. Illicit synthesis and use of fentanyl contribute to OUD crisis
- 100x more potent than morphine
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Loperamide
An over-the-counter drug that leverages a common side effect of opioids = constipation
- used to treat diarrhea
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Chemical structure or Loperamide
Very little enters and remains in the circulation, but instead stays in the intestine or is quickly metabolized
- prevents illicit use cause it doesn't cause substantial analgesia or euphoria
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Methadone
Used for analgesia and can be used in treatment of OUD
- does not cause euphoria in a stabilized patient
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Opioid Receptors Location
1. CNS
2. PNS
3. GI tract (responsible for the constipation caused by opioids)
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3 Types of Opioid Receptors
1. MU (u)
2. KAPPA (k)
3. DELTA (8)
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MU Opioid Receptor
1. present in all structures of the brain and spinal cord
2. mediate analgesia
3. responsible for morphine-mediated depression of respiration in the brain stem
***since the same receptor is responsible for both effects, it is difficult to obtain drugs with a separation between the 2 responses
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What is KAPPA Opioid Receptor Involved in?
1. Analgesia
2. Dysphoria: state of dissatisfaction or unease
3. Miosis: pinpoint pupils
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DELTA Opioid Receptor
1. Involved in analgesia at the level of the spinal cord and brain
2. Modulate the emotional response to opioids
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Mechanism of Action of Opioids
Morphine and other opioids block pain pathways in the brain and spinal cord
- occurs through MU opioid receptors
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2 Ways Opioids Inhibit Pain Impulses
1. Reduce neurotransmitter release
2. Reduce emotional reaction
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Reduce neurotransmitter release to inhibit pain impulses
Opioids prevent pain signals from travelling by reducing neurotransmitter release from presynaptic neurons and reducing the effect on the postsynaptic neuron
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Reduce emotional reaction to inhibit pain impulses
Opioids reduce emotional reaction to pain through modulation of the limbic system
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Administration of Morphine
1. Orally in a tablet form
2. Intravenously
3. Smoked or sniffed
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Short-Term Effects of Opioids
1. Analgesia
2. Sedation and hypnosis
3 .Suppression of cough centre
4. Respiratory depression
5. Endocrine effects
6. Miosis
7. HR and thermoregulation
8. Decreased intestinal motility
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Short-Term Effects of Opioids - Analgesia
1. Reduces the intensity of pain and perception or reaction to pain
2. No ceiling to the intensity of pain which can be relieved
3. Respiratory depression is the limiting factor
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Short-Term Effects of Opioids - Sedation and Hypnosis
1. Not as intense as CNS depressants do
2. Patient can be aroused buy may experience a drowsy, dreamy, mild dozing state
- all opioid analgesics produce a sedation
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Short-Term Effects of Opioids - Suppression of Cough Centre
relief or prevention of cough occurs through suppression of the cough centre in the medulla
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Short-Term Effects of Opioids - Respiratory Depression
Suppress the respiratory centre in the brain stem
- mostly, the response to respiratory drive by CO2 is blunted
***most important side effect of opioids - usually cause death in overdose
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What receptors mediate respiratory depression with opioids?
MU and DELTA
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Short-Term Effects of Opioids - Endocrine Effects
1. Reduce release of hormone that is responsible for regulating the release of sex hormones from the hypothalamus
2. Reduction in the production of testosterone, estrogens, and progesterone
- overall result is a drop in libido in men
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Short-Term Effects of Opioids - Miosis
1. Opioids cause constriction of the pupils (miosis)
2. All opioids that gain access to the CNS will cause pinpoint pupils
- this can indicate that someone has an opioid in their system
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Short-Term Effects of Opioids - HR and Thermoregulation
With high doses, the HR is irregular, body temperature is low and the skin is cold and clammy
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Short-Term Effects of Opioids - Decreased Intestinal Motility
Constipation will occur
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Long-Term Effects of Opioids
marked physiological deterioration or psychological impairment does not seem to occur
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3 Main Therapeutic Uses of Opioids
1. Relief of severe pain (main use for post-surgical pain)
2. Treatment of diarrhea (Loperamide)
3. Cough suppression
- all opioids are effective cough suppressants, BUT there are better alternatives with lower misuse potential
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Potential for Misuse of Opioids
have powerful euphoric effects
- large risk for misuse
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Inherent Harmfulness of Opioids at Low-Moderate Doses
not very high for morphine
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Inherent Harmfulness of Opioids at High Doses
Life threatening
- those taking illicit opioids are at higher risk as they are not always sure of the actual dose of opioid
- a lethal dose can be administered inadvertently
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Risk of Injections of Opioids
1. higher risk for developing abscesses at the site of administration and other infections
2. If contaminated needles are used, there is also the risk of spreading pathogens (hepatitis, HIV)
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Overdose of Opioids
Medical emergency
- can produce profound respiratory depression, which can cause death
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Treatment of Opioid Overdose
1. NALOXONE - opioid antagonist used for opioid overdose
2. NALTREXONE - opioid antagonist used to treat mostly alcohol use disorder
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Opioid Use Disorder (OUD)
specific type of SUD and can occur after both clinical and non-clinical use of opioids
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Tolerance of Opioids
1. Occurs to most pharmacological effects of opioids, except the constriction of the pupils and the constipating effects
2. Dvelops slower to respiratory depression than to the analgesic effects of the opiates
3. Tolerance reverses in a few days after the opioid is discontinue
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Cross-Tolerance of Opioids
Occurs between all opioid analgesics providing they act on the same receptor
- those with a tolerance to morphine will also have tolerance to methadone (both drugs bind to opioid receptors)
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Withdrawal of Opioids
a pronounced withdrawal syndrome can occur after opioid discontinuation - NOT life threatening
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Symptoms of Opioid Withdrawal
- restlessness, anxiety, insomnia
- sweating, fever, chills
- increased respiratory rate
- cramping, retching, vomiting
- diarrhea
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What do symptoms of opioid withdrawal depend on?
1. drug
2. chronicity
3. pattern of use
4. typically daily dose
5. route of administration
6. if there is concurrent use of other drugs
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Addiction to Opioids
1. Pronounced craving and compulsion for opioids can develop
2. Due to euphoric action results in very powerful reinforcement
3. Use of opioids with other psychoactive drugs (ex. cocaine) can occur in an attempt to achieve an even greater euphoria
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Opioid Use During A Pregnancy:
1. Increased risk of premature delivery and a low birth weight infant
2. At birth, the infant undergoes an abrupt termination of opioid exposure
- results in a specific withdrawal reactions including irritability, sleep disturbances, poor feeding and occasionally seizures (may last weeks to months)
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Treatment of OUD
1. Psychological supports
2. Counselling
3. Treatment of concurrent physical and mental issues to optimize recovery
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2 Examples of Pharmacological Treatment for OUD
1. Buprenorphine/Naloxone
2. Methadone
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Buprenorphine
1. Long-acting synthetic opioid that binds to MU receptors
2. Provided enough opioid agonist activity to prevent withdrawal symptoms while having decreased euphoria and sedation compared to other opioid agonists
3. Combined with antagonist Naxalone
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Naxolone if Injected
blocks the opioid receptors, which causes withdrawal symptoms
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Naxolone if taken orally
mainly broken down before getting into the circulation and therefore has no significant effects on the individual
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Methadone for treatment of OUD
1. Misuse potential is much lower
2. since taken orally, removes risk of injections
3. oral administration leads to slower onset of pharmacological effects and therefore less euphoria
4. long-lasting, so it is taken less often leading to a lower misuse potential again
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Why is methadone used in the treatment of OUD?
It transfers individuals with OUD to an opioid that is long-lasting and doesn’t cause euphoria in stabilized patients
