Module 3 - PHAR 100 Flashcards
(136 cards)
1
Q
What are the four stages (low dose to high dose) of sedatives?
A
Anti-anxiety
Sedation - calm person
Hypnosis (sleep) - produce drowsiness
General anesthesia - unconsciousness with absence of pain sensation
2
Q
What are the mechanism of action of sedative hypnotics?
A
Decrease glutamate-induced nerve firing by increasing inhibitory signalling
3
Q
What happens without sedatives?
A
Excitatory neurons release NT glutamate - neurons fire when excitatory input exceeds inhibitory
4
Q
What happens with sedatives?
A
Inhibitory signals from GABA increase, resulting in decreased glutamate nerve firing.
5
Q
Each GABAA receptor has four transmembrane-spanning regions. Receptor itself is a pentameter: ________, _______, ________. Channel is closed when nothing bound to it. When drug binds, opens channel and allows influx of chloride ions.
A
Two alpha, two beta, one gamma
6
Q
Influx of chloride ion channels … synaptic inhibition and dampens neuronal responses. Enhance inhibitory effect of GABA.
A
increase
7
Q
What are the most widely prescribed drug in the world? (5-10% of Canadians prescribed it)?
A
Benzodiazepines
8
Q
What is the route of administration for benzodiazepines?
A
Intravenous & intranasal
9
Q
What is the mechanism of action of benzodiazepines?
A
Increases frequency of chloride channel openings
10
Q
What are the therapeutic effects? (3)
A
Relaxation, calmness
Skeletal muscle relaxation
Anticonvulsant effects
*some effective hypnotics
11
Q
Do benzodiazepines or barbiturates have minimal suppression of REM sleep?
A
Benzodiazepines
12
Q
Do benzodiazepines have a high therapeutic index? Are overdose deaths rare? But do they happen?
A
Yes, yes, yes
Deaths occur following ingestion of ENORMOUS doses, rapid intravenous injection of large dose or in combination with other sedating drugs
13
Q
What is antidote for benzodiazepines?
A
Flumazenil - benzodiazepine receptor antagonist that blocks effects of benzodiazepines
14
Q
What are effects of short term benzodiazepine use? (3)
A
CNS - drowsiness, lethargy, fatigue, impairment of thinking
Breathing - respiratory depression following rapid IV administration
Motor coordination - impaired
15
Q
What are adverse long term effects?
A
Vary
16
Q
Does benzodiazepine cross placenta? How does it impact pregnancy/chestfeeding?
A
Yes, if first semester, may cause fetal abnormalities
May cause sedation or death when breastfeeding
17
Q
How do benzodiazepines impact older adults? Is it metabolized faster or slower in adults?
A
Metabolized slowly, over-sedation, falls, injury
18
Q
What is misuse potential?
A
Low, low inherent harmfulness
19
Q
Does magnitude of tolerance for benzodiazepines (for anxiolytic effect) produce any clinical concerns?
A
No
20
Q
Is there a high degree of cross-tolerance between benzodiazepines and other sedative-hypnotic drugs (ex. barbiturates and alcohol)?
A
Yes
21
Q
Can withdrawal happen with benzodiazepines? Is it severe?
A
Yes - Mild after therapeutic use (can exhibit anxiety, headache) discontinuation after chronic use can make more pronounced
BUT LESS COMMON THAN BARBITURATES
22
Q
Can addiction occur benzodiazepines?
A
Yes
23
Q
How are barbiturates classified? What are the three classe?
A
According to duration of action
Long acting (1-2 days)
Short acting (3-8 hours)
Ultra short acting (20 minutes)
24
Q
Are barbiturates still used?
A
Generally replaced by safer, more effective sedatives
25
Route of administration of barbiturates?
Different based on what they are treating: for epilepsy - orally, for anesthesia, IV
26
What is the mechanism of action of barbiturate?
Activation increases duration of opening of chloride channel
27
Do barbiturates activate full spectrum of dose-dependent CNS depression?
Yes
Anti-anxiety, Sedation, Hypnosis, General Anesthesia
28
In low doses, what are therapeutic uses?
Tranquility, relaxation, a bit higher dose --> sleep
29
Although clinical uses of barbiturates are limited, what do ultra-short acting and short-acting do? What about long acting?
Induce anesthesia
Epilepsy
30
What are short term effects barbiturates?
- mild euphoria, reduced interest in surroundings
- impairment of motor conditions
- pleasurable state of intoxication and euphoria
- high doses: depress CV system, slow heart rate and lower blood pressure
31
What are long term effects of barbiturates?
Chronic inebriation - memory, judgement, thinking impaired
32
What are the potential for misuse of barbiturates?
Should be avoided, equal or greater to alcohol
- high degree of reinforcement
- injected to maintain rush effect
- inherent harmfulness is very high due to risk of death from respiratory depression/withdrawal
33
Can tolerance to barbiturates develop? Is there high cross tolerance between other sedatives?
Yes, yes
34
Does withdrawal occur? What are withdrawal symptoms?
Yes
Postural hypotension, insomnia, weakness, anxiety, tremors, seizures, delirium
35
Barbiturates must be withdrawn slowly under...
medical supervision
36
Can addiction occur?
Yes - from regular use, crave drug and panic when they don't get enough
37
What are therapeutic uses for benzodiazepines vs barbiturates?
Benzodiazepines:
* Acute anxiety states
* Sedation for minor surgical
procedures
* Insomnia
* Absence seizures, status
epilepticus
* Skeletal muscle spasms
* Alcohol withdrawal
Barbiturates:
*Tonic-clonic (i.e., grand mal) seizures, partial seizures
38
Do barbiturates have a high or low therapeutic index?
Low
39
Do barbiturates cause dose-dependent and CV depression?
Yes
40
What are benzodiazepine like drugs? Why are the advantageous over benzodiazepines? Are they more sedative or anxiolytic?
- zolpidem, zopiclone
- disrupt REM sleep less
- more sedative than anxiolytic
41
The benzodiazepines, by binding to .... receptors, facilitate the actions of GABA
benzodiazepine
42
The barbiturates have ... and distinct binding sites on the chloride channel. Do not enhance GABA,, but rather they bind to the GABAA receptor __________ opening chloride channel.
directly
43
What is buspirone? What does it act on? What is an advantage of using buspirone?
- acts on serotonin receptor
- used in generalized anxiety states and is advantageous since it doesn't have additive effects (not on same GABA, acts on serotonin)
- prescribed when person already taking other CNS depressant
44
What is a drug class?
Group of drugs that have same mechanism of action and similar pharmacological properties (ex. thiopental, secobarbital, phenobarbital)
45
What are the three most used non-medicinal drugs used in Canada?
caffiene, nicotine, alcohol
46
What is the major reason for extensive use of alcohol?
Permissive attitudes of society
47
Is alcohol a CNS depressant or stimulant?
Depressant, slows down brain functioning and neuronal activity
48
What is the only type of alcohol that can be safely consumed?
Ethanol
49
Describe the absorption of alcohol. Where is most absorbed?
20% stomach
80% small intestine
50
What is the overall absorption rate for a given dose affected by (2)
Stomach emptying time
Ethanol concentration in GI tract & presence of food
51
Ethanol distributes throughout the total body water and readily gains access to the brain. Ethanol can also readily travel across the ... and distribute throughout a ...
placenta, developing fetus
52
What are the four main steps of metabolism of alcohol?
1) Ethanol converted to acetaldehyde by ADH - rate limiting step because speed of conversion is constant
2) Acetaldehyde converted to acetate by aldehyde dehydrogenase (ALDH)
3) Acetate/acetic acid metabolized by tissues into carbon dioxide and water.
MEOS - part of cytochrome P450. Breaks down into acetaldehyde (especially when ADH saturated)
53
What is considered protective against alcoholism causing unpleasant side effects (ex. flushed face)?
accumulation of acetaldehyde - individuals that can rapidly convert alcohol to acetaldehyde
54
What is there genetic variability in in ethanol metabolism pathway?
ADH
ALDH
55
What is the rate of ethanol metabolism?
120 mg ethanol/kg body weight/hour
56
Where is 95% of ethanol excreted? What about remaining 5% (3)?
Liver
Breath, Urine, Sweat
57
Where does some alcohol metabolism happen? Does more happen in women or men?
In stomach. In women.
58
When does MEOS happen?
at 0.1% BAC, when cofactor NAD+ runs out
59
What are medical uses of ethanol?
- topically to treat fever
- skin disinfectant
- antidote in treatment of methanol poisoning
- hand sanitizer
60
Effects of alcohol are proportional to BAC. Can you show what BAC% corresponds to clinically?
0.05 - 0.1% - sedation, slower reaction times
0.1-0.2% - impaired motor function, slurred speech, clumsy
0.2-0.3% - emesis, stupor
0.3-0.4% - coma
>0.4% - respiratory depression, death
61
What are mechanism of action of alcohol? What explains reinforcing effects?
- binds to chloride ion channel and augments GABA mediated neuronal inhibition
- interaction with chloride channels on dopaminergic neurons in reward areas may explain reinforcing effects
62
What are effects of short term alcohol use on cardiovascular?
Few drinks - vasodilation (flushing) of vessels to skin, feeling of warmth
High doses - depress CV system - alterations in normal heart rhythm
63
What are effects of short term alcohol use on stomach?
Few dose: increased gastric secretion
Long: irritate stomach lining, inflammation & erosion (gastritis). Aggravated ulcers
64
What are effects of short term alcohol use on liver?
Low dose: not big effect
High dose - inhibit glucose production, and lead to hypoglycemia (low blood sugar) with fasting
65
What are three effects of short-term high dose alcohol use?
memory loss
psychiatric effects
overdose
66
Is alcohol teratogenic?
Yes
67
What does alcohol use during pregnancy manifest as?
Fetal alcohol spectrum disorder - 1 per 1000 live births - short nose, thin upper lip
68
What are two ways alcohol use during drug therapy makes an impact?
- additive or synergistic effect of CNS depression
- inhibition of metabolism of certain drugs
69
What are two ways chronic alcohol use before drug therapy makes an impact? (abstained during drug therapy)
- increases activity of metabolizing enzymes in liver (increased metabolism for certain drugs) - only if no co-existing ethanol-induced liver injury
70
What is the potential for misuse of alcohol?
Moderate
- ease of availability
- inherent harmfulness moderate
- death can happen from high dose
71
Does tolerance to chronic consumption occur? To what?
Yes
- to ethanol-indued impairment of performance of a task when performed repeatedly under influence of alcohol
72
What are two things alcohol develops cross tolerance to?
Sedative-hypnotics
General anesthetics
73
What can occur during withdrawal which can involve convulsions, coma, and death?
Delirium tremors
74
Does alcohol cause addiction?
yes
75
What is used to treat alcohol withdrawal?
Initial treatment: maintain fluid and electrolyte balance, and prevent seizures.
Benzodiazepines (diazepam) - not as addictive, manage withdrawal symptoms
76
What is used to treat alcohol use disorder?
Naltrexone (opioid agonist) - diminishes craving. Blocks dopaminergic reward pathways.
77
What plant does cannabis come from?
Cannabis sativa - herbaceous annual
78
How many chemical compounds found in Cannabis sativa? What are they called? What is the most potent psychoactive substance?
60
Cannabinoids
THC
79
What were cannabis plants initially used for?
Manufacturing rope
80
How did USA try to destroy cannabis in Mexico? What did that result in?
Herbicide paraquat
USA citizens smoking cannabis products with paraquat
81
1997 - Ontario court dismissed charges related to possession and cultivation of cannabis on basis that individual was using it to control .... Canada changed law to allow the cultivation of some varieties of cannabis that contain small amounts of THC for the use in manufacturing ..., ..., or other hemp products. Farmers need special license to grow
Epilepsy, rope, clothing
82
Pharmacologically, what is cannabis classified as? (3)
CNS depressant, euphoriant, hallucinogen
83
When did cannabis become legal in Canada?
2018
84
What are three methods cannabis is taken?
Dried flowering plant - smoked or inhaled - extracts containing concentrated amounts (ex. in oil) can be administered through vaping or oral consumption
85
What is the endogenous ligand for CB receptors involved in learning and memory processes?
Anandamide
86
Is anandamide a retrograde transporter? What does that mean?
Yes. Released from postsynaptic neuron and influences the presynaptic neuron. Cannabis works the same way
87
What does activating CB1 receptors do?
Inhibits release of excitatory neurotransmitters, such as glutamate, into synaptic cleft.
88
Is THC an effective agonist? So how does it produce a response?
No. Large number of receptors exist.
89
A large number of ... receptors are in the brain, more than any receptor.
CB1
90
What do CB1 receptors in cerebral cortex mediate?
Distortions of time, colour, sound, taste. Mediate decrease in cognitive function and concentration.
91
What do CB1 receptors in hippocampus affect?
Changes in memory and learning
92
Are there CB1 receptors in brain stem?
No - do not depress respiration - relatively non-lethal
93
Where are CB2 receptors found? Are they involved in psychoactive effects of THC?
Outside CNS
No
94
The binding of THC to CB2 receptors on ... is thought to be responsible for the ... properties of THC
lymphocytes
immunosuppressive
95
How is THC taken? How does absorption differ based on the different routes?
Inhaled or ingested
Inhaled - rapid absorption, immediate onset of symptoms effect: 3-4 hours
Ingested - slow absorption, incomplete. Onset of action delayed 30-60 minutes. Less effect than smoking cannabis
96
Does THC rapidly distribute throughout the body, to tissues with high blood perfusion (ex. lung, heart, brain, liver)? Does it cross placenta?
Yes Yes
97
Is THC metabolized fast?
No slowly, may test positive weeks after use
98
What is the half-life of THC? What makes it longer?
30 minutes
Elimination from adipose tissue may take longer
99
What are four areas of short term effects of cannabis?
CNS - relaxation, drowsiness, increased appetite
CV System - increased heart rate, increased blood flow, postural hypotension
GI Tract - increased appetite, dryness of mouth and throat
Other - reduction of sex drives in males, as THC reduce testosterone, disrupt ovarian cycle, hangover similar to alcohol
100
What are long term effects of Cannabis use?
- psychological: harmful psychological effects, loss of short term memory
- cardiovascular - usually reversible (changes in blood pressure don't appear to be serious, but increase in HR can be problem for those with heart disease)
- respiratory - bronchitis, asthma, sore throat, lung cancer, COPD
- fertility: decrease sperm count, cause FSH to reduce, no ovulation
101
Is cannabis typically inhaled deeply to maximize absorption of THC and other cannabinoids?
Yes
102
How does cannabis impact pregnant women?
Developmental delays in baby - cognitive deficits
103
The challenge for pharmacological use is to separate the beneficial effects (e.g., analgesia) from the ... effects.
psychotropic
104
Is Cannabis a Health Canada approved therapeutic?
No
105
What is medical marijuana potentially for? What type?
Prevention of nausea and vomiting associated with anticancer drugs
Synthetic THC derivatives used for treating nausea
106
What is misuse potential of cannabis?
Low to moderate
- euphoria and reinforcement less
- inherent harmfulness lower
*car accidents may be greatest risk
107
What does tolerance occur to cannabis?
Psychoactive properties
Effects on CV system
impairment of performance and cognitive function
108
Does withdrawal occur? What about addiction?
Yes, mild
- sleep disturbances, irritability, nervousness
Yes, especially if using to deal with stress
109
Is cannabis a narcotic?
Yes
110
What plants do opioids come from?
Papaver somniferum
111
Initially, was used as a ... but for last 200 years has been used as a purified substances, producing clinically used drugs like morphine and codeine.
crude extract
112
What are endogenous opioids?
Opioids made in body that bind to opioid receptors and exert analgesic effects
113
What are the three families of endogenous opioids?
Enkephalins, dynorphins, beta-endorphins
114
What do endogenous opioids affect? 3
Perception of pain and emotional response
May influence mood and associated with reward pathways in brain.
115
What are natural opioids?
Morphine
Codiene
116
What are semisynthetic opioids from? What are two types of them? How much more potent? What are they used for?
Morphine that are chemically changed to obtain different pharmacological properties.
Hydromorphine - 5x more potent: analgesia
Diacetylmorphine - Heroin - injectable opioid agonist therapy, to manage OUD 2-5x more potent
117
Are synthetic opioids derived from morphine? What are three examples?
No
Fentanyl - supposed to be for treatment of severe acute and chronic pain (100x more potent) - illicit and other more potent (carfentanyl, furafent)
Loperamide - over counter to treat diarrhea. Little enters circulation, stays in intestine or quickly metabolized so that it is not illicitly used
Methadone - analgesia can be used to treat OUD, prevents withdrawal but doesn't cause euphoria in stabilized patient
118
What are the three opioid receptors? What are they each in charge of?
Mu - brain and spinal cord, mediate analgesia (morphine-mediated depression of respiration in brain stem), difficult to obtain drug with separation of effects
Kappa - analgesia, dysphoria, miosis
Delta - analgesia (brain and spinal cord) - modulate emotional response
119
These receptors are also located in the GI tract and cause... caused by opioids.
constipation
120
What are two mechanism of action of opioids?
Bind to opioid receptor.
prevent release of neurotransmitters from presynaptic to post.
Reduce emotional reaction through limbic system
121
What are short term effects of opioids? Are there any long term marked deteriorations?
Analgesia
Sedation and Hypnosis
Suppression of Cough Center
Respiratory Depression
Endocrine effects (drop libido in men)
Miosis
Heart Rate low body temp, cold hands
Decreased intestinal motility
Nope!
122
What are the therapeutic uses of opioids (3)
Relief of severe pain
Treatment of Diarrhea
Cough Suppression
123
What is the potential for misuse of opioids?
Large risk
124
What is inherent harmfulness at low doses? High?
Low - not high
High - life threatening
125
People who administer drugs by injection are at a higher risk of developing ...
abscesses at site of administration and other infections, HIV
126
What is primarily used to treat opioid overdose?
Opioid overdose is a medical emergency. Overdose of all opioids can produce profound respiratory depression, which can cause death.
Naloxone
127
What does tolerance occur to opioids? Does it reverse?
Most pharmacological effects (except constriction of pupils and constipating effects). Tolerance does reverse
128
Does cross-tolerance between opioid analgesics occur? Provided what?
Yes. Provided they all act on same receptor
129
Is withdrawal life threatening for opioids?
No
130
Are opioids addictive? What's the basis for addiction?
Yes, euphoric action
131
What happens when you take opioids during pregnancy?
Premature delivery, low birth weight, opioid withdrawal
132
What receptors does buprenorphine bind to?
Mu
133
Does buprenorphine provide enough opioid agonist activity to prevent withdrawal? But does it have high euphoria and sedation?
Yes, no low compared to others
134
What is buprenorphine combined with?
Antagonist naloxone
135
What does naloxone do which causes withdrawal? What about when taken sublingually/orally?
binds to opioid receptors, causes withdrawal. When orally, broken down before circulation - no significant effects, but when injected fasttttt
Naloxone REVERSES overdoses
136
What does methadone do? Is it long lasting? Does it have a lot of reinforcement? is it addictive? Taken orally?
- long lasting *not taken often so lowers misuse potential
- prevents withdrawal (satisfies brain's need for opioids)
- low euphoria, not that addictive *slower onset of effects, so less euphoria
- taken orally and removes risk of injections
