Final Flashcards
(217 cards)
1
Q
The following 3 monoamines are known to project to which location/system in the brain?
1. Serotonin (5HT) (raphe nucleus)
2. norepinephrine (NE) (locus coeruleus)
3. dopamine (DA) (VTA)
A
The limbic system and the forebrain (aka MEDIAL FOREBRAIN BUNDLE)
2
Q
What stress hormone is released from the adrenal glands, and is known to travel to the hippocampus, amygdala, and the prefrontal cortex?
A
Cortisol
3
Q
Which brain region secretes corticotropin-releasing hormone (CRH)?
A
Hypothalamus
4
Q
Which brain region secretes adrenocorticotropic hormone (ACTH)
A
Anterior pituitary
5
Q
Which brain region produces glucocorticoid(stress) hormones (AKA cortisol)?
A
Adrenal cortices
6
Q
Which stress hormones can act back on the hypothalamus and pituitary (to suppress CRH and ACTH production) in a negative feedback cycle?
A
Glucocorticoids
7
Q
How do first generation monoamine oxidase inhibitors (MAOIs) work to increase serotonin in the brain? BONUS if you can name the two enzymes that destroy monoamines
A
MAOIs increase 5HT by degrading monoamine oxidase enzymes that breakdown 5HT
Bonus: MAO-A degrades 5HT, NE and DA and MAO-B degrades DA only
8
Q
How do first generation tricyclic antidepressants (TCAs) work to increase MAs?
A
TCAs block reuptake transporter proteins on 5-HT and NE neurons
9
Q
Clonazepam, diazepam and lorazepam are examples of what type of anxiolytic medications?
A
Benzodiazepines
10
Q
Amobarbital and pentobarbital are examples of what type of anxiolytic medications?
A
Barbiturates
11
Q
Imipramine and Amitriptyline are examples of what class of antidepressant medications?
A
TCAs
12
Q
Escitalopram and citalopram are examples of what class of antidepressant medications?
A
SSRIs
13
Q
Rasagiline and selegiline are examples of what class of antidepressant medications?
A
MAOIs
14
Q
Duloxetine and venlafaxine are examples of what class of antidepressant medications?
A
SNRIs
15
Q
Marijuana and hashish are forms of which class of drugs?
A
Cannabis
16
Q
delta-9-tetrahydrocannabinol or △-9-THC is the main ingredient of which drug?
A
Cannabis
17
Q
What is the most common cannabinoid in the Cannabis plant?
A
delta-9-tetrahydrocannabinol or △-9-THC
18
Q
How many cannabinoids are known to exist in Cannabis?
A
85
19
Q
What are the 3 prevalent chemicals in Cannabis?
A
delta-9-tetrahydrocannabinol or △-9-THC, cannabinol (CBN) and cannabidiol (CBD)
20
Q
What is the name of cannabinoids that come from a cannabis plant?
A
Phytocannabinoids
21
Q
What is the name of cannabinoids that are endogenous to the body?
A
Endocannabinoids
22
Q
What is the abbreviation for anything that binds to a cannabinoid receptor?
A
CB
23
Q
What is the name for a cannabinoid that is synthesized or made in a lab?
A
Synthocannabinoid
24
Q
What is the psychoactive and appetite inducing chemical in cannabis?
A
THC
25
What is the non psychoactive and possibly therapeutic/anxiolytic/antipsychotic chemical in cannabis?
CBD
26
What is the abbreviated term for the drug 3,4-methylenedioxy-methamphetamine?
MDMA
27
What is a drug formulation?
A combination of excipients and active ingredients
28
What is the term for an observable action or state that occurs in response to a stimuli?
A behaviour
29
What is the name class of a drug that has not been patented, and is the common name of the chemical makeup?
Generic name
30
What is the name for a range of doses plotted on a graph, with the dose indicated on the horizontal axis and the effect on the vertical axis?
Dose response curve
31
What is measured on each axis of a DRC?
Y-axis: Typically demonstrates the dose mg/kg.
X-axis: Generally demonstrates the effect change in a % of animals according to the dose administered
32
What type of curve is the usual result of dose responses?
A continuous curve
33
Define ED50.
Mean therapeutic (effective) dose for 50% of the sample
34
Define LD50.
Mean lethal dose for 50% of the sample
35
How do you calculate the therapeutic index of a drug?
LD50/ED50
36
What can the therapeutic index of a drug tell us?
The safety of a drug
37
What does a HIGH TI signify?
The drug is very safe
38
What does a LOW TI signify?
The drug is not safe
39
How are potency and effectiveness different? Define potency, then define effectiveness.
Potency is the amount of drug needed to produce ANY given effect.
Effectiveness is whether the drug produces a given effect at its target location.
40
Name *TWO* ways drugs can be agonistic. There are 6 total ways.
Increasing synthesis of a molecule
Destroying degrading enzymes
Increase release of molecule
Inhibit autoreceptors
Binding to postsynaptic receptors
Blocking deactivation
41
Name *TWO* ways drugs can be antagonistic. There are 5 total ways. Think back to agonistic effects.
Blocking synthesis of a molecule
Increasing vesicle leaks
Blocks release
Activating autoreceptors
Blocking receptors
42
A drug that blocks NT synthesis by destroying enzymes is an example of an **agonist or antagonist?**
Antagonist
43
A drug that binds to an autoreceptor leaves more neurotransmitters in the cleft is an example of an **agonist or antagonist?**
Agonist
44
What are the two categories of drug effects?
Primary effects and side effects
45
The effect for which a drug is taken (i.e. morphine for pain) is known as what?
Primary effect
46
Any other effect that results from the drug (i.e nausea and vomiting with morphine) is known as what?
Side effect
47
Name the 4 routes of administration.
Parenteral
Inhalation
Per Oral
Transdermal
48
Give *TWO* examples of parenteral administration.
Intramuscular injection (through the muscle)
Intraperitoneal injection (through the abdominal cavity)
Intravenous (directly into the blood stream)
Subcutaneous injection (into the fatty layer of skin)
49
Give *TWO* examples of inhalation administration.
Gasses, smokes and solids
50
Give *TWO* examples of per oral administration.
Taken by mouth and swallowed
Buccal membranes (think chewing tobacco)
Suppositories (into the rectum)
51
Give *TWO* examples of transdermal administration.
Creams or patches.
52
Describe the route of absorption of parenteral administration.
Absorbed into the circulatory system
53
Describe the route of absorption of inhalation administration.
Capillaries in the lungs or the nasal cavities
54
Describe the route of absorption of per oral administration.
Capillaries in the intestines
55
Describe the route of absorption of transdermal administration.
Determined entirely by the lipid solubility of the drug, goes into the blood eventually.
56
Name one advantage to parenteral administration.
Blood is constantly circulating and being replaced by new blood with a low concentration of drug→ more will be absorbed as the blood circulates through the area
57
Name one advantage to per oral administration.
Significant absorption will take place even if only a small percentage of molecules is not ionized
58
Name one advantage to inhalation administration.
Rapid absorption without passing through the liver
59
Name one advantage to transdermal administration.
Can be administered at a controlled rate which maintains stable blood levels of a drug
60
Name one disadvantage to per oral administration.
Drugs taken with food slows absorption
→ empty stomach = fast absorption
Depends on lipid solubility as well (how well the drug dissolves in fats)
61
Name one disadvantage of transdermal administration
Very slow.
62
Name *TWO* of the 6 factors affecting absorption.
Lipid solubility
Ion trapping
Blood-brain barrier
Transport mechanisms
Placenta
Protein binding
63
Explain *TWO* of the 6 factors in how they affect absorption.
Choose from the following:
1. Lipid solubility
2. Ion trapping
3. Blood-brain barrier
4. Transport mechanisms
5. Placenta
6. Protein binding
1. Drugs concentrate in body fat outside CNS
Pass through membranes easily
2. Drugs get trapped on one side of membrane that has different pH
3. Special cells in the central nervous system that wrap themselves around the capillaries and block the pores through which substances normally diffuse
4. Active transport mechanisms concentrate cells on one side of the membrane.
Passive transport involves a large protein molecule creating a channel for a non-ionized cell to pass through the cell membrane
5. Similar to BBB
6. Large proteins can’t diffuse because they are too big to pass through pores of capillaries
64
What are two factors that are involved in eliminating a drug?
Metabolism and excretion
65
Where does metabolism occur in the body?
The liver (mainly)
66
Where do excretion mechanisms occur?
The kidneys and the nephron
67
What occurs during the process of metabolism?
Enzymes act as a catalyst to modify molecules to form new substances useful to the body
68
What happens during excretion? Specifically, what do the kidneys and the nephron do?
Kidney→ filtering everything out of the blood and then allowing selective reabsorption of what is required.
Nephron→ reabsorption→ accomplished by the mechanisms of distribution
69
Name and explain *TWO* factors that alter metabolism.
1. Stimulation of Enzyme Systems
- Metabolic tolerance
- The body expects the drug to be there
(because of past experience) so
produces compensatory enzymes to
process faster.
2. Depression of Enzyme Systems
- Competition for enzymes or depressing
enzymes
- Two drugs that use the same enzyme to
process can make for the drugs to not be
properly processed
3. Age
- Lack of enzymes/underdeveloped or too
old
- Enzyme systems are not fully functional
at birth
- Enzyme systems also deplete with age
4. Species
- Different enzymes
- Livers of different species process
substances differently
70
What is the therapeutic window of a drug? Is a larger therapeutic window better?
The therapeutic window of a drug is the range of concentration of a doseage between the ED50 and the LD50. The larger the therapeutic window the better.
71
Name two examples of barbiturates.
Amobarbital
Pentobarbital
72
Name two examples of benzodiazepines.
Diazepam
Lorazepam
Clonazepam
73
What are the routes of administration of anxiolytics?
If long-term→ oral medications
If needed immediately→ intravenous
74
Are anxiolytic medications weak acids, or weak bases?
Weak acid (pKa 3.5) → fast absorption in the stomach
75
Are antidepressant medications weak acids, or weak bases?
Weak acid (pKa 3.5) → absorbed in the stomach
76
Are methylxanthines weak acids, or weak bases?
Weak base (pKa 0.5) → SLOW in the stomach, fast in the intestines.
77
Are stimulants weak acids, or weak bases?
Weak base → but HIGH pKa of 9-10 → slow absorption
78
Are opioids weak acids, or weak bases?
Weak base→ BUT pKa of 8 → not rapid absorption
79
How are anxiolytics excreted in the body?
Biphasic excretion.
- Redistribution (2-10 hr half life) (distributes from bloodstream to fat)
- THEN Slow release (1-2 day half life) (distributes from the fat to body tissues)
80
What are some effects of barbiturates on the body?
Sleepiness, mild euphoria, decreased anxiety.
Decreased blood pressure and breathing rate
High doses→ lack of coordination
81
What are some effects of benzodiazepines on the body?
Muscle relaxation and headache relief
Ataxia and muscle tremor
82
What are some positive effects of barbiturates on sleep?
Helps with insomnia
83
What are some positive effects of benzodiazepines on sleep?
Shorten time it takes to fall asleep, decreases awakenings during the night, and increase sleep time
84
What are some effects benzodiazepines can have on human behaviour? Think back to the ones on alcohol.
Euphoria and liking for the drug, memory loss, long half-life, increased driving risk
85
What are the unconditioned behaviours anxiolytics can have on animals?
Taming effect, reduces defensive aggression
86
Can animals discriminate anxiolytics from placebo and alcohol?
Yes.
87
True or false: Acute tolerance → can develop within one administration of benzo or barbiturates.
True
88
True or false: Chronic tolerance → benzos become less effective at modulating the effects of GABA and become less effective at treating seizures
True
89
Describe the **iatrogenic pattern** of anxiolytic administration.
Drug has a purpose but then is continued unnecessarily→ great abuse potential
90
Describe the **street-use pattern** of anxiolytic administration.
Taken with another drug→ with opioids to increase effects, with cocaine to decrease effect
91
What are some harmful effects of anxiolytic abuse?
Reproduction→ Teratogenic effects in rats
Overdose→ Benzos accidental or deliberate, no death→ Barbs are suicide and death
92
Name the 3 sources of methylxanthines.
Caffeine (isolated in 1820) → arabica and robusta
Theophylline → from tea!
Theobromine → from chocolate!
93
Name two routes of administration of methylxanthines.
Per oral
Sometimes in pill form, but usually liquid
Inhalation
Medicinal methylxanthine (bronchodilator) given as salts → rapid absorption
94
What does if mean if drugs are not ionized (not ion trapped)?
They can free flow according to lipid solubility. This means they can cross the BBB and reach all points in the body.
95
Which chemical source of methylxanthines crosses the BBB more quickly than theophylline or theobromine?
Caffeine.
96
Name TWO factors affecting elimination of methylxanthines.
Genetic differences: → fast and slow metabolizers (different genes for building P450 enzyme for caffeine metabolism)
slow metabolizers experience more effects of caffeine
→ enzyme stimulation/inhibition by medicines and foods
Sex: → In women, half-life of caffeine differs by menstrual phase→ longer after ovulation (luteal phase)
→ Half-life is doubled for women taking oral contraceptives
→ Elimination slowed during pregnancy (half life of 18 hrs by end of pregnancy – caffeine build up) DANGEROUS!!!
Age: Infants→ half-life is 4 days
→ can’t metabolize methylxanthines until about 7-9 months of age
97
What is the site of action of caffeine?
Adenosine Receptors
98
What responsibility do adenosine receptors have in the brain?
Partially responsible for modulating DA as it *inhibits* the transmission of other NTs
99
How do methylxanthines increase the action of DA in the brain?
methylxanthines increase DA by blocking action of A1 adenosine receptors (at presynaptic receptors)
100
We know that adenosine receptors are partially responsible for modulating DA release. What happens when A2 adenosine receptor and cannabinoid receptors are affected by methylxanthines?
Leads to increased transmission at D2 receptors
101
What is adenosine responsible for in the body? How do methylxanthines, such as caffeine, affect this?
Adenosine buildup triggers sleep, caffeine prevents buildup because it inhibits these receptors.
102
What happens when methylxanthines release epinephrine from adrenal glands?
Leads to sympathetic action in response to stimulation
103
What are some of the effects of caffeine on blood flow?
vasodilation in body (need to pee more!!) vasoconstriction in brain (less headaches)
104
How does the blocking of adenosine receptors lead to decreased sleepy feelings?
By blocking the A1 receptor, caffeine promotes wakefulness, and by blocking the A2A receptor, it increases dopamine.
105
What are some effects of caffeine on sleep?
Delays sleep and reduces length of sleep
Sounds wake people more easily (this goes away with tolerance)
Caffeine counteracts sleep effects of pentobarbital (a barbiturate)
106
What are some behavioural effects of high and moderate doses of methylxanthines in humans?
High doses → jitters, some people even think they are on cocaine when given a lot
Moderate doses → reverses deficits caused by boredom, fatigue, some drugs, and caffeine withdrawal→ improvements in attention and working memory→ improvements in reaction time on visual and cognitive tasks
107
Name some conditioned and unconditioned effects of methylxanthines on behaviour of Non-Humans.
Conditioned
CNS increased excitability
Increases reactivity to stimuli
Unconditioned
High doses causes rats to self-mutilate and attack other rats→ also causes cause death from seizure (maybe because of increased glutamate from adenosine receptor blocking)
Increases spontaneous motor activity
108
Can animals discriminate methylxanthines from placebo? Give an example.
Can discriminate from saline→ AT LOW DOSES DA receptor blockers interfere with this
109
Can humans discriminate methylxanthines from placebo? Give an example.
Can discriminate caffeine→ rare with theophylline and theobromine
110
What type of tolerance might we see with methylxanthines?
Acute tolerance → Effects right away after first dose
Chronic tolerance → Gradually need more caffeine to achieve the same effects.
111
Describe the self administration of methylxanthines in animals.
Will not self administer without being forced addicts first
112
Describe the self administration of methylxanthines in humans.
Humans will self-administer because prefer caffeine to placebo (in double blind studies) but this is variable
113
What are some possible harmful effects of caffeine?
Reproduction→ Can reduce blood flow to fetus, no concrete info because ethically wrong to test→ general recommendation DO NOT TAKE WHEN PREGNANT
Cardiac disease→ increased risk of heart attack
Bone density→ reduced bone density in post-menopausal women
Caffeinism and anxiety→ if predisposed to anxiety, you can become more anxious
5-10 cups can cause sensory disturbance
1 g per day (7.5, 8-oz cups) → agitation, twitching, irregular heart rhythm, rambling speech
Lethal at 3 to 8 g
Many treatments for toxicity→ about 15,000 per year in the US
114
What are some possible beneficial effects of caffeine?
Possibly protective against Parkinson’s disease→ also reduces some PD symptoms (think connection to DA modulation in adenosine)
Weight loss→ reduced risk of T2 diabetes
Reduces risk of cognitive disease (dementias) later on in life → again think connection to PD
115
Why is there no "caffeine use disorder"?
It is recognized as any other addiction/withdrawal
116
Name TWO sources of stimulant drugs.
Naturally sourced → eg. Cocaine, cathinones (khat) and ephedrine from plants→ used for “fun”
Isomers (synthetic) → d-amphetamine and l-amphetamine (dl-amphetamine) → used for ADHD and narcolepsy
Non-amphetamine stimulants →eg. Ritalin
Methamphetamines → e.g methedrine
Street sources → “crack” made from cold medications
117
Name a route of administration of stimulants that results in *RAPID* absorption.
Injection (to feel a ’rush’)
Chewing of leaves (coca and khat)
Inhalation → smoking & general inhalation of vapours
118
Name a route of administration of stimulants that results in *SLOW* absorption.
Per oral → to prevent sleep and fatigue
119
Describe the rapid absorption process of stimulants through buccal membranes.
Buccal absorption → increased pH of saliva & digestive tract; reduces ionization; increases absorption (maybe less than 30mins)
120
Describe the rapid absorption process of stimulants per oral.
Per oral→ amphetamines absorbed after 30 mins or so
121
Describe the rapid absorption process of stimulants by inhalation.
Inhalation → cocaine = rapid absorption because capillaries in the lungs/nasal cavity
122
Where are stimulants most likely to concentrate in the body?
Lipid soluble → crosses BBB
Concentrate in kidney, spleen, and brain
123
Why is the elimination of methamphetamines longer than that of cocaine?
For amphetamines → Generally long but depends on pH of urine
If acidic, NO reabsorption by nephron→ shorter half-life (7-14 hrs)
If basic→ reabsorbed by nephron → metabolized by liver → longer half life (16-34 hours)
Several enzymes involved in metabolism
→ Metabolites are active with long half-lives
Cocaine→ Fast excretion→ half-life of 45 to 75 mins
Excretion depends on acidity of urine
124
What is the site of action of stimulant drugs?
Stimulants act at monoamine synapses (esp. DA)
125
Name *FOUR* examples of monoamines.
DA, NE, E and 5-HT
126
How does cocaine enhance monoamine NTs (specifically DA) in the brain?
blocks the action of DA transporter proteins which leaves DA in the synapse
127
How do amphetamines enhance monoamine NTs (specifically DA) in the brain?
They indirectly inhibit monoamine reuptake at the synapse.
128
Where are the binding effects of cocaine?
DATs, NETs, SERTs
129
Where are the binding effects of amphetamines?
DATs & NETs, in high concentrations SERTs
130
Where are the binding effects of Methylphenidate?
NETs, then DATs, then SERTs
131
What are some effects stimulants may have on the CNS?
In the CNS→ increased DA release in mesolimbic dopamine system and nigrostriatal system→ happy feelings!!!!!
To get high more than half of the MATs are blocked
132
What are some effects stimulants may have on the PNS?
In the PNS→ action on epinephrine → makes you feel hyper and alert/focused
→ fight or flight → increased BP, HR, vasodilation, bronchodilation
133
How can stimulants have anaesthetic effects?
Na+ channels are blocked→ prevents action potentials
134
What are some effects stimulants may have on sleep?
No sleep→ think fight or flight activated → can even cause insomnia
135
What are the general effects of stimulants on human behaviour?
GENERALLY → Improved mood → Decreased fatigue → Increased energy → Clarity of thought
136
What is a characteristic point in a stimulant high?
For both cocaine and amphetamine: rush followed by ‘crash’ (mild depression)
137
Give a couple of examples of unconditioned stimulant response.
Punding – repeated behaviours (e.g., cleaning, re-sorting things, taking things apart and putting them back together)
Irritated when interrupted
Monoamine psychosis→ similar to schizophrenia→ major thing is formication (feeling that bugs are under your skin)
Sensory effects (distorted views)
Increased endurance (good for sports), more focus (punding) (good for ADHD)
Bad for driving
138
True or false: Amphetamines increase responding on a fixed-interval schedule (behaviour reinforced only when a certain amount of time has passed) AND decrease responding on a fixed ratio schedule (behaviour reinforced after a certain number of responses)→ Depends on baseline rate of responding (more on the FR schedule)
True
139
Can animals discriminate stimulant drugs from placebo?
Can discriminate amphetamines from saline at low doses
BUT discrimination poor when mesolimbic D1/D2 receptors blocked (but not midbrain DA system)
140
What are some characteristics of acute tolerance of stimulants?
Subjective effect of improved mood → coke out (no longer happy), NO tolerance to effects on body
141
What are some characteristics of chronic tolerance of stimulants?
can become tolerant to lethal doses and appetite suppression, but can’t become tolerant to sleep blocking
142
What is a COMMON characteristic of self-administration of stimulants in both animals and humans?
Run abstinence cycle administrations.
143
Morphine, codeine and thebaine (paramorphine) come from what?
Opium
144
Hydrocodone comes from what type of opioids?
Semi-synthetic opioids (morphine)
145
Where are opioids concentrated in the brain?
Concentrated in basal ganglia, amygdala, and periaqueductal gray (pain sensation area)
146
The metabolites of this drug class are excreted by the kidneys and unchanged drug molecules can also be found in urine, feces, and bodily fluids, such as sweat and tears.
Opioids.
147
Mu(𝝁), kappa (𝜅), delta (𝛿) and ‘opioid receptor-like’ (ORL1) are receptors for what class of drugs?
Opioids
148
Opioids act at which 4 receptors?
Mu(𝝁), kappa (𝜅), delta (𝛿) and ‘opioid receptor-like’ (ORL1)
149
Where are Mu receptors located?
limbic system, thalamus, locus coeruleus (brainstem), VTA, PAG) – most effects of drugs are on these
150
Where are kappa receptors located?
Nacc, VTA, hypothalamus
151
Where are delta receptors located?
Limbic system (but doesn’t overlap with mu), cortex, hypothalamus, Nacc, medulla
152
Where are ORL1 receptors located?
CNS (forebrain, brainstem, PAG, substantia nigra...)
153
Where do most opioids act?
Mu(𝝁) receptors → metabotropic (g-protein) and release second messengers
154
Which inhibitory G-protein coupled receptor activates the Gi alpha subunit, inhibiting adenylate cyclase activity, lowering cAMP levels? *This is an opioid related receptor*
Mu(𝝁) receptors
155
How do opioids act at the synapse?
inhibits NTs at postsynaptic membrane, and inhibits NT release at button
156
What happens when Mu receptors are activated by opioids?
analgesia and sedation effects of opioids→ many side effects (respiratory depression, pupil dilation, lower body temperature, for example)
157
What is a pure opioid antagonist at mu, delta, and kappa receptors (replaces opioids) and TERMINATES ACTION OF AGONIST OPIOIDS?
Naloxone
158
How are opioids reinforcing drugs?
Mu receptors in VTA inhibit GABA interneurons→ leads to more DA
Mu agonists are therefore most reinforcing→ physical dependence is due to action in PAG
159
What are some general behaviour effects of opioids in humans?
Mood effects
→ positive feelings followed by negative feelings
→ when in pain, feelings of sleepiness are not there
Performance
→ slowed psychomotor performance
→ tolerance develops to some tasks
160
Explain a bit about withdrawal from chronic use of opioids. How long does this last?
→ Starts in 6-12 hrs, peaks in 72 hrs (3 days)
→ Restless, yawning, chills & goose bumps (“going cold turkey), , short breaths
→ Then, “yen sleep” (deep sleep for 8-12 hrs), vomiting, sweating, twitching (“kicking the habit”)
PAG involved - inhibition of PAG reduces symptoms; injection of heroin directly to PAG causes physical dependence
161
What are some harmful effects of opioids?
Reduced sex hormone (this can be dramatic)
- Can reduce fertility
Overdose
- Depressed breathing → think vital life functions (concentration in the brainstem)
162
What are TWO examples of withdrawal therapies for opioid addicts?
Detoxification
→ by abstinence or opioid antagonist
→ by tapering off – using methadone (drugs may be given to block action of the sympathetic nervous system – minimizes some withdrawal symptoms, e.g., sweating)
Maintenance Therapy
→ Methadone – oral admin.; antagonist to heroin (acts at mu receptors); lasts for 24 hrs
→ Buprenorphine (safer than methadone, fewer side effects)
→ Social and psychological intervention desirable
→ Tapering can occur over 6 months
Antagonist Therapies (drugs) plus other interventions (e.g., 12-step program)
163
What is the main purpose of antipsychotic use?
Used to treat psychotic symptoms in patients with schizophrenia, and other psychotic disorders
164
What percent of people have schizophrenia worldwide?
est. 1%
165
What is the DA theory of schizophrenia?
Hyperactivity of dopamine D2 neurotransmission contributes to positive symptoms of schizophrenia
Underactivity of dopamine D1 receptor neurotransmission in the prefrontal cortex contributes to negative symptoms
166
What is the glutamate hypothesis of schizophrenia?
Reduced glutamate activity may have an agonist effect through activation of NMDA receptors on GABA interneurons→ Blockade of these NMDA receptors causes inhibition of (inhibiting) GABA neurons→ Result is excitability, release of GLU, and activation of AMPA
167
How is damage to the cortex associated with negative symptoms of schizophrenia?
Damage to cortex causes reduced glutamate activity→ Result is that DA to cortex is reduced (think back to DA theory)
168
What is the TI of antipsychotic medications?
TI of 1000
169
True or false:
Typical antipsychotics have...
→ long half-lives (11-58 hrs)
→ tendency to bind to proteins and stay in fat tissue
→ traces found in urine months later
Atypical antipsychotics have...
→ Shorter half-lives (don’t accumulate in fat tissue)
True
170
What is the site of action of antipsychotic medications?
Antipsychotics are DA blockers
171
Typical antipsychotics block which DA receptors? What is a problem with blocking these receptors?
D2 --> bad for EPS
172
Atypical antipsychotics block which DA receptors?
D1, D3, D4 and 5HT2A
173
Third generation antipsychotics block which receptors?
D2, D3 and D4 receptors→ only advantage is causing less EPSs
174
EPS (parkinson’s type movements), akathisia (compulsive movements) and tardive dyskinesia (tics and involuntary movements/lasting symptoms) can be caused by which generation of antipsychotics?
First generation (typicals)
175
Which class of antipsychotics are known for causing weight gain and dry mouth?
Atypical antipsychotics
176
Which class of antipsychotics are known for having far fewer side effects, but are not necessarily better at treating symptoms?
Third generation antipsychotics
177
What are some effects antipsychotics may have on sleep?
Can have sedative effects, can also lengthen sleep
178
What are some effects of antipsychotics on behaviour in humans?
Unpleasant feelings (confusion, irritability)
Impairs attention and processing
179
What are some effects of antipsychotics on behaviour in animals?
Unconditioned
- Suppressed movement
- Can immobilize animals
- Reduces aggression
Conditioned
- Decreased avoidance
180
What is characteristic about self-administration of antipsychotic medications in both humans and animals?
They both actively avoid antipsychotics.
181
What are some harmful effects of antipsychotic medications?
EPSs
Akathisia
Tardive dyskinesia
WBC reduction (clozapine)
182
Hiccups, stuttering, delirium tremens, stimulant psychosis, depression, bipolar disorder and autism can all be treated by which medications?
Antipsychotics
183
What class of medications are used to restore chemical imbalances in the brain that may contribute to symptoms of depression and depressive disorders? Bonus if you can name all 4 types.
Antidepressants
184
Give two examples of first generation antidepressants.
MAOIs
TCAs
185
Give two examples of second generation antidepressants.
SSRIs and SNRIs
- escitalopram and citalopram
186
Give two examples of third generation antidepressants.
SNRIs
187
This theory suggests underactivity in monoamine systems causes symptoms of depression.
Monoamine theory of depression
188
This theory suggests hyperactivity in the HPA axis systems causes symptoms of depression due to a buildup of cortisol (stress hormone)
Glucocorticoid theory of depression (HPA axis)
189
How do the MA theory of depression, and HPA axis theory of depression interact?
→ When overexcited, 5HT and NE (MA theory!) override the PFC which affects our mood (HPA theory)!
→ High levels of stress hormones (HPA) lead to a reduction in number of 5-HT receptors in hippocampus (MA)
→ When we remove adrenal glands (HPA), we end up with more serotonin (MA!)
190
Escitalopram and citalopram are examples of which class of antidepressants?
SSRIs (second generation)
191
Imipramine and amitriptyline are examples of which class of antidepressants?
TCAs (first generation)
192
Rasagiline and selegiline are examples of which class of antidepressants?
MAOIs (first generation)
193
Duloxetine and venlafaxine are examples of which class of antidepressants?
SNRIs (third generation)
194
Why should you not mix MAOIs and TCAs with alcohol?
Absorption of MAOIs and TCAs is greatly increased (this is not true for the SSRIs/SNRIs)
195
These antidepressants have a short half-life of 2-4 hrs
MAOIs
196
These antidepressants have a long half-life of 24 hours
TCAs
197
These two antidepressants have a long half-life of 15-25 hrs (more frequent dosing than TCAs) and NO active metabolites
SSRIs and SNRIs
198
How do these antidepressants work in the context of MA theory of depression?
Antidepressants work to increase MA transmission; this improves amount of MAs (specifically serotonin) in the brain and ultimately relieves symptoms of depression
199
How do these antidepressants work in the context of HPA theory of depression?
Antidepressants increase the number of cortical receptors; this improves feedback and ultimately lowers the level of stress hormone.
200
What is the site of action of antidepressants?
Antidepressants act on monoamines (esp. 5HT & NE
201
How do MAOIs increase availability of monoamines?
MAOIs increase monoamines by degrading monoamine oxidase enzymes (MAO-A and MAO-B) that breakdown MAs→ increases availability and activity of monoamines
202
How do TCAs increase availability of monoamines?
TCAs block reuptake transporter proteins on 5-HT and NE neurons
203
How do SSRIs increase availability of monoamines?
Selective Serotonin Reuptake Inhibitors (SSRIs) block reuptake transporters for 5-HT by causing a buildup of 5-HT in the synapse, which prolongs stimulation on the postsynaptic cell
204
How do SNRIs increase availability of monoamines?
Serotonin & Norepinephrine Reuptake Inhibitors (SNRIs) block reuptake transporters of NE, 5HT and (sometimes) DA
205
What are some effects of MAOIs on the body?
→ Can cause tremors, weight gain, dry mouth, postural hypotension (low blood pressure on sitting up or standing up)
206
What are some effects of TCAs on the body?
Inhibition of the parasympathetic nervous system (via ACh changes) therefore effects like fluid retention, constipation, dry mouth
→ Some experience dizziness, low bp, weight gain (major reason for stopping drug), reduced seizure threshold, block calcium channels → can cause heart attack
207
What are some effects of SSRIs on the body?
→ Nausea, headache, nervousness, agitation, gastro problems (only at first)
→ Weight loss (sometimes used to treat obesity)
208
What are some effects of SNRIs on the body?
→ Side effects to do with ACh and histamine receptor function
→ Increased appetite, weight gain, gastro problems
209
True or false: Many antidepressants reduce REM sleep.
True. REM deprivation reduces depression symptoms.
210
What are some effects of antidepressants on behaviour?
→ Reduction in symptoms of depression, e.g. apathy, fatigue, sadness
→ Effect not immediate and will be more likely with moderate to severe depression
211
True or false: Cannabis is highly lipid soluble so distributed to fat → concentrations in lungs, kidneys
True
212
→ Delta-9-THC is converted to 11-hydroxy-delta-9-THC turns into 100 metabolites (fortunately these are more easily excreted)
→ CBD and CBN interact with THC (can speed or slow metabolism in liver; can displace from blood)
→ THC has biphasic half-life – rapid drop in the first 30 min; followed by 20-30 hour half-life
No answer. Just read this
213
________ activates potassium (K+) channels and inhibits voltage-gated calcium (Ca2+) channels → cell hyperpolarization and inhibition of neurotransmitter release
CB receptor binding.
214
The stimulation of endocannabinoid receptors leads to the inhibition of adenylyl cyclase, which causes a reduction in _______?
AMP and protein kinase A (PKA)
215
Where are CB1 receptors mainly found?
CNS
216
Where are CB2 receptors mainly found?
PNS; Immune system
Located on lymphocytes and leukocytes (white blood cells), in bone marrow, the thymus gland, the spleen, liver, pancreas, and lungs
217
CB1 receptors are presynaptic and modulate neurotransmission via _____________
Retrograde signalling
