Psychopharmacology (CNS pharmacology) Flashcards
(51 cards)
1
Q
Antidepressants are _______________
A
Among the most prescribed drugs
2
Q
Mania and depression have been described as ____________________________
Patients experiencing both are often described as ____________________________
A
Poles apart in terms of affective disorders
Bipolar (manic-depressive)
3
Q
Depression (definition and stats)
A
The most common psychiatric disorder
Affects 15% of industrialized Western population at some point in their lives
Point prevalence increases with age
Women are 2X more likely than men to be depressed
- Married males less likely than unmarried males
- Married females more likely than unmarried females
4
Q
Classification of depression and mania
A
Depression:
- Depressed mood (sad, hopeless, withdrawal)
- Guilt
- Anxiety
- Somatic (insomnia, fatigue, anorexia)
Mania:
- Over-excitement and over-activity
- Elation
- Delusions of grandeur
- Irritability
- Aggressive behaviour
5
Q
Checklist for depression and mania
1. Name: _______________
- You have to be______________________
A
- Diagnostic and statistical manual of mental disorders (DSM)
- Diagnosed by several symptoms present on the checklist to be clinically diagnosed as depressed or manic
6
Q
PET scan
1. Can compare ____________________ and _______________
- In depressed individuals, uptake of glucose is ______________________ than in non depressed individuals.
- Depressed individuals have decreased ____________
A
- Brain activity during periods of depression and brain normal brain activity
- Considerably less
- Brain activity
7
Q
Origins of nuclei of monoaminergic CNS neurones
- Noradrenaline
- Dopamine
- Serotonin
- Histamine
A
- Locus coeruleus
- Substantia nigra and ventral segmental area (VTA)
- Raphe nuclei
- Thalamus
8
Q
What happens when patients take antidepressants? (5Rs)
A
- Response: 50% reduction of symptoms
- Remission: all symptoms are relieved (up to 6 months)
- Recovery: longer remission (6-12months)
- Relapse: symptoms worsen than before recovery (<6-12 months)
- Recurrence: symptoms worsen than after recovery (> 12 months)
9
Q
Depression is due to a _______________ in one or more of three catecholamines: _____________, ______________, ______________
A
Deficiency
Serotonin, NE, E
10
Q
Simple mechanism of antidepressant medication
A
Increasing the level of one (or combination of three catecholamines) by:
- Blocking their reuptake pumps
- Inhibiting their destruction by monoamine oxidase
11
Q
Problems with monoamine hypothesis (n=3)
A
- No antidepressant effect associated with some drugs that increase nt (cocaine, amphetamine)
- Long delay (2-3 weeks) between rise in nt and clinical effect
- Decreased levels of nt have only been clearly associated with few types of depression
12
Q
Why do SSRI-type drugs continue to work even if post-synaptic receptors are down regulated?
A
SSRI-type antidepressants increase:
- Neurogenesis (make new connections)
- Beahvioural improvement
13
Q
Brain derived neurotrophic factors (BNDF)
- Incoming neurone is in normal state, there’s an __________ of BNDF which helps build _____________
- Incoming neurone is in depressed state, so there’s a ___________ of BNDF which means there’s a decrease in ___________________
- Incoming neurone is in treated state, so there’s an ________________ of BNDF and monoamine. This means there’s an _______________ in number of connections
A
- Increase; connectivity/brain connections
- Decrease; connections
- Increase; increase
14
Q
Brain atrophy in depression
A
Some MRI show that certain parts of the brain undergoes atrophy when person is in depressed state
15
Q
Amygdala:
- Part of the _____________ system
- Group of structures deep in brain associated with emotions such as (n=5): _____________________
- MRI studies done only on _____________ individuals showed an increase in amygdala volume in depression
- MRI studies done only on _______________ individuals showed a decrease in amygdala volume in depression
A
- Limbic
- Anger, pleasure, sorrow, fear, sexual arousal
- Medicated
- Unmedicated
16
Q
Classes of antidepressant drugs (n=7)
A
- Monoamine oxidase inhibitors
- Tricyclic antidepressants
- Serotonin Selective Reuptake Inhibitors (SSRIs)
- NE/DA reuptake inhibitors (NDRIs)
- Serotonin/NE reuptake inhibitors (SNRIs)
- Serotonin antagonists/reuptake inhibitors (SARIs)
17
Q
Monoamine oxidase inhibitors (MAO)
- 2 classes of MAOs: ___________ and _________
A
- MAO A and MAO B
18
Q
MAO A
- Classical _________________
- Drugs: _______________ and _______________
- Non - __________ and ir____________ inhibitors
- Severe interactions with food, drugs and wine:
- Action is _________________ because of irreversibility
A
- MAO inhibitors
- Phenylzine and Tranylcypromine
- Non-selective and irreversible
- Tyramine: cheese, beer, liver
Drugs: TCA, sympathomimetic
Meperidine: fever - Long-lasting
19
Q
MAO A (suite ...) - Tyramine effect (n = 3 steps)
Tyramine is _____________ by MAO so levels _____________ sharply with MAO inhibitors
A
- Tyramine increases release of NE
- Irreversible MAO A inhibitor causes MAO enzyme to stop destroying NE
- Increase in NE can lead to dangerous elevations of blood pressure
- Metabolized; increase
20
Q
MAO B
- MAO A specific ______________
- Reversible inhibitors of MAO A (RIMA) (n=3)
MAO B inhibitors
- Used in in metabolism of ____________ and __________
- Used to treat _________________
A
- Inhibitors
- Mocloblemide
Reversible, competitive inhibitor
Removes danger of tyramine effect - Dopamine and pro toxins
- Parkinson’s
21
Q
Serotonin (5HT) receptors can be found in many tissues including (n=5): ______________________
- Drugs affecting 5HT in the ___________, therefore often demonstrate ___________ in these other tissues
A
CNS, blood vessels, smooth muscle, platelets, GI tract
- CNS; side effects
22
Q
Side effects of MAOs can include: __________________
- Mild symptoms may consist of (n=6): ____________
- Moderate intoxications includes additional abnormalities such as (n=4): ________________
- Mental changes include (n=2): ________________
- Severe symptoms include _________ and ________ that may lead to ____________ -> temperature _____
A
Serotonin syndrome: excessive levels of 5HT
- Increased HR, shivering, sweating, dilated pupils, myoclonus, over responsive reflexes
- Hyperactive bowel sounds, high blood pressure, hyperthermia and temperature as high as 40 degrees
- Hypervigilance/insomnia and agitation
- Severe increase in HR and blood pressure; shock; 41.1 degrees
23
Q
Tricyclic antidepressants (TCA)
- First tested as ________________
- Block reuptake of (n=3): ________________
- Drugs (n=2): ___________________
- Have many functional groups (n=4): _____________
A
- Antipsychotics
- DA, 5HT and NE
- Imipramine, amatriptyline
- alpha-1 adrenergic R: antagonism
histamine-1 R: antagonism
Ach muscarinic R: antagonism
5HT and NA: reuptake inhibition
24
Q
TCA side effects:
- Inhibition of _____________ stimulation
- Inhibition of _____________ stimulation
- Inhibition of _____________ neurotransmission
A
- Histaminic
- Cholinergic
- Adrenergic
25
Autoreceptors: receptors found on ___________ and ________________ that inhibit nt release (Ex: ________)
Heteroreceptors: a receptor for a ____________ different from the nt made by neurone it's present on
- Activation inhibits ______________ from that neurone
Dendrites; presynaptic membrane (ex: histamine receptors)
Monoamine
- Neurotransmission
26
Serotonergic neurons project to _________________ where they affect ____________ and have effects on ____________________
Higher brain centres; mood; secondary neurotransmission
27
SSRIs
- Resulted from search for better drugs than ______ without side effect profile or potential toxicity
- Removed _________ , __________ , _________ and ________ reuptake blocker activities
- TCA
| - alpha1, muscarinic, histamine and NA
28
SSRI mechanism of actions
1. Causes initial increase in serotonin mainly at _________ and and ________, NOT at _______________
2. Immediate consequence: ___________ rate of firing of serotonin neurone by acting on __________ somatodendritic auto receptors
3. Longterm exposure to serotonin eventually causes _________________ of 5HT1A auto receptors and ______________ of serotonin release at axon terminals.
4. Reduction in dendritic auto-R results in _________ of stimulation of _______________, electrical transmission and increased release
1. Cell body; dendrites; axonal terminals
2. Inhibit; 5HT1A
3. Downregulation; disinhibition
4. Increase; serotonin synthesis
29
Reason for delayed onset of action of the SSRIs: ___________________________________________
Delay in producing the increase of serotonin at the terminals
30
SSRI will eventually down regulate, invoking ____________
Neurogenic hypothesis
31
SSRIs are ____________________
Examples (n=4): ________________
Advantages:
- Safer than ___________
- Fluoxetine: long ____________
the most prescribed classe of antidepressants
Fluoxetine, paroxetine, sertraline, citalopram
TCAs
Half-life
32
Exposure to light stimulates _______________
Altered serotonin levels may be linked to low __________
Exposure to light at night diminished _______________
Serotonin production
Melatonin
Melatonin production
33
Reduced melatonin production in pineal gland can result in _________________
Disturbed circadian rhythm
34
SSRI side effects (n=5)
```
Nausea
Anorexia
Insomnia
Sexual dysfunction
Possible increase of suicidal thoughts
```
35
NA/DA reuptake inhibitors (NDRIs)
- Key drug: ___________
- Used in ___________ since increase DA levels help reduce craving
Side effects:
- Feeling of __________
- High _______________
- Buprorpion
- Smoking cessation
- Restlessness
- Blood pressure
36
Domains affected by both 5HT and NE (n=6)
```
Depressed mood
Anxiety
Aches/pains
Irritability
Loss of energy
Cognitive function
```
37
SNRIs
- Inhibit __________ of 5HT, NA and some DA
- Effects on reuptake of nt vary according to ________
- Claim to produce more _______ effect (1 week)
- Ex: ____________
- Reuptake
- Dose (5HT -> NA -> DA)
- Rapid
- Venlafaxine
38
Disinhibition: antagonists of a ____________ prevent inhibitory effects of an ___________
Heteroreceptor; agonist
39
Serotonin and NE disinhibitors (SNDI)
- Alpha-2 ____________
- Work by __________ alpha-2 receptor-mediated ___________________________, resulting in increased release of 5HT and NE
- Antagonists
| - Blocking; negative feedback inhibition
40
Different serotonin receptors:
- 5HT1D: _________________
- 5HT1A: _________________
- 5HT1A, 5HT2A,B: ___________________
- 5HT2C: ________________
- Presynaptic autoreceptors
- Dendritic autoreceptor
- Postsynaptic stimulatory receptor
- Postsynaptic heteroreceptor
41
Effects of activation of subtypes of 5HT receptors
- 5HT1A (n=3)
- 5HT2A (n=3)
- 5HT2C (n=4)
- 5HT1A: antidepressant, anxiolytic, pro-cognitive
- 5HT2A: insomnia, sexual dysfunction, anxiety
- 5HT2C: insomnia, sexual dysfunction, anxiety, appetite (satiety)
42
SNDI (ex: Mirtazapine)
Boost nt 5HT and NE by:
1. Blocking alpha-2 adrenergic ____________________, thereby increasing NE neurotransmission
2. Blocking alpha-2 adrenergic presynaptic receptors on ________________________, thereby increasing 5HT neurotransmission
1. Presynaptic autoreceptor
| 2. Serotonin neurons (heteroreceptors)
43
Mirtazapine (LOOK AT SLIDE 63 IMAGE)
- Is also a noradrenergic and _________ serotonergic antidepressant
Blocks 5HT receptors:
- 5HT2C antagonism: more ________ secretion (anxiolytic)
- 5HT2A/5HT2c antagonist: reduced (n=2) _________________
- 5HT3 antagonism: reduces ___________ and GI upset
- Blocks H1 histamine receptors to reduce __________
- Specific
- NA
- Insomnia and sexual dysfunction
- Nausea
- Insomnia
44
SARI (ex: trazodone)
- Highly ____________
- SARIs increases ________ levels and block (n=2) _________ and _________ receptors that are responsible for some side effects associated with high 5HT levels
- Sedating
| - 5HT; 5HT2A and 5HT2C
45
Blocking of 5HT2A/2C receptors with ___________ combined with SSRI, we can potentially treat effects of ____________________
Trazodone
Activation of subtype of 5HT-Rs
46
SARI side effects:
- Low levels of alpha-1 antagonist activity can result in ____________
- Metabolite is also active: trazodone is converted into an active metabolite known as ___________________
- Active metabolite has high ________ for a number of 5HT -Rs (i.e 5HT1A/2A/2C where it results mostly as agonist -> can result in ___________ in some patients)
- Hypotension
- Meta-chloro-phenyl piperazine (mCPP)
- Affinity; Anxiety
47
With bipolar disorder, there's a ________________
| Cannot be treated like ________________
Shift between 2 extreme mood poles
| Depression
48
Mood stabilizers for treatment of manic phase (ex: Lithium)
- Limits recycling of lipid ___________ or any receptors that use the ________ pathway to signal
- Mainly used ________________ in bipolar disease
- Long ____________, narrow _____________
- Side effects: nausea, ___________ and __________, tremor
- Mediators; IP1
- Prophylactically (not only taken during the manic phase, but constantly taken to reduce effects of that phase)
- Half-lige, therapeutic window
- Polyuria and thirst
49
Lithium overall effects:
- Anxiety
- __________ in NE effects
- __________ in 5HT effect
- __________ is the only receptor affected by lithium
- Decreases
- Increases
- 5HT2
50
Lithium promotes __________ neurotransmission
It will:
- Increase _________ levels in CSF
- Presynaptic: _________ GABA release
- Postsynaptic: _________ GABA-beta receptors
GABAergic
- GABA
- Facilitates
- Upregulates
51
Valproic acid
- Used to treat ____________
- Elevates [_____] in brain and inhibits neuronal __________________
- An option if patient can't tolerate side effects of _______
- Bipolar disorder
- GABA; voltage-gated Na+ channels
- Lithium
