Lecture 39: Principles of Psychopharmacology Flashcards

1
Q

What are the psychiatric drugs?

A
  1. Antipsychotic
  2. Antidepressant
  3. Mood stabilizer
  4. Benzodiazepines
  5. Anti-Dementia
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2
Q

What is psychopharamacology?

A

Study of drug-induced changes in BEHAVIOR and mood/sensation

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3
Q

What do all psychiatric medication share in properties?

A

Lipophilic
Can cross the blood brain barrier
Most were discovered b serenditpidty and their MOA is largely unknown!!

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4
Q

What is the monoamine hypothesis?

A

Theory that depression is a result of DEPLETION of monoamines, specifically serotonin, NE and dopamin

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5
Q

Where do serotonergic neurons originate from?

A

Raphe nuclei in midbrain

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6
Q

What are the psychiatric conditions related to serotonin?

A

Eating Disorders
OCD
Anxiety
Mood

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7
Q

Where do noradrenergic neurons originate from?

A

Locus coeruleus

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8
Q

What is NE’s primary function?

A

Alertness (which you would need when running away from a tiger)
NOT attention
Attention carried out by dopamine

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9
Q

What are psychiatric conditions related to NE?

A

Pain disorders
ADHD
Anxiety disorders
Mood disorders

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10
Q

Where do dopaminergic neurons origninate from?

A
  1. Ventral tegmental area
    • midbrain and cortical projection
  2. Substantia nigra
  3. Tuberoinfundibulum
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11
Q

What is dopamine’s primary function?

A

ATTENTION

Reward

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12
Q

What are psychiatric conditions related to dopamine?

A

Schizophrenia
ADHD
Mood disorders
Addictions

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13
Q

What behaviors does glutamate mediate?

A
  1. Seizures
  2. Psychosis
  3. learning and memory
  4. mood
  5. can cause cell death
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14
Q

What drugs block NMDA receptors?

A
  1. Ketamine
  2. Phencyclidine (PCP)
    - mimic schizophrenic symptoms
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15
Q

What psychiatric conditions are related to glutamate?

A
  1. Schizophrenia
  2. Alzheimer’s Disease
  3. Mood disorders
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16
Q

What are examples of drugs that bind GABA chloride channels?

A
  1. Benzos
  2. Barbiturates (anticonvulsants)
    Which makes sense because seizures are due to the excitatory/inhibitory balance being out of whack
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17
Q

What does GABA mediate?

A

Anxiety, memory, sleep and consciousness, seizures, muscle tone, pain

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18
Q

What psychiatric conditions are related?

A

Anxiety disorders
Insomnia
Alcohol withdrawal
Pain disorders

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19
Q

What is the significance of histamine?

A

Biogenic amine involved in appetite, weight and sleep

H1 receptors are altered by certain psychiatric medications and modulate hypothalamic neurons

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20
Q

What is the mechanism that all ANTIPSYCHOTICS share? Significance?

A

Antagonist of the D2 receptor
Antipsychotic = LESS dopamine
Led to dopamine hypothesis of schizophrenia (leading and most prominent)

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21
Q

What agents can increase dopamine and lead to psychosis?

A
  1. cocaine

2. amphetamines

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22
Q

What causes the negative symptoms of schizophrenia? What are negative symptoms?

A

Overabundance of dopamine Mesocortical pathway

Negative symptoms = social isolation, poor hygiene

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23
Q

What is the mesocortical pathway?

A

The pathway that connects the ventral tegmentum to the cerebral cortex, particularly the frontal lobe

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24
Q

What causes the positive symptoms of schizophrenia? What are the symptoms?

A

Overabundance of dopamine in the mesolimbic pathway
Positive symptoms
1. Delusions
2. Perceptual disturbances

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25
What is the mesolimbic pathway?
The pathway that connects the ventral tegmentum to the nucleus accumbens, amygdala and hippocampus
26
What happens if you block dopamine transmission in nigrostriatum?
Dystonia Movement disorders Parkinson like disorders Akathisia (syndrome characterized by unpleasant sensations of inner restlessness) Tardrive dyskinesia (slow repetitive disorders) Neuroleptic Malignant Syndrome (muscle rigidity, fever, delirium)
27
What happens if you block dopamine in the tuberoinfundibular pathway?
Prolactin effects Galactorrhea Gynecomastia
28
What is the tuberoinfundibular pathway?
Arcuate nucleus in hypothalamus dopamine projections to the median eminence (of anterior pituitary gland)
29
What is a neuroleptic?
A major tranquilizer | An antipsychotic
30
What are the side effects of antipsychotics?
1. Lower seizure threshold Seizes earlier 2. Prolongs QTc prolongation 3. used as TRANQUILIZERS
31
What are the two types of antipsychotics?
1. First generation Example: Haldol, chlorpromazine 2. Second generation Example: Abilify
32
What are the 2 classes of first generation antipsychotics?
1. High Potency 2. Low Potency How effective agent is at blocking D2 receptor
33
What are the characteristics of the HIGH POTENCY first generation antipsychotics?
``` Example: Haloperidol Does not need high dose for same effect Has LESS side effects of i. antihistamine effects ii. antiadrenergic effects iii. anticholinergic effects ```
34
What are the characteristics of the LOW POTENCY first generation antipsychotics?
``` Example: chlorpromazine Needs higher dose for same effect Has MORE side effects of i. antihistamine effects ii. antiadrenergic effects iii. anticholinergic effects ```
35
What are the common side effects of antipsychotics?
``` Antihistamine effect i. weight gain ii. sedation Anticholinergic (muscarinic) effect i. delirium ii. blurry vision iii. Xerostomia (dry mouth) iv. constipation v. urinary retention Antiadrenergic effect i. Orthostasis ii. Arrhythmias ```
36
What are the characteristics of the second generation antipsychotics?
``` Example: Clozapine, Risperidone, Abilify Known as “atypicals” Derivatives of Clozapine MOST EFFECTIVE antipsychotic because they are BETTER TOLERATED Has the following effects in addition to antipsychosis i. mood-stabilizing ii. antidepressant iii. anxiolytic effects ```
37
What are the MOA of second generation?
D2 receptor AND blocking of 5-HT receptors
38
What are the side effects of second generation of antipsychotic?
1. Agranulocytosis (leukopenia, absence of white blood cells like neutrophils) 1-2% -only in clozapine 2. Weight gain 3. Metabolic Syndrome (blood glucose dysregulation, lipid profiles) -unmask underlying symptoms?
39
What is the rule of when you can stay on atypical antipsychotics?
If no metabolic syndrome in 6 months, then you are good
40
What is metabolic syndrome?
1. diabetes 2. dyslipidemia 3. weight gain
41
What is Abilify? Significance?
An atypical antipsychotic An “atypical amongst the atypicals” Only antipsychotic that is also a partial dopamine AGONIST!
42
What is clozapine (Clozaril)? Significance?
An atypical antipsychotic Can lead to AGRANULOCYTOSIS -prevents suicides
43
What is the mechanism of action of antidepressants?
Increase monoamines such as 5-HT, NE and DA
44
What is the locus of depressive symptoms?
5-HT1A | However, we can’t target this guy because we don’t know the serotonin profile of our patients
45
If you have sexual dysfunction from one SSRI, does that mean that will happen for all SSRIs?
No, side effect from SSRI can be different
46
What are the different classes of antidepressants?
A. MAOI Example: Iproniazid, used as anti-tuberculosis medication B. Tricyclic Antidepressants (TCA) Example: Imipramine C. Serotonin Reuptake Inhibitors (SRI or SSRI) Example: Fluoxetine, prozac D. Serotonin Norepinephrine Reuptake Inhibitors Example:
47
What is the Delineating factor for MAOI?
Food restrictions Cant eat tyramine (derived from tyrosine) Must have antihypertensive in pocket just in case
48
What is the delineating factors of Tricyclic Antidepressants?
Fatal in overdoses Arrhythmias, fatal cardiac events -that’s why they are not first line
49
What are delineating factors of Serotonin Reuptake Inhibitors (SRI aka SSRI)?
Safest and best tolerated
50
What are delineating factors of Serotonin Norepinephrine Reuptake Inhibitors (SNRI)?
Used to treat Comorbid Pain syndrome
51
Do antidepressants make patients suicidal? Significance?
No they are not They just unmask already present depression That means you need to constantly check up on patient after prescribing antidepressants REGULARLY
52
What are mood stabilizers?
Primary treatments for bipolar affective disorder No known MOA but it works Example: Lithium + ANTICONVULSANTS, including Carbamazepine,valproic acid
53
What is lithium known for?
Has both antidepressant and anti-suicidal properties
54
What are two potential MOA of lithium?
1. Enhance monaminergic function 2. Inhibits the recycling of neuronal membrane phosphoinositides involved in generation of IP3 and DAG Inhibits recycling of IP3 and DAG Overall, stabilizes membrane potentials 3. blockade of sodium channels 4. hyperpolarization by enhancing K channel permeability 5. may modulate VGCaChannels and GABA neurotransmission
55
What are the side effects of lithium and mood stabilizers?
1. Weight gain 2. Acne 3. Impaired cognition 4. neural tube defects So it is not first line; use anti-epileptics first
56
What are the two drugs to effectively reduce the rate of suicide?
1. Lithium (mood stabilizer) | 2. Clozapine (atypical antipsychotic)
57
What are benzodiazepines?
Drugs used to treat symptoms of ALCOHOL withdrawal, anxiety and epilepsy Sedates patients by binding to GABA_A chloride channel Example: Librium Leads to CNS depression, confusion, disinhibition Most common sedatives used in psychiatry
58
How are benzos metabolized? Significance?
Glucuronidation and oxidation by liver | -implications on which benzo you pick to treat alcohol withdrawal or patient with bad liver
59
When you use a GABA drug, are you treating a symptom or underlying condition?
You are only treating the symptom | Benzodiazepines
60
What is the MOA of benzo? Significance?
Act via the GABA_A receptor Increase Cl- permeability Example: Librium (Chlordiazepoxide)
61
Remember this for benzodiazepines:
Not all benzodiazepines are created equal, some benzos pass through liver once and other twice -benzos also have different speed of onsets and risks of abuse
62
What are the three benzos that have the LEAST hepatic burden?
Lorazepam Oxazepam Temazepam
63
Which benzo has the highest risk of abuse? Why?
Alprazolam, because of quick onset and SHORT duration | That means you’ll try to take more to get same effect
64
Which benzo has lowest risk of abuse? Why?
Clonazepam - long onset - longer duration - wont have to take as much to get same effect
65
What are the 2 therapeutic strategies used to treat dementia?
1. AchE inhibitors | 2. NMDA receptor antagonist