Principles of Psychopharmacology

Question 1

What brain process is thought to be exclusively the domain of 5-HT?

Answer 1

Obsessions / compulsions

Question 2

What brain process is thought to be exclusively the domain of NE?

Answer 2

Alertness

Question 3

What brain process is thought to be exclusively the domain of dopamine?

Answer 3

Attention, pleasure/reward, motivation

Question 4

What 2 monoamines are thought to affect anxiety?

Answer 4

5-HT and NE

Question 5

Review: Main source of 5-HT in the brain?

Answer 5

Raphe nuclei.

Question 6

Four 5-HT -related psychiatric conditions?

Answer 6

Mood disorders
Anxiety disorders
OCD
Eating disorders

Question 7

Review: Main source of NE in the brain?

Answer 7

Locus ceruleus (but it doesn’t project to the nucleus accumbens)

Question 8

Four NE-related psychiatric conditions?

Answer 8

Mood disorders
Anxiety disorders
ADHD
Pain disorders

Question 9

Review: 2 areas which dopamine for the brain is produced?

Answer 9

Substantia nigra, ventral tegmental area

Question 10

Four dopamine-related psychiatric conditions?

Answer 10

Schizophrenia
ADHD
Mood disorders
Addictions

Question 11

What’s the most important glutamate receptor for psychopharmacology?

Answer 11

NMDA receptor.

Question 12

3 glutamate-related psychiatric conditions?

Answer 12

Schizophrenia
Mood disorders
Alzheimer’s disease

Question 13

4 psych conditions involving GABA?

Answer 13

Anxiety disorders (note that benzos treat symptoms, but not cause of anxiety)
Insomnia
EtOH withdrawal
Pain disorders

Question 14

3 things histamine is involved with in the brain?

Answer 14

appetite, weight, and sleep

Question 15

What’s the MoA that all antipsychotics share?

Answer 15

They’re all D2 dopamine receptor antagonists (some to other things in addition to this).

Question 16

Why do cocaine and amphetamine cause psychosis at high levels?

Answer 16

Because they increase dopamine levels.

Question 17

What are the 2 areas of the brain that are affected by dopamine levels during psychotic episodes? With what signs and symptoms are they associateed?

Answer 17

Mesocortical: Negative symptoms of social isolation, poor hygiene.
Mesolimbic: Positive signs of delusions, perceptual disturbances.

Question 18

What are the 2 areas of the brain associated with the side effects of antipsychotics? Side effects associated with each?

Answer 18

Nigrostriatal: Extrapyramidal symptoms (EPS), dystonia, akathisia
Tuberoinfundibular: Prolactin effects -> galactorrhea, gynecomastia

Question 19

What is a dystonic episode?

Answer 19

Uncomfortable contractions, eg. eyes rolling painfully back into head, lock-jaw, etc.

Question 20

What’s akathisia? (wasn’t on slides)

Answer 20

Inability to not move.

Question 21

Major cardiovascular side effect of antipsychotics?

Answer 21

QTc prolongation -> risk for arrhythmia.

Question 22

What effects do antipsychotics have on seizures?

Answer 22

They lower the seizure threshold.

Question 23

What’s the practical difference between a high-potency and a low-potency antipsychotic? What’s an example of one high-potency drug and one low-potency drug?

Answer 23

High potency antipsychotics have fewer side effects (but some of these side effects can be desirable).
Haloperidol (Haldol) = high-potency
Chlorpromazine = low-potency

Question 24

What does “potency” actually mean when talking about a 1st gen. antipsychotic?

Answer 24

Ability to inhibit the D2 dopamine receptor.

Question 25

3 types of side effect caused by 1st gen. antipsychotics?

Answer 25

Antihistamine effects Antiadrenergic effects Anticholinergic effects (which make actually be useful for sedation, in context)

Question 26

2 specific antihistaminic side effects from antipsychotics?

Answer 26

Weight gain | Sedation

Question 27

5 specific anticholinergic side effects from antipsychotics?

Answer 27

``` Delirium Blurry vision Xerostomia (dry mouth) Constipation Urinary retention (nobody likes these) ```

Question 28

2 specific antiadrenergic side effects from antipsychotics? What receptor do they most affect?

Answer 28

Orthostasis (can't increase blood pressure when going from sitting to standing) Arrythmias. These act on alpha-1 receptors.

Question 29

What's the practical difference between 1st and 2nd generation antipsychotics?

Answer 29

2nd generation are not more effective, but they're better tolerated.

Question 30

What's the mechanistic difference between 1st and 2nd gen. antipsychotics?

Answer 30

2nd gen. drugs acts on 5-HT receptors (mostly 5-HT2) in addition to the D2 receptor.

Question 31

What's a very significant side effect of clozapine?

Answer 31

1-2% risk of agranulocytosis. (must get CBC before and monitor while using)

Question 32

What side effect profile are most atypical, 2nd gen. antipsychotics associated with?

Answer 32

Weight gain & metabolic syndrome. (Dr. Dube notes that this may be "unmasking" of underlying predisposition, and if this doesn't happen after 6mo, it probs won't happen)

Question 33

What are some desirable additional effects of atypical, 2nd gen. antipsychotics? (3 things)

Answer 33

Mood-stabilizing, antidepressant, and anxiolytic effects.

Question 34

What's a unique risk of aripiprazole (Abilify)?

Answer 34

Being a partial DA agonist in some parts of brain makes it have risk of increasing psychosis. (but it works well for most people)

Question 35

Which 2 drugs (1 of which is an antipsychotic) decrease suicide risk?

Answer 35

Lithium | Clozapine (brand name: Clozaril)

Question 36

What serotonin receptor is most associated with depression?

Answer 36

5-HT 1a (but not all brains are the same!)

Question 37

4 classes of antidepressants?

Answer 37

MAOIs TCAs (tricyclics) SRIs / SSRIs SNRIs (5-HT and NE reuptake inhibitors)

Question 38

What serious cardiovascular event are people on MAOIs at risk for? Why?

Answer 38

Hypertensive crises. | Decreased tyramine breakdown. Tyramine in the circulation appears to increase blood pressure.

Question 39

What is one additional effect or consideration for each of the 4 classes of antidepressant?

Answer 39

MAOIs - food restrictions TCAs - fatal in overdoses SSRIs - safest, fewest side effects SNRIs - can be used to treat pain

Question 40

Do antidepressants increase suicidal ideation? Clinical implication?

Answer 40

No - but they may give people who are already suicidal the energy to go through with it. Don't put somebody on an antidepressant and then not follow up for 3 months.

Question 41

Why might anticonvulsants stabilize mood?

Answer 41

Stablizing membrane potentials in the brain. Maybe.

Question 42

What's the MoA of valproic acid?

Answer 42

Hyperpolarization via increasing K+ channel permeability.

Question 43

Do mood-stabilizers have lots of side effects?

Answer 43

Yep. (impaired cognition, weight gain, neural tube defects, etc.)

Question 44

What property of a benzodiazepine is most associated risk of addiction?

Answer 44

Speed of onset and duration (quicker and shorter duration -> more likely to cause addiction)

Question 45

What receptor to the most common benzos (eg. clonazepam, lorazepam) act on?

Answer 45

GABA-A

Question 46

Which benzo has the highest risk of abuse?

Answer 46

Alprazolam - has a quick onset and short duration.

Question 47

What 2 classes of drugs are used to treat dementia?

Answer 47

acetylcholinesterase inhibitors | NMDA receptor antagonist (memantine)