Principles of Psychopharmacology Flashcards
What brain process is thought to be exclusively the domain of 5-HT?
Obsessions / compulsions
What brain process is thought to be exclusively the domain of NE?
Alertness
What brain process is thought to be exclusively the domain of dopamine?
Attention, pleasure/reward, motivation
What 2 monoamines are thought to affect anxiety?
5-HT and NE
Review: Main source of 5-HT in the brain?
Raphe nuclei.
Four 5-HT -related psychiatric conditions?
Mood disorders
Anxiety disorders
OCD
Eating disorders
Review: Main source of NE in the brain?
Locus ceruleus (but it doesn’t project to the nucleus accumbens)
Four NE-related psychiatric conditions?
Mood disorders
Anxiety disorders
ADHD
Pain disorders
Review: 2 areas which dopamine for the brain is produced?
Substantia nigra, ventral tegmental area
Four dopamine-related psychiatric conditions?
Schizophrenia
ADHD
Mood disorders
Addictions
What’s the most important glutamate receptor for psychopharmacology?
NMDA receptor.
3 glutamate-related psychiatric conditions?
Schizophrenia
Mood disorders
Alzheimer’s disease
4 psych conditions involving GABA?
Anxiety disorders (note that benzos treat symptoms, but not cause of anxiety)
Insomnia
EtOH withdrawal
Pain disorders
3 things histamine is involved with in the brain?
appetite, weight, and sleep
What’s the MoA that all antipsychotics share?
They’re all D2 dopamine receptor antagonists (some to other things in addition to this).
Why do cocaine and amphetamine cause psychosis at high levels?
Because they increase dopamine levels.
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?
Mesocortical: Negative symptoms of social isolation, poor hygiene.
Mesolimbic: Positive signs of delusions, perceptual disturbances.
What are the 2 areas of the brain associated with the side effects of antipsychotics? Side effects associated with each?
Nigrostriatal: Extrapyramidal symptoms (EPS), dystonia, akathisia
Tuberoinfundibular: Prolactin effects -> galactorrhea, gynecomastia
What is a dystonic episode?
Uncomfortable contractions, eg. eyes rolling painfully back into head, lock-jaw, etc.
What’s akathisia? (wasn’t on slides)
Inability to not move.
Major cardiovascular side effect of antipsychotics?
QTc prolongation -> risk for arrhythmia.
What effects do antipsychotics have on seizures?
They lower the seizure threshold.
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?
High potency antipsychotics have fewer side effects (but some of these side effects can be desirable).
Haloperidol (Haldol) = high-potency
Chlorpromazine = low-potency
What does “potency” actually mean when talking about a 1st gen. antipsychotic?
Ability to inhibit the D2 dopamine receptor.
3 types of side effect caused by 1st gen. antipsychotics?
Antihistamine effects
Antiadrenergic effects
Anticholinergic effects
(which make actually be useful for sedation, in context)
2 specific antihistaminic side effects from antipsychotics?
Weight gain
Sedation
5 specific anticholinergic side effects from antipsychotics?
Delirium Blurry vision Xerostomia (dry mouth) Constipation Urinary retention (nobody likes these)
2 specific antiadrenergic side effects from antipsychotics? What receptor do they most affect?
Orthostasis (can’t increase blood pressure when going from sitting to standing)
Arrythmias.
These act on alpha-1 receptors.
What’s the practical difference between 1st and 2nd generation antipsychotics?
2nd generation are not more effective, but they’re better tolerated.
What’s the mechanistic difference between 1st and 2nd gen. antipsychotics?
2nd gen. drugs acts on 5-HT receptors (mostly 5-HT2) in addition to the D2 receptor.
What’s a very significant side effect of clozapine?
1-2% risk of agranulocytosis. (must get CBC before and monitor while using)
What side effect profile are most atypical, 2nd gen. antipsychotics associated with?
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)
What are some desirable additional effects of atypical, 2nd gen. antipsychotics? (3 things)
Mood-stabilizing, antidepressant, and anxiolytic effects.
What’s a unique risk of aripiprazole (Abilify)?
Being a partial DA agonist in some parts of brain makes it have risk of increasing psychosis. (but it works well for most people)
Which 2 drugs (1 of which is an antipsychotic) decrease suicide risk?
Lithium
Clozapine (brand name: Clozaril)
What serotonin receptor is most associated with depression?
5-HT 1a (but not all brains are the same!)
4 classes of antidepressants?
MAOIs
TCAs (tricyclics)
SRIs / SSRIs
SNRIs (5-HT and NE reuptake inhibitors)
What serious cardiovascular event are people on MAOIs at risk for? Why?
Hypertensive crises.
Decreased tyramine breakdown. Tyramine in the circulation appears to increase blood pressure.
What is one additional effect or consideration for each of the 4 classes of antidepressant?
MAOIs - food restrictions
TCAs - fatal in overdoses
SSRIs - safest, fewest side effects
SNRIs - can be used to treat pain
Do antidepressants increase suicidal ideation? Clinical implication?
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.
Why might anticonvulsants stabilize mood?
Stablizing membrane potentials in the brain. Maybe.
What’s the MoA of valproic acid?
Hyperpolarization via increasing K+ channel permeability.
Do mood-stabilizers have lots of side effects?
Yep. (impaired cognition, weight gain, neural tube defects, etc.)
What property of a benzodiazepine is most associated risk of addiction?
Speed of onset and duration (quicker and shorter duration -> more likely to cause addiction)
What receptor to the most common benzos (eg. clonazepam, lorazepam) act on?
GABA-A
Which benzo has the highest risk of abuse?
Alprazolam - has a quick onset and short duration.
What 2 classes of drugs are used to treat dementia?
acetylcholinesterase inhibitors
NMDA receptor antagonist (memantine)
