Antipsychotics and antidepressants

Dopamine purposes

Reward, motivation, motor control, attention

Serotonin purpose?

Mood regulation, sleep, appetite, digestion

Low DA?

anhedonia, low motivation, fatigue, attention deficits, impulsivity, working memory

Excess DA?

hallucinations/delusions.  Drives reinforcement learning (addiction), mania

Low serotonin?

•Depression, anxiety, OCD, nausea, GI, schiz

Haloperidol

1st gen, typical antipsychotic agent

Aripiprazole

atypical antipsychotic agent

Clozapine?

atypical antipsychotic agent

Olanzapine?

atypical antipsychotic agent

Quetiapine?

atypical antipsychotic agent

For a dx of scizo?

6 month history and ruling out alternatives

positive symptoms of scizo?

• delusions

• hallucinations

• disorganized speech

negative symptoms of scizo?

affective flattening (flat face)

alogia (less speech)

abolition (less motivation)

anhedonia (not getting up)

scizo men or women more severe?

men

scizo progression of disease?

cognitive and social functioning precedes psychotic symptoms by >10 years

Antipsychotics block what receptors?

D2 receptors in the limbic system (mesolimbic-mesocortical dopamine pathways)

• serotonin 5ht appear to play a role too

Side effects of antipsychotic drugs

• Parkonsonian like symptoms

  • nigrostriatal and tuberinfundibular dopamine pathways

• Block a1, H1, muscarinic receptors

Haloperidol MOA?

competitive antagonist

• block D2 receptors

  • needs to be block like 70%

Side effects of haloperidol?

Higher probability of extrapyramidal symptoms

• Parkinsonian

Aripiprazole MOA?

Partial agonist

Quetiapine, Clozapine, Olanzapine,

• D2 receptor block

• 5HT receptors block

• FEWER Movement disorder symptoms

Short term/acute antipsychotic?

• haloperiodol

  • 1st gen

Long term antipsychotics?

• 2nd gen/atypical anti psychotic

B52

diphenhydramine, haloperidol, lorazepam

Schizophrenia drug efficacy

All good, clozapine slightly better

To treat negative symptoms, conventional or atypical antipsychotics?

atypical

to treat agitation sczio

IM

• minutes

Longer term scizo treatment time of response?

• shortest

  • 1-2 weeks

• longest

  • 4-6 weeks

ventral tegmental nucleus purpose?

}Motivation, affect, goal-directed thinking

substantia nigra purpose?

intended movement

arcuate and periventricular nuclei of hypothalamus

• DA inhibits prolactin release

Antipsychotic induced Parkinsonism?

Imbalance of Ach (too much), DA (too little)

Short term side effects of antipsychotic drugs

• Acute dystonia

• Akathisia

Acute dystonia tx?

• ANTI MUSCARINIC

  • Benzotropine

  • Diphenhydramine

Akathisia

motor restlessness

Akathisia tx?

decrease dose of antipsychotic

Parkinsonism tx?

• Anticholinergic

  • lower dose

Neuroleptic malignant syndrome?

• Hyper-rigidity

Catatonia, stupor, fever, BP, myoglobinemia

Neuroleptic malignant syndrome tx

SEND TO ER

Tardive Dyskinesia treatment

• PREVENTION

  • ???Not being on 1st gen for long period of time?

Tardive dyskinesia cause?

DA receptor sensitivity

Adverse effects of antipsychotics

• weight gain

• elevated Cholesteral

• others:

  • endocrine

    • infertility

  • ANS

    • BP

    • OH

    • dry mouth

    • difficulty peeing

    • constipation

Dementia tx with antipsychotics?

NOOOOO

• increased death risk

Clozapine specific adverse effect

excessive drooling

What is usually the first line SSRI?

Citalopram

What kind of drug is Citalopram?

SSRI

What kind of drug is Escitalopram?

SSRI

What kind of drug is Sertraline?

SSRI

What kind of drug is Sertraline?

SSRI

What kind of drug is Fluoxetine?

SSRI

What kind of drug is Paroxetine?

SSRI

What do SSRIs do?

Inhibit reuptake of serotonin

Drugs that increase synaptic serotonin do?

anti depressant activities

Stimulation of 5HT1 receptors causes?

o Decreases aggression, impulsivity, drug-seeking behavior

o Increase sociability, mood

SSRI conditions it treats?

oDepression, aggression, anxiety, Obsessive Compulsive Disorder (and more)

SSRI chronic actions

How long does it usually take for SSRI maximal effects?

8-12 weeks

SSRI MOA?

•Inhibit SERT 300-3000x> NET

• more serotonin in synapse

Which SSRI for anxiety?

Sertraline

Escitalopram useful application?

• no adverse drug interactions

Half life Fluoxetine vs Paroxetine

• Fluoxetine

  • longer half life

• Paroxetine

  • shorter half life

Why is fluoxetine half life important?

• Longer half life, self tapering if compliance is an issue.

SSRI adverse effects

• Mood/aggression/social interactions

• Nausea/vomiting

• GI motility; digestion

• Thermoregulation

• Appetite and satiety

• Sexual function

• Sleep

Which SSRI can cause fetal harm?

Paroxetine

SSRI overdose?

Drowsiness, mental status changes, tremor, GI distress. Seizures

Which SSRIs at high doses inhibit CYP2D6?

Fluoxetine, Paroxetine

Life threatening effects of SSRI

• Prolonged QT interval

• Suicidal thoughts

• Serotonin syndrome

  • when taken with other serotonergic agents

• Overdose

Escitalopram withdrawal syndrome?

• F

  • Flu like

• I

  • insomnia

• N

  • Naseua

• I

  • Imbalance

• S

  • sensory disturbance

• H

  • Hyperarousal

SNRI block which receptors?

• Serotonin

• Epinephrine

SNRI indications?

• Depression

• Neuropathic pain

Duloxetine use?

neuropathic pain

Bupropion MOA

• Noncompetitive antagonist of nicotinic receptor

  • Inhibits NE uptake

  • Weak inhibitor of DA Uptake

Bupropion random usage?

• Smoking cessation

Contraindication of Bupropion?

• Seizure problems

• Lowers the threshold

Mirtazapine MOA?

•Antagonist of presynaptic α2

•5HT3 antagonist

•5HT2a and 5HT2c antagonist

•H1 antagonist

Effects of Mirtazapine?

oDecreased aggression, anxiety

oIncreased sociability, mood

oDecreased impulsivity

oInhibition of drug-seeking behavior

oInhibition of penile erection

Adverse effect of Mirtazapine?

Sleepy, weight gain