Pharm- Psych

Which drugs are atypical/second generation antipsychotics?

risperidone, quetiapine, olanzapine, clozapine, aripiprazole, brexpiprazole, lumateperone, lurasidone, ziprasidone, pimvanserin

In addition to treatment of psychotic symptoms, what else can aripiprazole be used to treat?

Tourette disorder

Which second generation antipsychotic has no affinity for dopamine, histaminergic, or adrenergic receptors?

pimvanserin

Cariprazine Class and MOA

Class: third generation antipsychotic

MOA: Partial agonist at D2 and 5-HT1A with antagonist activity at 5-HT2A and 5-HT2B Receptors

Which drug is a VMAT2 inhibitor used to treat tardive dyskinesia?

Valbenazine

Indications for tricyclic antidepressants (nortriptyline and amitriptyline)?

depressive disorders

off label- chronic pain, fibromyalgia, anxiety, enuresis, ADHD

What is the MOA of tricyclic antidepressants (nortriptyline and amitriptyline)?

inhibit SERT, NET, block 5HT2a receptors= increases concentration serotonin and norepinephrine in synapse

Mirtazapine Class and MOA

Class: tetracyclic antidepressant

MoA: central presynaptic alpha2-adrenergic antagonist= increased release of norepinephrine and serotonin

Trazodone Class and MOA

Class: Serotonin Reuptake Inhibitor/Antagonist (SARI)

MoA: increases serotonin concentration

Treatment options for depression?

1. SSRIs

2. SNRIs- great if concurrent pain syndromes

3. atypicals (bupropion or mirtazapine)

4. TCAs

5. MAOIs

MOA of SSRIs?

Selectively inhibit SERT → increased 5HT in synapse

Which drugs are SSRIs?

fluoxetine (prototype), sertraline, citalopram, escitalopram, fluvoxamine, paroxetine

Venlafaxine Class and MOA

Class: serotonin & NE reuptake inhibitor (SNRI)

MoA: inhibits SERT at lower doses, NET at higher doses

Duloxetine Class and MOA

Class: serotonin & NE reuptake inhibitor (SNRI)

MoA: elevates levels of 5HT, NE and DA; elevates DA levels in PFC

Phenelzine Class and MOA

Class: monoamine oxidase inhibitor (MAO inhibitor)

MOA: inhibition of MAO= increases NE, DA, 5HT

Bupropion Class and MOA

Class: norepinephrine, dopamine reuptake transporter inhibitors

MoA: increases concentration of NE, DA

Which antidepressant can also be used to help with smoking cessation?

bupropion

Vortioxetine Class and MOA

Class: SSRI, 5HT1A agonist, 5HT3 antagonist

MoA: Inhibits SERT, partial agonist at 5HT1A and 5HT3 antagonist= increases serotonin concentration

Which drugs are serotonin modulators that can be used to treat depression?

vortioxetine, vilazodone, trazodone

Vilazodone Class and MOA

Class: SPARI (serotonin partial agonist reuptake inhibitor)

MoA: inhibits SERT= increases serotonin concentration; little to no effect on NE, DA

Which nonselective beta blocker can be used to treat anxiety?

Propranolol

Valproate Class and MOA

Class: anticonvulsant, mood stabilizer

MoA: increases GABA concentration

MOA of benzodiazepines (diazepam, oxazepam, clonazepam, alprazalam, temazepam, lorazepam)?

bind to and stabilize BZD receptor on post-synaptic GABA neuron in limbic system and reticular formation= enhances GABA impact

Indications for benzodiazepines?

bridge therapy in anxiety disorders, sedative, alcohol withdrawal

Which drugs are hypnotic non-benzodiazepine receptor agonists (BZDRAs)? What is their MOA?

zolpidem, eszopiclone, zaleplon- increase GABA-A impact

Ramelteon Class and MOA

Class: Hypnotic

MoA: selective agonist of melatonin receptors MT1 (sleep induction) & MT2 (circadian rhythms)

Suvorexant Class and MOA

Class: Hypnotic, Orexin Receptor Antagonist

MoA: blocks wake-promoting orexin-A and orexin-B receptors= suppresses wake drive

Which medications are indicated for insomnia?

Zaleplon, Zolpidem, Temazepam, Eszopiclone, Ramelteon, Suvorexant

How does buspirone treat anxiety?

miscellaneous anxiolytic- 5HT1A partial agonist, modulates 5HT levels

Methylphenidate Class and MOA

Class: CNS stimulant

MoA: Blocks reuptake of norepinephrine and dopamine into presynaptic neurons

Which alpha 1 receptor antagonist can be used off label to treat PTSD?

Prazosin - primarily for violent dreams

Flumazenil Class and MOA

Class: Benzodiazepine Receptor Antagonist

MoA: Prevents benzodiazepines binding to GABA-A receptor

Flumazenil indications

Reversal of benzodiazepine impact: reverse benzodiazepine induced sedation, conscious sedation anesthesia, management of benzodiazepine overdose

Acamprosate Class and MOA

Class: GABA agonist / Glutamate antagonist

MoA: Structurally similar to GABA; increases activity GABA-ergic system; increases activity of glutamate in CNS

Acamprosate indications

Maintenance of alcohol abstinence

Naltrexone Class and MOA

Class: Opioid antagonist

MoA: Competitive antagonist at opioid receptor sites, highest affinity for mu opioid receptor sites

Naltrexone indications

Maintenance of alcohol or opioid abstinence

(off-label: Cholestatic pruritis)

Methadone Class and MOA

Class: Opioid analgesic

MoA: Binds to CNS opiate receptors inhibiting ascending pain pathways; NMDA receptor antagonist activity

Methadone indications

Analgesia (low dose); treatment of opioid addiction (requires SAMSHA Center for Substance Abuse Treatment (CSAT) participation)

Buprenorphine Class and MOA

Class: Opioid partial agonist

MoA: High affinity binding to CNS mu opiate receptors; partial weak kappa receptor antagonism

Buprenorphine indications

Analgesia; Opioid withdrawal, dependence (requires specific training and participation in FDA Program)

Buprenorphine + Naloxone indications

Maintenance therapy for opioid dependence (not for induction of abstinence)

Which drug is our prototype first generation antipsychotic (FGA) drug?

Haloperidol

Which antidepressant drug is an "atypical" antidepressant otherwise categorized as a "norepinephrine-dopamine reuptake inhibitor" (NDRI)?

Bupropion

Which lobe or site of the brain is responsible for "executive functions" such as planning, emotional control, prioritizing actions?

prefrontal cortex - executive function, attention, integration of emotion, guilt, suicidality

Which site in the brain is responsible for sensations of "...fear, anxiety, panic..."?

amygdala

Which nerve circuit or pathway is primarily responsible for movement, pleasure, psychic reward, etc. ?

Dopamine pathways - primarily reward circuit, movement, and pleasure

Which symptoms are key features (i.e. target symptoms) of psychotic disorders which we monitor to see if they improve with drug therapy?

hallucinations, delusions

People who experience serotonin syndrome have which receptors overstimulated?

5-HT

The pharmacodynamics of first generation antipsychotics includes strong antagonism of which receptors in the brain?

Dopamine

The pharmacodynamics of second generation antipsychotics includes strong antagonism of which receptors in the brain?

Dopamine and serotonin

Also antagonism of H1 and alpha receptors

What is a prominent side effect of second generation antipsychotics?

weight gain because of 5HT2C and H1 blockage

Which antipsychotics have the highest risk of glucose dysregulation and weight gain?

clozapine and olanzapine

Which antipsychotics have an increased risk of extrapyramidal symptoms?

first generation

What is our prototype second generation antipsychotic?

risperidone

Which antidepressant has minimal to no sexual dysfunction side effect?

buproprion

What are some common adverse reactions of antipsychotics?

extrapyramidal syndrome- imbalance between ACh and dopamine activity

tardive dyskinesias- late appearing oral/facial dyskinesias due to D2 receptor blockage

neuroleptic malignant syndrome- excess antagonism of D2= muscle rigidity, fever, unstable BP, myoglobinemia

serotonin syndrome- excess 5HT

malignant hypertension- genetic

What is a serious side effect of clozapine?

severe neutropenia/agranulocytosis- most effective but not a first line drug anymore

What are disorders with psychosis as a defining feature?

schizophrenia, substance-induced psychotic disorder, schizoaffective disorder, delusional disorder

What are disorders with psychosis as associated features?

mania, depression, Alzheimer's, cognitive disorders

Which type of schizophrenia symptoms can antipsychotics treat best?

positive symptoms- delusions, hallucinations, agitation

Where do first generation antipsychotics exert their impact?

work primarily in mesolimbic pathway (positive sx) but active at DA receptors throughout CNS → make negative and cognitive sx more pronounced

How do first generation antipsychotics cause extrapyramidal syndromes?

DA suppression → relative secondary ACh excess

Side effects of first generation antipsychotics?

sedation, hypotension, QT prolongation, EPS, TD

What should you do every 6-12 months in a patient on a first generation antipsychotic?

attempt dose reduction to reduce risk of TD

What needs to be monitored in people on first generation antipsychotics?

weight, BP, glucose, lipids, AIMS

Why do males prefer second generation antipsychotics over first generation?

less gynecomastia b/c minimal prolactin release

How are second generation antipsychotics different from first generation antipsychotics?

combination of D2 antagonism and 5-HT2A antagonist/inverse agonist action

inhibit 5HT2A receptors in prefrontal cortex → more impact on negative symptoms

Side effects of second generation antipsychotics?

weight gain, obesity, dyslipidemia, diabetes, accelerated CVD, early death

Which second generation antipsychotic has a lower risk of weight gain?

aripiprazole

Contraindications for quetiapine?

history of seizures or alcoholism, elderly

How do the indications for quetiapine change depending on the dosing?

50mg- hypnotic

300mg- antidepressant

>400mg- antipsychotic

What is a unique side effect of aripiprazole?

compulsive behavior disorder

Side effects of brexpiprazole?

akathesia, blood dyscrasias, CeVD, esophageal dysmotility, EPS, elevation of glucose, impulse control disorder, NMS, suicidal ideation *tend to be mild*

Which second generation antipsychotic can cause galactorrhea?

lurasidone

Contraindications for lurasidone?

Parkinson's, seizures, dementia

Which second generation antipsychotic can cause rash and SJS?

ziprasidone

Why are SGAs less likely to cause tardive dyskinesia?

have larger therapeutic window before extrapyramidal symptoms appear

Why do patients on cariprazine need monthly follow ups at first?

adverse effects may not be prominent until on drug for weeks

How are third generation antipsychotics different from second generation antipsychotics?

side effects are broad but severity tends to be less

Treatment for serotonin syndrome?

IV lorazepam for acute treatment, then periactin for 1 week to counteract elevated serotonin

In a patient with depression who is worried about sexual dysfunction side effects and has a history of a seizure disorder, what drug can you prescribe?

mirtazapine

Which anti-psychotic drug is considered to be a "third generation" antipsychotic because of its agonist/antagonist impacts at multiple receptor classes?

Cariprazine

Which second generation antipsychotic has FDA approval for treatment of Parkinson's Disease dementia/psychosis ONLY?

Pimvanserin

What disorder must be ruled out prior to prescribing any anti-depressant medication?

coexisting mania

Anti-depressant medications appear to be most effective in patients in what age range?

24-65

What timeframe is the typical time to improvement in emotions seen in depressed adults treated with antidepressants?

2-4 weeks

What timeframe is the typical time to full therapeutic impact of antidepressants?

6-8 weeks

Your patient has a major depressive disorder including hyper-somnolence such that he sleeps 14 hours per day. Which anti-depressant medication would be contra-indicated for this patient due to its extensive sedation potential?

Mirtazapine- very sedating

Your patient has depression and a history of a marginally controlled seizure disorder. Which antidepressant would be contra-indicated for this patient?

Buproprion

Depression is thought to be caused by an imbalance of what neutrotransmitters in the brain?

5HT, NE, DA

What is the BBW for antidepressants?

increased suicide risk

What is the goal response for antidepressants?

50% or more symptom reduction

What are augmenting agents for antidepressants?

lithium, triiodthyronine, aripiprazole, dopaminergic drugs (ropinerole or pramipexol)

Side effects of MAO inhibitors?

weight gain, sexual dysfunction, HTN, urinary retention

Contraindications to MAOi?

concurrent use of dopamine or other sympathomimetics, CHF, significant renal or hepatic disease

Why is nortriptyline the prototype tricyclic antidepressant?

it has less side effects

Caution with using nortriptyline in elderly?

need small dose to not induce urinary retention

Side effects of TCAs?

gynecomastia, galactorrhea, anticholinergic effects (dry mouth, urinary retention, constipation, H1 (sedation, weight gain), alpha 1 (ortho hypotension, dizziness), voltage sensitive Na channels (seizures, arrhythmias)

Caution with prescribing SSRIs?

caution in patients on anticoagulants- not an absolute contraindication but should be monitored