Term
|
Definition
| Dopamine -> Norepinephrine -> epinephrine |
|
|
Term
|
Definition
• Many pathways come from raphe or midline region of pons/upper
brainstem
• Responsible for variety of effects
• Target for many antidepressants and antipsychotics |
|
|
Term
|
Definition
• Receptor effects are dose-dependent:
• Low doses: D1-like (D1, D5), D2-like (D2, D3, D4) and β1
• High doses: α1 and α2
• Links substantia nigra to neostriatum and ventral tegmental region to limbic structures, including limbic cortex |
|
|
Term
| Dopamine Mesocortical pathway |
|
Definition
Important for “higher order” cognitive
functions (motivation,
impulse control, emotion) |
|
|
Term
| Dopamine Mesolimbic pathway |
|
Definition
|
|
Term
| Dopamine Nigrostriatal pathway |
|
Definition
|
|
Term
| Dopamine Tubero- infundibular pathway |
|
Definition
|
|
Term
Dopamine Receptor
Antagonist affects |
|
Definition
Mesocortical (prefrontal cortex)
Worsening negative symptoms (anhedonia)
Mesolimbic (basal ganglia)
Relief of positive symptoms (hallucinations)
Nigrostriatal (substantia nigra)
Extrapyramidal symptoms
Tuberoinfundibular (hypothalamus)
Increased prolactin release |
|
|
Term
Dopamine Receptor
Agonist affects |
|
Definition
Mesocortical (prefrontal cortex)
Theorized improvement in negative symptoms
Mesolimbic (basal ganglia)
Reward pathway (addiction), psychosis
Nigrostriatal (substantia nigra)
Target of action for relief of movement disorders in Parkinson’s
Tuberoinfundibular (hypothalamus)
Decrease in prolactin release |
|
|
Term
First Generation Antipsychotics (FGAs)
• MOA |
|
Definition
Blockade of post- synaptic D2 receptors in brain
• Other receptors may be affected, which accounts for differences in side effects
• Ex: Histaminergic, muscarinic, adrenergic |
|
|
Term
| First gen antipsychotic agents |
|
Definition
| Haloperidol, Thiothixene (thio thick scene), Chloropromazine (chlorine pro maze), Thioridazine (thio rid of magazines), Trifluoperazine (try flower pie magazines), Perphenazine (perfect hen magazine), Fluphenazine (floop hen mazagine) |
|
|
Term
Has ADE: • Blockade of D2 receptors in other areas leads to variety of adverse effects
• Nigrostriatal -> movement disorders
• Tuberoinfundibular ->hyperprolactinemia
• Mesocortical ->worsening negative symptoms |
|
Definition
| first generation antipsychotic agents |
|
|
Term
Black box warning for ALL
antipsychotics |
|
Definition
| Increased death associated with treatment in patients with dementia-related psychosis |
|
|
Term
| Has AVE: sedation, EPS, Anticholinergic, Cardiovascular |
|
Definition
| First generation antipsychotics |
|
|
Term
| Chlorpromazine indicxation |
|
Definition
schizophrenia, bipolar disorder (mania), N/V
*Also indicated for treatment of acute intermittent porphyria, presurgical apprehension, intractable hiccoughs, problem behavior (severe), tetanus |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Trifluoperazine indication |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| FGA Prescribing Considerations |
|
Definition
• Monitor for symptoms of EPS
• May require use of anticholinergic agent as adjunct to minimize movement side effects- Ex: benztropine (Cogentin) 0.5 mg BID
• Generic availability, so relatively inexpensive
• Immediate acting injections (haloperidol, fluphenazine,
and chlorpromazine)àoption for hospitalized agitated patients
• May be ordered as a cocktail: “B52” • Haloperidol 5 mg po/IM/IV
• Lorazepam 2 mg po/IM/IV
• Diphenhydramine 50 mg po/IM/IV
• High-potency agents require addition of anticholinergic medication to reduce risk of developing EPS
• Low potency agents do not require additional meds
• Ex: A patient treated with chlorpromazine does NOT need
adjunctive anticholinergic medication or lorazepam • Highly sedating itself and highly anticholinergic |
|
|
Term
Second Generation Antipsychotics (SGAs)
• MOA |
|
Definition
| Post-synaptic D2 and 5HT2A blockade |
|
|
Term
|
Definition
has a unique mechanism of action
• Partial agonist at D2 and 5HT1A receptors • Antagonist at 5HT2A
• High affinity for D2, D3, and 5HT2A /1A |
|
|
Term
| Second generation antipsychotic agents |
|
Definition
| Aripiprazole (abilify), brexpiprazole (rexulti)- break pipe razor, clozapine (clozaril)- closet pine, olanzapine (zyprexa), quetiapine (seroquel), risperidone (risperdal), paliperidone (invega)- palpate dome, lurasidone (latuda), iloperidone (fanapt)- little parrot dome, asenapine (saphris)- aspen pine |
|
|
Term
| 2D6 second generation antipsychotics |
|
Definition
| ariprazole, iloperidone, risperidone (converted to active metabolite paliperidone) |
|
|
Term
| 1A2 second generation antipsychotics |
|
Definition
| Asenazpine, Clozapine, Olanzapine |
|
|
Term
| 3A4 second generation antipsychotics |
|
Definition
| aripiprazole, lurasidone, quetiapine, ziprasidone *Two-thirds of ziprasidone metabolism occurs via aldehyde oxidase and one- third by CYP450 system (3A4). |
|
|
Term
|
Definition
• 1A2
• Smoking induces this enzyme by 20–30%
• May need to adjust dose if changes in smoking status
• Watch for 1A2 inhibitors like fluvoxamine
• 2D6
• Genetic variations between PM, UM, RM*
• 2D6 inhibitors: paroxetine, fluoxetine, and bupropion
• If patient is taking risperidone + 2D6 inhibitor, may not get full effect of antipsychotic
• 3A4
• Many medications are metabolized through this enzyme
• Watch for strong inhibitors such as azole class of antifungals |
|
|
Term
Has ADE: • Metabolicabnormalities(lipidsandglucose)
• Weight gain
• QTc prolongation
• Prolactin elevation
• Sedation
• Akathisia
• Anticholinergic effect
• Orthostatic hypotension |
|
Definition
| second generation antipsychotics |
|
|
Term
|
Definition
|
|
Term
| prolactin elevation due to (SGA) |
|
Definition
| D2 blockade in tuberoinfundibular pathway |
|
|
Term
| anticholinergic effects due to (SGA) |
|
Definition
|
|
Term
|
Definition
| D2 blockade in nigrostriatal pathway |
|
|
Term
| second generation drugs and weight gain side effect from most likely to least likely to cause |
|
Definition
| Clozapine, Olanzapine -> Quetiapine, Iloperidone -> Risperidone, Paliperdone -> Arpiprazole, Lurasidone, Ziprasidone |
|
|
Term
| second gen antipsychotics and prolactin elevation most likely to cause to least likely to cause |
|
Definition
| Risperidone, Paliperidone -> Lurasidone ,Ziprasidone -> Iloperidone, Olanzapine ,Asenapine -> Quetiapine, Aripiprazole |
|
|
Term
| second gen antipsychotics and sedation SE most likely to cause to least likely to cause |
|
Definition
| Clozapine -> Olanzapine ,Quetiapine ,Ziprasidone -> Asenapine, Risperidone, Lurasidone -> Aripiprazole, Iloperidone, Paliperidone |
|
|
Term
| Antipsychotics and Qtc Prolongation, agents most likely to cause |
|
Definition
| Thioridazine, Ziprasidone |
|
|
Term
|
Definition
| Bipolar Disroder, MDD, Schizophrenia, Autism disorder |
|
|
Term
| Brexpiprazole indicaitons |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| Bipolar Disorder, MDD (in combo w fluoxetine), schizophrenia |
|
|
Term
|
Definition
| bipolar disorder, MDD, Schizophrenia |
|
|
Term
|
Definition
| bipolar disorder, Schizophrenia, autism disorder |
|
|
Term
|
Definition
|
|
Term
|
Definition
| bipolar disorder, schizophrenia |
|
|
Term
|
Definition
|
|
Term
|
Definition
| bioplar disorder, schizophrenia |
|
|
Term
| SGA Prescribing Considerations |
|
Definition
• Risperidone
• Clinicalmaxof6–8mg
• >8mgbeginsactingsimilartotypicalantipsychotics • Paliperidone
• DoseadjustmentrequiredwhenCrCl<80mL/min
• Quetiapine
• Highlyanticholinergicmetabolite
• Doses<100mg/dayprimaryactionatH1receptorà no real antipsychotic effect
• Effectonmood:200–400mg/day
• Antipsychoticdoses:500–800mg/day
• Clozapine generally reserved for treatment refractory cases
• Requires registering with clozapine REMS program
• Aripiprazole and lurasidone have higher incidence of akathisia
• Cost to patients |
|
|
Term
|
Definition
Haloperidol
$14
Risperidone
$25
Olanzapine
$26
Aripiprazole
$770
Brexpiprazole
$865
Lurasidone
$921
Cariprazine
$1,000 |
|
|
Term
|
Definition
• Reservedfortreatmentrefractorycases
• Generallyafterfailureof>twoadequatetrialsof antipsychotics
• Requirespatient,pharmacy,andphysician registration with clozapine REMS program
• Priortoinitiationandthroughouttimeon clozapine, blood draws are required due to risk of neutropenia
• Fiveblackboxwarnings(BBW)associatedwith clozapine |
|
|
Term
| Clozapine: BBW and Adverse Effects |
|
Definition
| myocarditis (mostly in 1st 8 weeks), agranulocytosis (ANC >1500), orthostatic hypotension (slowly titrate dose to minimize), seizure, death in dementia-related psychosis |
|
|
Term
Has ADE: • Highlyanti-cholinergicmedication
• Tachycardia
• Constipation
• Prescribe sufficient bowel regimen!
• Cholinergic agonist at M4 receptors in mouth • Excessivesalivation
• Stronghistaminergiceffect • Sedating
• Weightgain |
|
Definition
|
|
Term
| Clozapine: Prescribing Considerations |
|
Definition
• Consider in patients who have failed adequate doses and trials of other agents
• May not be appropriate in patients with adherence issues
• Dose will need to be re-titrated from initial 25 mg QHS if patient missed > 48 hours of dose
• Patient will need to travel for blood work • Weekly for 1st six months
• Biweekly for 2nd six months • Then monthly for life |
|
|
Term
| Which of the following is the most common form of extrapyramidal symptoms (EPS)? |
|
Definition
|
|
Term
| You have a patient stable on clozapine 600 mg QHS. You diagnose him with OCD and wish to start treatment. Which SSRI should you avoid? |
|
Definition
|
|
Term
|
Definition
• Group of potentially serious adverse effects associated with antipsychotic medications or metoclopramide
• Antagonize D2 receptors in nigrostriatal pathway (substantia nigra) |
|
|
Term
|
Definition
| Repetitive, involuntary, purposeless body or facial movements Ex: Lip smacking, tongue movements, finger movements |
|
|
Term
|
Definition
| Occurs after longer duration of use, may be permanent |
|
|
Term
|
Definition
| Extreme form of internal or external restlessness, inability to sit still, urge to move constantly |
|
|
Term
|
Definition
| Muscle tension disorder -> strong muscle contractions, unusual twisting of parts of body, especially neck |
|
|
Term
|
Definition
| Mask-like facies, resting tremor, cogwheel rigidity, shuffling gait, bradykinesia |
|
|
Term
| antipsychotics with high risk for EPS |
|
Definition
| haloperidole, thiothixene, fluphenazine, paliperidone, risperidone |
|
|
Term
| antipsychotics with low risk for EPS |
|
Definition
• Chlorpromazine
• Aripiprazole
• Brexpiprazole
• Clozapine
• Iloperidone • Olanzapine
• Quetiapine • Ziprasidone |
|
|
Term
|
Definition
• HistoricallyassociatedwithFGAs>SGAs
• Generaltreatment:
• Diphenhydramine(Benadryl):25–50mgpoorIM
(prn or scheduled)
• Benztropine(Cogentin):0.5–4mgpo • Typically divided into BID dosing
• Propranololmayhelpwithtreatmentofakathisia
• Anticholinergics may worsen Parkinsonian symptoms or tardive dyskinesia |
|
|
Term
| Tardive Dyskinesia Clinical features: |
|
Definition
Oral, Facial, Lingual Dyskinesia:
• Abnormal movements of the tongue
• Facial grimacing
• Lip puckering, smacking, pouting
• Bulging of cheeks
• Chewing movements
Limbs and Trunk
• Twisting, spreading of fingers
• Foot tapping
• Dyskinesia of neck
• Shoulder shrugging
• Rocking/swaying
• Tremor (rare) |
|
|
Term
| Tardive Dyskinesia Treatment |
|
Definition
No standard treatment approach has been established:
Discontinue medication • Low response rate
Switch to less potent dopamine
antagonist
• FGA -> SGA
Adjunctive agents
• Clonazepam, gingko biloba, amantadine
• VMAT2 inhibitors? |
|
|
Term
| Valbenazine (Ingrezza®) MOA |
|
Definition
| Reversibly inhibits VMAT2 transporteràregulates uptake of monoamine from cytoplasm to synaptic vesicle for storage/release (↓ monoamine levels in synapse) |
|
|
Term
| Valbenazine (Ingrezza®) indication |
|
Definition
|
|
Term
| Has ADE: Drowsiness, fatigue, sedation |
|
Definition
|
|
Term
| Long-Acting Injectable Antipsychotics |
|
Definition
• Noncompliance to antipsychotic medications may lead to relapsing psychiatric illness.
• Worsening psychiatric symptoms
• Need for emergent treatment or admission
• Readmission rate with schizophrenia is 20–46% in one year
• The monthly or bimonthly administration of long-acting injectable (LAI) antipsychotics may improve treatment adherence.
• Conflicting evidence regarding impact on hospital readmission rate |
|
|
Term
| Available LAI Antipsychotics |
|
Definition
First-Generation Antipsychotics:
Fluphenazine decanoate
Prolixin Decanoate®
Haloperidol decanoate
Haldol Decanoate®
Second-Generation Antipsychotics:
Aripiprazole lauroxil
Aristada®
Aripiprazole monohydrate
Abilify Maintena®
Olanzapine pamoate
Zyprexa Relprevv®
Paliperidone palmitate
Invega Sustenna®, Invega Trinza®
Risperidone
Risperdal Consta® |
|
|
Term
| Oral Antipsychotic Overlap w LAI |
|
Definition
**Tolerability to oral formulation should be established prior to administration of LAI antipsychotic. **
Fluphenazine
Varies depending on oral dose (next slide)
Haloperidol
Based on clinical effect with goal to discontinue oral
within 1 month
Aripiprazole
Abilify Maintena®: Continue oral medication for 14 days Aristada®: Continue oral medication for 21 days
Olanzapine
May begin tapering oral medication immediately after first injection
Paliperidone
May begin tapering oral medication immediately after first injection
Risperidone
Continue oral medication for 3 weeks |
|
|
Term
| Monitoring Recommendations for LAI antipsychoitics |
|
Definition
Metabolic Effects
Weight gain
Weight and BMI
Monthly x 3 months, then quarterly
Central obesity
Waist circumference
Annually
Diabetes
Fasting glucose or HgbA1c
3 months, then annually
Hyperlipidemia
Fasting lipid profile
3 months
Neurologic Effects
EPS
Involuntary movements
Every visit
Sedation
Daytime somnolence
Every visit
Cardiovascular Effects
QT prolongation
QT interval on EKG
With addition of other QT prolonging drugs |
|
|
