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Antipsychotics Flashcards

1
Q

Antipsychotics

A

Schizophrenia

Bipolar

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2
Q

Psychosis

A
  • Break from reality (distorted or non-existent sense of reality)
  • Hallucinations: seeing, hearing feeling things that aren’t there
  • Delusions: firm, fixed beliefs that are untrue and seem irrational to others
  • Sx of mental illness
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3
Q

Psychotic disorder

A

Mood disorders with psychotic features

  • Bipolar
  • Major depression

Substance-induced psychosis
Dementia/delirium with psychotic features
Schizophrenia
Schizoaffective disorder

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4
Q

Antipsychotics

A

Dopamine hypothesis: overstimulation of DA receptors
- Chlorpromazine: induced state of mental indifference in pts; sedation w/o narcosis

Motivational salience

  • Antipsychotics block dopaminergic effects
  • Drugs don’t erase delusions by blocking dopamine
  • Delusions/hallucinations are dormant
  • Normal thoughts also blocked
  • Patients report dysphoria
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5
Q

Indications

A
  • Schizophrenia
  • Bipolar disorder
  • Acute psychosis (mania)
  • Major depression with psychotic features
  • Severe behavioral problems
  • Tourette syndrome (haloperidol)
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6
Q

First Generation Antipsychotics

A 
Haloperidol (Haldol)
Fluphenazine (Prolixin)
Perphenazine (Trilafon)
Thioridazine (Mellaril)
Chlorpromazine (Thorazine)
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7
Q

First Generation Antipsychotics MOA

- Don’t get used much due to the blocking of dopamine receptors, causing movement problems

A

D2 receptor antagonist
- Antipsychotic effects: relief of positive sx (delusions hallucinations, thought disorders, movement disorders)
ADR:
- Induction of EPS: abnormal, involuntary movements (akathisia, dystonia, dyskinesia, pseudoparkinsonism)
- Increased prolactin levels (lacrimation/ breast development)

5HT2c receptor antagnoist
- ADR: contributes to wt gain

Alpha 1 antagonist
- ADR: sedation

H1 antagonist
- ADR: sedation, wt gain

M1 antagonist
- ADR: anticholinergic effects (urinary retention, constipation, dry mouth, blurred vision, confusion)

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8
Q

First generation ADRs

A
  • Movement disorder (dystonia, bradykinesia, tremor, akathisia, choreoathertosis)
  • Anhedonia
  • Sedation
  • Wt gain
  • Temperature dysregulation
  • Hyperprolactinemia (galactorrhea/ amenorrhea)
  • Postural hypotension
  • Sunburn
  • Prolonged QT
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9
Q

Second generation (Atypical) antipsychotics

A 
Aripiprazole (Abilify)
Brexpiprazole (Rexulti)
Asenapine Maleate (Saphris)
Clozapine (Clozaril) 
Iloperidone (Fanapt)
Lurasidone (Latuda)
Olanzapine (Zyprexa)
Paliperidone (Invega)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
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10
Q

Second Generation Antipsychotics MOA

A
  • Antipsychotic effects w/o the extrapyramidal sx
  • Helps with negative sx: apathy, social withdrawal, decreased motivation, cognitive impairment

D2 receptor antagonist
5HT1 receptor agonist: antidepressant/anxiolytic
5HT2A antagonist: negative sx improvement
5HT2c receptor antagonist
Alpha 1 antagonist
H1 antagonist
M1 antagonist

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11
Q

Second generation ADR

A
  • DM
  • Hypercholesterolemia
  • Sedation
  • Moderate movement disorder
  • Hypotension

Risperidone
- Hyperprolactinemia

Olanzapine
- Wt gain

Clozapine

  • Seizures
  • Nocturnal salivation
  • Agranulocytosis
  • Myocarditis
  • Lens opacities
  • Wt gain
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12
Q

Avoiding second generation ADR best choices

A

Sedation

  • W/O: Aripiprazole, Iloperidone, Lurasidone
  • W/: Clozapine

Wt Gain

  • W/O: Aripiprazole, Lurasidone, Ziprasidone
  • W/: Clozapine

EPS

  • W/O: Clozapine, Iloperidone, Quetiapine
  • w/ Paliperidone
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13
Q

Antipsychotic black box

A
  • Increased mortality in eldery pts with dementia related psychosis
  • Causes varied: CV (heart failure, sudden death); Infection (pneumonia)
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14
Q

Aripiprazole

A
  • Schizophrenia
  • Bipolar disorder (monotherapy or adjunctive to Li or valproate)
  • Adjunct treatment of major depressive disorder
  • Irritability associated with autistic disorder
  • Acute treatment of agitation
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15
Q

Brexpiprazole (Rexulti)

- Schizophrenia, adjunct for MDD

A
  • WARNING: increased mortality and CVA in elderly dementia pts with psychosis, tardive dyskinesia, NMS
  • Hyperglycemia, hyperlipidemia, wt gain, blood dyscrasias, akathisia, somnolence, anxiety, restlessness
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16
Q

Asenapine (Saphris)

  • Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults (monotherapy or adjunctive therapy with either Li or valproate)
  • Acute and maintenance treatment of schizophrenia in adults
A
  • MOA: DA, 5HT, NE, H1 receptor antagonist

- ADR: Insomnia, somnolence, N/V, anxiety, agitation, HA, constipation, psychosis; same warning as iloperidone

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17
Q

Clozapine (Clozaril, Versacloz)

  • Treatment resistant schizophrenia
  • Reduce the risk of suicidal behavior in younger pts with schizophrenia
A

WARNING

  • Increased risk of angranulocytosis
  • Myocarditis, orthostasis, bradycardia
  • Lower seizure threshold

DRUG INTERACTION

  • Decreases cigarette smoking (may change drug metabolism): Clozapine 1A2 substrate vs Tobacco 1A2 inducer
  • Lower dose with P450 1A2 inhibitors (Ciprofloxacin)
  • Avoid use of strong P450 3A4 inducers
18
Q

Olanzapine

A
  • Schizophrenia
  • Bipolar disorder
  • Treatment resistant depression
  • Agitation associated with schizophrenia and bipolar I mania
19
Q

Quetiapine

A
  • Schizophrenia
  • Bipolar disorder
  • Adjunctive therapy for major depressive disorder
20
Q

Iloperidone (Fanapt)

- Treatment of schizophrenia in adults

A
  • MOA: unknown, likely DA and 5 HT2 antagonist, alpha adrenergic antagonism
  • ADR: dizziness, somnolence, tachycardia, N, dry mouth; Impaired thinking, judgement, motor skills; Long QT; NMS, tardive dyskinesia; Orthostasis; hyperprolactinemia; priapism
  • DRUG INTERACTION: 2D6 and 3A4 substrate
21
Q

Paliperidone (Invega)

- Schizophrenia, schizoaffective disorder

A
  • MOA: active metabolite of risperidone; DA, 5HT2a, H1, alpha receptor antagonist
  • ADR: HA, tachycardia, somnolence, anxiety, akathisia, EPS; same warning as iloperidone
22
Q

Risperidone

A
  • Schizophrenia
  • Bipolar disorder
  • Irritability associated with autism
23
Q

Ziprasidone

A
  • Schizophrenia

- Bipolar disorder

24
Q

Monitoring SGAs

A
  • Medication and FH, CVD
  • Weight
  • Waist circumference
  • Blood pressure
  • Fasting plasma glucose level
  • Fasting lipid profile
25
Antipsychotics treatment goals
Initial response - Positive subjective response immediately following therapy: predicts potential benefit with medication - Is there onset of dysphoria or anxiety: leads to negative attitude towards therapy - No initial dose is too low, high doses are less effective-- start low and go slow 7 day goals - Decrease in agitation, hostility, aggression, and anxiety - Normalization of sleeping and eating patterns - Titrate medication close to or to effective dose 2-3 week goals - Increase socialization, self care habits, and mood - Reach target dose and maintain
26
Schizophrenia Treatment
Consider - Major suicide risk - Metabolic issues (especially with Olanzapine) and treatment induced side effects - Severe agitation or violence - Non-compliance - Depression or mood sx - Substance abuse - Prodromal or first episode - Catatonia or NMS Monotherapy of atypical - Aripiprazole - Olanzapine - Quetiapine - Risperidone - Ziprasidone - If not available, a trial of Haloperidol, Chlorpromazine If psychosis persists, trial of second atypical
27
Acute Psychosis Treatment
If no past successful treatment Less Urgent (regular oral) - Olanzapine - Risperidone - Quetiapine In the middle (rapid dissolving oral) - Olanzapine - Risperidone - Aripiprazole More urgent (IM) - Olanzapine - Ziprasidone - Haloperidol IM (or IV) alone w/ Lorazepam
28
Good response
- Prior response to a drug - Absence of EtOH or drug abuse - Acute onset/short duration of illness - Acute stressors or other precipitating factors - Later age of onset - Affective sx (depression and anxiety) - Family history of affective illness - Medication compliance - Negative sx don't response as well
29
Treatment of Extrapyramidal Sx
Acute Dystonia - Benzotropine mesylate (Cogentin) - Diphenhydramine (Benadryl) - Trihexyphenidyl (Artane) Akathisia - Clonazepam - Lorazepam - Pramipexole - Propranolol - Ropinirole Neuroleptic Malignant Syndrome - Dantrolene - Anticholinergics (Benztropine, Trihexyphenidyl) - Dopamine agonists (Amantadine, Bromocriptine, Ropinirole, Pramipexole) Parkinsonism - Amantadine - Anticholindergics (Benztropine, Trihexyphenidyl) - Pramipexole - Ropinirole Neuroleptic-induced catatonia - Anticholinergics (Benztropine, Trihexyphenidyl) - Bromocriptine - Dopamine agonist (Amantadine, Bromocriptine, Ropinirole, Pramipexole)
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d
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31
Lithium | - First line for manic episodes/maintenance treatment of bipolar disorder
- CONTRAINDICATION: renal or cardiovascular dz; severe debilitation, dehydration, or sodium depletion; pts receiving diuretics; risk of Li toxicity is very high in these pts - WARNING: pregnancy; Renal toxicity - NTI drug
32
Lithium toxicity
- Early sx: D/V, drowsiness, muscle weakness, lack of coordination - Higher levels: giddiness, ataxia, blurred vision, tinnitus and a large output of dilute urine
33
Lithium ADR
Neuro - tremor, muscle hyperirritability, ataxia, hyperactive DTR, blackout, seizures, slurred speech) CV - Cardiac arrhythmia, hypotension, peripheral circulatory collapse, sinus node dysfunction with severe bradycardia - BRUGADA SYNDROME: ST elevation (can lead to afib, fever, nightmares, syncope, risk of sudden death) GI - Anorexia, N/V/D GU - Albuminuria, oliguria, polyuria, glycosuria Derm - Drying and thinning of hair, alopecia, chronic folliculitis, xerosis cutis, and exacerbation of psoriasis Autonomic Nervous System - Blurred vision, dry mouth Thyroid abnormalities - Euthyroid goiter, hypothyroidism EEG changes - Diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm EKG changes - Reversible flattening, isoelectricity or inversion of T waves Miscellaneous - Fatigue, lethargy, dehydration, wt loss, tendency to sleep
34
Bipolar Mania
Over joyful or excited state
35
Treatment
Lithium Anticonvulsant - divalproex - lamotrigine - carbamazepine - topiramate - oxcarbazemine (only of CBZ intolerance) Atypical antipsychotic - olanzapine - risperidone - quetiapine - ziprasidone Electroconvulsive
36
Euphoric Mania/ hypomania
Monotherapy - Lithium OR Divalproex OR Olanzapine Two drug combination - (Lithium OR Anticonvulsant) + Anticonvulsant - (Lithium OR Anticonvulsant) + Atypical antipsychotic Triple combination - Lithium + Anticonvulsant (Divalproex, Carbamazepine) + Atypical antipsychotic (Olanzapine, Risperidone, Quetiapine, Ziprasidone) Electroconvulsive OR add clozapine
37
Dysphoric Mania/ hypomania
Monotherapy - Divalproex OR Olanzapine Two drug combination - (Lithium OR Anticonvulsant) + Anticonvulsant - (Lithium OR Anticonvulsant) + Atypical antipsychotic Triple combination - Lithium + Anticonvulsant (Divalproex, Carbamazepine) + Atypical antipsychotic (Olanzapine, Risperidone, Quetiapine, Ziprasidone) Electroconvulsive OR add clozapine
38
Psychotic Mania
Monotherapy - Lithium OR Divalproex OR Olanzapine Two drug combination - (Lithium + Anticonvulsant-- Divalproex, Carbamazepine) + Atypical antipsychotic-- Olanzapine, Risperidone, Quentiapine, Ziprasidone
39
Bipolar Treatment
Mania treatment | Mixed Episode treatment
40
Mania
- Lithium - Valproate - Carbamazepine - Aripiprazole - Olanzapine - Quetiapine - Risperidone - Ziprasidone Combination - (Lithium OR Valproate) + (Aripiprazole OR Olanzapine OR Quetiapine OR Risperidone) Maybe helpful - Clozapine - Oxcarbazepine
41
Mixed Episode
- Valproate - Carbamazepine - Aripiprazole - Olanzapine - Risperidone - Ziprasidone May be helpful - Clozapine - Lithium - Oxcarbazepine - Quetiapine

Pharm Exam 3 (5 decks)

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