Updated: 4/1/2019

Antipsychotics

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  • A 23-year-old male is brought into the inpatient psychiatric hospital after a suicide attempt.  When talking with the patient he seemed to be responding to internal stimuli at times.  He states that he heard voices telling him to kill himself.  He said he has heard these voices for over a year now but within the past month they have become louder, more persistent and convincing.
Overview
  • 2 classes
    • typical
      • older
      • stronger D2 receptor antagonism 
        • ↑ [cAMP]
    • atypical
      • newer
      • weaker D2 receptor antagonism and stronger 5-HT2, α, and H1 antagonism 
  • Targets
    • dopaminergic neurons
      • specific pathways affected include:
        • nigrostriatal (extrapyramidal motor)
        • mesolimbic (mood and reward)
        • tuberoinfundibular (prolactin release) 
Typical Antipsychotics Overview

Typical Antipsychotics
High Potency Antipsychotics (in Descending Order)
Advantages Disadvantages Unique Features
Haloperidol  • Fewer side effects of sedation and hypotension
 • High association with extrapyramidal symptoms
 • Able to use as long-acting depot injections

 • Can be given IM in acute situations
Fluphenazine
Perphenazine
Chlorpromazine  • Lower frequency of extrapyramidal side effects
 • Greater incidence of anticholinergic side-effects, hypotension, sedation
 • Corneal deposits
Thioridazine  • Retinal deposits
QT prolongation
 
Introduction
  • Overview
    • also known as neuroleptics
    • highly fat soluble results in storage for long time in body fat
  • Drugs ("haloperidol + -azines")
    • high potency - low dose needed
      • haloperidol
      • trifluoperazine
      • fluphenazine 
    • low potency - high dose needed
      • thioridazine
      • chlorpromazine
  • Clinical use
    • schizophrenia
      • primarily positive symptoms
    • psychosis
    • acute mania
      • temporary treatment because lithium has slow onset
    • Tourette's syndrome
  • Toxicity
    • high potency
      • ↑ extrapyramidal system (EPS) side effects
        • due to high affinity for D2 receptor
        • has characteristic time course
          • early onset/reversible symptoms
            • 4 hours = acute dystonia
              • spasm of face, neck, tongue, extraocular muscles
              • treat with benztropine or diphenhydramine 
            • 4 days = Parkinsonism
              • muscle rigidity, ankinesia, tremor, shuffling gait
            • 4 days to 4 weeks = akathisia 
              • urge to move
          • late onset/irreversible symptoms
            • 4 months = tardive dyskinesia 
              • involuntary, repetitive movements of facial, tongue, neck muscles
              • anticholinergics worsen!
              • must reduce dose or switch to an atypical antipsychotic
              • can be treated with valbenazine
                • a vesicular monoamine transporter 2 inhibitor
      • ↓ non-specific side effects
      • fluphenazine has been implicated in causing hypothermia in select cases 
    • low potency
      • ↓ EPS side effects
      • ↑ non-specific side effects
        • due to low affinity to D2 receptors and high concentrations needed to achieve effect
        • muscarinic receptor antagonism
          • dry mouth and constipation
          • vision problems
        • α receptor antagonism
          • orthostatic hypotension
          • sexual dysfunction
        • histamine receptor antagonism
          • sedation
        • chlorpromazine can cause corneal deposits
        • thioridazine can cause retinal deposits
    • endocrine side effects
      • dopamine normally inhibits prolactin secretion
        • antagonism of receptor may result in hyperprolactinemia can cause galactorrhea 
    • neuroleptic malignant syndrome (NMS)   
      • presentation
        • high fever, hypertension, tachycardia, “lead pipe” rigidity, elevated CPK, leukocytosis, metabolic acidosis
      • treatment 
        • discontinue offending agent
        • use of muscle relaxant (e.g., dantrolene)
 Side Effects of High Potency Antipsychotics
 
Extrapyramidal Side Effects of High Potency D2 Blockers (Haloperidol, Fluphenazine, Perphenazine)
3 Hours: Acute Dystonia
3 Days - Weeks: Bradykinesia (Pseudo-Parkinsonism)
3 Months: Akathisia
3 Years: Tardive Dyskinesia
Emergency: Neuroleptic Malignant Syndrome
 • Muscle spams (neck, eye, diffuse)
 • Trouble swallowing
 • Symptoms of Parkinson's disease: tremors, bradykinesia, rigidity
 • Sustained feeling of motion/restlessness
 • Uncontrollable repetitive, stereotypical writhing movements, usually of the tongue
 • High fever
 • Muscle rigidity
 • Unstable vitals
 • Increased CK, K+, and WBC's
Treatment of Side Effects
 • Anticholinergic medications:(benztropine, diphenhydramine, trihexyphenidyl)
 • β-blockers
 • Benzodiazepines

 • Stop high potency D2 blockers and swith to atypicals
 • Can be treated with valbenazine

 • Stop antipsychotic
 • IV fluids
 • Cooling
 • Dantrolene 
NOTE: You can always decrease the dose or switch to a different antipsychotic – choose the drug with the side-effect profile that the patient can tolerate.
 
Atypical Antipsychotics Overview
 
Atypical Antipsychotics
Medication Unique features and side effects
Risperidone  • High potency
 • Usually first line
 • Hyperprolactinemia
 • Weight gain

Olanzapine

 • Severe weight gain
 • Very sedating
Ziprasidone  • Minimal to no weight gain
 • Increased QTc
Quetiapine  • Low potency
 • Sedating
 • Weight gain
 • Useful in bipolar depression and augmentation of major depression therapy
Lurasidone  • Minimal weight gain
 • Useful in biploar depression
Clozapine 

 • Weight gain
 • Most effective anti-psychotic
 • Decreased suicide risk
 • Agranulocytosis
 • Myocarditis
 • Sialorrhea
 • Orthostatic hypotension
 • Increased seizures

Aripiprazole  • D2 partial agonist
 • Augmentation of major depression therapy
 
Introduction
  • Drugs
    • olanzapine
    • clozapine
    • quetiapine
    • risperidone
    • aripiprazole
    • ziprasidone
  • Mechanism
    • antagonist at 5-HT2, α, H1, and dopamine receptors
  • Clinical use
    • schizophrenia
      • both positive and negative symptoms
    • olanzapine
      • OCD
      • anxiety disorder
      • depression
      • mania
      • Tourette's syndrome
  • Toxicity 
    • less EPS and anticholinergic side effects as compared to traditional antipsychotics
    • olanzipine
      • weight gain 
        • monitor weight, blood lipids, blood glucose, and HbA1C 
    • clozapine
      • agranulocytosis 
        • requires patients to have weekly WBC monitoring 
        • treat with drug cessation, neutropenic protocol, possibily filgrastim
      • weight gain
    • ziprasidone
      • prolonged QT and possible resultant torsades
    • risperidone
      • EPS
 

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Questions (10)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.PY.4817) A 27-year-old male arrives to your walk-in clinic complaining of neck pain. He reports that the discomfort began two hours ago, and now he feels like he can’t move his neck. He also thinks he is having hot flashes, but he denies dyspnea or trouble swallowing. The patient’s temperature is 99°F (37.2°C), blood pressure is 124/76 mmHg, pulse is 112/min, and respirations are 14/min with an oxygen saturation of 99% O2 on room air. You perform a physical exam of the patient's neck, and you note that his neck is rigid and flexed to the left. You are unable to passively flex or rotate the patient's neck to the right. There is no airway compromise. The patient's past medical history is significant for asthma, and he was also recently diagnosed with schizophrenia. The patient denies current auditory or visual hallucinations. He appears anxious, but his speech is organized and appropriate. Which of the following is the best initial step in management? Review Topic

QID: 109375
1

Change medication to clozapine

12%

(2/16)

2

Dantrolene

0%

(0/16)

3

Diphenhydramine

88%

(14/16)

4

Lorazepam

0%

(0/16)

5

Propranolol

0%

(0/16)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.PY.4867) A 24-year-old woman presents to her primary care physician for bilateral nipple discharge. She states that this started recently and seems to be worsening. She denies any other current symptoms. The patient states that she is not currently sexually active, and her last menstrual period was over a month ago. Her medical history is notable for atopic dermatitis and a recent hospitalization for an episode of psychosis. Her temperature is 99.5°F (37.5°C), blood pressure is 110/65 mmHg, pulse is 70/min, respirations are 15/min, and oxygen saturation is 98% on room air. Cardiopulmonary and abdominal exam are within normal limits. Which of the following is the most likely cause of this patient's symptoms? Review Topic

QID: 109605
1

Alteration of the tuberoinfundibular pathway

0%

(0/0)

2

Alteration of the nigrostriatal pathway

0%

(0/0)

3

Alteration of the mesolimbic pathway

0%

(0/0)

4

Prolactin-secreting mass

0%

(0/0)

5

Normal pregnancy

0%

(0/0)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M2.PY.4681) A 23-year-old male is brought by police officers from a social gathering due combative behavior and altered mental status. The police say that phencyclidine was found on the premises. The patient is alone, and acquiring an accurate history proves difficult. However, you do learn that the patient is having visual hallucinations. Vital signs show a blood pressure of 155/95 mmHg, pulse is 103/min, respirations is 20/min, oxygen saturation of 99%. Airway, breathing, and circulation are intact. The patient appears violent, and is trying to remove his clothes. Multiple hospital staff are needed to restrain the patient in bed. A finger-stick glucose show 93 mg/dL. The team is unable to place an IV, and thus intramuscular midazolam is administered to achieve sedation; however, he is still agitated. What is the mechanism of action of the best alternative sedative drug for this patient? Review Topic

QID: 107295
1

Increases duration of chloride channel opening of GABA-A receptors

0%

(0/0)

2

Alpha-2 and H1 receptor antagonist

0%

(0/0)

3

Competitive opioid receptor antagonist

0%

(0/0)

4

Antagonist of D2 receptors

0%

(0/0)

5

Mu-opioid receptor partial agonist

0%

(0/0)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4

(M2.PY.49) A 35-year-old woman is diagnosed with schizophrenia after nine months of experiencing auditory hallucinations and persecutory delusions. Over the next year, she fails to experience symptom relief from separate and appropriately dosed trials of olanzapine, quetiapine, and risperidone. At this point, which of the following treatment options is most likely to be effective? Review Topic

QID: 105049
1

Aripiprazole

0%

(0/17)

2

Haloperidol

6%

(1/17)

3

Clozapine

88%

(15/17)

4

Clonidine

0%

(0/17)

5

Cognitive behavioral therapy

0%

(0/17)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.PY.4681) A 35-year-old male patient is brought into the emergency department by emergency medical services. The patient has a history of schizophrenia and is on medication per his mother. His mother also states that the dose of his medication was recently increased, though she is not sure of the specific medication he takes. His vitals are HR 110, BP 170/100, T 102.5, RR 22. On exam, he cannot respond to questions and has rigidity. His head is turned to the right and remains in that position during the exam. Labs are significant for a WBC count of 14,000 cells/mcL, with a creatine kinase (CK) level of 3,000 mcg/L. What is the best treatment for this patient? Review Topic

QID: 107296
1

Diazepam

0%

(0/0)

2

Morphine

0%

(0/0)

3

Dantrolene

0%

(0/0)

4

Valproate

0%

(0/0)

5

Lamotrigine

0%

(0/0)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3
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