Updated: 4/25/2019

Antipsychotics

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Snapshot
  • A 19-year-old male is brought into the ED by his parents.  The patient recently started college and was living in the dorms.  He struggled with school and friends and had some issues with his roommate so he moved back home.  His parents have noticed that he has become more reclusive and often stays in his room alone.  He no longer cares for himself, and has not showered in over a month.  The patient is often seen talking to himself, and when his parents ask him what he is doing he says, "It's classified information."
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
 
Typical Antipsychotics
  • Overview
    • AKA neuroleptics
    • two types
      • high potency
      • low potency
    • highly fat soluble → stored for long time in body fat
  • Drugs ("haloperidol + -azines")
    • high potency - low dose needed (more movement side-effects)
      • haloperidol
      • trifluoperazine
      • fluphenazine
    • low potency - high dose needed (more anti-cholinergic side-effects)
      • 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, and extraocular muscles
          • intermediate-onset symptoms (days to weeks)
            • Parkinsonism
              • muscle rigidity, bradykinesia, tremor, and shuffling gait
            • akathisia
              • urge to move
          • late onset/irreversible symptoms 
            • 4 months = tardive dyskinesia 
              • involuntary, repetitive movements of facial, tongue, and neck muscles
              • anticholinergics worsen!
              • must reduce dose or switch to an atypical antipsychotic
        • can be treated with diphenhydramine or benztropine 
      • ↓ non-specific side effects (SE)
    • low potency
      • ↓ EPS SEs
      • ↑ non-specific SEs  
        • 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 → corneal deposits
        • thioridazine → retinal deposits 
    • endocrine side effects
      • dopamine normally inhibits prolactin secretion
        • antagonism of receptor may result in hyperprolactinemia→ galactorrhea
    • neuroleptic malignant syndrome (NMS) 
 
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
  • Switch to atypicals
  • 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
 
Atypical Antipsychotics
  • 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
    • olanzapine
      • weight gain/metabolic syndrome
    • clozapine 
      • agranulocytosis
        • requires patients to have weekly WBC monitoring 
      • weight gain/metabolic syndrome
    • ziprasidone
      • prolonged QT and possible resultant torsades
    • risperidone
      • may result in hyperprolactinemia→ galactorrhea                                                   
      • 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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(M1.PY.41) A 58-year-old male presents to his primary care doctor with the complaint of vision changes over the last several months. The patient's past medical history is notable for schizophrenia which has been well-controlled for the last 25 years on chlorpromazine. Which of the following is likely to be seen on ophthalmoscopy? Review Topic

QID: 101705
1

Retinitis pigmentosa

16%

(30/191)

2

Macular degeneration

10%

(19/191)

3

Glaucoma

8%

(16/191)

4

Retinal hemorrhage

3%

(5/191)

5

Corneal deposits

62%

(118/191)

M1

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