Schizophrenia: Clinical Features and Pathogenesis
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Questions and Answers

What neurochemical imbalance is primarily associated with the pathogenesis of schizophrenia?

  • Decreased GABA activity
  • Increased levels of serotonin
  • Overactivity of dopamine (correct)
  • Underproduction of norepinephrine

    • Which of the following symptoms is classified as a positive symptom of schizophrenia?

  • Withdrawal from social contacts
  • Flattening of emotional responses
  • Hallucinations (correct)
  • Anhedonia

    • What characterizes first generation antipsychotics?

  • They target serotonin receptors more than dopamine receptors.
  • They are known as atypical antipsychotics.
  • They were discovered in the 1950s. (correct)
  • They were developed in the 1970s.

    • Which antipsychotic drug was clinically introduced in the 1970s?

    <p>Clozapine</p> Signup and view all the answers

    What is a common misconception about schizophrenia?

    <p>It is solely caused by environmental factors.</p> Signup and view all the answers

    Which symptom is a hallmark of a negative symptom in schizophrenia?

    <p>Cognitive impairment</p> Signup and view all the answers

    What do the terms 'neuroleptic drugs' and 'antipsychotic drugs' refer to?

    <p>Drugs that alleviate symptoms of psychosis.</p> Signup and view all the answers

    What is one of the most pronounced clinical features of schizophrenia?

    <p>Disorganized behavior</p> Signup and view all the answers

    Which generation of antipsychotic drugs is characterized by a higher incidence of extrapyramidal side effects?

    <p>First generation antipsychotics</p> Signup and view all the answers

    What distinguishes atypical antipsychotics from typical antipsychotics in terms of receptor affinity?

    <p>Higher binding to serotonin receptors</p> Signup and view all the answers

    Which of the following conditions is treated with antipsychotic drugs?

    <p>Bipolar disorder</p> Signup and view all the answers

    Why are neuroleptic drugs not considered curative for schizophrenia?

    <p>They do not eliminate thought disorders</p> Signup and view all the answers

    Which of the following is a typical antipsychotic drug?

    <p>Haloperidol</p> Signup and view all the answers

    What is the primary action of atypical antipsychotics on schizophrenia symptoms?

    <p>Efficacy against negative symptoms</p> Signup and view all the answers

    Which step in dopamine synthesis is considered the rate-limiting step?

    <p>Conversion of tyrosine to dopa</p> Signup and view all the answers

    What is the role of dopamine hydroxylase in dopaminergic neurons?

    <p>To convert dopamine into noradrenaline</p> Signup and view all the answers

    Which of the following extrapyramidal side effects is characterized by sustained muscle contractions?

    <p>Dystonia</p> Signup and view all the answers

    What is a common endocrine effect associated with dopamine receptor blockade in patients taking antipsychotics?

    <p>Gynecomastia</p> Signup and view all the answers

    Which drug class is most often associated with tardive dyskinesia after prolonged treatment?

    <p>Typical neuroleptics</p> Signup and view all the answers

    What is the primary mechanism behind the development of tardive dyskinesia in patients?

    <p>Increased dopamine receptor synthesis</p> Signup and view all the answers

    What is one of the adverse effects associated with the blockade of D2 receptors by typical antipsychotics in males?

    <p>Gynecomastia</p> Signup and view all the answers

    Which symptom is NOT typically associated with neuroleptic malignant syndrome?

    <p>Weight gain</p> Signup and view all the answers

    Which atypical antipsychotic is effective in some patients with schizophrenia who are resistant to other antipsychotic treatments?

    <p>Clozapine</p> Signup and view all the answers

    Which atypical antipsychotic is most commonly associated with significant weight gain?

    <p>Clozapine</p> Signup and view all the answers

    What potential effect might the blockade of cholinergic receptors have in patients taking antipsychotic medications?

    <p>Urinary retention</p> Signup and view all the answers

    Which of the following is NOT a clinical use for antipsychotic drugs mentioned?

    <p>Relief of acute allergic reactions</p> Signup and view all the answers

    Which condition is characterized as a reversible early phase extrapyramidal effect?

    <p>Akathisia</p> Signup and view all the answers

    What should be monitored in patients taking atypical antipsychotics due to potential metabolic issues?

    <p>Glucose and lipid profiles</p> Signup and view all the answers

    What is one adverse effect associated with the blockade of H1-histamine receptors by antipsychotics?

    <p>Sedation</p> Signup and view all the answers

    Which class of antipsychotic drugs is less likely to produce elevations in prolactin levels?

    <p>Atypical antipsychotics</p> Signup and view all the answers

    What is one primary reason atypical antipsychotics are preferred in the management of negative symptoms of schizophrenia?

    <p>They improve emotional blunting and social withdrawal</p> Signup and view all the answers

    What is a significant side effect in patients due to the blockade of α-adrenergic receptors from antipsychotic medications?

    <p>Orthostatic hypotension</p> Signup and view all the answers

    What is a common side effect associated with the use of chlorpromazine?

    <p>Failure to ejaculate in men</p> Signup and view all the answers

    Which treatment is recommended for acute agitation due to withdrawal from substances?

    <p>Administering a simple sedative, like a benzodiazepine</p> Signup and view all the answers

    What serious risk is associated with the use of clozapine?

    <p>Agranulocytosis requiring monitoring</p> Signup and view all the answers

    Which atypical antipsychotic was noted for potentially prolonging the QT interval on an ECG?

    <p>Quetiapine</p> Signup and view all the answers

    What primary treatment should be avoided in elderly patients with dementia-related psychosis?

    <p>Atypical antipsychotics</p> Signup and view all the answers

    Which substance is particularly contraindicated for patients with seizure disorders?

    <p>Chlorpromazine</p> Signup and view all the answers

    Which autonomic effect is most pronounced with the use of thioridazine?

    <p>Urinary retention</p> Signup and view all the answers

    Which adverse effect is commonly associated with high doses of thioridazine?

    <p>Fatal ventricular arrhythmias</p> Signup and view all the answers

    Study Notes

    Schizophrenia

    • Schizophrenia is a type of psychosis affecting young people, chronic and often disabling
    • Etiology: hereditary and evidence suggests a fundamental biological disorder
    • Dopamine and serotonin are the main neurotransmitters involved in the pathogenesis
    • Psychosis may be due to dopamine overactivity in the mesolimbic and mesocortical pathway of the brain

    Clinical features of Schizophrenia

    • Positive symptoms (abnormality or exaggeration of normal functions):
      • Delusions (paranoid)
      • Hallucinations (often auditory voices)
      • Thought disorder (wild trains of thought)
      • Abnormal disorganized behavior (stereotyped movements, disorientation, aggression)
      • Catatonia (immobility or purposeless motor activity)
    • Negative symptoms (loss or decrease in function):
      • Withdrawal from social contacts
      • Flattening of emotional responses
      • Anhedonia (inability to experience pleasure)
      • Cognitive impairment
      • Reluctance to perform everyday tasks

    History of Antipsychotics

    • Antipsychotic drugs are commonly used for over 50 years
    • Chlorpromazine and risperidone were the first drugs found useful in schizophrenia
    • First-generation antipsychotics (typical antipsychotics), were discovered in the 1950s
    • Second-generation antipsychotics (atypical antipsychotics), clozapine, were discovered in 1960s, clinically introduced in 1970s

    Antipsychotic Drugs

    • Also called neuroleptic drugs or major tranquilizers
    • Reduce psychotic symptoms in various conditions: schizophrenia, bipolar disorder, psychotic depression, senile psychoses, drug-induced psychoses (levodopa, CNS stimulants, apomorphine)
    • Not curative, do not eliminate fundamental thought disorder, but may decrease symptom intensity
    • Classification:
      • Typical antipsychotics (1st generation)
      • Atypical antipsychotics (2nd generation)

    Typical vs Atypical Antipsychotics

    • Receptor profile:
      • Typical: high binding to dopamine receptors
      • Atypical: high affinity for serotonin, dopamine, and other receptors
    • Incidence of extrapyramidal side effects:
      • Less in atypical antipsychotics compared to typical antipsychotics
    • Efficacy:
      • Typical: efficacy against positive symptoms
      • Atypical: efficacy against negative symptoms of schizophrenia

    Dopamine

    • Synthesized from tyrosine to dopa (rate-limiting step), followed by decarboxylation to form dopamine
    • Dopaminergic neurons lack dopamine hydroxylase, thus do not convert dopamine to noradrenaline

    Hyperprolactinemia

    • Typical antipsychotics block D2 receptors in the pituitary, leading to increased prolactin release
    • Males: gynecomastia
    • Females: menstrual disturbances
    • Atypical neuroleptics are less likely to cause prolactin elevations

    Blockade of Cholinergic Receptors

    • Blurred vision, dry mouth, confusion, inhibition of gastrointestinal and urinary tract smooth muscle: constipation and urinary retention
    • This anticholinergic property may reduce the risk of extrapyramidal symptoms

    Blockade of α-Adrenergic Receptors

    • Orthostatic hypotension and light-headedness

    Blockade of H1-Histamine Receptor

    • Sedation

    Other Effects of Antipsychotics

    • Sexual dysfunction
    • Weight gain
    • Temperature regulation problems

    Clinical Uses of Antipsychotics

    • Treatment of Schizophrenia:
      • Typical antipsychotics reduce positive symptoms: hyperactivity, hallucinations, delusions
      • Atypical drugs improve negative symptoms: emotional blunting, social withdrawal, lack of motivation
      • Clozapine effective in patients resistant to other antipsychotics
      • Beneficial effects may take weeks to develop
    • Mania (bipolar disorder):
      • Initial Treatment: atypical antipsychotics are used with lithium
      • Maintenance: olanzapine, aripiprazole and quetiapine
      • Adjunct to antidepressants: aripiprazole and quetiapine
    • Tranquilizer for agitated and disruptive behavior
    • Pimozide for treating psychotic symptoms of Tourette's disorder (motor and phonic tics)
    • Antipsychotics for managing toxic psychoses caused by CNS stimulant overdose
    • Risperidone for disruptive behavior and irritability in autism
    • Prevention of severe drug nausea and vomiting: procholperazine
    • Treatment of chronic pain with severe anxiety (adjuvant with opioids)
    • Hiccups: chlorpromazine
    • Antipruritis & sedation: promethazine

    Side Effects of Antipsychotics

    • Extrapyramidal Side Effects (Blocking of dopamine receptors in the nigrostriatal pathway or overactivity of acetylcholine due to blockade of dopamine receptors)
      • Dose-dependent
      • More frequent with typical neuroleptics (haloperidol, fluphenazine) compared to atypical neuroleptics
      • Early Phase (reversible):
        • Dystonia (sustained muscle contraction, twisting postures)
        • Akathisia (motor restlessness)
        • Parkinson-like syndrome (bradykinesia, rigidity, tremor)
        • Can be reversed by muscarinic blocking agents
      • Late Phase (irreversible):
        • Tardive dyskinesia (involuntary Tongue, lips, neck, trunk, limbs movements) occurs after months or years of treatment
        • Results from increased dopamine receptors (compensatory response to long-term dopamine receptor blockade) making neurons supersensitive to dopamine
        • May be temporarily attenuated by increasing neuroleptic dosage
        • Anticholinergic drugs increase tardive dyskinesia
    • Endocrine Effects (due to blockade of D2 receptors in the pituitary)
      • Hyperprolactinemia
        • Males: gynecomastia, infertility
        • Females: menstrual disturbances (amenorrhea-galactorrhea)
      • Prominent with typical neuroleptics and risperidone
      • Weight gain with atypical agents, especially clozapine and olanzapine
      • Glucose and lipid profiles should be monitored due to the potential for atypical agents to increase these parameters and exacerbate diabetes or hyperlipidemia
    • Neuroleptic Malignant Syndrome
      • Sensitive patients may develop malignant hyperthermia syndrome
      • Symptoms: muscle rigidity, impaired sweating, hyperpyrexia, autonomic instability (life threatening)
      • Treatment:
        • Discontinue neuroleptics
        • Dantrolene
        • Diazepam
        • Bromocriptine

    Autonomic Effects

    • Muscarinic Receptor Blockade:
      • Dry mouth, constipation, urinary retention, visual problems
      • Pronounced with thioridazine, chlorpromazine, clozapine
    • α-Receptor Blockade:
      • Postural hypotension caused by older drugs (chlorpromazine, clozapine, ziprasidone)
      • Considerations for elderly patients
      • Failure to ejaculate in men treated with chlorpromazine
    • H1 Receptor Blockade:
      • Sedation more marked with chlorpromazine than other antipsychotics

    Miscellaneous Toxicities

    • Visual impairment from retinal deposits with thioridazine
    • Thioridazine may cause severe cardiac conduction defects at high doses, leading to fatal ventricular arrhythmias
    • Quetiapine and ziprasidone prolong the QT interval, potentially leading to cardiac arrhythmias (torsades)
    • Clozapine: reserved for severely schizophrenic patients resistant to traditional therapy
      • Low but significant incidence of bone marrow suppression (1-2%)
      • Potential for seizures and cardiovascular side effects at high doses
      • Risk of agranulocytosis requires frequent white-blood-cell count monitoring

    Cautions and Contraindications

    • Acute agitation from alcohol or drug withdrawal may be aggravated by neuroleptics
    • Benzodiazepines are preferred treatment for stabilization
    • Chlorpromazine and clozapine contraindicated in patients with seizure disorders because they may aggravate epilepsy
    • High incidence of agranulocytosis limits clozapine use to resistant patients
    • Atypical antipsychotics have increased risk for mortality in elderly patients with dementia-related behavioral disturbances and psychosis

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    Description

    This quiz explores schizophrenia, a chronic psychotic disorder primarily affecting young individuals. It covers its etiology, including biological factors and neurotransmitter involvement, as well as distinguishing between positive and negative symptoms characteristic of the condition.

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