SCHIZOPHRENIA

Definition: Schizophrenia is a chronic and major psychosis.
Main Characteristics:
- Delusions of thought
- Visual and/or auditory hallucinations
- Speech disturbances
- Distortion of reality
- Disorganized thought patterns
- Social withdrawal
- Hallucinations
- Poor judgment

Prevalence: Affects about 1% of the population worldwide; more rare than other mental health conditions.
Onset: Typically occurs from late teens, after puberty begins, to the mid-20s.
- Women may not develop symptoms until the mid-20s to early 30s.
- The onset of symptoms after age 45 is rare.
Heredity: Schizophrenia runs in families.
Environmental Factors: Linked to exposure to viruses, fetal malnutrition, and substance abuse.

Schizoaffective Disorder:
- Patient exhibits both mood disorders and symptoms of schizophrenia.
- Hard to diagnose, resembles bipolar or depression with psychoses; important for treatment.
Types of Schizophrenia:
- Example: Paranoid schizophrenia characterized by paranoia, extreme suspicion, and delusions of persecution.
- Difficult to treat.

Negative Symptoms: Associated with no visible signs of emotion and demonstrate monotonous speech.
- Lack of emotion or expression.
Positive Symptoms: May manifest as bizarre behaviors.
- Delusions: Irrational thoughts or false beliefs dominating the individual’s behavior.
- Hallucinations: Perceptions, such as visions and voices, that only the individual with schizophrenia can experience.
Cognitive Symptoms: Decrease the person's capacity to interpret information and make decisions.
Catatonia: Causes individuals to be unresponsive and immobile.

Neurotransmitter Imbalance: Schizophrenia is thought to be associated with excess dopamine levels.
Treatment Drugs:
- Drugs capable of blocking transmission of signals in the dopaminergic system are employed.
Other Neurotransmitters Involved:
- Serotonin
- Cholecystokinin
- Neurotensin
- $ ext{GABA}$ (gamma-aminobutyric acid)
- Glutamate

General Information:
- Antipsychotic drugs represent the major treatment for psychotic disorders.
- They work by blocking receptors for dopamine, acetylcholine, histamine, and norepinephrine.
- Cause a variety of adverse effects, often related to excessive extrapyramidal activity (affecting movement control).
- Also known as Neuroleptics.

By Structure and Function:
- Typical Antipsychotics:
- High-potency drugs strongly binding to dopamine receptors.
- Atypical Antipsychotics:
- Low-potency drugs with a weaker affinity for dopamine receptors, producing fewer side effects associated with blockade.
- Many atypical agents also act on serotonin receptors.

Generic Names & Examples:
- Phenothiazines:
- chlorpromazine
- fluphenazine
- methotrimeprazine
- perphenazine
- thioridazine
- Butyrophenones:
- haloperidol
- Thioxanthenes:
- zuclopenthixol

Generic Names & Examples:
- Atypical Neuroleptics:
- aripiprazole
- loxapine
- lurasidone
- olanzapine
- paliperidone
- quetiapine
- risperidone
- ziprasidone
- Clozapine:
- Prototypes include clozapine and risperidone, strong affinity for serotonin receptors and dopaminergic receptor blockade.
- Requires patients, prescribers, and pharmacists to be enrolled in a registry for dispensing; necessitates regular lab monitoring.
- Quetiapine Usage:
- Used in managing both schizophrenia and bipolar disorder.

Characteristics:
- Good absorption.
- Metabolized by liver.
- Some antipsychotics are available in slow-release formulations (administered through every 4-12 week injections).

Prevalence: Up to 80% of individuals taking antipsychotic drugs may experience adverse reactions.
Types of Adverse Effects:
- Extrapyramidal effects
- Neuroleptic malignant syndrome
- Anti-cholinergic (anti-muscarinic) effects: blurred vision, dry mouth, urinary retention
- Alpha-adrenergic blockade: orthostatic (postural) hypotension, lightheadedness
- Weight gain and increased appetite
- Decreased ability to regulate body temperature
- Photosensitizers
- Increased release of certain endocrine hormones, e.g., prolactin leading to pseudo-pregnancy

Observed Adverse Effects:
- Extrapyramidal effects
- Neuroleptic malignant syndrome
- Anti-adrenergic issues causing dizziness, drowsiness, confusion
- Diabetes concerns
- Hypotension
- Nausea and weight gain
- Urinary issues: increased urination, urinary retention
- Dry mouth and thirst
- Sexual dysfunction
- Increased mortality risk in elderly patients with dementia-related psychosis

General Information: Extrapyramidal effects occur more frequently in the elderly leading to Parkinsonian effects.
- Symptoms:
- Excessive muscle movement (treatable with benztropine)
- Akathisia: Characterized by motor restlessness
- Tardive dyskinesia: Involuntary movements affecting limbs, trunk, and neck – no effective prevention/treatment available, sometimes managed by a drug holiday.

Overview: Rare but life-threatening side effect.
- Symptoms include muscle rigidity, elevated body temperature, confusion, and renal failure.
Treatment Strategies:
- Cooling the body.
- Discontinuation of neuroleptic medication.
- Medications to increase dopamine (such as amantadine and bromocriptine).
- Dantrolene for muscle relaxation.

Selection Process: Based on a balance between achieving the desired response from the drug and the patient’s ability to tolerate the drug's side effects.

Mechanism of Action: Blocks dopamine and serotonin type 2 receptors.
Effects:
- Improves both positive and negative symptoms, often with better results compared to older drugs.
- Reserved for treatment-resistant schizophrenia.
Adverse Effects:
- Sedation and weight gain.
- Lower incidence of extrapyramidal adverse effects.
- Risk of agranulocytosis (dangerously low white blood cell count).

Distribution Rules:
- CLOZARIL (clozapine) is available only through a distribution system requiring weekly or biweekly hematological testing prior to the next supply of medication delivery due to the risk of agranulocytosis or granulocytopenia.