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Queen's University
Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Drugs used in the treatment of mental illness – I (Antipsychotics) Outline Introduction History Schizophrenia Theories of Schizophrenia Typical andAtypicalAntipsychotics Pharmacokinetics Pharmacological Effects Other Clinical Indications Review: Chapter4 Introduction • historically not many available treatments for “mind diseases” • modern psychiatry was revolutionized by the advent of medications to treat psychotic disorders ◦ drugs that have both antipsychotic and neuroleptic (tranquilizing) properties History • accidental discovery in 1950 to relieve anxiety and reduce the death rate associated with surgical shock (decrease blood pressure, heart rate, could be quite fatal) • hypothesized: surgical shock involved neurotransmitters (ACh, etc.) ◦ first developed antihistamines (mild sedating properties) ◦ patients became sleepy and lost interest but did not lose consciousness (neuroleptic state) ◦ introduced the drug to psychiatrists who used it to treat schizophrenia • first generation antipsychotics blocked D (2opamine) receptors, which improved positive symptoms, but caused extrapyramidal symptoms • search continued for more effective drugs with fewer side effects Schizophrenia • derived from Greek ◦ “schizein” = to split and “phren” = mind • debilitating neuropsychiatric illness • typical onset during the time young people are maturing into adulthood • premorbid Phase: subtle motor, cognitive and social impairments • prodromal Phase (early, non-specific symptoms): mood, cognitive symptoms, social withdrawal, OCD • full syndrome: substantial functional deterioration in self-care, work and interpersonal relationships Symptoms Positive Symptoms (typical of psychoses) • hallucination and delusions • irrational beliefs (that can be quite complex and organized) • grandeur and paranoia • unconnected thoughts (though unaware) Negative Symptoms (blunting of emotional expression) • affective flattening (immobile and unresponsive face) • diminished range of emotional expressiveness • alogia: speech that is brief and uncommunicative • avolition: inability to initiate or engage in goal-directed activities • anhedonia: inability to experience pleasure • social withdrawal Symptoms • classical drugs treat positive symptoms, but not the negative symptoms (in mood) • significant clinical limitation • newer drugs designed to improve cognitive systems – memory, attention, executive function • enable patients to reintegrate into society Dopamine Theory • dysregulation of dopaminergic brain pathways leading to excessive dopamine activity in brain • theory developed due to two main observations: 1. Drugs that increase dopamine function (ie. cocaine, amphetamines) can cause a state similar to schizophrenia 2. The antipsychotics drugs block dopamine receptor (antagonists) Dopamine Theory • not all antipsychotics have affinity for all receptor subtypes (increase specificity) • side effects: extrapyramidal symptoms ◦ predominantly the first generation antipsychotics ◦ due to antagonism in the basal ganglia (symptoms similar to Parkinson’s disease) ▪ play a large role in motor movement (rigidity, tremors, inability to initiate movement) • Newer drugs (second- generation) have fewer extrapyramidal symptoms Serotonin (5-HT) Theory • based on the effects of
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