Schizophrenia

• Psychosis is a symptom of several mental health disorders that causes people to perceive or interpret things differently from those around them, losing touch with the reality.
• Hallucinations are perceptions disconnected from external stimuli.
• Illusions are severely distorted perceptions or misinterpretations of stimuli.
• Delusions are fixed and false beliefs maintained despite being contradicted by reality or rational argument.
• Ideas of reference are beliefs that ordinary objects, such as license plates, contain specific messages for the person.
• Thought insertion or deletion are beliefs that some outside agency has removed or added thoughts to their brain.
• Schizophrenia is the best known psychotic disorder.
• Psychotic symptoms can occur in mood disorders (e.g., mania and severe depression), with drugs of abuse or alcohol, brain tumors and stroke.
• Schizophrenia is a severe psychotic disorder affecting thinking, feeling, and cognitive function.
• Schizophrenia usually starts between the ages of 15 to 35 and affects about 1% people during their lifetime.
• One in ten people with schizophrenia has a parent with the condition.
• Damage to the brain during pregnancy or birth, viral damage to fetal brain, and stress can lead to schizophrenia.
• Generic names of conventional antipsychotic drugs include chlorpromazine (Thorazine), trifluoperazine (Stelazine), perphenazine (Trilafon), fluphenazine (Prolixin), thioridazine (Mellaril), haloperidol (Haldol), thiothixene (Navane), mesoridazine (Serentil), loxapine (Loxitane), molidone (Moban), pimozide (Orap).
• The search for clozapine analogues in the 1970s and 1990s led to the development of Atypicals (SGAs), which include D2/5-HT2A antagonists.
• Aripiprazole, a glutamate-related agent, is present.
• Clozapine was reintroduced after a 1988 trial showed it was effective in treatment resistance.
• First generation (typical) antipsychotic drugs include D2 antagonists, 5-HT2A/D2 antagonists, and D2 partial agonists.
• Schizophrenia is most prevalent among the urban poor and those who use recreational drugs such as ecstasy, LSD, amphetamines (speed), cannabis and crack.
• Cannabidiol, an antipsychotic drug, is a D2 antagonist.
• Clozapine was introduced in Europe in 1971 but was abandoned due to agranulocytosis.
• The potency of first generation antipsychotic drugs in treating positive symptoms is strongly correlated with their affinity for D2-like dopamine receptors.
• Conventional antipsychotic drugs are rapidly absorbed from the gut but undergo extensive first-pass metabolism, with elimination by metabolism in the liver.
• Pimavanserin, a selective 5-HT2A antagonist, is in Phase III for PD psychosis and more.
• Mechanism of action of antipsychotic drugs is the blockade of CNS dopamine receptors in mesolimbic pathways, with high affinity for the family of D2 receptor.
• Positive (psychotic) symptoms of schizophrenia include delusions, hallucinations, disorganised speech, and erratic or catatonic behaviour.
• D2 antagonists are very effective antinauseants in the Area Postrema.
• Chronic extrapyramidal symptoms include tardive dyskinesia, which is not anticholinergic responsive, and tardive dystonia, which is anticholinergic responsive.
• The mechanisms of tardive dyskinesia include DA receptor up-regulation by antipsychotics, which may be masked during treatment, and possibly neurotoxic effects, which can be permanent.
• Dopamine released from this pathway inhibits the release of prolactin from lactotrophs of the Anterior Pituitary.
• Negative symptoms of schizophrenia include reduced expression of emotions, emotional responses out of context, poverty of speech (alogia), and social withdrawal.
• The Area Postrema, which is located outside the blood-brain barrier, detects foreign substances in the bloodstream and initiates Nausea and Vomiting.
• Acute extrapyramidal symptoms include pseudoparkinsonism, dystonia, and akathisia.
• The pathway regulates the "extrapyramidal system" which contributes to the control of movement.
• DA receptors are present in the Area Postrema, but there is no identified DA pathway.
• Tardive dyskinesia develops after months or years (hence 'tardive') in 20 - 40% of patients treated with first generation (i.e. conventional) antipsychotic drugs.
• Tardive dyskinesia is characterized by generalised chorea, involuntary movements of face, tongue and limbs, and risk factors such as female, age, treatment duration, and rapid antipsychotic discontinuation.
• DA agonists, L-DOPA etc., cause nausea in the Area Postrema.
• Second-generation antipsychotic drugs, also known as "atypical" antipsychotics, partly mitigate these side effects due to weaker antagonism of D2 receptors and by possessing other receptor binding properties (5-HT2A Rs).
• Tardive dyskinesia may be seen on withdrawal and may become permanent.
• New second generation (atypical) antipsychotics are rapidly absorbed from the gut but undergo extensive first-pass metabolism to inactive metabolites.