Drugs for Schizophrenia Flashcards
Who is affected by schizophrenia
- almost 1% of the population
- more men than women
“prodromal period” of schizophrenia
of 2-5 years before diagnosis (subclinical behavioral changes noted by friends and family)
Causes of schizophrenia
- 80% genetic risk
- Urbanicity is a risk factor
- prenatal development and early childhood
- early cannabis use
Positive/ Psychotic Symptoms
presentation of behaviours that are not normally seen in healthy people
(Hallucinations, delusions and illogical disturbances in the flow, order, and content of though)
Negative symptoms
lack of behaviours that are normally present in healthy people
(avolition- decreased motivation, anhedonia- decreased ability to experience pleasure or identify activities as being pleasurable, flattened affect- lack of emotion/ expression, poverty of speech- small vocab, social withdrawal)
Neurological changes caused by Schizophrenia
- enlarged lateral ventricles
- reductions in white matter tracts
- reduced grey matter
- reduced synapses (not cell #)
Environmental Risk Factors of schizophrenia
- Maternal starvation or infection in 2nd
trimester - Infection with plasmodium gondii (cat feces)
- Obstetric complications
- Physical or psychological abuse/trauma in childhood
- Low socioeconomic status
- Urbanicity
- Drug exposure (amphetamine, cannabis, phencyclidine)
Who discovered the first antipsychotics?
Henri Laborit (French surgeon)
Why did Laborit and Rhone-Poulenc develop the antipsychotic?
- was trying to develop new anesthetics that would be a combination of sedative, narcotic and hypnotic
- lowered body temperature with “reduced antihistamine and enhanced sedative properties”
The first antipsychotic/ the “chemical lobotomy”
Chlorpromazine
target for all antipsychotics
- D1 & D2 dopamine receptors
- Antipsychotics are all antagonist for D2 receptors
First Generation/ Typical Antipsychotics
CHLORPROMAZINE
HALOPERIDOL
Second Generation/ Atypical Antipsychotics
CLOZAPINE
OLANZAPINE
RISPERIDONE
Adverse reactions to 1st generation APS
- Parkinsonian effects
- Tardive dyskinesia
- Hyperprolactinemia
- anhedonia
Hyperprolactinemia
elevated prolactin hormone causes breast development in men & women, lactation in women, impotence in men, disruptions in menstrual cycle in women
Anhedonia
reduced ability to experience pleasure due to D2R antagonism
Extrapyramidal Side Effects (EPS)
- First generation APS can cause immobility and muscle rigidity similar to Parkinson’s disease at or near therapeutic dose
- Can also cause dystonia or akathisia/ restlessness
- Thought to be a result of D2 antagonism
- Can also cause dystonia or akathisia/ restlessness
Tardive Dyskinesia
- Occasionally occurs after long-term treatment with typical APS
- Symptoms persist even after APS is discontinued
- Patients have involuntary twitches of facial muscles predominantly, but also hands and legs
- Symptoms persist even after APS is discontinued
Positive reactions to 1st generation APS
- antiemetic properties (preventing or treating nausea and vomiting)
- do not cause withdrawal symptoms
Adverse reactions to 2nd generation APS
- Metabolic disorders
- Cardiovascular disorders
- Blood disease (clozapine)
Clozapine target
antagonizes serotonin receptors (5HT2A) as well as dopamine D2 receptors (also acts on other receptors – muscarinic, histamine).
First discovered 2nd Generation APS
Clozapine (1960s)
- Did not cause parkinson’s side effect
Olanzapine
Causes extreme weight gain
can cause 20-40 pound gains in one month) – increase in appetite
Positive reactions to 2nd generation APS
- Do not cause Parkinsonian motor impairments (EPS) and tardive dyskinesia
- have dual actions on serotonin and dopamine receptors
“treatment-resistant” schizophrenia is best treated with
clozapine
(not chosen first because of risk for WBC- white blood cell loss)
2 NEW IDEAS ABOUT THE CAUSES OF SCHIZOPHRENIA
- A rare de novo mutation in one of hundreds of genes that can lead to schizophrenia
- A combination of several risk genes plus environmental stressors
