Schizophrenia: Watts Flashcards
What is the general consideration of Schizophrenia?
- Its a severe illness that is the most debilitating of the psychotic disorders
What is the etiology of schizophrenia?
- Neurodevelopmental, Genetice-Neuronal Growth, Environmental, Gene-Environment Interaction, Nerodevelopment-Enviroment Interaction
What is the way that Neurodevelopment has an effect of Schizophrenia?
- Increases the ventricle size and changes in gray & white matter
What is the way that Genetics-Neuronal Growth has an effect on Schizophrenia?
- Twins studies or families-multiple genes
What is the way that Environment has an effect on Schizophrenia?
- Birth complications, Infections, Stressful events…
What are the symptoms of Schizophrenia?
- Positive, Negative, Cognitive
What are Positive Symptoms of Schizophrenia?
- Symptoms that are generally not there in people that don’t have the disorder
- Respond well to treatment
- EX: Hallucinations, Delusions, Bizarre Behavior, Disorganized Speech…
What are Negative Symptoms of Schizophrenia?
- The experiences that involve loss of normal function
- Little response toward drug therapy
- EX: Blunted Emtions, Poor Self-care, Social Withdrawal, Catatonia
What are Cognitive Symptoms of Schizophrenia?
- A decrease in cognitive function that involves the D1 receptors and Glutamate receptors
- DECREASE in concentration, memory, cognitive ability
What is the Neurotransmitter Hypotheses?
- Suggest an imbalance of neurotransmitters with in the brain
- DOPAMINE [main one], SEROTONIN, GLUTAMATE
What is the Serotonin Hypothesis of Schizophrenia?
- LSD & Mescaline are 5HT Agonists
- 5HT2A mediates Hallucinations
- Antagonism and Inverse Agonism = Antipsychotic
- 5HT2A modulates Dopamine release in cortex, limbic, striatum
- 5HT2A modulates Glutamine release
- 5HT2C agonist good in schizophrenia?
What is the Glutamate Hypothesis of Schizophrenia?
- Glutamate is the major EXCITATORY neurotransmitter
- Phencyclidine and Ketamine exacerbate psychosis and cognitive deficits
- LY2140023-mGLuR2/3 effective in Schizo
- Ampakine [AMPA] good in animals
- GlyT Inhibitors help activate the Glutamate receptor
What is the Dopamine Hypothesis of Schizophrenia?
- Dopamine Agonist EXACERBATE Schizophreina
- INCREASED Dopamine receptors EXACERBATE Schizophrenia
- Dopamine metabolites in CSF will increase in CNS first then decrease in CNS later
What are the receptors that are antagonized by antipsychotics in Schizophrenia?
- Dopamine [D2 mostly], Serotonin [5HT], Norepinephrine [NE], Acetylcholine [ACh], Histamine [H1]
Which receptor is key for therapeutic effectiveness in Schizophrenia?
- MULTIPLE receptors = individualize therapy
- With multiple receptors causes many SE and poor adherence
What one of the dopamine has the greater affinity toward Antipsychotic drugs in Schizophrenia?
- D2; due to correlation between binding potency and clinical effectiveness
What does the D2 receptor do on the Presynaptic terminal.
- Receives that Dopamine and puts it back into the Presynapse
What do D2 Receptor Antagonist do in the presynaptic terminal?
- Will block in the receptor; INCREASING dopamine being made?
What do D2 Receptor Antagonist do in the presynaptic terminal?
- Blocks the receptors that receive the Dopamine so that the INCREASE in dopamine being made wont have a HUGE effect on adverse events?
What are some of the sites that D2 antagoinst affect the CNS?
- Basal Ganglia: Motor Effects and EPS
- Mesolimbic: Decrease Cognition
- Mesocortical: EXACERBATE cognitive deficits
- Hypothalamus: Block endocrine [increase prolactin]
- Medulla: CTZ; Decrease Nausea/Vomiting
What are the drug-induced movement disorders caused my D2 Antgonism in Schizophrenia?
- Extrapyramidal Symptoms [EPS], Tardive Dyskinesia, Neuroleptic Malignant Syndrome [NMS]
What is Extrapyramidal Symptoms [EPS] in Schizophrenia?
- Group of movement disorders caused by blocking dopamine
- Occurs EARLY, up to days/weeks, REVERSIBLE
What are the symptoms of EPS?
- Dystonia [Increased muscle tone], Pseudoparkinsonism [Muscle Rigidity], Tremor, Akathisia [Resttlessness]
What are the Drug Therapies for EPS?
- Antiochonlinergics [Benztropine, Trihexyphenidyl, Akinetion], Antihistamines [Benadryl], Dopamine Agoinst [Amantadine], Propranolol [For Akathisia]
What happens within the neuron in D2 Antagonism in Schizophrenia?
- Dopamine release in decreased causing an increase in ACh in the synapse and cause an excitatory effect
What is Tardive Dyskinesia in Schizophrenia?
- Result of prolonged blockade of dopamine receptors in the brain
- Occurs LATE, up to a month to a year, IRREVERSIBLE
What are the symptoms of Tardive Dyskinesia in Schizophrenia?
- Rhythmic Involuntary Movements [Mouth], Athetiod [worm-like], Axial Hyperkinesia [To-and-Fro movement]
What is the drug therapies for Tardive Dyskinesia in Schizophrenia?
- PREVENTION: Reduce does, Change meds, Eliminate Anticholinergics, VMAT inhibitors
What is the purpose of the VMAT2 Inhibitors within Tardive Dyskinesia in Schizophrenia?
- VMAT2 will help put dopamine out into the synapse
- VMAT2 Inhibitor will put block dopamine from being put into the synapse and will have it be broken down via MAO
What is Neuroleptic Malignant Syndrome [NMS] in Schizophrenia?
- Life threatening Neurological disorder
- SERIOUS and RAPID
What are the symptoms for NMS in Schizophrenia?
- EPS [with fever], Impaired cognition, Muscle Rigidity
What are the drug therapies for NMS in Schizophrenia?
- D/C Drug; DA Agonist, Diazepam, Dantrolene
How long does psychosis treatment usually last?
- 2 to 3 weeks for effectiveness
- 6 weeks to 6 months for max efficacy
What is the side effects of the Muscarinic Cholinoceptor Blockade?
- Loss of vision, Dry Mouth, Urinary Retention, Constipation
What is the side effects of the Alpha Adrenoceptor Blockade?
- Orthostatic hypotension, Impotence, Failure to Ejaculate
What is the side effects of Dopamine Receptor Blockade?
- Parkinson’s Syndrome, Akathasia, Dystonias
What is the side effects of Supersensitivity Dopamine Receptors?
- Tardive Dyskinesia
What is the side effects of Muscarinic Blockade?
- Toxic Confusional State
What is the side effects of Histamine [H1] Receptor blockade?
- Sedation
What is the side effects of Dopamine Receptor Blockade resulting in Hyperprolactinemia?
- Amenorrhea Galactorrhea, Infertility, Impotance
- Increased Prolactin
What is the side effects of H1 and 5HT2A Blockade?
- Weight Gain
What are the precautions and contraindications for Schizophrenia?
- Car
What are the Typical First Generation Antipsychotics for Schizophrenia?
- Chlorpromazine, Promethazine, Thioridazine, Fluephenazine, Prochlorperazine, Perphenazine, Thiothixene, Haloperidol, Molindone, Pimozide
What is important to know about Chlorpromazine?
- 1st Antipsychotic made
- SE: Antihistamine [Drowsiness, Dizziness, Dry Mouth, Constipation…]
What is important to know about Promethazine?
- H1 Antagonist Properties
- SE: Antiemtic [Decrease N/V], Antihistamine [Drowsiness, Dizziness, Dry Mouth, Constipation…]
What is important to know about Thioridazine?
- SE: Sedation, Hypotension, Anticholinergic Effects
- QTc Prolongation
What is important to know about Fluephenazine?
- Can cause EPS
What is important to know about Prochlorperazine?
- Is an antiemetic [Decrease Nausea/Vomiting]
What is important to know about Perphenazine?
- CATIE Study: showed that the newer antipsychotics were better than Perphenazine and caused less EPS
What is important to know about Thiothixene?
- Can cause moderate EPS
What is important to know about Haloperidol?
- Can cause EPS
What is important to know about Molindone?
- Can cause moderate EPS
- Found weight gain with newer agents
What is important to know about Pimozide?
- Helps with Tourette’s disease; suppress motor and vocal tics
What are the Atypical/Second Generations Antipsychotics in Schizophrenia?
- Clozapine, Olazapine, Quetiapine, risperdone, Ziprasidone, Lurasidone, Apripirazole.
What is important to know about Clozapine?
- VERY Effective [affects a lot of receptors] - Makes it 2nd or 3rd line
- Can cause Agranulocytosis
- SE: Anticholinergic [Dry Mouth, Constipation, Blurred Vision, Urinary Retention], Antihistamine[Dry Mouth, Drowsiness], Risk of diabetes
What is important to know about Olanzapine?
- Very similar to Clozapine
- SE: Weight gain, Risk of Diabetes
- Less risk of Nausea/Vomiting and Movement disorder
What is important to know about Loxapine?
- Has a metabolite [Amoxipine], that can inhibit NET causing an Antidepressant effect as well as an Antipsychotic effect
What is important to know about Quetiapine?
- Has a metabolite that causes antidepressant activity
- SE: Low EPS, Hypotension [a1], Sedation [H1], Risk of diabetes
What is important to know about Risperidone?
- Designed to target BOTH 5HT2A & D2
- SE: Weight gain & Sedation [H1 & a1]
What is important to know about Paliperidone?
- 9-Hydroxyrisperidone
What is important to know about Iloperidone?
- Structurally related to risperidone
- VERY potent at a1
What is important to know about Ziprasidone?
- It has 5HT2A, D2, a1 affinity
- SE: QT interval prolongation
What is important to know about Asenapine?
- It has 5HT2A & D2 affinity
What is important to know about Lurasidone?
- It has 5HT2A & D2 affinity
- SE: Less weight gain & metabolic effects [vs. Olanzapine]
What is important to know about Pimavanserin?
- It is an Inverse agonist toward 5HT2A
- Used for Parkinson’s Disease Psychosis
What is important to know about Aripiprazole?
- Has HIGH 5HT2A & D2 affinity, Partial Agonist to 5HT1A, and Moderate Affinity for D4, a, & H
- SE: Weight gain
