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PHRM 845: Therapeutics III > Schizophrenia: Watts > Flashcards

Schizophrenia: Watts Flashcards

1
Q

What is the general consideration of Schizophrenia?

A
  • Its a severe illness that is the most debilitating of the psychotic disorders
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2
Q

What is the etiology of schizophrenia?

A
  • Neurodevelopmental, Genetice-Neuronal Growth, Environmental, Gene-Environment Interaction, Nerodevelopment-Enviroment Interaction
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3
Q

What is the way that Neurodevelopment has an effect of Schizophrenia?

A
  • Increases the ventricle size and changes in gray & white matter
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4
Q

What is the way that Genetics-Neuronal Growth has an effect on Schizophrenia?

A
  • Twins studies or families-multiple genes
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5
Q

What is the way that Environment has an effect on Schizophrenia?

A
  • Birth complications, Infections, Stressful events…
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6
Q

What are the symptoms of Schizophrenia?

A
  • Positive, Negative, Cognitive
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7
Q

What are Positive Symptoms of Schizophrenia?

A
  • 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…
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8
Q

What are Negative Symptoms of Schizophrenia?

A
  • The experiences that involve loss of normal function
  • Little response toward drug therapy
  • EX: Blunted Emtions, Poor Self-care, Social Withdrawal, Catatonia
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9
Q

What are Cognitive Symptoms of Schizophrenia?

A
  • A decrease in cognitive function that involves the D1 receptors and Glutamate receptors
  • DECREASE in concentration, memory, cognitive ability
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10
Q

What is the Neurotransmitter Hypotheses?

A
  • Suggest an imbalance of neurotransmitters with in the brain
  • DOPAMINE [main one], SEROTONIN, GLUTAMATE
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11
Q

What is the Serotonin Hypothesis of Schizophrenia?

A
  • 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?
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12
Q

What is the Glutamate Hypothesis of Schizophrenia?

A
  • 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
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13
Q

What is the Dopamine Hypothesis of Schizophrenia?

A
  • Dopamine Agonist EXACERBATE Schizophreina
  • INCREASED Dopamine receptors EXACERBATE Schizophrenia
  • Dopamine metabolites in CSF will increase in CNS first then decrease in CNS later
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14
Q

What are the receptors that are antagonized by antipsychotics in Schizophrenia?

A
  • Dopamine [D2 mostly], Serotonin [5HT], Norepinephrine [NE], Acetylcholine [ACh], Histamine [H1]
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15
Q

Which receptor is key for therapeutic effectiveness in Schizophrenia?

A
  • MULTIPLE receptors = individualize therapy
  • With multiple receptors causes many SE and poor adherence
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16
Q

What one of the dopamine has the greater affinity toward Antipsychotic drugs in Schizophrenia?

A
  • D2; due to correlation between binding potency and clinical effectiveness
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17
Q

What does the D2 receptor do on the Presynaptic terminal.

A
  • Receives that Dopamine and puts it back into the Presynapse
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18
Q

What do D2 Receptor Antagonist do in the presynaptic terminal?

A
  • Will block in the receptor; INCREASING dopamine being made?
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19
Q

What do D2 Receptor Antagonist do in the presynaptic terminal?

A
  • Blocks the receptors that receive the Dopamine so that the INCREASE in dopamine being made wont have a HUGE effect on adverse events?
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20
Q

What are some of the sites that D2 antagoinst affect the CNS?

A
  • Basal Ganglia: Motor Effects and EPS
  • Mesolimbic: Decrease Cognition
  • Mesocortical: EXACERBATE cognitive deficits
  • Hypothalamus: Block endocrine [increase prolactin]
  • Medulla: CTZ; Decrease Nausea/Vomiting
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21
Q

What are the drug-induced movement disorders caused my D2 Antgonism in Schizophrenia?

A
  • Extrapyramidal Symptoms [EPS], Tardive Dyskinesia, Neuroleptic Malignant Syndrome [NMS]
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22
Q

What is Extrapyramidal Symptoms [EPS] in Schizophrenia?

A
  • Group of movement disorders caused by blocking dopamine
  • Occurs EARLY, up to days/weeks, REVERSIBLE
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23
Q

What are the symptoms of EPS?

A
  • Dystonia [Increased muscle tone], Pseudoparkinsonism [Muscle Rigidity], Tremor, Akathisia [Resttlessness]
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24
Q

What are the Drug Therapies for EPS?

A
  • Antiochonlinergics [Benztropine, Trihexyphenidyl, Akinetion], Antihistamines [Benadryl], Dopamine Agoinst [Amantadine], Propranolol [For Akathisia]
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25
Q

What happens within the neuron in D2 Antagonism in Schizophrenia?

A
  • Dopamine release in decreased causing an increase in ACh in the synapse and cause an excitatory effect
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26
Q

What is Tardive Dyskinesia in Schizophrenia?

A
  • Result of prolonged blockade of dopamine receptors in the brain
  • Occurs LATE, up to a month to a year, IRREVERSIBLE
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27
Q

What are the symptoms of Tardive Dyskinesia in Schizophrenia?

A
  • Rhythmic Involuntary Movements [Mouth], Athetiod [worm-like], Axial Hyperkinesia [To-and-Fro movement]
28
Q

What is the drug therapies for Tardive Dyskinesia in Schizophrenia?

A
  • PREVENTION: Reduce does, Change meds, Eliminate Anticholinergics, VMAT inhibitors
29
Q

What is the purpose of the VMAT2 Inhibitors within Tardive Dyskinesia in Schizophrenia?

A
  • 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
30
Q

What is Neuroleptic Malignant Syndrome [NMS] in Schizophrenia?

A
  • Life threatening Neurological disorder
  • SERIOUS and RAPID
31
Q

What are the symptoms for NMS in Schizophrenia?

A
  • EPS [with fever], Impaired cognition, Muscle Rigidity
32
Q

What are the drug therapies for NMS in Schizophrenia?

A
  • D/C Drug; DA Agonist, Diazepam, Dantrolene
33
Q

How long does psychosis treatment usually last?

A
  • 2 to 3 weeks for effectiveness
  • 6 weeks to 6 months for max efficacy
34
Q

What is the side effects of the Muscarinic Cholinoceptor Blockade?

A
  • Loss of vision, Dry Mouth, Urinary Retention, Constipation
35
Q

What is the side effects of the Alpha Adrenoceptor Blockade?

A
  • Orthostatic hypotension, Impotence, Failure to Ejaculate
36
Q

What is the side effects of Dopamine Receptor Blockade?

A
  • Parkinson’s Syndrome, Akathasia, Dystonias
37
Q

What is the side effects of Supersensitivity Dopamine Receptors?

A
  • Tardive Dyskinesia
38
Q

What is the side effects of Muscarinic Blockade?

A
  • Toxic Confusional State
39
Q

What is the side effects of Histamine [H1] Receptor blockade?

A
  • Sedation
40
Q

What is the side effects of Dopamine Receptor Blockade resulting in Hyperprolactinemia?

A
  • Amenorrhea Galactorrhea, Infertility, Impotance
  • Increased Prolactin
41
Q

What is the side effects of H1 and 5HT2A Blockade?

A
  • Weight Gain
42
Q

What are the precautions and contraindications for Schizophrenia?

A
  • Car
43
Q

What are the Typical First Generation Antipsychotics for Schizophrenia?

A
  • Chlorpromazine, Promethazine, Thioridazine, Fluephenazine, Prochlorperazine, Perphenazine, Thiothixene, Haloperidol, Molindone, Pimozide
44
Q

What is important to know about Chlorpromazine?

A
  • 1st Antipsychotic made
  • SE: Antihistamine [Drowsiness, Dizziness, Dry Mouth, Constipation…]
45
Q

What is important to know about Promethazine?

A
  • H1 Antagonist Properties
  • SE: Antiemtic [Decrease N/V], Antihistamine [Drowsiness, Dizziness, Dry Mouth, Constipation…]
46
Q

What is important to know about Thioridazine?

A
  • SE: Sedation, Hypotension, Anticholinergic Effects
  • QTc Prolongation
47
Q

What is important to know about Fluephenazine?

A
  • Can cause EPS
48
Q

What is important to know about Prochlorperazine?

A
  • Is an antiemetic [Decrease Nausea/Vomiting]
49
Q

What is important to know about Perphenazine?

A
  • CATIE Study: showed that the newer antipsychotics were better than Perphenazine and caused less EPS
50
Q

What is important to know about Thiothixene?

A
  • Can cause moderate EPS
51
Q

What is important to know about Haloperidol?

A
  • Can cause EPS
52
Q

What is important to know about Molindone?

A
  • Can cause moderate EPS
  • Found weight gain with newer agents
53
Q

What is important to know about Pimozide?

A
  • Helps with Tourette’s disease; suppress motor and vocal tics
54
Q

What are the Atypical/Second Generations Antipsychotics in Schizophrenia?

A
  • Clozapine, Olazapine, Quetiapine, risperdone, Ziprasidone, Lurasidone, Apripirazole.
55
Q

What is important to know about Clozapine?

A
  • 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
56
Q

What is important to know about Olanzapine?

A
  • Very similar to Clozapine
  • SE: Weight gain, Risk of Diabetes
  • Less risk of Nausea/Vomiting and Movement disorder
57
Q

What is important to know about Loxapine?

A
  • Has a metabolite [Amoxipine], that can inhibit NET causing an Antidepressant effect as well as an Antipsychotic effect
58
Q

What is important to know about Quetiapine?

A
  • Has a metabolite that causes antidepressant activity
  • SE: Low EPS, Hypotension [a1], Sedation [H1], Risk of diabetes
59
Q

What is important to know about Risperidone?

A
  • Designed to target BOTH 5HT2A & D2
  • SE: Weight gain & Sedation [H1 & a1]
60
Q

What is important to know about Paliperidone?

A
  • 9-Hydroxyrisperidone
61
Q

What is important to know about Iloperidone?

A
  • Structurally related to risperidone
  • VERY potent at a1
62
Q

What is important to know about Ziprasidone?

A
  • It has 5HT2A, D2, a1 affinity
  • SE: QT interval prolongation
63
Q

What is important to know about Asenapine?

A
  • It has 5HT2A & D2 affinity
64
Q

What is important to know about Lurasidone?

A
  • It has 5HT2A & D2 affinity
  • SE: Less weight gain & metabolic effects [vs. Olanzapine]
65
Q

What is important to know about Pimavanserin?

A
  • It is an Inverse agonist toward 5HT2A
  • Used for Parkinson’s Disease Psychosis
66
Q

What is important to know about Aripiprazole?

A
  • Has HIGH 5HT2A & D2 affinity, Partial Agonist to 5HT1A, and Moderate Affinity for D4, a, & H
  • SE: Weight gain

PHRM 845: Therapeutics III (25 decks)

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