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69 Cards in this Set
- Front
- Back
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What are the functions impaired in Psychosis?
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Mental capacity
Affective response Capacity to recognize reality Communication Relating to others |
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What is Schizophrenia?
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Breakdown of integration between
Emotions Thought Actions |
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What are POSITIVE Symptoms of Schizophrenia?
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Positive symptoms -An EXCESS of normal functions
Delusion Thought disorder Perceptual disturbances Incongruous mood Increased motor function |
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A dimunition or loss of normal functions in Schizophrenia is termed?
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NEGATIVE Symptoms
Poverty of Speech Loss of emotional responsiveness Reduced motor function Social withdrawal |
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What is the biological basis of the Positive symptoms in Schizophrenia?
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Overactivity of DOPAMINE neurons in - MESO-LIMBIC Dopamine Pathway
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What evidence supports this Dopaminergic activity in Schiz?
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Drugs that Increase Dopaminergic Activity - Increase or Produce Positive psychotic symptoms
Drugs that Decrease Dopaminergic Activity - Decrease or Stop Positive symptoms |
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Which 2 drugs can cause a Paranoid psychosis indistinguishable from Schiz?
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Amphetamines and Cocaine
If given repeatedly |
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Which receptor does Antipsychotics block?
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D2 recptors
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Name the 4 well defined Dopamine pathways in the brain
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Mesolimbic
NIgrostriatal Mesocortical Tuberoinfundibular |
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The Mesolimbic Pathway involves ..?
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It projects from the Brainstem to the Limbic area
Controls BEHAVIOUR |
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Overactivity of the Mesolimbic pathway produces..?
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Delusions
Hallucinations These symptoms are decreased when the Mesolimbic pathway is shut down by blocking Post synaptic dopamine receptors (hypothesized) |
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The Nigrostriatal Pathway projects from...?
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the Substantia Nigra to the Corpus Striatum
Controls MOVEMENT |
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Blocking the dopamine receptors in the Nigrostriatal Pathway causes?
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Disorders of movement like those in Parkinson's disease
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How are the side effects of blocking post synaptic dopamine receptors in the Nigrostriatal Pathway caused?
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The Nigrostriatal Pathway projects to the Basal Ganglia which forms part of the Extrapyramidal nueronal system of the CNS
Side effects are called EXTRA PYRAMIDAL symptoms - a set of movement disorders |
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How is the Mesocortical Pathway involved in Schiz?
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It may be involved in mediating..
Positive and perharps Negative symptoms |
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How does Classical or Typical antipsychotics affect the Mesocortical Pathway?
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Blockade of dopamine receptors in the pathway
They produce Blunting of emotions and various Cognitive side effects They are not useful for negative symptoms |
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How does blockade of dopamine receptors affect the Tuberoinfundibular pathway?
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When dopamine receptors are blocked...
They cause Prolactin levels to rise - Galactorrhea Dopamine released from neurons in this pathway INHIBITS Prolactin secretion |
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What are the other names for antipsychotic drugs?
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NEUROLEPTIC drugs
MAJOR TRANQUILIZERS |
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List the Classical or Typical antipsychotics.
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Chlopromazine
Fluphenazine Haloperidol Thioridazine Thiothixene Two famous drugs are Chlopromazine and Haloperidol |
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List the Atypical antipsychotics
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Clozapine
Risperidone Olanzapine Quetiopine Ziprasidone Aripiprazole Paliperidone |
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What is the efficacy of Classical antiphych. drugs related to?
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The efficacy is closely related to their ability to block D2 receptors in - Mesolimbic pathway
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How are the Atypical antiphych. drugs different to Classical ?
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They have Higher affinities for other receptors particularly 5-HT than D2
They appear to exert part of their action by blocking 5-HT receptors They are MUCH less likely to cause Extrapyramidal symptoms |
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Clozapine an atypical antiphych. drugs has a high affinity for which receptors?
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D1, D4, 5HT2, M, Alpha adrenergic
But it also blocks D2 |
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Risperidone blocks which recptor to a greater extent than D2?
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5HT2
Unlike Clozipine it can cause EPS but this is rare at normal therapeutic doses |
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Most of the Atypicals have High affinity for which 5-HT receptors?
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'5-HT2A'
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List the differences of Clozapine from Typical antipsychotic agents.
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*Minimal. if any, Extrapyramidal Symptoms (EPS)
*Essentially, NO Tardive dyskinesia *Minimal Increases in Prolactin *Negative symptom efficacy *Efficacy in treatment of refractory populations |
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What is the minimal definition for an Atypical antipsychotic?
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*Dual antagonism of Serotonin 5-HT2A and Dopamine D2 receptors
*Reduced propensity for EPS |
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What effect does Classical antipsych. have on the Mesolimbic and Nigrostriatal system?
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D2 blockade of the Mesolimbic -Relieves the Positive symptoms of Schizophrenia
but.... D2 blockade of the Nigrostriatal system causes Extrapyramidal side effects |
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How does SDAs (serotonin-dopamine antagonists) affect the Mesolimbic and Nigrostriatal system?
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D2 blockade of the Mesolimbic -Relieves the Positive symptoms of Schizophrenia (same as classical)
however..... They are Competitive Antagonists at Pre synaptic 5HT2 receptors in the Nigrostriatal pathway |
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How does the Competitive Antagonism at Pre synaptic 5-HT2 receptors in the Nigrostriatal pathway assist in reducing the EPS effects by SDAs?
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5-HT2 receptors function like alpha 2 receptos on presyaptic neurons
They inhibit the release of Dopamine when acted on by Serotonin but SDAs block this inhibition and so Dopamine is released This decreases the Dopamine blockade and prevents the EPS |
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What are the 2 major actions of antipsychotics?
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*Antipsychotics (as the name suggests)
-they reduce halucination and agitation they have a calming effect *Antiemetics -mediated by blockade of D2 at the chemoreceptor trigger zone (most older antpsychotics hve this effect) Many also block Muscarinic, alpha 1 adrenergic, and H1 receptors this causes a variety of side effects |
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What are the Extra pyramidal effects associated with?
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High potency of the drug for D2 receptors
The more potent the drug for D2, the more EPS |
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What r the 2 drugs that have a high affinity for D2 receptors?
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Haloperidol
Fluphenazine both are Classical antipsychotics with High Potency |
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Which classical antipsych. is low potency at D2 receptors?
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Thiorizadine
EPS are less likely to occur |
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Which 2 classical antipsych. are Stong anticholinergics?
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Thiorizadine
Chlopromazine EPS are less likely to occur because of this |
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Which 2 antipsych. has no Antiemetic effects?
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Aripiprazole
Thioridazine Clopromazine is useful as pharmacological antiemetic |
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How are antipsych. different from barbituates?
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Antipsych. DO NOT depress intellectual function
Motor incoordination is minimal |
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Antipsych. that have Low Potency at D2 also have what effect on EPS?
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They have low Extra-pyramidal symptoms
Remember this is the same for High potency at 5HT2 |
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Which drug causes the worse EPS?
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Haloperidol
High potency at D2 -High EPS Low potency at M or 5HT2 No sedation |
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The Best antipsych. drug?
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Clozapine
Medium potency D2 Medium potency M High potency at 5HT2 - NO EPS |
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Which 2 antipsych. drugs cause Hypotension?
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Chlopromazine
Thioridazine They block alpha 1 receptors |
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Which receptor acted on by antipsych. drugs causes sedation?
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5HT1
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Rispiridone has High potency at D2 and at 5HT2. It thus has what effect on EPS?
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Low EPS
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What is the Most important unwanted AE of antipsych. drugs?
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Tardive dyskinesia
late occuring syndrome of abnormal choreoathetoid movements |
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What is the possible cause of Tardive dyskinesia ?
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May be due to UP-regulation of Dopamine receptors - due to longterm blockade
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Which antipsych. causes Agronulocytosis in 1-2% of patients?
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Clozapine
This makes it a 2nd line drug NOT the DOC |
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What causes Galactorrhea from use of antipsych.?
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Blockade of D2 in Pituitary
Increase Prolactin secretion In women- amenorrhea-galactorrhea syndrome and infertility |
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What are the endocrine effects of antipsych. in men?
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Impotence
Loss of Libido Infertility |
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Which group of antipsych. is less likely to produce elevations in Prolactin?
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Atypicals
They cause more Weight gain and incr. in Lipids than some Typical agents |
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Which 2 Atypicals cause the worse Weight gain?
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Clozapine
Olanzipine Consequence of Wt gain: HTN, DM type 2, Hyperlipidemia |
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Which Atypical drug causes the LEAST Weight gain?
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ZIPRASIDONE
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Blockade of Muscarinic receptors can cause..?
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Anticholinergic effects
but... This antimuscarinic effect may be beneficial in relation to EPS |
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Beside orthostatic Hypotension, blockade of alpha 1 can cause........in men?
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Impaired Ejaculation
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What effect does Thioridazine have on the eye?
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Thioridazine cause Retinal deposits
Chlopromazine causes Cornea and Lens deposits |
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Which drug causes reversible abnormalities in T waves?
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Thiorazidine - at High doses
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Which Atypical has the Greatest risk of QT prolongation?
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Ziprasidone
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What is the Rare but life-threatning disorder of antipsych.?
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Neuroleptic Malignant Syndrome
Occurs in patients who are extremely sensitive to the EPS of antipsych. |
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What are the symptoms of Neuroleptic Malignant Syndrome?
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Muscle rigidity
Fever altered mental status Stupor Unstable BP Myoglobinemia |
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Apart from Schizophrenia what are the other clinical uses of antipsych.?
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Bipolar disorder
Tourette's syndrome Huntington's disease -paranoid behaviour Alzheimer's Dementia-Control of disturbed behaviour |
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What are Non-pyschyatric uses of antipsych.?
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Nausea, vomiting
Droperidol is used in combo with Fentanyl in Neuroleptic -anesthesia |
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2 antipsych promoted solely as antiemetics?
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Prochloperazine
Benzquinamide |
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Which antipsych is Category B in pregnancy?
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Only Clopazine
all others are Category C |
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Why are Atypicals prefered as DOC?
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*Benefit for Negative symptoms and cognition
*Diminished risk of Tardive Dyskinesia, EPS *Lesser incr. of prolactin levels |
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Clozapine is reserved for refractory patients, why?
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Potential for Agranulocytosis
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Antipsych may be used to control Agitation or psychosis in ....?
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Depressed patients
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Jaundice is caused by which drug?
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Chlopromazine
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AE of Parkinsonism can be treated with?
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Conventional antiParkinson's drugs of the Muscarinic type
Never Levadopa |
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What are some EPS?
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Parkinsonism
Akathisia -uncontrollable restlessness acute Dystonic Reactions -spastic retrocollis or torticollis |
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Whose reality is 'The real reality" ??
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Us or them
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