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67 Cards in this Set
- Front
- Back
Two broad categories of antipsychotic drugs.
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Typical and Atypical
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1st Generation Antipsychotics are called:
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Typical Antipsychotics
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2nd Generation Antipsychotics are called:
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Atypical Antipsychotics
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3rd Generation Antipsychotics are called:
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Dopamine Partial Agonists
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What is the one major 3rd Gen. Antipsychotic?
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Aripiprazole
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A/typical antipsychotics block what receptor?
What other receptor does atypical drugs block? |
- D2 Receptors
- 5-HT2 Receptors |
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What are the subtypes of Dopamine receptors?
How are these further divided? |
- D1-D5
- D1 like (D1, D5) - D2 like (D2-D4) |
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What is the difference between an antagonist and an inverse agonist?
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Antagonists have no activity but have affinity to sites. Inverse agonists have affinity site, but they also produce the opposite effect of an agonist.
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What symptoms do 1st Generation Antipsychotics treat best?
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Positive symptoms
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What symptoms do 2nd Generation Antipsychotics treat best?
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Negative symptoms
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What symptoms do 3rd Generation Antipsychotics treat best?
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Extrapyrimidal symptoms due to the 5-HT2A receptors.
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What is the order of binding for Typical (1st Gen) Antipsychotics?
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D2~D1>a1~5-HT2
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What is the order of binding for Atypical (2nd Gen) Antipsychotics?
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D2~5-HT2>>D1>a1
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What is the order of binding for 3rd Generation antipsychotics?
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Partial agonism of D2,
5-HT1a There is ANTAGONISM of 5-HT2a |
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Phenothiazine Derivatives:
What is the name of the standout drug? |
Chlorpromazine
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Phenothiazine Derivatives:
What kind of receptors do they act on? |
They DO NOT differentiate between D1 or D2 receptors.
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Phenothiazine Derivatives:
What is the specific structure that deals with the receptor? |
The 3* Amine
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Phenothiazine Derivatives:
Hydro or Lipophilic? |
They are VERY lipophilic
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Phenothiazine Derivatives:
What is the significance of bioisosteres in this class? |
Although bioisosteres can occur, activity is still retained.
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Phenothiazine Derivatives:
The phenyl rings are lipo/hydrophilic. |
Lipophilic
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Phenothiazine Derivatives:
What effect do the benzene rings do to the acidity of the N? |
They are electron withdrawing so it causes the N to become weakly BASIC.
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Phenothiazine Derivatives:
True/False, The N can be cationized at physiological pH. |
False. It is not cationized at physiological pH.
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Phenothiazine Derivatives:
What effect does the 3* amine have on the basicity of the compound? |
The 3* amine also gives strong basicity to the compound.
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Phenothiazine Derivatives:
What must you do to the compound to make it suitable for oral suspensions? |
You must make the compound more hydrophilic.
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Phenothiazine Derivatives:
What must you do in order to decrease the hydrophilicity make it long-acting? Describe the specific mechanism. |
You must make the compound more lipophilic by esterifying the --OH group on the 3* amine chain. (Prodrug)
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Phenothiazine Derivatives:
Why is the 3-C spacer very important for activity? |
This allows free rotation of the bonds around the N.
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Phenothiazine Derivatives:
How do you lock the free rotation? |
A bioisostere should be formed (Double-bond will form).
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Phenothiazine Derivatives:
What conformation has more activity? |
The CIS conformation does.
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Schizophrenia:
True/False - It is an idiopathic psychosis. What does that mean? |
True. Schizophrenia is idiopathic. That means that the cause is not known.
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Schizophrenia:
What are the two broad categories of symptoms? |
Positive/Negative symptoms
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Schizophrenia:
True/False - Both positive and negative symptoms of Schizophrenia can be found in unaffected patients. |
False. Only negative symptoms are found in un/affected patients.
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Schizophrenia:
Describe some of the positive symptoms: |
Hallucinations (Auditory), Delusions, Grandiosity, Catatonia, Paranoia.
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Schizophrenia:
Describe some of the negative symptoms: |
Disordered (Illogical) Thinking, Withdrawal, Depersonalization, Emotional Changes.
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Schizophrenia:
What is the age range of onset? |
Late adolescence to young adulthood.
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Schizophrenia:
What are possible sources of this disorder? |
It can be genetic, or environmental/experiential contribution.
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Schizophrenia:
True/False - If a twin has this disorder, only 10% chance that other twin will have disorder. |
False. The chance is around 50%.
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Schizophrenia:
Although the disease is chronic, what effect does treatment have on patients? |
1/3 of patients will improve w/ medication.
1/3 of patients will have periodic relapses. 1/3 of patients will worsen. |
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Schizophrenia: What receptor must be blocked in order to treat the disease?
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The DA receptor.
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Supporting The dopamine theory of Schizophrenia:
What is the significance of blocking DA receptors? |
Psychotic symptoms are reduced, especially positive ones.
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Supporting The dopamine theory of Schizophrenia:
What is the significance of Amphetamine/Cocaine? |
These two substances will also produce similar symptoms to schizophrenia.
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Supporting The dopamine theory of Schizophrenia:
What happens to the D2 receptors of untreated schizophrenic patients? |
There is an increase in the number of receptors.
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Supporting The dopamine theory of Schizophrenia:
How are the blockade of D2 receptors and anti-psychotic durg potency related? |
There is a correlation between those two things.
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Against the dopamine theory of Schizophrenia: How are the DA levels, DA cell activity evidence agianst the theory.
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There is no evidence showing increased levels of DA cell activity or DA levels in the bain.
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Against the dopamine theory of Schizophrenia: What is the wrong with the correlation between receptor blockade and antipsychotic effect? On what dose should effects appear to be a good antipsychotic drug?
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Correlation also does not prove cause. The antipsychotic effect takes too long to appear. (Up to weeks). 1st dose is the standard.
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Schizophrenia: What receptor do all current drugs act on? What are the difficulties with this, and what are the side effects?
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They all act on blocking DA receptors. However, it is hard to selectively block the receptors only in the limbic area and this causes EPS and endocrine s/e.
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What are the 3 antipsychotic drug classes?
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Phenothiazine derivatives, Thioxanthene derivatives and Butyrophenone derivatives.
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What are the drugs in the phenothiazine derivative class?
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Chlorpromazine (Prototype)
Thioridazine Trifluoperazine Perphenazine Fluphenazine |
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What are the drugs in the thioxanthene derivative class?
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Thioxanthene
Chlorprothixene |
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What are the drugs in the butyrophenone derivative class?
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Haloperidol
Droperidol Spiroperidol |
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How much more effective is Haloperidol over Chlorpromazine?
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100x more.
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What are the drugs in the atypical antipsychotic drug class?
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Pimozide
Molindone Clozapine Risperidone Olanzapine Loxapine Quetiapine Ziprasidone Aripiprazole |
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Instead of D2 receptors, what receptors are atypical antipsychotics better at blocking?
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They are better at blocking
5-HT2 receptors. |
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Antipsychotic Drugs: What are some CNS s/e?
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Sedation, Antianxiety, NEUROLEPTIC Syndrome: (Only common with older drugs) = No rapid responses, impaired vigilance.
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Antipsychotic Drugs: What are some endocrine s/e?
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Increase prolactin secretion
Up F, Down M libido Increase appetite/weight gain Type 2 Diabetes Hypothermic effect |
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What happens when prolactin secretion is increased?
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Breast enlargement in M
Ameno/Galactorrhea in F |
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What antipsychotic drugs will cause prolactin secretion?
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All typical antipsychotics and risperidone. The atypicals have minimal effects on secretion.
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Antipsychotic Drugs: What are CRTZ and Autonomic side effects?
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Anti-emetic
Muscarinic blockade (Blurred vision, dry mouth, constipation, difficulty urinating) A-receptor blockade (Orthostatic hypertension, reflex tachycardia, impotence) |
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Antipsychotic Drugs: What are the CVS s/e:
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Hypotension, ECG changes, Cardiotoxicity
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Antipsychotic Drugs: What are some blood disorders?
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Leukopenia (Decreased WBC count)
Eisinophilia (Increased certain elements) |
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What is a major blood disorder that Clozapine can cause?
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Marrow suppression and Agranulocytosis. Symptoms would appear w/in the first few weeks of use.
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Antipsychotic Drugs: What are some EPS? Why do these occur?
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Parkinsonian (It is NOT Parkinson's disease), Dystonic Reactions (Seizure-like), Akathesia, Neuroleptic Malignant Syndrome, Tardive Dyskinesia.
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How can you treat tardive dyskinesia?
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You can't. The only way is to avoid using strong D2 blockers or to only use the lowest effective dose as possible.
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What is the mechanism of tardive dyskinesia?
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By blocking the DA receptors, this causes an increase in the number of D2 receptors in the striatum.
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Antipsychotic Drugs: What are some skin s/e?
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Hypersensitivity
Contact Dermatitis Photosensitivity (Sunburn-like) Abnormal skin colors (Only with long-term use) |
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Antipsychotic Drugs: Why must care be taken when dealing with epileptics?
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This is because the sizure threshold is lowered.
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Antipsychotic Drugs: What are some possible drug interactions?
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CNS Depressants, Sedatives, Alcohol, Opiates, Benzodiazepines.
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Antipsychotic Drugs: Clozapine can suppress or not cause what major side effects?
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EPS and Tardive Dyskinesia
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