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2 Pharm Unit > 28 Antipsychotics > Flashcards

28 Antipsychotics Flashcards

(49 cards)

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1
Q

Define psychosis:

A

Disturbances of perception, impaired cognitive function

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2
Q

What percent of the population is affected by schizophrenia?
What is the general age range of onset?
Is it progressive?

A

Affects 1% (~0.7) of world population - independent of culture, politics, and geography
Early onset - adolescence or young adulthood
Life-long progressive illness

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3
Q

T/F

Females are affected by schizophrenia more than males

A

Males > Females

1.4:1

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4
Q

What is a possible cause of developing schizophrenia? What factors can reveal it?

A

Can develop due to prenatal viral infections in the brain of developing fetus
can be revealed due to environmental stress and changes in lifestyle

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5
Q

What are the comorbidities of schizophrenia?

A

Depression and smoking

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6
Q

What is the label for the presence of inappropriate behaviors in schizophrenia?
List a few of these symptoms:

A

Positive symptoms of schizophrenia

  • marked disorganized thinking with loosely connected thoughts (hallucinations)
  • false ideas/beliefs (delusions)
  • paranoid delusions
  • mood disturbances
  • confusion and suicidal thoughts
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7
Q

What are these behaviors called in the context of schizophrenia?

  • loss of normal function
  • social withdrawal
  • reduced speech and thought
  • loss of energy and inability to experience mental or physical pleasure
A

Negative symptoms of schizophrenia

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8
Q

What is the biochemical abnormality in schizophrenia?

Hint: receptor change?

A

Increased number of dopamine receptors

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9
Q

What are the structural abnormalities in schizophrenia?

Hint: 3 gross changes to the brain?

A

Enlarged cerebral ventricles
atrophy of cortical layers
reduced volume of the basal ganglia

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10
Q

What are the functional abnormalities in schizophrenia?

Hint: changes in blood flow and metabolism?

A

Reduced cerebral blood flow

reduced glucose utilization in prefrontal cortex

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11
Q

What are the genetic abnormalities in schizophrenia?

A

Genetic predisposition

Involvement of multiple genes

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12
Q

What are the therapeutic goals of antipsychotic drugs?

A

Prevent self-inflicted harm or harm to others
Provide the patient’s basic needs
Improve quality of life

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13
Q

Do schizophrenia drugs cure the disease, eliminate the fundamental thought disorder, or treat the symptoms?

A

Treat the symptoms

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14
Q

What is the major reason for therapeutic failure of antipsychotic drugs?

A

Non-compliance

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15
Q

What other uses are there for antipsychotic drugs besides for schizophrenia?

A

also used for treatment of other psychoses, agitate states, and drug-induced psychoses (from amphetamine & cocaine)

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16
Q

What are chlopromazine & fluphenazine derivatives of?

A

Phenothiazine

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17
Q

What is the thioxanthene derivative?

A

thiothixene

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18
Q

What is haloperidol a derivative of?

A

butyrophenone

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19
Q

What are the other names for typical antipsychotics?

A

Conventional antipsychotics

1st generation antipsychotics

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20
Q

What is the receptor selectivity for typical antipsychotics? Agonist/antagonist?

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A

Relatively selective DA antagonists

More selective for D2 vs D1

21
Q

What is the receptor selectivity for atypical antipsychotics? Agonist/antagonist?

Study These Flashcards
A

Selective antagonists for serotonin and DA receptors

22
Q

What is another name for atypical antipsychotics?

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A

2nd generation antipsychotics

23
Q

What is another name for dopamine partial agonists?

Study These Flashcards
A

3rd generation antipsychotics

24
Q

1) Are dopamine partial agonists competitive? Non? Selectivity?
2) Is there other receptor selectivity? Agonist/antagonist?

Study These Flashcards
A

1) Competitive partial DA agonists (more selective for D2)

2) Antagonize serortonin receptors

25
What is the DA hypothesis for schizophrenia?
Symptoms are in part due to increase in the activity of dopaminergic neurons
26
What is the evidence for the DA hypothesis for schizophrenia?
- Correlation between therapeutic potency and their binding affinity as antagonist for DA receptors (D2>>>D1) - Drugs that enhance DA transmission can induce/enhance schizophrenia symptoms - D2 receptors are increased in the brains of schizophrenics
27
``` Which DA pathways have increased activity in schizophrenia? Dorsal mesostriatal (nigrostriatal) Ventral mesostriatal (mesolimbic) Mesolimbocortical Tuberohypophyseal ```
``` Ventral mesostriatal (mesolimbic) Mesolimbocortical ```
28
T/F | Typical antipsychotics lead to an increase in cAMP in the presynaptic terminal
False - increased cAMPT in the postsynaptic membrane Typical antipsychotics antagonize mainly the D2 receptors, which are located on the postsynaptic membrane. These receptors would normally decrease cAMP, so inhibition would increase it.
29
What are the intracellular steps of signaling starting with DA binding to the D2 receptor in schizophrenia?
1-activation of postsynaptic D2 receptors 2-inhibit adenylate cyclase 3-decrease PKA activity 4-decrease NMDAR-mediated glutamatergic transmission and LTP (transmission strength) 5-schizophrenic pathophysiology
30
What is the time to onset of action of typical antipsychotics?
4-8 weeks
31
Which P450 enzymes metabolize typical antipsychotics to inactive metabolites?
CYP2D6 | CYP3A4
32
What are the typical antipsychotics that are: slow release formula given by deep gluteal IM injections used for patients non-compliant with oral medications
fluphenazine decanoate & haloperidol decanoate
33
Is there any tolerance or physical dependence seen in typical antipsychotics?
Some tolerance due to prolonged administration at higher doses Little physical dependence
34
Which typical antipsychotic affects M, alpha-adren, and H1 receptors as well as D2?
chloropromazine
35
Which receptor block leads to antiemetic effects of low potency antipsychotics?
H1 (histamine) receptor blockade
36
What is neuroleptic malignant syndrome? | What are the signs/symptoms?
Instability and collapse of the autonomic NS -excessive sweating and salivation -unstable BP and cardiovascular instability fever, muscle stiffness, delirium, stupor
37
Patients with what other disease can present with neuroleptic malignant syndrome?
Parkinson's disease patients who stop/reduce the dose of dopaminergics
38
What is the cause of neuroleptic malignant syndrome?
Caused by a sudden, marked decrease in DA activity (either strong blockade of DA receptors or withdrawal of DA agents) - prolonged use of high-potency neuroleptics - rapid increase in neuroleptic dosage
39
Treatments for neuroleptic malignant syndrome?
stop neuroleptics and treat hyperthermia aggressively supportive care in ICU with circulatory and ventilator support bromocriptine (DA agonist) dantrolene (to reduce muscle rigidity)
40
What are tardive dyskinesias? | Reversible/irreversible?
Involuntary oral-facial movements | irreversible or slowly reversible
41
What is the issue of prescribing an antipsychotic (mostly typical) to someone with Parkinson's disease?
L-DOPA is used to treat Parkinson's and typical antipsychotics are D2 antagonists that block the therapeutic effects of L-DOPA
42
What are the intracellular steps of neurotransmitter signaling starting with the release of 5-HT in schizophrenia?
- incr 5-HT release - activation of postsynaptic 5-HT2A receptors - activate phospholipase C - activate PKC, CK1, & PP2B - decr glutamatergic neurotransmission and LTP - schizophrenic pathophysiology
43
Initially atypical psychotics were thought to have greater efficacy in reducing psychotic symptoms than typical antipsychotics. What did the NIMH-sponsored CATIE study show?
only olanzapine | outperformed other typical antipsychotics due to superior efficacy and discontinuation rate
44
``` Which class has a higher likelihood of extrapyramidal symptoms and neuroleptic malignant syndrome? Typical/atypical antipsychotics? ```
typical antipsychotics
45
``` Which class has an increased risk of weight gain and metabolic adverse events? Typical/atypical antipsychotics? ```
atypical antipsychotics
46
What drugs lead to an inhibition of CYP2D6 and CYP3A4?
SSRIs, macrolide antibiotics, and antifungals
47
What drugs/activities can lead to induction of CYP1A2 and CYP3A4?
Cigarette smoking (CYP1A2), barbs, and some anticonvulsives (CYP3A4)
48
The activities of which drugs are affected by inhibition of CYP2D6 and CYP3A4? How?
Decreased drug elimination of all atypical antipsychotics except paliperidone
49
The activities of which drugs are affected by induction of CYP1A2 and CYP3A4? How?
Increased drug elimination of all typical antipsychotics and atypicals except paliperidone (only clozapine and olanzapine for CYP1A2)

2 Pharm Unit (17 decks)

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