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Medical Pharmacology Exam 2 > Anti-Psychotics > Flashcards

Anti-Psychotics Flashcards

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USMLE® Step 1 flashcards
1
Q

How do psychosis and schizophrenia differ?

A

Psychosis - Broad, all encompassing disturbance in perception
Schizophrenia - Specific subtype of psychosis

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2
Q

What are 2 functional and I biochemical abnormality associated with schizophrenia?

A 
Biochem 
- Increased DA receptors
Functional
- Reduced cerebral blood flow
- Reduced glucose utilization in prefrontal cortex
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3
Q

True or false: There is a genetic component / predisposition with schizophrenia?

A

True. e.g. neuregulin-1 in northern european population

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4
Q

True or false: Drugs used to treat schizophrenia control symptoms vs. treat cause of disease?

A

True

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5
Q

What is the major reason for therapeutic failure in the treatment of schizophrenia?

A

Non-compliance

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6
Q

Among the antipsychotics, what are the 3 synthetic benzodiazapine derivatives?

A

Clozapine
Olanzapine
Quetiapine

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7
Q

Among the 1st generation antipsychotics, what is the general mechanism of action? What receptor subtype are they selective for?

A

Selective antagonists at dopamine receptors

Block D2 over D1

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8
Q

Among the 2nd generation antipsychotics, what is the general mechanism of action?

A

Selective antagonists at serotonin and dopamine receptors

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9
Q

Among the 3rd generation antipsychotics, what is the general mechanism of action?

A

Competitive partial agonists at dopamine receptors, antagonists at serotonin receptors

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10
Q

What are the 4 examples of 1st generation / conventional antipsychotics provided? What receptor do they preferentially bind?

A 
Chlorpromazine
Fluphenazine
Thiothexene
Haloperidol
D2 over D1 antagonists
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11
Q

What is the dopamine hypothesis of schizophrenia?

A

That increased activity of dopaminergic neuron underlies the symptoms of schizophrenia

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12
Q

What is the receptor target of most typical antispsychotics? What happens as with increased potency / activity at the receptor? Where within the synapse are these receptors typically found?

A

D2 dopamine receptors
Increased therapeutic efficiency
Post-synaptically

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13
Q

What is the net effect of D2 receptor activation by dopamine (regarding PKA activity and glutamatergic signalling)?

A

Activation - Decreased PKA, and decreased NMDAR activity

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14
Q

What is the net effect of increased D2 receptors as observed in many schizophrenic patients?

A

Enhanced reduction in PKA and NMDAR signalling, stronger schizophrenic pathology

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15
Q

Among the 1st generation antipsychotics, rank them as high, medium and low potency.

A

High - Haloperidol, Fluphenazine
Med - Thiothixene
Low - Chlorpromazine

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16
Q

True or false: 1st generation antipsychotics show effects as soon as 3-5 days after the first dose.

A

False. Effects aren’t observed until 4-8 weeks after starting treatment.

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17
Q

What are Fluphenazine decanoate and haloperidol decanoate? How are they administered? What are they used for?

A

Slow release formulas of fluphenazine and haloperidol
Deep gluteal IM injections
Used for patients non-compliant with oral medication

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18
Q

What is the basis of side effects from use of 1st generation antipsychotics?

A

Blockade of dopaminergic and other* receptor pathways

Other* - Chlorpromazine also blocks cholinergic, adrenergic and histamine signaling

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19
Q

Which 1st generation antipsychotic is most likely to produce Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation and confusion? Why?

A

Chlorpromazine

Blockade of Cholinergic muscarinic activity

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20
Q

Which 1st generation antipsychotic is most likely to produce Vasodilation, orthostatic hypotension & lightheadedness, reflex tachycardia and sexual dysfunction? Why?

A

Chlorpromazine

Blockade at alpha adrenergic receptors

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21
Q

All 1st generation antipsychotics are associated with Increase in prolactin release – infertility and impotence. Which is most prominently assocated with these symptoms? Why?

A

Haloperidol

Pituitary block of D2 receptors

22
Q

Which 1st generation antipsychotic is most likely to produce Sedation and weight gain? Why?

A

Chlorpromazine

H1 histamine receptor block

23
Q

In addition to antipsychotic use, low potency antipsychotics can be used as antiemetics. What are the 2 examples provided?

A

Promethazine

Prochlorperazine

24
Q

What is a antipsychotic side effect syndrome associated with instability / collapse of the autonomic NS?

  • excessive sweating and salivation
  • unstable blood pressure, cardiovascular instability
  • fever, muscle stiffness, delirium and stupor
A

Neuroleptic malignant syndrome

25
Q

What is a patient population that is at risk for neuroleptic malignant syndrome?

A

Patients with Parkinson’s disease who

stop/reduce the dose of dopaminergics

26
Q

What is the mechanistic basis of neuroleptic malignant syndrome?

A

Marked decreased in dopamine activity (e.g. receptor block, rapid increase in antipsychotic dose)

27
Q

What are 2 drugs that can be used to aid treatment of neuroleptic malignant syndrome? How do they work?

A

Bromocriptine - Dopamine agonist

Dantrolene - Reduces muscle rigidity

28
Q

What are CNS side effects of antipsychotics (3)? Disruption of what area brings about these symptoms?

A

Parkinsonian effects
Dystonias
Akathisia
Striatum

29
Q

With long term use of antipsychotics, what occurs to dopamine receptor numbers? What is the effect of this phenomenon? What is an example of a manifestation of this change?

A

Increased number of dopamine receptors
Supersensitivity to DA
Tardive dyskinesias - involuntary orofacial movements

30
Q

1st generation antipsychotics inhibit what 2 CYP enzymes? Metabolism of what drugs are affected by this?

A

CYP2A6, CYP3A4

SSRIs, macrolide antibiotics and antifungals

31
Q

1st generation antipsychotics induce CYP3A4. What effect does this have on their own metabolism?

A

It increases their own elimination, decreases efficacy

32
Q

What is the effect of antipsychotics of CNS depressants (alcohol, anesthetics, analgesics)?

A

Potentials their effects

33
Q

How do 1st generation antipsychotics affect L-DOPA used in the treatment of Parkinson’s disease?

A

Blocks its effects, reduces it therapeutic efficiency

34
Q

5 examples were provided of atypical antipsychotics that act as selective serotonin and dopamine antagonists. They are _

A 
Paliperidone
Clozapine
Olanzapine
Quetiapine
Risperidone
35
Q

What is the example of an atypical antipsychotic that acts as a competitive partial agonist at dopamine receptors and antagonist at serotonin receptors?

A

Aripiprazole

36
Q

How does 5HT2A activation lead to schizophrenic symptoms? How does this compare with D2 activation leading to schizophrenic symptoms?

A

Ends up activating PLC, PKC and ultimately inhibiting glutamatergic signaling and LTP
Same end game following D2 activation, but via PKA blockade

37
Q

What are 2 major metabolic side effects associated with Olanzapine?

A

Major weight gain

Increased glucose, cholesterol and triglycerides

38
Q

Majority of the atypical antipsychotics produce inactive metabolites for excretion. What is the exception? What is its active metabolite?

A 
Risperidone
Makes paliperidone (active metabolite)
39
Q

What are risperidone microspheres? What are they used for?

A

Slow release formula, deep gluteal IM admin

Used for orally non-compliant patients

40
Q

How can withdrawal / relapse after using risperidone be avoided?

A

Gradually discontiuning the medication

41
Q

Which 2nd generation antipsychotics are most likely to produce Hyperthermia, tachycardia, urinary retention, memory impairment, blurred vision, constipation and confusion? (3) Why?

A

Clozapine, olanzapine and quetiapine

Cholinergic muscarinic blockade

42
Q

Which 2nd generation antipsychotics are most likely to produce Vasodilation, orthostatic hypotension & lightheadedness, reflex tachycardia and sexual dysfunction? (4) Why?

A

Clozapine, olanzapine, aripiprazole and quetiapine

Alpha-adrenergic blockade

43
Q

Under what conditions would 2nd generation antipsychotics produce a minimal increase in prolactin? Why?

A

In cases of overdose

Pituitary D2 block

44
Q

Why might 2nd generation antipsychotics produce sedation and weight gain?

A

Blockade of 5HT and H1 receptor signaling

45
Q

What is an advantage of 2nd generation antipsychotics over 1st generation, regarding CNS side effects?

A

Lower risk of extrapyramidal side effects i.e. less chance of parkinsonian effects, dystonias or tardive dyskinesia

46
Q

Except for aripiprazole, what is a disadvantage of 2nd generation antipsychotics over 1st generation, regarding metabolic side effects?

A

Higher chance of glucose intolerance, lipid abnormalities and diabetes type 2

47
Q

What is a specific risk associated with the use of clozapine?

A

Agranulocytosis and leukopenia (delayed onset)

48
Q

What CYP enzymes are inhibited by atypical antipsychotics? What drugs are affected?

A

CYP2D6 and CYP3A4

SSRIs, macrolide antibiotics and antifungals

49
Q

What is the effect of atypical antipsychotics on CNS depressants like alcohol, general anesthetics?

A

Potentiate their effects

50
Q

Under what conditions can atypical antipsychotics cuse, hypotension, hyperthermia, seizures, coma or ventricular tachycardia?

A

In cases of overdose

Medical Pharmacology Exam 2 (16 decks)

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