Anti-Psychotics Flashcards by Uche PM

How do psychosis and schizophrenia differ?

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

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

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

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

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

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

True

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

Non-compliance

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

Clozapine
Olanzapine
Quetiapine

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

Selective antagonists at dopamine receptors

Block D2 over D1

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

Selective antagonists at serotonin and dopamine receptors

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

Competitive partial agonists at dopamine receptors, antagonists at serotonin receptors

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

Chlorpromazine
Fluphenazine
Thiothexene
Haloperidol
D2 over D1 antagonists

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What is the dopamine hypothesis of schizophrenia?

That increased activity of dopaminergic neuron underlies the symptoms of schizophrenia

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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?

D2 dopamine receptors
Increased therapeutic efficiency
Post-synaptically

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

Activation - Decreased PKA, and decreased NMDAR activity

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

Enhanced reduction in PKA and NMDAR signalling, stronger schizophrenic pathology

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

High - Haloperidol, Fluphenazine
Med - Thiothixene
Low - Chlorpromazine

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

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

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

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

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

Blockade of dopaminergic and other* receptor pathways

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

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

Chlorpromazine

Blockade of Cholinergic muscarinic activity

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

Chlorpromazine

Blockade at alpha adrenergic receptors

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

Haloperidol

Pituitary block of D2 receptors

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

Chlorpromazine

H1 histamine receptor block

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

Promethazine

Prochlorperazine

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

Neuroleptic malignant syndrome

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

Patients with Parkinson’s disease who | stop/reduce the dose of dopaminergics

What is the mechanistic basis of neuroleptic malignant syndrome?

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

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

Bromocriptine - Dopamine agonist | Dantrolene - Reduces muscle rigidity

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

Parkinsonian effects Dystonias Akathisia Striatum

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?

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

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

CYP2A6, CYP3A4 | SSRIs, macrolide antibiotics and antifungals

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

It increases their own elimination, decreases efficacy

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

Potentials their effects

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

Blocks its effects, reduces it therapeutic efficiency

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

``` Paliperidone Clozapine Olanzapine Quetiapine Risperidone ```

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

Aripiprazole

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

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

What are 2 major metabolic side effects associated with Olanzapine?

Major weight gain | Increased glucose, cholesterol and triglycerides

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

``` Risperidone Makes paliperidone (active metabolite) ```

What are risperidone microspheres? What are they used for?

Slow release formula, deep gluteal IM admin | Used for orally non-compliant patients

How can withdrawal / relapse after using risperidone be avoided?

Gradually discontiuning the medication

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

Clozapine, olanzapine and quetiapine | Cholinergic muscarinic blockade

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

Clozapine, olanzapine, aripiprazole and quetiapine | Alpha-adrenergic blockade

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

In cases of overdose | Pituitary D2 block

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

Blockade of 5HT and H1 receptor signaling

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

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

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

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

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

Agranulocytosis and leukopenia (delayed onset)

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

CYP2D6 and CYP3A4 | SSRIs, macrolide antibiotics and antifungals

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

Potentiate their effects

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

In cases of overdose