Antipsychotic Pharmacology (Dr. Hamouda) flashcards |

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What are the two main groups of antipsychotic medications?

1. First generation (older)
2. Second generation (er)

All of the older generation antipsychotics have this MOA...

D2 blockers

All of the er generation antipsychotics have this MOA...

D2 and 5HT2A receptor blockers

Most antipsychotics have an ______ effect.

Antiemetic

What is the dopamine hypothesis of schizophrenia?

Blocking dopamine correlates with time course of behavioral effects

What is the serotonin hypothesis of schizophrenia?

Many atypical antipsychotics are potent 5-HT2C receptor antagonists/inverse agonists.
- 5HT2A (5HT2C) activity activity modulates the release of several neurotransmitters

Atypical antipsychotics are effective with much less effect on _____.

Dopamine receptors

Atypical antipsychotics have a higher affinity for _____ receptors.

5-HT2

Most typical antipsychotics have a higher affinity for _____ receptors.

D2

What is the prototype drug for typical antipsychotics?

Chlorpromazine

Side effects of antipsychotics come from binding....

- Alpha adrenoreceptors
- Muscarinic receptors
- H1 histamine reseptors

Aripiprazole is a ______ at D2 receptors.

Partial agonist

Chlorpromazine has a higher affinity for _____ receptors.

D2

Which is most widely used typical antipsychotic?

Haloperidol

Haloperidol has a high risk of ____ (side effect).

Extra pyramidal symptoms

Which is the prototype for atypical antipsychotics?

Clozapine

Clozapine is typically used now for ______ schizophrenia.

Refractory

Atypical antipsychotics lack _____ at therapeutic levels.

Extra pyramidal symptoms

Typical antipsychotics must occupy ____ of D2 receptors in the striatum.

>60%

The "therapeutic" window for typical antipsychotics is ____ occupancy of D2 receptors.

65-80%

At >80% occupancy of D2 receptors by typical antipsychotics ____ can occur.

Extra pyramidal side effects

Atypical antipsychotics are effective at _____ occupancy of receptors.

30-50%

Aripiprazole is a _____ at D2 receptors.

Partial agonist

Haloperidol is an ______ of D2 receptors.

Antagonist

Atypical antipsychotics are ______ of the 5-HT2A receptor.

Inverse agonists

Aripiprazole reduces ______ levels. (Hormone)

Prolactin

Aripiprazole stimulates D2 receptors if ______.

Synaptic DA is limited

Aripirazole decreases DA activity when...

DA activity is high

T/F: Antupsychotics are highly lipophilic.

True

T/F: Most antipsychotics undergo extensive CYP metabolism?

True

T/F: Most antipsychotics have no active metabolites.

False; They typically have one or more active metabolites

Side effects from blocking muscarinic receptors?

- Dry mouth
- Loss of accommodation
- Difficulty urinating
- Constipation
- Toxic confusional state

Side effects from blocking alpha- adrenergic receptors?

- Orthostatic hypotension
- Impotence
- Failure to ejaculate

Side effects from blocking dopamine receptors?

- Parkinson's syndrome
- Akathisia
- Dystonias
- Hyperprolactinemia (except aripiprazole)

Side effects of combines H1 and 5-HT receptors?

Weight gain

T/F: With the exception of aripiprazole, all antipsychotics have D2 blockade properties.

True

The most important and unwanted side effect of antipsychotic drugs is...

Tardive dyskinesia

What should be done if a patient develops tardive dyskinesia?

Switch therapy to quetiapine or clozapine

T/F: Neuroleptic malignant syndrome is a life threatening condition?

True

What are signs/symptoms of neuroleptic malignant syndrome

Severe case of Parkinsonism
- Extreme muscle rigidity
- Very high fever
- Autonomic instability
-Elevated muscle type creatine kinase levels

T/F: All typical antipsychotics can cause hyperprolactinemia

True

Effects of hyperprolactinemia?

- Breast enlargement
- Galactorrhea
- Amenorrhea and osteoporosis in women
- Sexual dysfunction and infertility in men

Main side effects predicted by H1 receptor...

Sedation
Weight gain via appetite stimulation

Other side effects of antipsychotics...

- Agranulocytosis
- Retinal deposits
- Deposits in the cornea and lens
- Seizures
- QT prolongation

Treatment options for Bipolar Disorder...

- Lithium
- Anticonvulsants (Valproate, Carbamazepine)
- Antipsychotics (Aripiprazole, Olanzapine, Ziprasidone)

Lithium inhibits these enzymes...

- Inositol monophosphatase
- Inositol polyphosphate 1-phosphatase

Lithium MOA...

Inhibits the rate limiting enzyme in inositol recycling, and this depletes PIP2 and second messangers

Lithium side effects...

Polyuria and compensatory polydipsia
- Cardiovascular side effects at overdose levels
- Benign thyroid enlargement, hypothyroidism
- Weight gain
- Fine postural hand tremor

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