Antipsychotics

Front 1

Where do all of antipsychotics cause their pharmacodynamic effects?

Back 1

They interact with neurotransmitter receptors in both central and the autonomic nervous system. (the effects of antipsychotics at the autonomic receptors are usually considered to be adverse effects)

Front 2

Most antipsychotics act as _____ at the receptors they bind to.

Back 2

antagonist

Front 3

What are 2 mechanisms which attribute to antipsychotic drugs efficacy?

Back 3

1. Blockade of D2 receptors (a type of dopamine receptor) in the CNS
2. Blockade of serotonin (5-HT) receptors in the CNS. (5-HT2A subtype appears to be especially impt. with regard to antipsychotic efficacy)

Front 4

The individual receptor blockade profile of each antipsychotic is an impt. factor in determining two things:

Back 4

1. the efficacy of the antipsychotic for treatment of various symptoms of schizophrenia and
2. the adverse effect profile of the antipsychotic

Front 5

What does the 5-HT2A/D2 Ki ratio represent?

Back 5

It represents the relative affinity of an antipsychotic for 5-HT2A blockade versus D2 blockade.

Front 6

What does a smaller Ki value mean?

Back 6

It means that a drug has a higher affinity for binding to and blocking a specific receptor.

Front 7

What happens if the Ki is lower for 5-HT2A bloackade then for D2 bloackade?

Back 7

Then the ratio will be a number less than 1. Since a lower Ki value means higher affinity, a 5-HT2A/D2 Ki ratio of less than 1 results.

Front 8

What does a 5-HT2A/D2 Ki ratio of less than 1 indicate?

Back 8

It indicates that the drug has a higher affinity for 5-HT2A receptor blockade than it does for D2 receptor blockade.

Front 9

Name 7 Atypical antipsychotics.

Back 9

Aripiprazole, Clozapine, Olanzapine, Paliperidone, Quetiapine, Risperidone, Ziprasidone

Hint 9

"CZARQOP"

Front 10

Name 4 Conventional antipsycotics.

Back 10

Chlorpromazine, Fluphenazine, Haloperidol, Perphenazine

Front 11

All conventional drugs are variations of which core chemical ring system?

Back 11

phenothiazine

Front 12

What is significant about chlorpromazine's chemistry?

Back 12

It's aliphatic chemistry decreases affinity for D2 receptor blockade. (aliphatic phenothiazine)

Front 13

What is significatn about fluphenazine's chemistry?

Back 13

It's piperazine ring increases affinity for D2 receptor blockade. (piperazine phenothiazine)

Front 14

What is the most commonly used conventional antipsychotic?

Back 14

Haloperidol

Front 15

What is haloperidol classified as?

Back 15

Butyrophenone

Front 16

What is the chemistry of Haloperidol?

Back 16

piperazine phenothiazine. It has much higher affinity for blackade of D2 receptors than any other CNS receptors.

Front 17

Which 2 conventional drugs are marketed as ester prodrug derivatives for use as depot injections?

Back 17

Haloperidol and Fluphenazine

Front 18

Chemically, what two esters are added to the drugs, resulting in prodrugs that will be converted to active drug upon injection into the body?

Back 18

Deconoate or enanthate esters

Front 19

What is the significance of prodrugs are formulated in sesame seed oil, which allows for deep IM injection.

Back 19

It results in a depot of drug in muscle tissue which significantly delays release and activation of prodrugs. They are especially useful for noncompliant patients.

Front 20

TRUE/FALSE. Most of the atypical antipsychotics are structurally unique in that they do not share a core ring structure.

Back 20

TRUE.

Front 21

Paliperidone is an active metabolite of?

Back 21

Paliperidone, as it is 9-hydroxyl-risperidone, an active metabolite of the atypical antipsychotic drug risperidone.

Front 22

What is a common difference between atypical and conventional antipsychotics?

Back 22

Most atypical antipsychotics have a lower 5-HT2A/D2 Ki ratior relative to conventional antipsychotics. This means they have higher selectivity for blocking serotonin receptors then dopamine receptors.

Front 23

Atypical drugs versus conventional drugs:

Back 23

1. Increased efficacy of atypical antipsychotics against negative symtoms of schizophrenia relative to conventional antipsychotics and
2. a lower incidence of adverse effects caused by D2 receptor blockade relative to conventional antipsychotics

Front 24

Name the 6 positive schizophrenia symtoms.

Back 24

1. Delusions
2. Hallucinations
3. Disorganized speech
4. Disorganized thinking
5. Diorganized behavior
6. Catatonia

Front 25

Name the 4 negative schizophrenia symptoms.

Back 25

1. Flattened affect
2. Social withdrawal
3. Avolition
4. Alogia

Front 26

Why are atypical antipsychotics superior for the treatment of negative schizophrenia symptoms?

Back 26

Because of their high affinity for 5-HT receptor bloackade, particularily 5-HT2A

Front 27

EPS (Extrapyramidal side effects) are more likely to occur with _________ antipsychotics and is less frequent with ______ antipsychotics.

Back 27

conventional antipsychotics, atypical antipsychotics

Front 28

What is EPS due to?

Back 28

potent blockade of D2 receptors in motor control regions of the brain.

Front 29

What kind of dose do conventional drugs with a high affinity for blocking D2 receptors?

Back 29

conventional antipsychotics high affinity for blocking D2 receptors are more potent, and therefore require a lower daily dose.

Front 30

What kind of dose do conventional drugs with a low affinity for blocking D2 receptors?

Back 30

conventional antipsychotics low affinity for blocking D2 receptors are less potent, and therefore require a higher daily dose.

Front 31

TRUE/FALSE. High potency conventional antipsychotics (haloperidol) are more likely to cause EPS than are low potency conventional antipsychotics (chloropromazine) or atypical antipsychotics (quetiapine).

Back 31

TRUE.

Front 32

Name the 3 major symptoms that EPS is divided into.

Back 32

1. Dystonia,
2. Akathisia
3. Pseudoparkinsonism

Front 33

What is dystonia?

Back 33

sudden muscle rigidity of the neck, pharyngeal-laryngeal areas, tongue, and other areas of the upper body

Front 34

What does Akathisia mean?

Back 34

The inability to sit still and is manifested as extreme restlessness.

Front 35

What is pseudoparkinsonism?

Back 35

Symotoms are similar to those seen in parkinson's disease (this should make sense, as parkinson's disease is due to loss of dopaminergic activity in motor control regions of the brain.)

Front 36

What are used to treat or prevetn dystonias and pseudoparkinsonism?

Back 36

Antimuscarinic drugs. Examples include benzotropine and diphenyhydramine.

Front 37

What is used for the management of akathisia?

Back 37

Beta adrenergic antagonist with significant CNS activity (propranolol)

Front 38

What is the cause for tardive dyskinesia?

Back 38

The exact cause is unknown, but is probably due to a "supersensitisation" of dopamine receptors secondary to chronic administration of an antipsychotic. It usually sppears after a long period (months to years) of exposure to an antipsychotic.

Front 39

Tardive antipsychotics are rare with _______ antipsychotics.

Back 39

atypical antipsychotics

Front 40

What is tardive dyskinesia?

Back 40

Tardive dyskinesia consists of involuntary motor movements, of which the patient is often completely unaware.

Front 41

What are the symptoms of tardive dyskinesia?

Back 41

Symptoms usually involve the face, but can also involve extremities. Typical symptoms are tongue protrusion, lip smacking, eyebrow arching, excessive blinking, grimacing, pelvic thrusting, and extension of fingers and toes.

Front 42

How can you treat tardive dyskinesia?

Back 42

changing antipsychotics, but usually some portion of the symotoms of tardive dyskinesia are permanent

Front 43

Which drugs cause the most ANS toxicities?

Back 43

Low potency (high dose) conventional antipsychotics, such as chlorpromazine.

Front 44

What are the common symptoms of ANS toxicities resulting from a blockade of muscarinic and alpha-1 adrenergic receptors?

Back 44

Antimuscarinic effects (dry mouth, constipation, urinary retention) and orthostatic hypotension.

Front 45

Which atypical antipsychotic has strong antimuscarinic effects?

Back 45

clozapine. Instead of causing dry mouth, it causes extreme excess in drooling.

Front 46

What are the sedative/drowsiness effects of antipsychotics due to?

Back 46

Blockade of histamine receptors in the CNS

Front 47

What is an adverse effect of clozapine?

Back 47

life-threatening agranulocytosis

Front 48

What is an adverse effect in many antipsychotics? Which drug is the worst and which drug is the mildest?

Back 48

significant weight gain. Olanzapine is the worst and Ziprasidone is the mildest.

Front 49

What is an adverse effect of ziprasidone?

Back 49

life-threatening widening of the QT interval, and must be used with ccaution in patients with certain cardiac diseases.

Front 50

What is an adverse effect of atypical antipsychotics

Back 50

increased risk for development of hyperlipidemia and type II diabetes mellitus

Front 51

TRUE/FALSE. Due to the numerous CNS and autonomic receptors bloacked by antipsychotics, there are many potential pharmacodynamic drug interactions that may occur with other medicines administered concurrently.

Back 51

TRUE

Front 52

Pharmacokinetic drug interactions involving antipsychotic are due to....

Back 52

inhibition of CYP450 enzymes

Front 53

The majority of antipsychotics are metabolized by?

Back 53

CYP2D6, a specific isoform of CYP450. Other drugs that inhibit this isoform may increase blood levels of many antipsychotics and lead to increased adverse effects.