Antipsychotics

Question 1

Dopamine hypothesis

Answer 1

Overstimulation of dopamine receptors are at the heart of schizophrenia

Question 2

Dopamine hypothesis formed the basis of the typical antipsychotic agents effects in

Answer 2

reducing the positive symptoms of schizophrenia, such as hallucinations and delusions.

Question 3

Current hypothesis of schizophrenia

Answer 3

involves overactivity of D2 receptors in the basal ganglia, hypothalamus, limbic system, brainstem and medulla
This is thought to contribute to the positive symptoms
Underactivity of D1 receptors in the prefrontal cortex.
This is thought to contribute to the negative symptoms, such as lack of motivation and social isolation

Question 4

The typical APs block D2 receptors in the basal ganglia, hypothalamus, limbic system, brainstem, and medulla and reduce the

Answer 4

positive symptoms of schizophrenia.

Question 5

The ____ APs block D2 receptors in the basal ganglia, hypothalamus, limbic system, brainstem, and medulla and reduce the positive symptoms of schizophrenia.

Answer 5

typical

Question 6

Typical APs are less effective in treating

Answer 6

the negative symptoms of schizophrenia, such as flat affect, decreased motivation, withdrawal from interpersonal relationships, and poor grooming and hygiene

Question 7

APs: Clinical effectiveness occurs when ___ of D2 receptors are blocked

Answer 7

60% to 70%

Question 8

Too much dopamine blockade from APs leads to symptoms resembling those of

Answer 8

parkinsonism

Question 9

APs: Prolactin elevation appears beyond __ D2 occupancy.

Answer 9

72%

Question 10

APs: As D2 occupancy nears 78%,

Answer 10

extrapyramidal symptoms (EPSs) are more prominent

Question 11

APs: Onset of oral agents

Answer 11

1 to 2 hours

Question 12

APs: Onset of IM injections

Answer 12

10 to 30 minutes

Question 13

APs: Onset of decanoate forms

Answer 13

1 to 9 days

Question 14

Typical APs are metabolized in the

Answer 14

liver and excreted in the urine

Question 15

Half-life varies ___ among Typical APs

Answer 15

widely

Question 16

Typical APs: Because of their lipid solubility,

Answer 16

several weeks may be required before their antipsychotic benefits become evident

Question 17

FDA Black-Box Warning for all APs

Answer 17

may result in increased mortality in elderly patients with dementia-related psychosis and are not approved for the treatment of such patients

Question 18

Typical APs may be grouped according to

Answer 18

high or low potency

Question 19

Low-potency drugs such as ____ and ___ carry less risk of EPSs but more risk of anticholinergic adverse reactions (dry mouth, constipation, urinary retention, blurred vision) and antiadrenergic effects (orthostatic hypotension).

Answer 19

chlorpromazine and thioridazine

Question 20

Low-potency drugs such as chlorpromazine and thioridazine carry less

Answer 20

risk of EPSs but more risk of anticholinergic adverse reactions (dry mouth, constipation, urinary retention, blurred vision) and antiadrenergic effects (orthostatic hypotension).

Question 21

Low-potency drugs such as chlorpromazine and thioridazine carry less risk of EPSs but more risk

Answer 21

of anticholinergic adverse reactions (dry mouth, constipation, urinary retention, blurred vision) and antiadrenergic effects (orthostatic hypotension).

Question 22

Typical Antipsychotics: Contraindications:

Answer 22

narrow-angle glaucoma, bone marrow depression, and severe liver or cardiovascular disease.

Question 23

Typical Antipsychotics: Caution:

Answer 23

CNS tumors, epilepsy, diabetes mellitus, respiratory disease, and prostatic hypertrophy

Question 24

Typical Antipsychotics: pregnancy and lactation.

Answer 24

unknown if it’s safe

Question 25

Neuroleptic malignant syndrome (NMS) characterized by

Answer 25

fever up to 107°F, elevated pulse, diaphoresis, rigidity, stupor or coma, and acute renal failure.

Question 26

The really bad ADRs of typical APs:

Answer 26

``` NMS EPSs and pseudoparkinsonism akathisia dystonia tardive dyskinesia ```

Question 27

tardive dyskinesia

Answer 27

involuntary buccolingual movements, difficulty speaking and swallowing, which may be irreversible

Question 28

tardive dyskinesia is involuntary buccolingual movements, difficulty speaking and swallowing, which may be

Answer 28

irreversible

Question 29

EPSs and pseudoparkinsonism

Answer 29

(shuffling, pill-rolling, cog-wheeling, tremors, drooling, rigidity)

Question 30

akathisia

Answer 30

(restlessness)

Question 31

dystonia

Answer 31

(involuntary, painful movements)

Question 32

___ and ___ drugs are used to counter EPS

Answer 32

antihistamine and anticholinergic drugs

Question 33

Less serious ADRs of typical APs

Answer 33

``` sedation weight gain anticholinergic effects photosensitivity reduction of seizure threshold orthostatic hypotension sexual dysfunction galactorrhea amenorrhea ```

Question 34

Typical Antipsychotic Drug Interactions: ____ depressants

Answer 34

it makes CNS depression worse with CNS depressants

Question 35

Typical Antipsychotic Drug Interactions: antihypertensives

Answer 35

increases hypotension

Question 36

Typical Antipsychotic Drug Interactions: lithium

Answer 36

when used with phenothiazines it can increase the risk of EPS and also mask early signs of Li toxicity

Question 37

Typical Antipsychotic Drug Interactions: anticholinergics

Answer 37

Anticholinergic effects increased with other agents having anticholinergic properties. Increased risk of hyperthermia

Question 38

EPSs can be decreased or eliminated by the addition of drugs such as benztropine (Cogentin), diphenhydramine (Benadryl), what are 3 others?

Answer 38

trihexyphenidyl (Artane), atenolol (Tenormin), or amantadine (Symmetrel).

Question 39

Some anticholinergic effects, such as constipation, can be addressed by nonpharmacological measures, such as increased

Answer 39

fluid intake and dietary bulk.

Question 40

The depot or decanoate form of medication may be used if compliance is an issue. It is usually administered every

Answer 40

2 to 4 weeks.

Question 41

Atypical APs: they treat both positive and negative symptoms. Also they are characterized by

Answer 41

less risk for EPSs, TD, and elevation of prolactin levels.

Question 42

Atypical APs: They have less risk for EPSs, TD, and elevation of prolactin levels, but they still cause

Answer 42

weight gain, which leads to a metabolic syndrome (abdominal obesity, high blood pressure, high cholesterol levels, and insulin resistance).

Question 43

Before starting any atypical antipsychotic, patients should be assessed for

Answer 43

waist circumference, body mass index (BMI), blood pressure (BP), fasting plasma glucose, and lipid profile.

Question 44

Atypical APs: The practitioners should recheck

Answer 44

BMI monthly and order laboratory work-ups at 3 months. After 3 months, the BMI should be checked quarterly and BP, laboratory work-ups, and waist circumference annually

Question 45

Atypical APs: Although the mechanism of action for these APs is not precisely understood, the atypical APs are thought to

Answer 45

block serotonin receptors in the cortex, which blocks the usual ability of serotonin to inhibit the release of dopamine.

Question 46

Although the mechanism of action for these APs is not precisely understood, the atypical APs are thought to block serotonin receptors in the cortex, which blocks the usual ability of serotonin to inhibit the release of dopamine. Thus,

Answer 46

more dopamine is released to the prefrontal cortex, which reduces the negative symptoms of schizophrenia. All drugs with antipsychotic properties block dopamine D2 receptors, but atypical APs generally have less D2 blockade than the typical APs.

Question 47

All drugs with antipsychotic properties block dopamine D2 receptors, but atypical APs

Answer 47

generally have less D2 blockade than the typical APs.

Question 48

Drugs with the least D2 blockade (clozapine, olanzapine) have the lowest incidence of

Answer 48

EPSs

Question 49

Drugs with the least D2 blockade (____, ____) have the lowest incidence of EPSs.

Answer 49

clozapine, olanzapine

Question 50

Drugs that are potent histamine H1 receptor antagonists (____, ____) produce more weight gain and sedation.

Answer 50

olanzapine, clozapine

Question 51

Drugs that block noradrenergic receptors (____) produce more hypotension.

Answer 51

clozapine

Question 52

Drugs that block noradrenergic receptors (clozapine) produce more

Answer 52

hypotension.

Question 53

Drugs that are potent histamine H1 receptor antagonists (olanzapine, clozapine) produce more

Answer 53

weight gain and sedation.

Question 54

With Lithium, be careful if the patient has

Answer 54

sodium depletion and diuretic use

Question 55

Absorption of Li

Answer 55

absorbed in the GI tract- not affected by food

Question 56

Distribution of Li

Answer 56

Widely distributed throughout the body

Question 57

Metabolism and excretion of Li

Answer 57

Not metabolized by the liver and excreted primarily unchanged in the urine Kidney function is crucial in lithium management

Question 58

Lithium monitoring

Answer 58

5-7 days after start of treatment (steady state) Obtain blood levels 14 days after starting and after every change in dose Take level 10-12 hours after last dose Goal: 0.5-1.2mEq/L

Question 59

Lithium: Clinical considerations

Answer 59

Indicated for maintenance of mood stability and prevention of mania or hypomania Lithium takes 10-14 days to reach maximum efficacy Initial supplement with agents such as haloperidol or risperidone may be used until symptoms of mania have subsided

Question 60

Lithium: Pregnancy

Answer 60

1st trimester- 10% chance of fetal abnormalities-> cardiac anomalies 3rd trimester- significant risk for neonatal lithium toxicity -Hypertonicity -Congenital hypothyroidism -Congenital goiter

Question 61

Lithium: Adverse effects

Answer 61

Fine tremors, nausea, dry mouth, polyuria, polydipsia | Weight gain, acne, hypercalcemia, muscle weakness

Question 62

Lithium: Signs of toxicity

Answer 62

Coarse hand tremor, slurred speech, confusion, hypotension, coma, seizures

Question 63

Lithium: Drug interactions

Answer 63

CYP450 is not involved in the drug interactions because lithium is not metabolized in the liver Drugs that alter the fluid balance will be the main cause of drug interactions Diuretics- can increase sodium excretion -> increase lithium concentrations NSAIDs and COX 2 inhibitors reduce renal elimination -> increase lithium concentrations Theophylline, caffeine, sodium salts, bulking agents (metamucil) -> decrease lithium concentrations Anticonvulsants -> may result in toxicity of both drugs

Question 64

Clozapine: overview

Answer 64

Atypical antipsychotic Less D2 blockade resulting is less EPS Potent H1 antagonist Produces more weight gain and sedation Blocks noradrenergic receptors-> produced more hypotension Clozapine is available only through a patient management system.

Question 65

Clozapine: Indication

Answer 65

Refractory severe schizophrenia (Reserved for treatment of severe schizophrenia refractory to complete trials of at least two different types of antipsychotics)

Question 66

Clozapine: Adverse effects

Answer 66

agranulocytosis

Question 67

Clozapine: Monitoring

Answer 67

Baseline CBC with differential prior to starting drug therapy, then once or twice a week Symptoms of low white blood cell count Fever, lethargy, buising, sore throat, flu-like symptoms

Question 68

Clozapine: Drug Interactions

Answer 68

Anticholinergics- > increased anticholinergic effects Caffeine-> increased effect of clozapine Lithium -> increased risk of neurotoxicity and agranulocytosis