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Pharm > Antipsychotics > Flashcards

Antipsychotics Flashcards

1
Q

Dopamine hypothesis

A

Overstimulation of dopamine receptors are at the heart of schizophrenia

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2
Q

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

A

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

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3
Q

Current hypothesis of schizophrenia

A

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

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4
Q

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

A

positive symptoms of schizophrenia.

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5
Q

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

A

typical

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6
Q

Typical APs are less effective in treating

A

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

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7
Q

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

A

60% to 70%

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8
Q

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

A

parkinsonism

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9
Q

APs: Prolactin elevation appears beyond __ D2 occupancy.

A

72%

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10
Q

APs: As D2 occupancy nears 78%,

A

extrapyramidal symptoms (EPSs) are more prominent

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11
Q

APs: Onset of oral agents

A

1 to 2 hours

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12
Q

APs: Onset of IM injections

A

10 to 30 minutes

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13
Q

APs: Onset of decanoate forms

A

1 to 9 days

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14
Q

Typical APs are metabolized in the

A

liver and excreted in the urine

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15
Q

Half-life varies ___ among Typical APs

A

widely

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16
Q

Typical APs: Because of their lipid solubility,

A

several weeks may be required before their antipsychotic benefits become evident

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17
Q

FDA Black-Box Warning for all APs

A

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

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18
Q

Typical APs may be grouped according to

A

high or low potency

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19
Q

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).

A

chlorpromazine and thioridazine

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20
Q

Low-potency drugs such as chlorpromazine and thioridazine carry less

A

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

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21
Q

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

A

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

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22
Q

Typical Antipsychotics: Contraindications:

A

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

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23
Q

Typical Antipsychotics: Caution:

A

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

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24
Q

Typical Antipsychotics: pregnancy and lactation.

A

unknown if it’s safe

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25
Q

Neuroleptic malignant syndrome (NMS) characterized by

A

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

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26
Q

The really bad ADRs of typical APs:

A 
NMS
EPSs and pseudoparkinsonism 
akathisia  
dystonia 
tardive dyskinesia
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27
Q

tardive dyskinesia

A

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

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28
Q

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

A

irreversible

29
Q

EPSs and pseudoparkinsonism

A

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

30
Q

akathisia

A

(restlessness)

31
Q

dystonia

A

(involuntary, painful movements)

32
Q

___ and ___ drugs are used to counter EPS

A

antihistamine and anticholinergic drugs

33
Q

Less serious ADRs of typical APs

A 
sedation
weight gain
anticholinergic effects
photosensitivity
reduction of seizure threshold
orthostatic hypotension
sexual dysfunction
galactorrhea
amenorrhea
34
Q

Typical Antipsychotic Drug Interactions: ____ depressants

A

it makes CNS depression worse with CNS depressants

35
Q

Typical Antipsychotic Drug Interactions: antihypertensives

A

increases hypotension

36
Q

Typical Antipsychotic Drug Interactions: lithium

A

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

37
Q

Typical Antipsychotic Drug Interactions: anticholinergics

A

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

38
Q

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

A

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

39
Q

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

A

fluid intake and dietary bulk.

40
Q

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

A

2 to 4 weeks.

41
Q

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

A

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

42
Q

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

A

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

43
Q

Before starting any atypical antipsychotic, patients should be assessed for

A

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

44
Q

Atypical APs: The practitioners should recheck

A

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

45
Q

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

A

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

46
Q

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,

A

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.

47
Q

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

A

generally have less D2 blockade than the typical APs.

48
Q

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

A

EPSs

49
Q

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

A

clozapine, olanzapine

50
Q

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

A

olanzapine, clozapine

51
Q

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

A

clozapine

52
Q

Drugs that block noradrenergic receptors (clozapine) produce more

A

hypotension.

53
Q

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

A

weight gain and sedation.

54
Q

With Lithium, be careful if the patient has

A

sodium depletion and diuretic use

55
Q

Absorption of Li

A

absorbed in the GI tract- not affected by food

56
Q

Distribution of Li

A

Widely distributed throughout the body

57
Q

Metabolism and excretion of Li

A

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

58
Q

Lithium monitoring

A

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

59
Q

Lithium: Clinical considerations

A

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

60
Q

Lithium: Pregnancy

A

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

61
Q

Lithium: Adverse effects

A

Fine tremors, nausea, dry mouth, polyuria, polydipsia

Weight gain, acne, hypercalcemia, muscle weakness

62
Q

Lithium: Signs of toxicity

A

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

63
Q

Lithium: Drug interactions

A

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

64
Q

Clozapine: overview

A

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.

65
Q

Clozapine: Indication

A

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

66
Q

Clozapine: Adverse effects

A

agranulocytosis

67
Q

Clozapine: Monitoring

A

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

68
Q

Clozapine: Drug Interactions

A

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

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