Antipsychotics Flashcards Preview

Pharm III - Exam 4 > Antipsychotics > Flashcards

Flashcards in Antipsychotics Deck (93)
Loading flashcards...
1

Goals of acute treatment of schizophrenia

-Relieve distressing psychotic symptoms
-Induce remission
-Minimize adverse effects

2

Goals of maintenance treatment of schizophrenia

-Prevent relapse
-Prevent re-hospitalization
-Improve quality of life

3

What NT systems are implicated in schizophrenia?

-Serotonin
-Dopamine
-Glutamate

4

Which NT system is NOT targeted by any antipsychotics currently?

Glutamate

5

What are the dopaminergic pathways in the CNS?

1. Mesocortical
2. Mesolimbic
3. Nigrostriatal
4. Tubero-infundibular

6

Function of mesocortical tract?

-Cognition
-Communication
-Social function
-Response to stress

7

Function of mesolimbic tract?

-Arousal
-Memory
-Stimulus processing
-Motivational behavior

8

Function of nigrostriatal tract?

-Extrapyramidal system
-Movement

9

Function of tubero-infundibular tract?

Regulation of prolactin release

10

Dopamine antagonistic effect in mesocortical tract?

-Relief of psychosis
-Akathisia

11

Dopamine antagonistic effect in mesolimbic tract?

Relief of psychosis

12

Dopamine antagonistic effect in nigrostriatal tract?

Movement disorders

13

Dopamine antagonistic effect in tubero-infundibular tract?

Hyperprolactinemia

14

1st generation vs. 2nd generation antipsychotics

Binding affinity is higher in 2nd generation so fewer side effects

15

What is the only antipsychotic that is NOT considered 1st line treatment?

Clozapine

16

MC used first generation antipsychotics (FGAs)?

Chlorpromazine
Fluphenazine
Perphenazine
Haloperidol

17

How do FGAs work?

-D2 blocking in all 4 DA pathways
-H1 blocking
-M1 (cholinergic) blocking and A1 blocking

18

How are FGAs classified?

By potency for D2 blocking

19

What are the effects of low dose, high potency FGAs? Which FGAs?

-Greater affinity for D2 receptors which means greater potential for extrapyramidal side effects, hyperprolactinemia
-Fluphenazine, Perphenazine, Haloperidol

20

What are the effects of high dose, low potency FGAs? Which FGAs?

-More likely to cause sedation, orthostatic hypotension (anticholinergic and antihistaminergic effects)
-Chlorpromazine

21

Which FGAs are immediate acting and what route?

Haloperidol and chlorpromazine (IM)

22

Which FGAs are long acting depot formulations and what route?

-IM biweekly or monthly
-Esters dissolved in sesame oil (haloperidol/fluphenazine decanoate)

23

What is the role for long acting depot formulation of FGAs?

Non-compliant patients with their oral meds

24

What is the role for immediate acting IM injections of FGAs?

Acutely psychotic/agitated patients (NOT meant to replace oral meds)

25

Adverse effects of FGAs?

-H1 blocking: sedation, wt gain
-M1 blocking: dry mouth, urinary retention, tachy, ED, cognitive dysfunction
-A1 blocking: orthostatic hypotension, dizzy
-QT prolongation (Torsades)
-D2 blocking (endocrine): hyperprolactinemia
-EPSEs (acute dystonia, akathisia, pseudoparkinsonism)

26

What are the CV effects of FGAs?

-A1 blocking: orthostatic hypotension, dizzy
-QT prolongation: Torsades (thioridazine, mesoridazine, haloperidol, pimozide)

27

Which FGAs have a black box warning for QT prolongation/Torsades?

Thioridazine and mesoridazine
(QT prolong/Torsades also seen in haloperidol, pimozide)

28

Types of EPSEs

-Acute dystonia
-Akathisia
-Pseudoparkinsonism
-Tardive dyskinesias

29

Define acute dystonia

-Spasmodic or sustained muscle spasms and abnormal postures (often painful)
-Treat as medical emergency!

30

When may acute dystonia occur with FGA therapy?

Within minutes to hours

31

Risk factors for acute dystonia

-Young males
-High potency FGAs
-Immediate release IM administration of FGAs

32

Treatment choices for acute dystonia

-Anticholinergics: benztropine, diphenhydramine
-BZDs
-IM or IV

33

Define akathisia

Combo of objective and subjective symptoms
-Motor restlessness
-Feeling of inner restlessness or compulsion to move
-20-40% w/high potency FGAs
-Quetiapine and clozapine appear to have lowest risk of SGAs

34

What is akathisia frequently accompanied with?

Dysphoria

35

Which SGAs have lowest risk for akathisia?

Quetiapine and clozapine

36

Treatment of akathisia

-B blockers: propranolol, treatment of choice!
-BZDs (CI in substance abuse pts)
-Anticholinergics are NOT helpful

37

Define pseudoparkinsonism

-D2 blocking in nigrostriatal tract
-Resembles idiopathic Parkinson's disease

38

Cardinal symptoms of pseudoparkinsonism

1. Akinesia/bradykinesia
2. Resting tremor (pill rolling)
3. Cogwheel rigidity
4. Postural abnormalities

39

Treatment of pseudoparkinsonism

Anticholinergics: benztropine, diphenhydramine

40

When do symptoms of pseudoparkinsonism resolve with treatment?

-Symptoms begin to resolve within 3-4 days
-Minimum 2 wks treatment required for full response

41

What is used as treatment of pseudoparkinsonism if anticholinergics are contraindicated?

Amantadine

42

Define tardive dyskinesia and when it occurs in antipsychotic use

-Abnormal involuntary movements (increased when pt is aroused, decreased when pt is asleep)
-Occurs late in relation to initiation of antipsychotic therapy
-MUST monitor every 6 mos with AIMS

43

How to monitor tardive dyskinesia?

Abnormal Involuntary Movement Scale (AIMS) every 6 months

44

Prognosis of tardive dyskinesia

May be reversible early
Often irreversible

45

Risk factors for tardive dyskinesia

-Older age
-EPSEs
-Poor antipsychotic response
-DM
-Mood disorders
-Females

46

Treatment of tardive dyskinesia

-Reassess need for continuing antipsychotic (switch to atypical agent)
-High doses of Vit E NOT recommended (CV effects)

47

Define neuroleptic malignant syndrome

-Rare SE of FGAs (high potency)
-Onset varies (early in treatment to months later)
-Develops rapidly (over 24-72 hrs)
-May be d/t disruption of central thermoregulatory process

48

Risk factors of neuroleptic malignant syndrome

Dehydration
Organic mental disorders
Exhaustion

49

Lab evaluations of neuroleptic malignant syndrome

-Leukocytosis w/left shift
-Increased CK and LFTs
-Myoglobinuria

50

Treatment of neuroleptic malignant syndrome

-D/c antipsychotic
-Supportive care
-DA agonists (bromocriptine, amantadine)
-Dantrolene (muscle relaxant)

51

How can antipsychotics cause seizures?

Decrease the seizure threshold via GABA depletion

52

When is prophylaxis for seizures given with antipsychotics?

At high doses and in pts on other agents that lower seizure threshold

53

Highest risk for seizures with which antipsychotics?

Cozapine
Chlorpromazine

54

Which antipsychotics are more likely to cause thermoregulation side effects?

Low potency FGAs
Anticholinergic SGAs

55

Define poikilothermia

-Body temp adjustment to ambient temp
-Serious side effect in temp extremes

56

Define hyperpyrexia

-Danger in hot weather or during exercise
-Inhibition of sweating due to anticholinergic properties

57

How do SGAs work?

5HT blocking more than DA blocking

58

How do SGAs compare to FGAs?

-Greater efficacy for negative symptoms and cognitive deficits
-Decreased risk of EPSEs, hyperprolactinemia
-Absence (or near absence) of TD
-More rapid dissociation from D2 receptor

59

When are all antipsychotics contraindicated?

Elderly pts w/dementia-related psychosis (increased risk of death)

60

SGAs and dopaminergic pathways

-Mesocortical: more 5HT receptors here
-Mesolimbic: more D2 here
-Nigrostriatal: many 5HT receptors
-Tuberoinfundibular: many 5HT

61

Clozapine is specific for which DA tracts?

Mesolimbic
NOT nigrostriatal

62

Black box warnings of clozapine

-Agranulocytosis
-Seizures
-Myocarditis
-Other CV and resp effects

63

When is clozapine used in schizophrenia?

Reserved for pts refractory to AT LEAST 2 other antipsychotics (3rd line)

64

When could clozapine be used earlier in schizophrenia treatment?

Pts with history of recurrent suicidality, violence, or comorbid substance abuse

65

How should clozapine be administered?

Cautious titration to minimize risks of hypotension, seizure, resp depression, sedation

66

Clozapine ADEs

-Sedation
-Tachy
-Hypersalivation
-Dizzy
-Wt gain
-Agranulocytosis ETC ETC

67

Which antipsychotic has the highest seizure risk?

Clozapine

68

When is orthostatic hypotension more likely to occur with clozapine use?

More likely during initial dose titration

69

Black box warnings of Clozapine?

-Agranulocytosis
-Seizures
-Myocarditis
-Other CV and resp effects

70

Clozapine drug interactions

-CYP1A2 inhibitors/inducers
-Other drugs that cause agranulocytosis or lower seizure threshold

71

Clozapine monitoring

-REMS for agranulocytosis (measure ANC)
-EPSEs (AIMS every 6 months)
-Lipid panel, fasting glucose every 6 months
-Vitals multiple times daily during dose titration
-Weekly wt and waist circumference

72

Risperidone ADEs

-Anxiety, somnolence, constipation, nausea, rash (common)
-EPSEs and hyperprolactinemia
-Orthostatic hypotension
-Priapism (rare)

73

Risperidone drug interactions

-CYP2D6 inhibitors
-Other drugs that cause orthostasis

74

Risperidone monitoring parameters

-Prolactin levels every 6 months
-EPSEs (AIMS every 6 months)
-Lipid, fasting glucose every 6 months
-Vital signs multiple times daily during dose titration
-Weekly wt and waist circumference

75

ADEs of Olanzapine

-Dizzy, orthostatic hypotension, wt gain, akathisia (common)
-Anticholinergic
-Sedation
-HyperTG, hyperlipid, hyperglycemia

76

Olanzapine drug interactions

-CYP1A2
-Clearance increased 30-40% in smokers
-Plasma concentrations higher in females

77

Role of Quetiapine XR

-Replacement of IR dosing after steady state achieved
-Pt can be switched directly to XR
-Total daily XR dose is same as total daily IR dose

78

Quetiapine drug interactions

CYP3A4

79

Ziprasidone drug interactions

CYP3A4

80

Ziprasidone cautions

Can prolong QT interval (Torsades)

81

When should Ziprasidone be d/c?

Pts with QTc over 500 msec

82

Aripiprazole drug interactions

CYP3A4 inducers
CYP3A4 and CYP2D6 inhibitors

83

Aripiprazole cautions

Mild postural hypotension and sedation during initiation and dose titration

84

What is the active metabolite of Risperidone?

Paliperidone (9-hydroxyrisperidone)

85

How should Paliperidone be administered?

Tablet swallowed whole (do not chew, crush, divide)

86

What is Paliperidone?

Active metabolite of risperidone (9-hydroxyrisperidone)

87

ADEs of Paliperidone

Higher risk of EPSEs, hyperprolactinemia, QT prolongation than other atypical antipsychotics

88

Iloperidone drug interactions

CYP3A4 inhibitors or inducers
CYP2D6 inhibitors

89

Which SGAs increase the risk of QT prolongation?

AQIPZ
Asenapine
Quetipaine
Iloperidone
Paliperidone
Ziprasidone

90

Which SGAs are most likely to cause wt gain?

Clozapine
Olanzapine

91

Which SGAs are most likely to cause diabetes?

Clozapine
Olanzapine

92

Which SGAs are most likely to cause hypercholesterolemia?

Clozapine
Olanzapine

93

What are the monitoring parameters for all antipsychotics?

-EPSEs (AIMS every 6 months)
-Lipid panel, fasting glucose every 6 months
-Vital signs multiple times daily during dose titration
-Weekly wt gain and waist circumference