1. NARROW Therapeutic Index 2. Target [ ] → 0.8-1.2 mEq/L in Acute Mania 3. Target [ ] → 0.6 -0.8 mEq/L

Antipsychotics Flashcards by Karla Navarro-Vega

Carbamazepine 
Divalproex 
Lamotrigine 
Lithium 
Valporoic Acid 
→General Use 
→Which are ONLY for mania?

General use:
MOOD STABILIZERS

Only mania:
Divalproex
Valproic acid
(*others are mania w/ maintenance)

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Lithium

MOA

→Not well defined
→Recycles phosphoinositides
Affects the 2nd messengers

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Lithium
→Absorption: 
→Distribution: 
→Metabolism: 
→Excretion:

Lithium
→Absorption: 
    PO (rapid &amp; complete) 
→Distribution: 
    All of a person's total body water 
→Metabolism: 
    NOT metabolized 
→Excretion: 
    Urine (100% unchanged)

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Reversible ECG changes
Thirst (nephrogenic diabetes)
Polyuria
Elevated WBC
Edema
Acneiform skin eruptions
Tremor 
Thyroid enlargement
Nausea
Weight gain
Cognitive impairment

Lithium

ADR

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Lithium

→Severe cardiovascular disease
→Severe renal disease
→Severe debilitation
→Dehydration
→Sodium depletion
→Concurrent use w/diuretics

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Lithium
Interactions
1. Thiazides/loops
2. NSAIDs
3. ACE-I/ARB
4. ↓ Salt 
5. Sodium bicarb
6. Theophylline/caffeine 
7. ↑ Salt

Thiazides/loops – ↑ [lithium]
NSAIDs – ↑ [lithium]
ACEIs/ARBs – ↑ [lithium]
Severe salt-restricted diet – ↑ [lithium]
Sodium bicarbonate – ↓ [lithium]
Theophylline/caffeine – ↓ [lithium] b/c increased secretion of lithium
Increased intake of sodium – ↓ [lithium]

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Lithium

Warnings

NARROW Therapeutic Index
Target [ ] → 0.8-1.2 mEq/L in Acute Mania
Target [ ] → 0.6 -0.8 mEq/L

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Lithium Target [ ] in Acute Mania

0.8-1.2 mEq/L in Acute Mania

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Lithium Target [ ] in Bipolar Maintenance

Target [ ] → 0.6 -0.8 mEq/L in Bipolar Maintenance

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Lithium Pregnancy Category

Category D

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Lithium

→How do you make sure the pts taking the right dose?

MONITOR LEVELS ALWAYS

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Monitoring levels of Lithium
→When you just changed the dose?
→When you are just now considering an ↑ dose (w/o a level recently)?
→When a patient is on a steady dose?
→Best practice when drawing a Lithium level?

→5-7 days after the change
→Draw a Lithium level
→6-12 mo
→Draw 12 hrs after last dose (before the next one)

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P(ee) T(he) BEER

→What does this stand for?

Things to monitor when pt is on Lithium
P: pregnancy (need 2 types of birth control) 
T: thyroid (risk of hypothyroid)
B: blood levels
E: ecg
E: electrolytes 
R: renal function

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Pt is on lithium for bipolar, finds out she’s pregnant, what med should she be switched to?

Lamotrigine

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Hallucinations
Delusions
Disorganized thinking
Agitation
→What is the only med that tx these sx?

Positive Schizophrenia Sx

→Typical (1st Gen) only cover positive sx

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Lack of drive or initiation
Social withdrawal/depression
Apathy
Lack of emotional response

Negative Schizophrenia Sx

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Chlorpromazine
Haloperidol
Prochlorperazine

→Which one has the worse anticholinergic SE & should be avoided in elderly?
→Order of MOST potent to LEAST potent?

Typical (1st Gen) Antipsychotics

Worse anticholinergic:
Chlorpromazine

MOST potent → Haloperidol
LEAST potent → Chlorpromazine

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Aripiprazole
Asenapine
Brexpiprazole
Clozapine
Iloperidone
Lurasidone
Olanzapine
Paliperidone
Quetiapine
Risperidone
Ziprasidone

Atypical (2nd Gen)

Antipsychotics

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Affect/inhibit these receptors: 
-Cholinergic
-Adrenergic
-Dopamine
-Serotonin
-Histamine
→Which one is most related to the clinical effect?

Antipsychotics

→Dopamine Antagonism most relates to antipsychotic effect

Typicals: focus is on dopamine effects
Atypicals: focus is on serotonin, dopamine effects

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Which hormone does dopamine antagonism affect?

Can ↑ prolactin (maybe lactation)

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Typical (1st Gen) Antipsychotics
→Absorption: 
→Distribution: 
→Metabolism: 
→Excretion:

→Absorption: ERRATIC
→Distribution: Brain > many tissues (lipophylic/highly protein bound)
→Metabolism: LIVER
→Excretion: URINE & BILE

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Typical (1st Gen) Antipsychotics

→Phenothiazine metabolixm

Can be found in fatty tissues → effects produced up to 3 mo after

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Typical (1st Gen) Antipsychotics
ADR
→What is it called when it is EXTREME?

Akathesia (can’t sit still)
Acute Dystonia
Dyskinesia
Tardive Dyskinesia
* Extrapyramidal sx

EXTREME: Neuroleptic Malignant Syndrome

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Typical (1st Gen) Antipsychotics
→Neuroleptic Malignant Syndrome
FALTER

Study These Flashcards

*Can be fatal
→Muscle rigidity (↑ CPK)
→Extreme EPS 
→Severely ↑ body temp
→↑ HR 
→Death from Respiratory Failure &amp; Cardiac Collapse

F: fever A: AMS L: leukocytosis T: tremors E: elevated CPK R: rigidity

Tx for Neuroleptic Malignant Syndrome

1. Dantrolene 2. Bromocriptine 3. DISCONTINUE offending agent

LEAST anticholinergic effects MOST EPS MOST antipsychotic potency

Haloperidol

Seizures & antipsychotics

Antipsychotics ↓ seizure threshold

ECG change w/ Haloperidol

↑ QT interval

Typical (1st Gen) Antipsychotics | →Black Box Warning

Black Box Warning: increased risk for mortality when used in elderly patients with dementia-related behavioral disturbances and psychosis

Typical (1st Gen) Antipsychotics | →CI: (3)

1. Parkingson's dz 2. Severe CNS depression 3. Coma

Haloperidol | →Clinical Utility (4)

1. N/V in advanced illness 2. ICU delirium 3. Psychosis w/ agitation 4. Rapid tranquilizaiton

Synergy with other CNS depressants CNS depressants may reduce phenothiazine effectiveness, resulting in ↑ psychotic behavior or agitation Synergy w/ other anticholinergics May reduce the antiparkinsonian effects of levodopa. Use with lithium ↑ risk of neurotoxicity Use with droperidol ↑ risk of EPS Threshold for seizures is lowered when phenothiazines are used with anticonvulsants May increase the serum levels of TCAs and beta-blockers

Interactions of Chlorpromazine & Prochlorperazine

DA-blocking activity can inhibit levodopa and may cause disorientation in patients on both meds May boost effects of lithium, producing encephalopathy Has the LEAST anticholinergic effects & MOST EPS and antipsychotic potency Treat EPS with Benztropine (basically benadryl)

Interactions of Haloperidol

**Treat POSITIVE and NEGATIVE symptoms of schizophrenia**

Typical (2nd Gen) Antipsychotics

Typical (2nd Gen) Antipsychotics MOA →Why are Aripiprazole & Brexpiprazole unique?

SGAs typically block the dopamine receptors, but to a lesser extent than typical antipsychotics Produces < EPS Aripiprazole and brexpiprazole: partial D2 agonists SGAs also block serotonin receptor activity to varying degrees

Typical (2nd Gen) Antipsychotics | →Absorption ↑ w/ food

Ziprasidone and paliperidone: absorption increased with food | Take ziprasidone w/ food (increasing its absorption is desired)

Typical (2nd Gen) Antipsychotics →Distribution: →Metabolism: →Excretion:

→Distribution: large volume & highly protein bound →Metabolism: usually P450 system in the liver – particularly CYP-2D6, CYP-1A2, and CYP-3A4 isoenzymes →Excretion: Urine & Stool

``` Weight gain Muscle rigidity Parkinsonism Constipation Dry mouth Dizziness Somnolence/ fatigue ```

Typical (2nd Gen) Antipsychotics Common ADR ``` Other: EPS: Akathesia, Acute dystonia, Dyskinesia, Tardive dyskinesia QTc Prolongation Myocarditis Hyperlipidemia Sexual side effects DM Cataracts ```

Necessary to enroll in REMS program to track wbc count (risk of agranulocytosis) →Use

Clozapine | →Use: only for tx resistant psychosis

→Known hypersensitivity →CNS depression →Blood dyscrasias in pts w/ parkingsons →Liver, renal, cardiac insufficiency →Caution in diabetics, elderly, or debilitated →SSRI + antipsychotic → sudden EPS →Cigarette smoking ↓ antipsychotic plasma [ ] →Carbamazepine + antipsychotic → 50% reduction in antipsychotic level →Fluvoxamine + antipsychotic →↑ haldol & clozaril →BB + antipsych → severe HYPO tension →Antidepressants + antipsych → ↑ antidepressant [ ]

CI for Atypical Antipsych

Typical (2nd Gen) Antipsychotic w/ these SE: Insomnia, agitation, prolactin ↑, EPS at higher doses →Use

Risperidone →Use: broad efficacy

Typical (2nd Gen) Antipsychotic w/ these SE: HA, sedation, weight ↑, hyperlipidemia, DM →Use

Olanzapine → Use: very effective w/ positive/negative sx

Typical (2nd Gen) Antipsychotic w/ these SE: | Sedation, postural HYPOtension, dizziness, constipation

Quetiapine →Use: broad efficacy (less weight gain than risperidone)

Typical (2nd Gen) Antipsychotic w/ these SE: Insomnia, EPS at higher doses, QT prolongation →Use

Ziprasidone →Use: only for tx resistant psychosis (less weight gain than clozapine)

Typical (2nd Gen) Antipsychotic w/ these SE: Mild, dose related EPS →Use

Aripiprazole →Use: novel mechanism (less weight gain)

Typical (2nd Gen) Antipsychotic w/ these SE: | Tachycardia, HA, somnolence, anxiety

Paliperidone

Typical (2nd Gen) Antipsychotic w/ these SE: | Nausea, dry mouth, somnolence, weight gain, muscle stiffness, arthralgia

Iloperidone

Typical (2nd Gen) Antipsychotic w/ these SE: | EPS, akathisia, hypoesthesia, dry mouth, ↑ appetite, abdominal pain

Asenapine

Typical (2nd Gen) Antipsychotic w/ these SE: | N/V, parkinsonism, dyspepsia, akathisia, anxiety, weight gain

Lurasidone

Typical (2nd Gen) Antipsychotic: | Used for tx of resistant schizophrenia & preventing suicide in schizophrenia

Clozapine

Typical (2nd Gen) Antipsychotic: | Highest EPS

Risperidone

Typical (2nd Gen) Antipsychotic: | Highest ↑ in prolactin

Risperidone

Typical (2nd Gen) Antipsychotic: | Highest anticholinergic SE

Clozapine

Typical (2nd Gen) Antipsychotic: | Highest sedation

Clozapine > Olanzapine > Quetiapine

Typical (2nd Gen) Antipsychotic: | Highest weight gain

Clozapine > Olanzapine

Typical (2nd Gen) Antipsychotic: | Highest risk of diabetes

Clozapine > Olanzapine

Typical (2nd Gen) Antipsychotic: | Highest dyslipidemia

Clozapine > Olanzapine

Typical (2nd Gen) Antipsychotic: | Used if concerned about QTc prolongation

Aripiprazole

Risperidone vs haloperidol compared at high potency with maintenance of psychosis

Risperidone has fewer relapses

Antipsychotics Flashcards

(59 cards)