Antipsychotics Flashcards
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)
Lithium
MOA
→Not well defined
→Recycles phosphoinositides
Affects the 2nd messengers
Lithium →Absorption: →Distribution: →Metabolism: →Excretion:
Lithium
→Absorption:
PO (rapid & complete)
→Distribution:
All of a person's total body water
→Metabolism:
NOT metabolized
→Excretion:
Urine (100% unchanged)Reversible ECG changes Thirst (nephrogenic diabetes) Polyuria Elevated WBC Edema Acneiform skin eruptions Tremor Thyroid enlargement Nausea Weight gain Cognitive impairment
Lithium
ADR
Lithium
CI
→Severe cardiovascular disease →Severe renal disease →Severe debilitation →Dehydration →Sodium depletion →Concurrent use w/diuretics
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]
Lithium
Warnings
- NARROW Therapeutic Index
- Target [ ] → 0.8-1.2 mEq/L in Acute Mania
- Target [ ] → 0.6 -0.8 mEq/L
Lithium Target [ ] in Acute Mania
0.8-1.2 mEq/L in Acute Mania
Lithium Target [ ] in Bipolar Maintenance
Target [ ] → 0.6 -0.8 mEq/L in Bipolar Maintenance
Lithium Pregnancy Category
Category D
Lithium
→How do you make sure the pts taking the right dose?
MONITOR LEVELS ALWAYS
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)
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
Pt is on lithium for bipolar, finds out she’s pregnant, what med should she be switched to?
Lamotrigine
Hallucinations Delusions Disorganized thinking Agitation →What is the only med that tx these sx?
Positive Schizophrenia Sx
→Typical (1st Gen) only cover positive sx
Lack of drive or initiation
Social withdrawal/depression
Apathy
Lack of emotional response
Negative Schizophrenia Sx
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
Aripiprazole Asenapine Brexpiprazole Clozapine Iloperidone Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone
Atypical (2nd Gen)
Antipsychotics
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
Which hormone does dopamine antagonism affect?
Can ↑ prolactin (maybe lactation)
Typical (1st Gen) Antipsychotics →Absorption: →Distribution: →Metabolism: →Excretion:
→Absorption: ERRATIC
→Distribution: Brain > many tissues (lipophylic/highly protein bound)
→Metabolism: LIVER
→Excretion: URINE & BILE
Typical (1st Gen) Antipsychotics
→Phenothiazine metabolixm
Can be found in fatty tissues → effects produced up to 3 mo after
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
Typical (1st Gen) Antipsychotics
→Neuroleptic Malignant Syndrome
FALTER
*Can be fatal →Muscle rigidity (↑ CPK) →Extreme EPS →Severely ↑ body temp →↑ HR →Death from Respiratory Failure & Cardiac Collapse
F: fever A: AMS L: leukocytosis T: tremors E: elevated CPK R: rigidity
Tx for Neuroleptic Malignant Syndrome
- Dantrolene
- Bromocriptine
- 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)
- Parkingson’s dz
- Severe CNS depression
- Coma
Haloperidol
→Clinical Utility (4)
- N/V in advanced illness
- ICU delirium
- Psychosis w/ agitation
- 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
