Chapter 24
CNS Depressants for Psychosis & Anxiety — Study Guide Fast Notes
1) Big Picture
CNS Depressants used for psychosis and anxiety:
Antipsychotics
Also known as NEUROLEPTICS. Preferred terms: antipsychotics or neuroleptics.
Anxiolytics
Also known as ANTIANXIETY medications; many are sedative-hypnotics.
Overlap of Uses: Some anxiolytics also treat:
Insomnia
Seizures
Alcohol withdrawal
Procedural sedation
Key Risks:
Antipsychotics:
↓ dopamine
Risk of Extrapyramidal Symptoms (EPS) and Neuroleptic Malignant Syndrome (NMS)
Benzodiazepines:
Risk of sedation, tolerance/dependence, and withdrawal
2) Psychopathology & Neurochemistry
Synaptic Basics:
Presynaptic vesicles release neurotransmitters (NT) into the synaptic cleft → bind to postsynaptic receptors → signal → removal by enzymes, diffusion, or reuptake.
Neurotransmitters Linked to Disorders:
GABA (Gamma-Aminobutyric Acid):
↓ GABA levels lead to ↑ anxiety.
Benzodiazepines bind to GABA_A receptor sites, increasing the effect of GABA.
Dopamine (DA):
Modulates cognition, emotion, and motivation.
Dysregulation is associated with disorders like schizophrenia/psychosis and depression.
Other relevant neurotransmitters:
Serotonin
Norepinephrine
Acetylcholine
3) Psychosis & Schizophrenia Symptoms
Psychosis:
Characterized by a loss of reality, leading to disorganized thought, impaired processing, delusions, hallucinations, catatonia, and aggression.
Schizophrenia Symptom Clusters:
Cognitive Symptoms:
Disorganized thinking, memory deficits, focus deficits.
Positive Symptoms:
Agitation, hallucinations, delusions, paranoia, and incoherence.
Negative Symptoms:
Avolition (lack of motivation), alogia (lack of speech), blunted affect, poor self-care, social withdrawal (more chronic).
4) Antipsychotics Overview
Mechanism of Action:
All antipsychotics block dopamine receptors.
Specifically, D₂ blockade drives the antipsychotic effect and causes EPS.
Atypicals (2nd-generation antipsychotics):
Weaker D₂ blockage, but stronger D₄ and serotonin (5-HT) blockade, effective for treating positive and negative symptoms with fewer EPS.
Other Effects:
Many antipsychotics block the Chemoreceptor Trigger Zone (CTZ)/vomiting center, serving as antiemetics.
Categories & Exemplars:
Typical (1st-generation):
Phenothiazines:
Subgroups:
Aliphatic (Chlorpromazine; effects: sedation, hypotension),
Piperazine (Fluphenazine, Perphenazine; ↑ EPS),
Piperidine (Thioridazine; strong sedation with fewer EPS).
Nonphenothiazines:
Haloperidol (potent with ↑ EPS), Loxapine, Molindone, Thiothixene.
Atypical (2nd-generation):
Examples include Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole, Paliperidone, Iloperidone, Cariprazine, Brexpiprazole, Lumateperone.
Treat both positive and negative symptoms, with decreased overall EPS.
Dosing & Kinetics Pearls:
Oral liquid formulations absorb faster; ensure checks for cheeking.
Highly protein-bound; slow excretion; urine may turn pink to red-brown with phenothiazines (benign).
Clinical response onset: some benefit in 7–10 days; full effect in 3–6 weeks.
Long-acting depot forms: Fluphenazine decanoate, Haloperidol decanoate (administered every 2–4 weeks; Z-track method; rotate injection sites; do not massage injection site; do not leave in plastic syringe for >15 min).
5) Adverse Effects & Emergencies
Extrapyramidal Symptoms (EPS):
Pseudoparkinsonism:
Timing: Days to weeks
Features: Tremor, rigidity, bradykinesia, masklike facies, shuffling gait
Management: ↓ dose; administer anticholinergics (e.g., Benztropine).
Acute Dystonia:
Timing: Hours to days (~5%)
Features: Painful spasms in face/tongue/neck/back; oculogyric crisis; laryngeal spasm.
Management: IM/IV Benztropine; Lorazepam as adjunct treatment.
Akathisia:
Timing: Days to weeks (~20%)
Features: Motor restlessness, pacing, rocking movements.
Management: Beta-blocker (Propranolol) or benzodiazepine (Lorazepam).
Tardive Dyskinesia:
Timing: Months to years (20–30% with long-term use)
Features: Tongue protrusion/rolling, lip smacking, choreoathetoid movements.
Management: Stop offending agent, consider switching to Clozapine; VMAT2 inhibitors like Tetrabenazine; Vit E or Amantadine may be used.
Neuroleptic Malignant Syndrome (NMS):
Rare but life-threatening.
Symptoms: Severe muscle rigidity, hyperthermia, altered mental status (AMS), diaphoresis, blood pressure fluctuation, tachycardia, dysrhythmias, ↑ creatine kinase (CK), rhabdomyolysis, renal failure, seizures.
Treatment: Discontinue antipsychotic immediately, administer aggressive IV hydration, cooling methods, benzodiazepines, dantrolene; ICU care may be necessary.
Other Common Effects:
Anticholinergic Symptoms:
Dry mouth, constipation, urinary retention, tachycardia.
Orthostatic Hypotension: Risk for falls, especially in elderly patients.
Photosensitivity: Patients should be advised on sun protection.
Blood Dyscrasias:
Risk of agranulocytosis (especially with Clozapine); WBC/ANC monitoring is essential.
Metabolic Effects:
Weight gain, hyperglycemia, and dyslipidemia (notably with Olanzapine, Quetiapine, Risperidone).
Cardiac Effects:
Ziprasidone risk of QT prolongation; avoid use in patients with prolonged QT and regular ECG monitoring is advised.
Herb Interactions (selected):
Kava Kava: Increases risk of dystonia when used with phenothiazines/Fluphenazine.
Ginkgo: May potentiate effects of Haloperidol/Olanzapine/Clozapine.
St. John's Wort: Decreases Clozapine levels.
6) Phenothiazines at a Glance
Group Characteristics:
Aliphatic:
Sedation: +++
Hypotension: +++
EPS: ++
Antiemetic: ++/+++
Chlorpromazine: Marked orthostasis noted.
Piperazine:
Sedation: ++
Hypotension: +
EPS: +++
Antiemetic: +++
Fluphenazine/Perphenazine: Noted for ↑ EPS.
Piperidine:
Sedation: +++
Hypotension: +++
EPS: +
Antiemetic: –
Thioridazine: Strong sedation observed with fewer EPS.
7) Nonphenothiazines (1st-generation)
Haloperidol:
Mechanism: Potent D₂ blockade causing ↑ EPS.
Administration caution: Use lower doses in older adults; photosensitivity precautions necessary.
Loxapine, Molindone, Thiothixene:
Potency: Moderate to high; ↑ EPS noted and variable sedation/orthostasis.
8) Atypical Antipsychotics (2nd-generation) — Pros & Cons
Pros:
Effective in treating both positive & negative symptoms with fewer EPS/Tardive Dyskinesia (TD) compared to older agents.
Cons:
Metabolic syndrome risk (increased weight, glucose, lipids); some have sedation and orthostatic effects.
Drug Pearls:
Clozapine: Effective for treatment-resistant cases but has significant agranulocytosis risk. Discontinue if WBC < 3000/mm³.
Risperidone: Generally low EPS risk at moderate doses but may cause weight gain, akathisia, sedation, and increased appetite.
Ziprasidone: Risk of QT prolongation; ECG telemetry is warranted; contraindicated in patients with prolonged QT.
Aripiprazole: Functions as partial D₂ agonist; may lead to impulse-control issues.
9) Special Populations & Safety
Older Adults:
Utilize 25–50% of the adult dose; black-box warning for increased mortality in dementia-related psychosis.
Pregnancy/Lactation:
Potential teratogenic effects or infant effects; use with caution and balance risks versus benefits; many medications can pass into breast milk.
Smoking: Increases metabolism for some antipsychotics, resulting in lower drug levels.
Caution: Do not administer multiple antipsychotics routinely; consider switching rather than layering medications.
10) Drug Interactions (High-Yield)
Additive CNS Depression: Caution with alcohol, opioids, sedatives, and benzodiazepines.
Additive Hypotension: Interaction with antihypertensives can lead to significant blood pressure drops.
Lowered Seizure Threshold: Phenothiazines may require higher doses of anticonvulsants.
Antacids: Inhibit phenothiazine absorption; should be administered 1 hour before or 2 hours after.
11) Anxiolytics: Benzodiazepines (Major Class)
Mechanism of Action:
Potentiate GABA → Increase frequency of chloride channel opening at GABA_A receptor → Resulting in CNS inhibition.
Uses:
Anxiety (short-term), insomnia (some efficacy), status epilepticus, muscle spasms, preoperative sedation, alcohol withdrawal.
Common Agents:
Lorazepam (prototype), Alprazolam, Diazepam, Clonazepam, Chlordiazepoxide, Oxazepam, Clorazepate, Midazolam.
Adverse Effects:
Commonly experience sedation, dizziness, ataxia, dry mouth, blurred vision, constipation; risks of tolerance, dependence, and withdrawal symptoms.
Overdose Management:
Assess airway and administer oxygen; gastric decontamination may be utilized; IV fluids may be required; Flumazenil (caution with seizure risk).
Withdrawal: Abrupt discontinuation should be avoided; tapering is necessary, especially for short-acting agents, which may lead to withdrawal symptoms sooner.
Avoid With:
Alcohol or other CNS depressants; Kava Kava can increase sedation; smoking and caffeine can decrease the effect of benzodiazepines.
12) Buspirone (Azapirone)
Mechanism of Action:
Acts on serotonin (5-HT) and dopamine (DA) receptors (not a benzodiazepine).
Onset: 1-2 weeks continuous use is required for effects.
Pros:
Minimally sedating with a low risk of dependence.
Caution:
Grapefruit juice increases levels, so consumption should be limited to ≤ 8 ounces/day or one-half grapefruit.
13) Nursing Process — Quick Checklist
Assessment:
Evaluate baseline vital signs, mental status, and comorbid conditions like cardiac, ocular, or respiratory diseases.
Assess current medications including anticonvulsants, antihypertensives, CNS depressants, and herbal supplements.
For benzodiazepines: Assess suicide risk and support system availability.
Planning/Goals:
Aiming for a calmer emotional state, improved communication, maintenance of activities of daily living (ADLs), organized thought processes, improved reality testing, improved sleep patterns (especially for anxiety).
Interventions:
Administer medication with food or milk to decrease gastrointestinal upset (common with many typical antipsychotics).
Liquid formulations (specifically phenothiazines): dilute in fruit juice, water, or milk while avoiding apple juice/caffeine for Fluphenazine; protect from light, and avoid skin contact.
Remain with the patient until the medication is swallowed to prevent cheeking.
When administering IM depot injections: use deep Z-track technique; rotate injection sites; avoid massaging the site.
Monitor parameters including orthostatic blood pressure (30 minutes post-injection), occurrence of EPS, NMS, glucose levels, and WBC/ANC counts (especially with Clozapine); monitor urine output for retention.
Engage with the patient in therapeutic interactions and support groups.
14) Patient Teaching
Adherence:
Emphasize that antipsychotics are not curative and simply help control symptoms; advise against abrupt discontinuation.
Onset:
Educate that full benefits may take weeks to manifest.
Precautions:
Advise patients to avoid alcohol and other CNS depressants, and refrain from driving until the medication’s effects are stabilized.
Emphasize sun protection measures; recommend rising slowly to prevent orthostasis.
Stress proper oral hygiene; inform that a benign red-brown urine effect may occur with phenothiazines.
Report any signs of infection (e.g., sore throat, fever), EPS symptoms, or severe dizziness/syncope, and symptoms indicative of NMS.
Provide counseling on the need for smoking cessation and contraception; consider recommending an identification bracelet for patients taking high-risk medications.
15) Rapid Drug Cards (High-Yield)
Fluphenazine (Piperazine Phenothiazine):
Uses: Schizophrenia/Psychosis, available in PO/IM routes and as depot formulations.
Mechanism: D₂ blockade.
Notables: ↑ EPS, orthostatic effects, photosensitivity; strong protein binding (~99%); long half-life (depot lasts weeks).
Serious Risks: Dysrhythmias, blood dyscrasia, NMS.
Overdose management includes airway management, gastric lavage/charcoal, hydration, and administration of anticholinergics, and norepinephrine if needed.
Haloperidol / Haloperidol Decanoate:
Uses: Acute psychosis, schizophrenia, administered PO/IM; depot IM once monthly.
Mechanism: D₂ blockade; potent, ↑ EPS.
Notables: QT concerns are observed, though less compared to Ziprasidone; necessitates monitoring and dose reduction in older patients.
Aripiprazole (Atypical):
Uses: Schizophrenia, bipolar disorder, MDD adjunct, autism, Tourette’s; administered PO and via Long-Acting Injection (LAI).
Mechanism: Modulates both DA and serotonin (5-HT).
Risks: Potential metabolic changes, EPS possible, impulse-control issues, NMS; grapefruit can increase levels, and SSRIs raise the risk of serotonin syndrome.
Lorazepam (Benzodiazepine):
Uses: Anxiety, status epilepticus, sedation, insomnia.
Mechanism: Potentiates GABA.
Risks: Sedation, potential for dependence; may raise levels when used with Cimetidine; interactions with alcohol and CNS depressants increase respiratory depression risk.
Buspirone:
Uses: Generalized Anxiety Disorder (GAD), scheduled administration.
Onset: Takes 1-2 weeks, offering no PRN relief.
Avoid excessive grapefruit consumption due to increased levels.
16) Practice Q&A (from study set)
Acute dystonia → b.
Blocks dopamine → a.
EPS with fluphenazine → d.
Atypicals → a. Clozapine, d. Olanzapine, e. Aripiprazole.
Lorazepam truths → a.
Aripiprazole nursing care → b, c, d, e.
Phenothiazine overdose care → a, b, c, f. (Rationales match the explanations in your text.)
17) Mnemonics & Exam Tips
EPS Timeline: “Park* (days) → Akathisia (days–weeks) → Dystonia (hours–days) → Tardive (months–years)”* (Remember that dystonia can be the earliest symptom; know treatments).
NMS Red Flags: Lead-pipe rigidity + Hyperthermia + AMS + Autonomic instability → “LaHAA” → Action: Stop drug + Administer Dantrolene.
Clozapine Labs: “CLOZed club needs a Bouncer (ANC/WBC)”.
Benzodiazepine Safety: “Don’t mix BENZO with BOoze” (CNS depression risk).
Ziprasidone: “Zip the QT” → Check ECG regularly.