Sedatives and Hypnotics​

Name of the Sedatives and Hypnotics​ Drugs

• Thiopental sodium
• Pentobarbital
• Alprazolam
• Quazepam
• Chloral Hydrate

1.  Thiopental Sodium

Mechanism of Action

Depresses the CNS and may inhibit ascending transmission of impulses in the reticular formation. Thiopental may enhance or mimic inhibitory action of gamma-aminobutyric acid, thereby causing anticonvulsant effect and producing sedation and hypnosis. Thiopental may reduce ICP by increasing cerebral vascular resistance, which decreases cerebral blood flow and volume.

Indications:

• Induction of anesthesia
• Adjunct for intubation in head injury patients
• Control of convulsive states
• Treatment of elevated intracranial pressure  

Cautions & Contraindications

• History of porphyria
• Hypersensitivity to thiopental, its components, or other barbiturates

Metabolism and Half-life:

The half-life of the elimination phase after a single intravenous dose is three to eight hours.

Approximately 80% of the drug in the blood is bound to plasma protein. Pentothal (thiopental sodium) is largely degraded in the liver and to a smaller extent in other tissues, especially the kidney and brain. excreted in the urine.

Drug Interactions:

• Clonidine, CNS depressants,magnesium sulfate, methyldopa, pargyline: additive CNS depressant effects
• Diazoxide, diuretics, trimethaphan: possibly additive hypotensive effect
• Ketamine: increased risk of hypotension or respiratory depression; possibly countered hypnotic effect of thiopental
• Phenothiazines: possibly increased CNS depression or excitation, increased hypotensive effect
• Alcohol use: additive CNS depressant effects

Side- Effects:

• CNS: Agitation, anxiety, seizures
• CV: Bradycardia, hypotension, shock, tachycardia, thrombophlebitis
• GI: Hiccups
• RESP: Apnea, bronchospasm, cough, laryngospasm, respiratory depression, wheezing
• SKIN: Hives, itching, rash, redness
• Other: Angioedema

Nursing Considerations

• Before administering thiopental, expect to premedicate patient with an anticholinergic, such as atropine or glycopyrrolate, to minimize secretions.
• Be prepared to administer a test dose of 25 to 75 mg (1 to 3 ml of 2.5% solution) to determine tolerance or sensitivity. Expect to observe patient for at least 1 minute after administering test dose.
• Dilute drug with a compatible I.V. solution before administering, such as D5W for injection, normal saline solution for injection, or sterile water for injection. Be aware that sterile water for injection shouldn’t be used to prepare 0.2% or 0.4% solution because it would result in a hypotonic solution and cause hemolysis.
• To prepare 0.2% solution, dilute 1 g of thiopental with 500 ml of compatible diluent to produce a final concentration of 2 mg/ml.
• To prepare 0.4% solution, dilute 1 g thiopental with 250 ml compatible diluent or 2 g thiopental with 500 ml compatible diluent to produce a final concentration of 4 mg/ml.
• To prepare 2.5% solution, dilute 1 g of thiopental with 40 ml of compatible diluent or 5 g of thiopental with 200 ml of compatible diluent to produce a final concentration of 25 mg/ml.
• Inspect solution for particles before administration. Use solution within 24 hours of reconstitution, and discard unused portion after 24 hours.
• Monitor patient’s blood and tissue oxygenation and vital signs during I.V. administration. Keep emergency equipment and drugs nearby in case respiratory depression occurs.​
• If patient has a history of CV disease or hypotension, monitor her for CV depressant effects, such as bradycardia, hypotension, or shock.​
• In patient with a history of seizures, institute seizure precautions according to facility protocol.​
• Monitor respiratory rate, rhythm, and quality for signs of respiratory depression in debilitated patient or one with a history of respiratory disease.​
• Monitor patient’s neurologic status every hour, or as ordered, in patient with increased ICP.​

Patient teaching

• Explain the need for frequent hemodynamic monitoring.
• Advise patient to use caution when driving or performing tasks that require alertness for at least 24 hours after receiving thiopental.
• Instruct patient not to consume alcohol or other CNS depressants for at least 24 hours after thiopental administration (unless prescribed) because they increase the effects of thiopental.
• Instruct patient to report persistent drowsiness, rash, severe dizziness, or skin lesions to prescriber.

2.   Pentobarbital

Mechanism of Action:

Inhibits ascending conduction in reticular formation, which controls CNS arousal to produce drowsiness, hypnosis, and sedation. Pentobarbital also decreases spread of seizure activity in cortex, thalamus, and limbic system. It promotes an increased threshold for electrical stimulation in the motor cortex, which may contribute to anticonvulsant effects.

Indications:

• Hypnotic – daytime sedation
• Short-term treatment of insomnia
• Preoperative sedation
• Barbiturate coma
• Emergency treatment of seizures associated with eclampsia, meningitis, status epilepticus, tetanus, or toxic reactions to local anesthetics or strychnine

Cautions & Contraindications:

• Hypersensitivity to drug or other barbiturates
• Nephritis (with large doses)
• Severe hepatic impairment
• Severe respiratory disease with dyspnea or obstruction
• Manifest or latent porphyria
• History of sedative-hypnotic abuse
• Subcutaneous or intra-arterial administration

Use cautiously in:

• Hepatic or renal impairment, increased risk for suicide, alcohol use
• History of drug addiction
• Labor and delivery
• Elderly or debilitated patients.

Metabolism and Half- Life:

Half-Life: 15-50 hr

Onset: 10-15 min (IM); 3-5 min (IV)

Duration: 3-4 hr

Metabolism: hepatic microsomal enzymes, glucuronidation

Excretion: Mostly urine

Drug Interactions:

• Acetaminophen: increased risk of hepatotoxicity
• Activated charcoal: decreased pentobarbital absorption
• Anticoagulants, beta-adrenergic blockers (except timolol), carbamazepine, clonazepam, corticosteroids, digoxin, doxorubicin, doxycycline, felodipine, hormonal contraceptives, metronidazole, quinidine, theophylline, verapamil: decreased efficacy of these drugs
• Antihistamines (first-generation), opioids, other sedative-hypnotics: additive CNS depression
• Chloramphenicol, hydantoins, narcotics: increased or decreased effects of either drug
• Alcohol use: increased sedation, additive CNS depression

Side- Effects:

• CNS: Agitation, anxiety, ataxia, confusion, delusions, depression, dizziness, drowsiness, fever, hallucinations, headache, insomnia, irritability, nervousness, nightmares, paradoxical stimulation, seizures, syncope, tremor
• CV: Orthostatic hypotension
• EENT: Vision changes
• GI: Anorexia, constipation, hepatic dysfunction, nausea, vomiting
• HEME: Agranulocytosis
• MS: Arthralgia, bone pain, muscle twitching or weakness
• RESP: Respiratory depression
• SKIN: Exfoliative dermatitis, rash, Stevens- Johnson syndrome
• Other: Physical and psychological dependence, weight loss

  Nursing Considerations

• Use pentobarbital with extreme caution in patients with depression, a history of drug abuse, or suicidal tendencies.
• Use drug cautiously in elderly or debilitated patients and those with acute or chronic pain because it may induce paradoxical stimulation.
• When using I.V. route, inject drug at 50 mg/min or less to avoid adverse respiratory and circulatory reactions.
• If patient shows premonitory signs of hepatic coma, withhold drug and notify prescriber immediately.
• Monitor I.V. site closely and avoid extravasation. Drug is highly alkaline and may cause local tissue damage and necrosis.

Patient teaching

• Inform patient that pentobarbital is habit forming, and stress the importance of taking it exactly as prescribed.
• Instruct patient who takes elixir form to use a calibrated measuring device and to close container tightly after use.
• Instruct patient who uses suppositories to refrigerate them.
• Advise patient to avoid hazardous activities until drug’s CNS effects are known.
• Urge patient to avoid alcohol and other CNS depressants because they may increase drug’s adverse CNS effects.

3. Alprazolam

Mechanism of Action:

Enhances the inhibitory effects of the neurotransmitter gamma-aminobutyric acid in the brain. Therapeutic Effect: Produces anxiolytic effect due to CNS depressant action.

Indications:

• Management of generalized anxiety disorders (GAD).
• Short-term relief of symptoms of anxiety, panic disorder, with or without agoraphobia.
• Anxiety associated with depression.
• OFF-LABEL: Anxiety in children. Preoperative anxiety

Cautions & Contraindications:

• Hypersensitivity to Alprazolam.
• Acute narrow angle-closure glaucoma
• concurrent use with ketoconazole or itraconazole or other potent CYP3A4 inhibitors.
• Cautions: Renal/hepatic impairment, predisposition to urate nephropathy, obese pts. Concurrent use of CYP3A4 inhibitors/inducers and major CYP3A4 substrates; debilitated pts, respiratory disease, depression (esp. suicidal risk), elderly (increased risk of severe toxicity). History of substance abuse

Metabolism and Half- life:

Well absorbed from GI tract. Protein binding: 80%. Metabolized in liver. Primarily excreted in urine. Minimal removal by hemodialysis. Half-life: 6–27 hrs.

Drug Interactions:

• CNS depressants (e.g., alcohol, morphine, zolpidem) may increase CNS depression.
• Strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir) may increase concentration/effect.
• Strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease concentration/effect.
• FOOD: Grapefruit products may increase level, effects.

Side- Effects:

Frequent: Ataxia, light-headedness, drowsiness, slurred speech (particularly in elderly or debilitated pts).

Occasional: Confusion, depression, blurred vision, constipation, diarrhea, dry mouth, headache, nausea

Rare: Behavioral problems such as anger, impaired memory; paradoxical reactions (insomnia, nervousness, irritability).

Nursing Considerations

Baseline assessment

• Assess degree of anxiety; assess for drowsiness, dizziness, light-headedness.
• Assess motor responses (agitation, trembling, tension), autonomic responses (cold/clammy hands, diaphoresis).
•  Initiate fall precautions.

Intervention/evaluation

• For pts on long-term therapy, perform hepatic/renal function tests, CBC periodically.
• Assess for paradoxical reaction, particularly during early therapy.
• Evaluate for therapeutic response: calm facial expression, decreased restlessness, insomnia.
• Monitor respiratory and cardiovascular status.

Patient/family teaching

• Drowsiness usually disappears during continued therapy.
• If dizziness occurs, change positions slowly from recumbent to sitting position before standing.
• Avoid tasks that require alertness, motor skills until response to drug is established.
• Smoking reduces drug effectiveness.
• Sour hard candy, gum, sips of water may relieve dry mouth.
• Do not abruptly withdraw medication after long-term therapy.

4.Quazepam

Mechanism of Action:

Depresses all levels of CNS (eg, limbic and reticular formation), by increasing neuronal permeability to chloride ions may increase inhibitory activity of GABA on neuronal excitability

Indications:

•  insomnia

Cautions & Contraindications:

• Hypersensitivity to quazepam or its components,
• Pregnancy
• Sleep apnea (known or suspected)

Metabolism and Half- Life :

• Half-life elimination: 39 hour (metabolite 73 hours)
• Protein bound: >95%
• Metabolism: Glucuronic acid conjugation; Excretion: Urine (31%), feces (23%)

Drug Interactions: 

• Addictive drugs: Possibly habituation carbamazepine: Decreased blood quazepam level, possibly increased blood carbamazepine level 
• cimetidine, diltiazem, disulfiram, erythromycin, oral contraceptives, propoxyphene, ranitidine, verapamil Possibly potentiated effects of quazepam 
• clozapine: Possibly syncope, with respiratory depression or arrest 
• CNS depressants, tricyclic antidepressants: Increased CNS depression 
• phenytoin: Increased risk of phenytoin toxicity 
• grapefruit juice: Increased quazepam level 
• alcohol use: Additive CNS depression 
• smoking: Possibly decreased effectiveness of  quazepam 

Side- Effects:

• CNS: Abnormal complex behaviors, such as sleep driving; amnesia (anterograde); anxiety; ataxia; confusion; depression; dizziness; drowsiness; euphoria; fatigue; headache; light-headedness; paresthesia; slurred speech; suicidal ideation; tremor; weakness
• CV: Chest pain, palpitations, tachycardia
• EENT: Blurred vision, dry mouth, hyperacusis, photophobia, throat tightness, worsening of glaucoma
• GI: Abdominal cramps, constipation, diarrhea, heartburn, nausea, thirst, vomiting
• GU: Renal dysfunction, urinary incontinence, urine retention
• MS: Muscle spasms
• RESP: Dyspnea, increased tracheobronchial secretions
• Other: Anaphylaxis, angioedema

Nursing Considerations

• Use quazepam cautiously in patients with angle-closure glaucoma because of drug’s anticholinergic effects
• In patients with hepatic dysfunction because this condition may prolong quazepam’s half-life
• In patients with myasthenia gravis because drug may worsen condition
• In patients with severe COPD because adverse effects of quazepam may compromise respiratory function
• •In patients with renal dysfunction because accumulation of metabolites may result in toxicity
• In elderly patients because of age-related decreases in hepatic, renal, and cardiac function.
• Monitor patient closely for signs and symptoms of hypersensitivity reactions, such as dyspnea, throat tightness, Nausea, vomiting, and swelling. If present, discontinue quazepam immediately, notify prescriber, and provide supportive care.
• Notify prescriber if eye pain develops in patient with angle-closure glaucoma.
• Be aware that quazepam may intensify signs and symptoms of depression.
• Monitor patient closely for evidence of suicidal ideation, and institute suicide precautions, as needed.

Patient teaching

• Instruct patient to stop taking quazepam and seek emergency care if she has trouble breathing, throat tightness, nausea, vomiting, or abnormal swelling.
• Advise patient that drug may cause abnormal behaviors during sleep, such as driving a car, eating, talking on the phone, or having sex without recall of the event. If family members notice such behavior, or if patient sees evidence of it upon awakening, prescriber should be notified.
• Urge patient to avoid consuming alcohol during quazepam therapy because sedation and risk of abnormal behaviors, such as sleep driving, may increase.
• Instruct patient not to stop drug abruptly after prolonged use (6 weeks or more).
• Instruct female patient of childbearing age to use effective contraception during therapy and to notify prescriber immediately of known or suspected pregnancy.
• Urge family or caregiver to watch patient closely for suicidal tendencies, especially when therapy starts or dosage changes.

5.Chloral Hydrate

Mechanism of Action:

Produces CNS depression by an unknown mechanism involving trichloro ethanol, the drug’s active metabolite.

Indications:

• Prevent or suppress alcohol withdrawal symptoms
• Act as an adjunct to opioids and analgesics to control postoperative pain
• Nocturnal sedation
• Preoperative sedation
• Sedation before dental or medical procedure

Cautions & Contraindications:

• Gastritis
• Hypersensitivity or idiosyncrasy to chloral hydrate or its components
• Severe cardiac, hepatic, or renal disease

Metabolism & Half- life:

Onset: 30-60 min; Duration: 4-8 hr

Metabolized by alcohol dehydrogenase, glucuronidation

Half-life: 8-11 hr (active metabolite)

Excretion: Mostly in urine; some feces

Drug Interactions:

• CNS depressants: increased CNS effects of chloral hydrate
• Furosemide (I.V.): Increased adverse effects when given after chloral hydrate
• Phenytoin: increased excretion and decreased effectiveness of phenytoin
• Warfarin: transient increase in anticoagulant effect
• Alcohol use: increased CNS effects of chloral hydrate

Side- Effects:

• CNS: ataxia, disorientation, hangover, incoherence, paranoia, somnolence
• GI: gastric irritation, nausea, vomiting
• SKIN: rash, urticaria
• Other: drug dependence

Nursing Considerations

• Administer with full glass of water or juice to minimize GI distress from chloral hydrate capsules. Dilute syrup in a half glass of water, ginger ale, or fruit juice.
• Monitor carefully for hypersensitivity reaction in patients with a history of tartrazine sensitivity.
• Suspect physical or psychological dependence if withdrawal of chloral hydrate produces confusion, hallucinations, nausea, nervousness, restlessness, stomach pain, tremor, unusual excitement, or vomiting.

Patient teaching

• Instruct patient to take capsules with a full glass of water or juice or to mix syrup in a half-glass of water, ginger ale, or fruit juice.
• Advise patient to avoid hazardous activities until CNS effects of chloral hydrate are known.
• Caution patient that drug may be habit forming.
• Advise taking it exactly as prescribed and not to stop taking it abruptly because withdrawal symptoms could occur.
• Instruct patient to notify prescriber right away about stomach pains or tarry stools.

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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