Benzodiazepine anticonvulsants are fast-acting medications that enhance GABA activity to control seizures, commonly used in emergency settings and chronic epilepsy management, including status epilepticus and Lennox-Gastaut syndrome.
Name of the Benzodiazepines Drugs
- Clonazepam
- Clorazepate
- Diazepam
1.CLONAZEPAM
| Clonazepam |
| Availability: Tablets: 0.5 mg, 1 mg, 2 mg. Tablets (Orally Disintegrating): 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg. |
| Administration/handling: PO • Give without regard to food. • Swallow whole with water. Orally Disintegrating Tablet : Open pouch, peel back foil; do not push tablet through foil. • Remove tablet with dry hands, place in mouth. • Swallow with or without water. • Use immediately after removing from package. |
| Seizures PO: Adults, elderly, children 10 yrs and older: Initial dose not to exceed 1.5 mg/ day in 3 divided doses; may be increased in 0.5- to 1-mg increments every 3 days until seizures are controlled or adverse effects occur. Maintenance: 2–8 mg/day in 1–2 divided doses. Maximum: 20 mg/day. Infants, children younger than 10 yrs or weighing less than 30 kg: 0.01–0.03 mg/kg/day (maximum initial dose: 0.05 mg/kg/day) in 2–3 divided doses; may be increased by no more than 0.25–0.5 mg every 3 days until seizures are controlled or adverse effects occur. Maintenance: 0.1– 0.2 mg/kg/day in 3 divided doses. Maximum: 0.2 mg/kg/day. |
| Panic Disorder: PO: Adults, elderly: Initially, 0.25 mg twice daily. Increase in increments of 0.125–0.25 mg twice daily every 3 days. Target dose: 1 mg/day. Maximum: 4 mg/day. Note: Discontinue gradually by 0.125 mg twice daily q3days until completely withdrawn. |
Mechanism of Action:
Enhances activity of GABA; depresses nerve impulse transmission in motor cortex. Therapeutic Effect: Produces anxiolytic, anticonvulsant effects.
Indications:
- Adjunct in treatment of lennox-gastaut syndrome (petit mal variant epilepsy)
- Akinetic, myoclonic seizures
- Absence seizures (petit mal) unresponsive to succinimides.
- Treatment of panic disorder.
- OFFLABEL: burning mouth syndrome, REM sleep behavior disorder, essential tremor.
Cautions & Contraindications:
- Hypersensitivity to clonazepam.
- Active narrow-angle glaucoma
- Severe hepatic disease
- Cautions: renal/hepatic impairment, impaired gag reflex, chronic respiratory disease, elderly, debilitated pts, depression, pts at risk of suicide or drug dependence, concomitant use of other CNS depressants
Metabolism and Half- Life:
Well absorbed from GI tract. Protein binding: 85%. Metabolized in liver. Excreted in urine. Not removed by hemodialysis. Half-life: 18–50 hrs.
Drug Interactions:
- Alcohol, other CNS depressants may increase CNS depressant effect.
- Strong CYP3A4 inhibitors may increase concentration/effect.
- Strong CYP3A4 inducers may decrease concentration/effect.
- St. John’s wort may decrease concentration/effects
Side- Effects:
- Mild, transient drowsiness
- Ataxia
- behavioral disturbances (aggression, irritability, agitation), esp. in children.
- Occasional : Dizziness, ataxia, URI, fatigue.
- Rare (4% or less): Impaired memory, dysarthria, nervousness, sinusitis, rhinitis, constipation, allergic reaction.
Nursing Considerations
Baseline assessment
- Review history of seizure disorder (frequency, duration, intensity, level of consciousness [LOC]).
- For panic attack, assess motor responses (agitation, trembling, tension), autonomic responses (cold/clammy hands, diaphoresis).
Intervention/evaluation
- Observe for excess sedation, respiratory depression, suicidal ideation.
- Assess children, elderly for paradoxical reaction, particularly during early therapy.
- Initiate seizure precautions, observe frequently for recurrence of seizure activity.
- Assist with ambulation if drowsiness, ataxia occur.
- For pts on long-term therapy, CBC, BMP, LFT should be performed periodically.
- Evaluate for therapeutic response: decreased intensity and frequency of seizures or, if used in panic attack, calm facial expression, decreased restlessness.
Patient/family teaching
- Avoid tasks that require alertness, motor skills until response to drug is established.
- Do not abruptly discontinue medication after long-term therapy.
- Strict maintenance of drug therapy is essential for seizure control.
- Avoid alcohol.
- Report depression, thoughts of suicide/self-harm, excessive drowsiness, GI symptoms, worsening or loss of seizure control.
2. CLORAZEPATE
| Clorazepate |
| Availability: tablet: Schedule IV: 3.75mg, 7.5mg,15mg |
| Administration and Handling: If GI upset occurs, give with food.; When discontinuing therapy after long-term use, taper dosage gradually over 4 to 8 weeks to avoid withdrawal symptoms.; Take suicide precautions if patient is depressed or anxious. |
| To relieve anxiety: Capsules, tablets: Adults and adolescents. Initial: 15 mg at bedtime or 7.5 to 15 mg b.i.d. Dosage adjusted, as needed, to 15 to 60 mg daily in divided doses b.i.d. to q.i.d. Maximum: 90 mg daily. E.R. TABLETS: Adults and adolescents. 11.25 mg daily as substitute for capsules or tablets in patients who were stabilized on 3.75 mg t.i.d. of those forms; 22.5 mg daily as substitute for capsules or tablets in patients who were stabilized on 7.5 mg t.i.d. of those forms. |
| To relieve symptoms of acute alcohol withdrawal: Capsules, tablets : Adults. Initial: 30 mg followed by 15 mg b.i.d. to q.i.d. on day 1 of therapy; 15 mg three to six times on day 2; 7.5 to 15 mg t.i.d. on day 3; 7.5 mg b.i.d. to q.i.d. on day 4; and thereafter, 3.75 mg b.i.d. to q.i.d. Maximum: 90 mg daily |
| As adjunct to treat partial seizure disorder : Capsules, tablets: Adults and adolescents. Initial: Up to 7.5 mg t.i.d. Increased, if needed, by up to 7.5 mg/wk. Maximum: 90 mg daily. Children ages 9 to 12. Initial: 7.5 mg b.i.d. Increased, if needed, by up to 7.5 mg/wk. Maximum: 60 mg daily. E.R. TABLETS : Adults and adolescents. 11.25 mg daily as substitute for capsules or tablets in patients who were stabilized on 3.75 mg t.i.d. of those forms; 22.5 mg daily as substitute for capsules or tablets in patients who were stabilized on 7.5 mg t.i.d. of those forms. |
Mechanism of Action:
Potentiates action of gamma-aminobutyric acid (GABA) and other inhibitory neurotransmitters by binding to specific benzodiazepine receptor sites in limbic and cortical areas of CNS, which helps control emotional behavior and suppresses spread of seizure activity. Drug also helps relieve symptoms of alcohol withdrawal by depressing CNS.
Indications:
- Anxiety
- Adjunctive therapy in partial seizure disorder
- Management of alcohol withdrawal
Cautions& Contraindications:
- Angle-closure glaucoma
- Hypersensitivity to clorazepate or its components
- Shock; Coma
- Acute alcoholic intoxication with depression of vital signs
- Pregnancy (risk of congenital malformations, neonatal withdrawal syndrome); labor and delivery (“floppy infant” syndrome); lactation (infants tend to become lethargic and lose weight).
- Use cautiously with impaired liver or renal function, debilitation; elderly patients
Metabolism and Half- Life:
Onset of action: 1-2 hr;
Half-Life: 50-70 hr
Duration: Variable 8-24 hour; Metabolism: Hydroxylation, glucuronic acid conjugation
Excretion: Urine
Drug Interactions:
- Barbiturates, MAO inhibitors, opioids, other antidepressants, phenothiazines: potentiated effects of clorazepate
- Cimetidine, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, oral contraceptives, propoxyphene, propranolol, valproic acid: increased blood clorazepate level
- Clozapine: possibly increased risk of shock
- Alcohol use: potentiated clorazepate effects
Side- Effects:
- CNS: dizziness, drowsiness, lethargy, sedation, depression, fatigue, nervousness, confusion, irritability, headache, slurred speech, difficulty articulating words, stupor, rigidity, tremor, poor coordination
- CV: hypertension, hypotension, palpitations
- EENT: blurred or double vision
- GI: dry mouth
- Hematologic: neutropenia
- Hepatic: jaundice
- Skin: rash, diaphoresisOther: weight gain or loss, drug dependence or tolerance
Black Box Warnings
Risks from concomitant use with opioids
- Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required
- Follow patients for signs and symptoms of respiratory depression and sedation
- Inform patients and caregivers that potentially fatal additive effects may occur if drug is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider
- Prescribers should advise caregivers that they expect to be informed immediately if a patient develops any new findings which are not typical of the patient’s characteristic seizure episode
Addiction, abuse, and misuse
- On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death
- Physical dependence can occur when taken steadily for several days to weeks, even as prescribed
- Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening
Nursing considerations
Baseline Assessment
- History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication; pregnancy; lactation; impaired liver or renal function; debilitation
- Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic examination; P, BP; R, adventitious sounds; liver evaluation, abdominal examination, bowel sounds, normal output; CBC, LFTs, renal function tests.
- Be aware that prolonged use of therapeutic doses can lead to dependence.
- Watch closely for evidence of suicidal thinking or behavior, especially when therapy starts or dosage changes.
Interventions
- Taper dosage gradually after long-term therapy, especially in epileptics.
- Arrange for patients with epilepsy to wear medical alert identification, indicating disease and medication usage.
Patient teaching
- Tell patient to take clorazepate with food if GI distress occurs.
- Advise patient to avoid alcohol and other CNS depressants while taking drug.
- Urge patient to avoid hazardous activities until CNS effects of drug are known.
- Urge caregivers to watch patient closely for evidence of suicidal tendencies, especially when therapy starts or dosage changes, and to report concerns to prescriber immediately
3. DIAZEPAM
| Diazepam |
| Availability: Injection, Solution: 5 mg/mL. Oral Concentrate: (Diazepam Intensol): 5 mg/mL. Oral Solution: 5 mg/5 mL. Rectal Gel: 2.5 mg, 10 mg, 20 mg. Tablet: (Valium): 2 mg, 5 mg, 10 mg. |
| Administration/handling: IV : Rate of administration: Give by IV push into tubing of flowing IV solution as close as possible to vein insertion point. • Administer directly into large vein (reduces risk of thrombosis/phlebitis). Do not use small veins (e.g., wrist/dorsum of hand). • Administer IV at rate not exceeding 5 mg/min for adults. For children, give 1–2 mg/min (too-rapid IV may result in hypotension, respiratory depression). • Monitor respirations q5–15 min for 2 hrs. Storage: Store at room temperature |
| IM: Injection may be painful. Inject deeply into large muscle mass |
| PO : Give without regard to food. • Dilute oral concentrate with water, juice, carbonated beverages; may be mixed in semisolid food (applesauce, pudding). • Tablets may be crushed. |
| GEL : Insert rectal tip and gently push plunger over 3 sec. Remove tip after 3 additional sec. • Buttocks should be held together for 3 sec after removal. |
| Anxiety : PO: Adults: 2–10 mg 2–4 times/day. Elderly: Initially, 1–2 mg 1–2 times/day. Children: 0.12–0.8 mg/kg/day in divided doses q6–8h. IV, IM: ADULTS: 2–10 mg; may repeat in 3–4 hrs if needed. |
| Skeletal Muscle Relaxation: PO: Adults: 2–10 mg 2–4 times/day. Elderly: Initially, 1–2 mg 1–2 times/ day. Children: 0.12–0.8 mg/kg/day in divided doses q6–8h. |
| Before cardioversion: Adults: 5 to 15 mg I.V. 5 to 10 minutes before cardioversion |
| Seizures: PO: Adults, elderly: (Adjunctive): 2–10 mg 2–4 times/day |
| Muscle spasms: PO: Adults, elderly: 2–10 mg 3–4 times/day. IV/IM: Initially, 5–10 mg, then 5–10 mg in 3–4 hrs if needed. |
| Alcohol Withdrawal: IM, IV: Adults, elderly: Initially, 10 mg, then 5–10 mg 3–4 hrs later. PO: Adults, elderly: 10 mg 3–4 times during first 24 hrs, then reduce to 5 mg 3–4 times/day as needed. |
| Status Epilepticus: IV: Adults, elderly: 0.15–0.2 mg/kg. Maximum: 10 mg. May repeat once. Infants, children: 0.1–0.3 mg/kg over 2 min; may repeat after 5–10 min. Maximum: 10 mg/dose. |
| Control of Increased Seizure Activity (Breakthrough Seizures) in Pts with Refractory Epilepsy Who Are on Stable Regimens of Anticonvulsants: Note: Do not use gel for more than 5 episodes/month or more than 1 episode q 5days. PO: Adults, elderly: 2–10 mg 2–4 times/day. Rectal gel: Adults, children 12 yrs and older: 0.2 mg/kg; may be repeated in 4–12 hrs. Children 6–11 yrs: 0.3 mg/kg; may be repeated in 4–12 hrs. Maximum: 20 mg. Children 2–5 yrs: 0.5 mg/kg; may be repeated in 4–12 hrs. Maximum: 20 mg. |
Mechanism of Action:
Depresses all levels of CNS by enhancing action of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. Therapeutic effect: produces anxiolytic effect, elevates seizure threshold, produces skeletal muscle relaxation.
Indications:
- Anxiety disorders
- Before cardioversion
- Before endoscopy
- Status epilepticus and severe recurrent convulsive seizures
- Muscle spasm associated with local pathology, cerebral palsy, athetosis, “stiff-man” syndrome, or tetanus
- Acute alcohol withdrawal
- Panic attacks
- Adjunct to general anesthesia
- Cautions& Contraindications:
- Hypersensitivity to diazepam.
- Acute narrow-angle glaucoma, untreated open-angle glaucoma
- Severe respiratory depression
- Severe hepatic insufficiency
- Sleep apnea syndrome
- Myasthenia gravis.
- Children younger than 6 months (oral).
Cautions: Pts receiving other CNS depressants or psychoactive agents, depression, history of drug and alcohol abuse, renal/hepatic impairment, respiratory disease, impaired gag reflex, concurrent use of strong CYP3A4 inhibitors or inducers.
Metabolism and Half- Life:
Well absorbed from GI tract. Widely distributed. Protein binding: 98%. Excreted in urine. Minimally removed by hemodialysis. Half-life: 20–70 hours (increased in hepatic dysfunction, elderly).
Drug Interactions:
- Alcohol, CNS depressants may increase CNS depression.
- CYP3A4 inducers may decrease concentration.
- CYP3A4 inhibitors (e.g., itraconazole, ketoconazole) may increase concentration/effect.
- Olanzapine may increase adverse effects.
- HERBAL: Herbals with sedative properties (e.g., chamomile, kava kava, valerian) may increase CNS depression.
- St. John’s wort may decrease concentration/effects.
- FOOD: Grapefruit products may increase concentration/ effects.
Side – Effects
- Pain with IM injection
- Drowsiness
- Fatigue
- Ataxia
- Ataxia
- Orthostatic hypotension
- Headache
- Hypoactivity
- Constipation
- Nausea
- Blurred vision
Nursing Considerations
Baseline assessment
- Assess B/P, pulse, respirations immediately before administration.
- Anxiety: Assess autonomic response (cold, clammy hands; diaphoresis), motor response (agitation, trembling, tension).
- Musculoskeletal spasm: Record onset, type, location, duration of pain. Check for immobility, stiffness, swelling.
- Seizures: Review history of seizure disorder (length, intensity, frequency, duration, LOC). Observe frequently for recurrence of seizure activity.
Intervention/evaluation
- Monitor heart rate, respiratory rate, B/P, mental status.
- Assess children, elderly for paradoxical reaction, particularly during early therapy.
- Evaluate for therapeutic response (decrease in intensity/frequency of seizures; calm facial expression, decreased restlessness; decreased intensity of skeletal muscle pain).
- Therapeutic serum level: 0.5–2 mcg/mL; toxic serum level: greater than 3 mcg/mL.
Patient/family teaching
- Avoid alcohol. • Limit caffeine.
- May cause drowsiness; avoid tasks that require alertness, motor skills until response to drug is established.
- May be habit forming.
- Avoid abrupt discontinuation after prolonged use.
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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