Diazepam
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diazepam (dye az' e pam) Apo-Diazepam (CAN), Diastat, Diazemuls (CAN), Diazepam Intensol, Valium, Vivol (CAN) Pregnancy Category D Controlled Substance C-IV Drug classes
Benzodiazepine Anxiolytic Antiepileptic Skeletal muscle relaxant (centrally acting) Therapeutic actions
Exact mechanisms of action not understood; acts mainly at the limbic system and reticular formation; may act in spinal cord and at supraspinal sites to produce skeletal muscle relaxation; potentiates the effects of GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well below those necessary to cause sedation, ataxia; has little effect on cortical function. Indications
• • •
• • • • •
Management of anxiety disorders or for short-term relief of symptoms of anxiety Acute alcohol withdrawal; may be useful in symptomatic relief of acute agitation, tremor, delirium tremens, hallucinosis Muscle relaxant: Adjunct for relief of reflex skeletal muscle spasm due to local pathology (inflammation of muscles or joints) or secondary to trauma; spasticity caused by upper motoneuron disorders (cerebral palsy and paraplegia); athetosis, stiff-man syndrome Parenteral: Treatment of tetanus Antiepileptic: Adjunct in status epilepticus and severe recurrent convulsive seizures (parenteral); adjunct in convulsive disorders (oral) Preoperative (parenteral): Relief of anxiety and tension and to lessen recall in patients prior to surgical procedures, cardioversion, and endoscopic procedures Rectal: Management of selected, refractory patients with epilepsy who require intermittent use to control bouts of increased seizure activity Unlabeled use: Treatment of panic attacks
Contraindications and cautions
•
Contraindicated with hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; pregnancy (cleft lip or palate, inguinal hernia, cardiac defects, microcephaly, pyloric stenosis when used in first trimester; neonatal withdrawal syndrome reported in newborns); lactation.
•
Use cautiously with elderly or debilitated patients; impaired liver or kidney function.
Available forms
Tablets—2, 5, 10 mg; SR capsule—15 mg; oral solution—1 mg/mL, 5 mg/5 mL; rectal pediatric gel—2.5, 5, 10 mg; rectal adult gel—10, 15, 20 mg; injection—5 mg/mL Dosages
Individualize dosage; increase dosage cautiously to avoid adverse effects. ADULTS Oral
• •
Anxiety disorders, skeletal muscle spasm, seizure disorders: 2–10 mg bid–qid. Alcohol withdrawal: 10 mg tid–qid first 24 hr; reduce to 5 mg tid–qid, as needed.
Oral sustained release
• •
Anxiety disorders: 15–30 mg/day. Alcohol withdrawal: 30 mg first 24 hr; reduce to 15 mg/day as needed.
Rectal
0.2 mg/kg PR; treat no more than one episode q 5 days. May be given a second dose in 4–12 hr. Parenteral
Usual dose is 2–20 mg IM or IV. Larger doses may be required for some indications (tetanus). Injection may be repeated in 1 hr. • Anxiety: 2–10 mg IM or IV; repeat in 3–4 hr if necessary. • Alcohol withdrawal: 10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary. • Endoscopic procedures: 10 mg or less, up to 20 mg IV just before procedure or 5– 10 mg IM 30 min prior to procedure. Reduce or omit dosage of narcotics. • Muscle spasm: 5–10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary. • Status epilepticus: 5–10 mg, preferably by slow IV. May repeat q 5–10 min up to total dose of 30 mg. If necessary, repeat therapy in 2–4 hr; other drugs are preferable for long-term control. • Preoperative: 10 mg IM. • Cardioversion: 5–15 mg IV 5–10 min before procedure. PEDIATRIC PATIENTS Oral
> 6 mo: 1–2.5 mg PO tid–qid initially. Gradually increase as needed and tolerated. Can be given rectally if needed. Rectal
< 2 yr: Not recommended. 2–5 yr: 0.5 mg/kg. 6–11 yr: 0.3 mg/kg. >12 yr: Adult dose; may give a second dose in 4–12 hr. Parenteral
Maximum dose of 0.25 mg/kg IV administered over 3 min; may repeat after 15–30 min. If no relief of symptoms after three doses, adjunctive therapy is recommended. • Tetanus (> 1 mo): 1–2 mg IM or IV slowly q 3–4 hr as necessary.
• • •
Tetanus (> 5 yr): 5–10 mg q 3–4 hr. Status epilepticus (> 1 mo–< 5 yr): 0.2–0.5 mg slowly IV q 2–5 min up to a maximum of 5 mg. Status epilepticus (> 5 yr): 1 mg IV q 2–5 min up to a maximum of 10 mg; repeat in 2–4 hr if necessary.
GERIATRIC PATIENTS OR THOSE WITH DEBILITATING DISEASE
2–2.5 mg PO daily–bid or 2–5 mg parenteral initially; reduce rectal dose. Gradually increase as needed and tolerated; use cautiously. Pharmacokinetics Route Oral IM IV Rectal
Onset 30–60 min 15–30 min 1–5 min Rapid
Peak 1–2 hr 30–45 min 30 min 1.5 hr
Duration 3 hr 3 hr 15–60 min 3 hr
Metabolism: Hepatic; T1/2: 20–80 hr Distribution: Crosses placenta; enters breast milk Excretion: Urine IV facts
Preparation: Do not mix with other solutions; do not mix in plastic bags or tubing. Infusion: Inject slowly into large vein, 1 mL/min at most; for children do not exceed 3 min; do not inject intra-arterially; if injected into IV tubing, inject as close to vein insertion as possible. Incompatibilities: Do not mix with other solutions; do not mix with any other drugs. Y-site Incompatibilities: Atracurium, heparin, foscarnet, pancuronium, potassium, vecuronium. Adverse effects
•
• •
• •
CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions, during first 2 wk of treatment, visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema Dependence: Drug dependence with withdrawal syndrome when drug is discontinued (common with abrupt discontinuation of higher dosage used for longer than 4 mo); IV diazepam: 1.7% incidence of fatalities; oral benzodiazepines ingested alone; no well-documented fatal overdoses Dermatologic: Urticaria, pruritus, skin rash, dermatitis GI: Constipation; diarrhea, dry mouth; salivation; nausea; anorexia; vomiting; difficulty in swallowing; gastric disorders; elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; hepatic dysfunction; jaundice
• • •
GU: Incontinence, urinary retention, changes in libido, menstrual irregularities Hematologic: Decreased hematocrit, blood dyscrasias Other: Phlebitis and thrombosis at IV injection sites, hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia; pain, burning, and redness after IM injection
Interactions
Drug-drug • Increased CNS depression with alcohol, omeprazole • Increased pharmacologic effects of diazepam if combined with cimetidine, disulfiram, hormonal contraceptives • Decreased effects of diazepam with theophyllines, ranitidine Nursing considerations Assessment
• •
History: Hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; elderly or debilitated patients; impaired liver or kidney function; pregnancy, lactation Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory nerve function, ophthalmologic exam; P, BP; R, adventitious sounds; bowel sounds, normal output, liver evaluation; normal output; liver and kidney function tests, CBC
Interventions
• • • • • • • • • • •
Do not administer intra-arterially; may produce arteriospasm, gangrene. Change from IV therapy to oral therapy as soon as possible. Do not use small veins (dorsum of hand or wrist) for IV injection. Reduce dose of narcotic analgesics with IV diazepam; dose should be reduced by at least one-third or eliminated. Carefully monitor P, BP, respiration during IV administration. Maintain patients receiving parenteral benzodiazepines in bed for 3 hr; do not permit ambulatory patients to operate a vehicle following an injection. Monitor EEG in patients treated for status epilepticus; seizures may recur after initial control, presumably because of short duration of drug effect. Monitor liver and kidney function, CBC during long-term therapy. Taper dosage gradually after long-term therapy, especially in epileptic patients. Arrange for epileptic patients to wear medical alert ID indicating that they are epileptics taking this medication. Discuss risk of fetal abnormalities with patients desiring to become pregnant.
Teaching points
•
Take this drug exactly as prescribed. Do not stop taking this drug (long-term therapy, antiepileptic therapy) without consulting your health care provider.
• • • •
Caregiver should learn to assess seizures, administer rectal form, and monitor patient. Use of barrier contraceptives is advised while using this drug; if you become or wish to become pregnant, consult with your health care provider. These side effects may occur: Drowsiness, dizziness (may lessen; avoid driving or engaging in other dangerous activities); GI upset (take drug with food); dreams, difficulty concentrating, fatigue, nervousness, crying (reversible). Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, palpitations, swelling of the ankles, visual or hearing disturbances, difficulty voiding.
Adverse effects in Italic are most common; those in Bold are life-threatening.
Benzodiazepine Anxiolytic Antiepileptic Skeletal muscle relaxant (centrally acting) Therapeutic actions
Exact mechanisms of action not understood; acts mainly at the limbic system and reticular formation; may act in spinal cord and at supraspinal sites to produce skeletal muscle relaxation; potentiates the effects of GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well below those necessary to cause sedation, ataxia; has little effect on cortical function. Indications
• • •
• • • • •
Management of anxiety disorders or for short-term relief of symptoms of anxiety Acute alcohol withdrawal; may be useful in symptomatic relief of acute agitation, tremor, delirium tremens, hallucinosis Muscle relaxant: Adjunct for relief of reflex skeletal muscle spasm due to local pathology (inflammation of muscles or joints) or secondary to trauma; spasticity caused by upper motoneuron disorders (cerebral palsy and paraplegia); athetosis, stiff-man syndrome Parenteral: Treatment of tetanus Antiepileptic: Adjunct in status epilepticus and severe recurrent convulsive seizures (parenteral); adjunct in convulsive disorders (oral) Preoperative (parenteral): Relief of anxiety and tension and to lessen recall in patients prior to surgical procedures, cardioversion, and endoscopic procedures Rectal: Management of selected, refractory patients with epilepsy who require intermittent use to control bouts of increased seizure activity Unlabeled use: Treatment of panic attacks
Contraindications and cautions
•
Contraindicated with hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; pregnancy (cleft lip or palate, inguinal hernia, cardiac defects, microcephaly, pyloric stenosis when used in first trimester; neonatal withdrawal syndrome reported in newborns); lactation.
•
Use cautiously with elderly or debilitated patients; impaired liver or kidney function.
Available forms
Tablets—2, 5, 10 mg; SR capsule—15 mg; oral solution—1 mg/mL, 5 mg/5 mL; rectal pediatric gel—2.5, 5, 10 mg; rectal adult gel—10, 15, 20 mg; injection—5 mg/mL Dosages
Individualize dosage; increase dosage cautiously to avoid adverse effects. ADULTS Oral
• •
Anxiety disorders, skeletal muscle spasm, seizure disorders: 2–10 mg bid–qid. Alcohol withdrawal: 10 mg tid–qid first 24 hr; reduce to 5 mg tid–qid, as needed.
Oral sustained release
• •
Anxiety disorders: 15–30 mg/day. Alcohol withdrawal: 30 mg first 24 hr; reduce to 15 mg/day as needed.
Rectal
0.2 mg/kg PR; treat no more than one episode q 5 days. May be given a second dose in 4–12 hr. Parenteral
Usual dose is 2–20 mg IM or IV. Larger doses may be required for some indications (tetanus). Injection may be repeated in 1 hr. • Anxiety: 2–10 mg IM or IV; repeat in 3–4 hr if necessary. • Alcohol withdrawal: 10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary. • Endoscopic procedures: 10 mg or less, up to 20 mg IV just before procedure or 5– 10 mg IM 30 min prior to procedure. Reduce or omit dosage of narcotics. • Muscle spasm: 5–10 mg IM or IV initially, then 5–10 mg in 3–4 hr if necessary. • Status epilepticus: 5–10 mg, preferably by slow IV. May repeat q 5–10 min up to total dose of 30 mg. If necessary, repeat therapy in 2–4 hr; other drugs are preferable for long-term control. • Preoperative: 10 mg IM. • Cardioversion: 5–15 mg IV 5–10 min before procedure. PEDIATRIC PATIENTS Oral
> 6 mo: 1–2.5 mg PO tid–qid initially. Gradually increase as needed and tolerated. Can be given rectally if needed. Rectal
< 2 yr: Not recommended. 2–5 yr: 0.5 mg/kg. 6–11 yr: 0.3 mg/kg. >12 yr: Adult dose; may give a second dose in 4–12 hr. Parenteral
Maximum dose of 0.25 mg/kg IV administered over 3 min; may repeat after 15–30 min. If no relief of symptoms after three doses, adjunctive therapy is recommended. • Tetanus (> 1 mo): 1–2 mg IM or IV slowly q 3–4 hr as necessary.
• • •
Tetanus (> 5 yr): 5–10 mg q 3–4 hr. Status epilepticus (> 1 mo–< 5 yr): 0.2–0.5 mg slowly IV q 2–5 min up to a maximum of 5 mg. Status epilepticus (> 5 yr): 1 mg IV q 2–5 min up to a maximum of 10 mg; repeat in 2–4 hr if necessary.
GERIATRIC PATIENTS OR THOSE WITH DEBILITATING DISEASE
2–2.5 mg PO daily–bid or 2–5 mg parenteral initially; reduce rectal dose. Gradually increase as needed and tolerated; use cautiously. Pharmacokinetics Route Oral IM IV Rectal
Onset 30–60 min 15–30 min 1–5 min Rapid
Peak 1–2 hr 30–45 min 30 min 1.5 hr
Duration 3 hr 3 hr 15–60 min 3 hr
Metabolism: Hepatic; T1/2: 20–80 hr Distribution: Crosses placenta; enters breast milk Excretion: Urine IV facts
Preparation: Do not mix with other solutions; do not mix in plastic bags or tubing. Infusion: Inject slowly into large vein, 1 mL/min at most; for children do not exceed 3 min; do not inject intra-arterially; if injected into IV tubing, inject as close to vein insertion as possible. Incompatibilities: Do not mix with other solutions; do not mix with any other drugs. Y-site Incompatibilities: Atracurium, heparin, foscarnet, pancuronium, potassium, vecuronium. Adverse effects
•
• •
• •
CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions, during first 2 wk of treatment, visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema Dependence: Drug dependence with withdrawal syndrome when drug is discontinued (common with abrupt discontinuation of higher dosage used for longer than 4 mo); IV diazepam: 1.7% incidence of fatalities; oral benzodiazepines ingested alone; no well-documented fatal overdoses Dermatologic: Urticaria, pruritus, skin rash, dermatitis GI: Constipation; diarrhea, dry mouth; salivation; nausea; anorexia; vomiting; difficulty in swallowing; gastric disorders; elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; hepatic dysfunction; jaundice
• • •
GU: Incontinence, urinary retention, changes in libido, menstrual irregularities Hematologic: Decreased hematocrit, blood dyscrasias Other: Phlebitis and thrombosis at IV injection sites, hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia; pain, burning, and redness after IM injection
Interactions
Drug-drug • Increased CNS depression with alcohol, omeprazole • Increased pharmacologic effects of diazepam if combined with cimetidine, disulfiram, hormonal contraceptives • Decreased effects of diazepam with theophyllines, ranitidine Nursing considerations Assessment
• •
History: Hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; elderly or debilitated patients; impaired liver or kidney function; pregnancy, lactation Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory nerve function, ophthalmologic exam; P, BP; R, adventitious sounds; bowel sounds, normal output, liver evaluation; normal output; liver and kidney function tests, CBC
Interventions
• • • • • • • • • • •
Do not administer intra-arterially; may produce arteriospasm, gangrene. Change from IV therapy to oral therapy as soon as possible. Do not use small veins (dorsum of hand or wrist) for IV injection. Reduce dose of narcotic analgesics with IV diazepam; dose should be reduced by at least one-third or eliminated. Carefully monitor P, BP, respiration during IV administration. Maintain patients receiving parenteral benzodiazepines in bed for 3 hr; do not permit ambulatory patients to operate a vehicle following an injection. Monitor EEG in patients treated for status epilepticus; seizures may recur after initial control, presumably because of short duration of drug effect. Monitor liver and kidney function, CBC during long-term therapy. Taper dosage gradually after long-term therapy, especially in epileptic patients. Arrange for epileptic patients to wear medical alert ID indicating that they are epileptics taking this medication. Discuss risk of fetal abnormalities with patients desiring to become pregnant.
Teaching points
•
Take this drug exactly as prescribed. Do not stop taking this drug (long-term therapy, antiepileptic therapy) without consulting your health care provider.
• • • •
Caregiver should learn to assess seizures, administer rectal form, and monitor patient. Use of barrier contraceptives is advised while using this drug; if you become or wish to become pregnant, consult with your health care provider. These side effects may occur: Drowsiness, dizziness (may lessen; avoid driving or engaging in other dangerous activities); GI upset (take drug with food); dreams, difficulty concentrating, fatigue, nervousness, crying (reversible). Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, palpitations, swelling of the ankles, visual or hearing disturbances, difficulty voiding.
Adverse effects in Italic are most common; those in Bold are life-threatening.
