Diazepam (Valium) Drug Study

Generic Name: diazepam

Brand Names:  Valium

Pregnancy Category D

Controlled Substance C-IV

Drug classes:

• Benzodiazepine
• Anxiolytic
• Antiepileptic
• Skeletal muscle relaxant (centrally acting)

Therapeutic actions of Valium

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 seizure 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 renal function; and in patients with a history of substance abuse.

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 give 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 opioids.
• 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: Use 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 PATIENTS 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

• Metabolism: Hepatic; T_1/2: 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 impairment; 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 renal function; pregnancy, lactation
• Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory nerve function, ophthalmologic examination; P, BP; R, adventitious sounds; bowel sounds, normal output, liver evaluation; normal output; LFTs, renal function tests, CBC

Interventions

[sws_red_box box_size="630"]

• WARNING: Do not administer intra-arterially; may produce arteriospasm, gangrene.[/sws_red_box]
• 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 opioid analgesics with IV diazepam; dose should be reduced by at least one-third or eliminated.
• Carefully monitor P, BP, respiration during IV administration.

[sws_red_box box_size="630"]WARNING: Maintain patients receiving parenteral benzodiazepines in bed for 3 hr; do not permit ambulatory patients to operate a vehicle following an injection.[/sws_red_box]

• 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 renal 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.
• It is advisable to wear a medical alert ID indicating your diagnosis and treatment (as antiepileptic).
• You may experience these side effects: 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 se

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