Pregnancy Category D

Controlled Substance C-IV

Drug classes: Benzodiazepine, Anxiolytic, Sedative-hypnotic

Therapeutic actions

Exact mechanisms are not understood; acts mainly at subcortical levels of the CNS, leaving the cortex relatively unaffected. Main sites of action may be the limbic system and reticular formation; benzodiazepines potentiate the effects of GABA, an inhibitory neurotransmitter; anxiolytic effects occur at doses well below those needed to cause sedation and ataxia.

Indications

• Oral: Management of anxiety disorders or for short-term relief of symptoms of anxiety or anxiety associated with depression; insomnia due to anxiety of transient situational stress
• Parenteral: Preanesthetic medication in adults to produce sedation, relieve anxiety, and decrease recall of events related to surgery; treatment of status epilepticus
• Unlabeled parenteral use: Management of chemotherapy-induced nausea and vomiting, acute alcohol withdrawal

Contraindications and cautions

• Contraindicated with hypersensitivity to benzodiazepines, propylene glycol, polyethylene glycol or benzyl alcohol (parenteral lorazepam); psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; pregnancy (crosses placenta; risk of congenital malformations and neonatal withdrawal syndrome); labor and delivery (“floppy infant” syndrome); lactation.
• Use cautiously with impaired hepatic or renal function.

Available forms

Injection—2, 4 mg/mL; oral solution—2 mg/mL; tablets—0.5, 1, 2 mg

Dosages

ADULTS

Oral

Usual dose is 2–6 mg/day; range 1–10 mg/day given in divided doses with largest dose hs.

• Insomnia due to transient stress: 2–4 mg given hs.

IM

0.05 mg/kg up to a maximum of 4 mg administered at least 2 hr before operative procedure.

IV

Initial dose is 2 mg total or 0.044 mg/kg, whichever is smaller. Do not exceed this dose in patients older than 50 yr. Doses as high as 0.05 mg/kg up to a total of 4 mg may be given 15–20 min before the procedure to those benefited by a greater lack of recall. Continuous infusion 0.5–1 mg/hr titrated, based on patient response.

PEDIATRIC PATIENTS

Drug should not be used in children < 12 yr.

GERIATRIC PATIENTS OR PATIENTS WITH HEPATIC DISEASE

Initially, 1–2 mg/day in divided doses. Adjust as needed and tolerated.

Pharmacokinetics

Metabolism: Hepatic; T_1/2: 10–20 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

IV facts

Preparation: Dilute lorazepam immediately before IV use. For direct IV injection or injection into IV line, dilute with an equal volume of compatible solution (sterile water for injection, sodium chloride injection, or 5% dextrose injection); do not use if solution is discolored or contains a precipitate. Protect from light.

Infusion: Direct inject slowly, or infuse at maximum rate of 2 mg/min.

Y-site incompatibilities: Do not mix with foscarnet, ondansetron.

Adverse effects

• CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, anger, hostility,episodes of mania and hypomania, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty concentrating, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions during first 2 wk of treatment
• CV: Bradycardia, tachycardia, CV collapse, hypertension and hypotension, palpitations, edema
• Dermatologic: Urticaria, pruritus, rash, dermatitis
• EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion
• GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, hepatic dysfunction
• GU: Incontinence, urinary retention, changes in libido, menstrual irregularities
• Hematologic: Elevations of blood enzymes: LDH, alkaline phosphatase, AST, ALT; blood dyscrasias—agranulocytosis, leukopenia
• Other: Hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia. Drug dependence with withdrawal syndrome when drug is discontinued; more common with abrupt discontinuation of higher dosage used for > 4 mo

Interactions

Drug-drug

• Increased CNS depression with alcohol and other sedating medications, such as barbiturates and opioids
• Decreased effectiveness with theophyllines
• Risk of toxicity if combined with probenecid, valproate; reduce lorazepam dose by 50%

Drug-herb

• Kava kava increases the sedative effects of benzodiazepines; coma has been reported with concurrent use

Nursing considerations

CLINICAL ALERT!

Name confusion has occurred between lorazepam and alprazolam; use caution.

Assessment

• History: Hypersensitivity to benzodiazepines, propylene glycol, polyethylene glycol or benzyl alcohol; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; 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

Interventions

• Sublingual administration has more rapid absorption than PO, and bioavailability compares to IM use.
• Do not administer intra-arterially; arteriospasm or gangrene may result.
• Give IM injections of undiluted drug deep into muscle mass, monitor injection sites.
• Do not use solutions that are discolored or contain a precipitate. Protect drug from light, and refrigerate oral solution.
• Intensol is a concentrated solution; it is recommended it be mixed with water, juice, soda, applesauce, or pudding.
• WARNING: Keep equipment to maintain a patent airway readily available when drug is given IV.
• Refrigerate injection and oral solution (36° to 46° F).
• Reduce dose of opioid analgesics by at least half in patients who have received parenteral lorazepam.
• Keep patients who have received parenteral doses under close observation, preferably in bed, up to 3 hr. Do not permit ambulatory patients to drive following an injection.
• WARNING: Taper dosage gradually after long-term therapy, especially in patients with epilepsy.

Teaching points

• Take drug exactly as prescribed; do not stop taking drug (in long-term therapy) without consulting health care provider.
• You may experience these side effects: Drowsiness, dizziness (may be transient; avoid driving or engaging in dangerous activities); GI upset (take drug with food); nocturnal sleep disturbances for several nights after discontinuing the drug if used as a sedative and hypnotic; depression, dreams, emotional upset, crying.
• Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, palpitations, edema of the extremities; visual changes; difficulty voiding.

Sources: (1), (2), (3), (4),

Lorazepam Original source at: Nurseslabs

Brand Name: Alprazolam Intensol, Apo-Alpraz (CAN), Niravam, Novo-Alprazol (CAN), Nu-Alpraz (CAN), Xanax, Xanax TS (CAN), Xanax XR

Other Info: Pregnancy Category D, Controlled Substance C-IV

Drug classes: Benzodiazepine, Anxiolytic

Therapeutic actions

Exact mechanisms of action not understood; main sites of action may be the limbic system and reticular formation; increases the effects of GABA, an inhibitory neurotransmitter; anxiety blocking effects occur at doses well below those necessary to cause sedation, ataxia.

Indications

• Management of anxiety disorders, short-term relief of symptoms of anxiety; anxiety associated with depression.
• Treatment of panic attacks with or without agoraphobia
• Unlabeled uses: Social phobia, premenstrual syndrome, depression

Contraindications and cautions

• Contraindicated with hypersensitivity to benzodiazepines, psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication with depression of vital signs, pregnancy (crosses the placenta; risk of congenital malformations, neonatal withdrawal syndrome), labor and delivery (“floppy infant” syndrome), lactation (secreted in breast milk; infants become lethargic and lose weight).
• Use cautiously with impaired liver or kidney function, debilitation.

Available forms

Tablets—0.25, 0.5, 1, 2 mg; XR tablets—0.5, 1, 2, 3 mg; oral solution—1 mg/mL; rapidly disintegrating tablets—0.25, 0.5, 1, 2 mg

Dosages

Individualize dosage; increase dosage gradually to avoid adverse effects.

ADULTS

• Anxiety disorders: Initially, 0.25–0.5 mg PO tid; adjust to maximum daily dose of 4 mg/day in divided doses or extended-release form once per day in theAM once dosage is established (immediate release, intensol solution).
• Panic disorder: Initially, 0.5 mg PO tid; increase dose at 3- to 4-day intervals in increments of no more than 1 mg/day; ranges of 1–10 mg/day have been needed; extended-release form once per day in AM once dosage is established (Xanax products, Niravam).

UNLABELED USES

• Social phobia: 2–8 mg/day PO.
• PMS: 0.25 mg PO tid.

GERIATRIC PATIENTS OR PATIENTS WITH ADVANCED HEPATIC OR DEBILITATING DISEASE

Initially, 0.25 mg bid–tid PO; gradually increase if needed and tolerated; ER tablets—0.5 mg PO once each day

Pharmacokinetics

Metabolism: Hepatic; T_1/2: 6.3–26.9 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

• CNS: Transient, mild drowsiness initially; sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, anger, hostility,episodes of mania and hypomania, 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
• CV: Bradycardia, tachycardia, CV collapse, hypertension, hypotension, palpitations, edema
• Dermatologic: Urticaria, pruritus, rash, dermatitis
• EENT: Visual and auditory disturbances, diplopia, nystagmus, depressed hearing, nasal congestion
• GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, hepatic impairment
• GU: Incontinence, changes in libido, urinary retention, menstrual irregularities
• Hematologic: Elevations of blood enzymes—LDH, alkaline phosphatase, AST, ALT; blood dyscrasias—agranulocytosis, leukopenia
• Other: Hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia. Drug dependence with withdrawal syndrome when drug is discontinued; more common with abrupt discontinuation of higher dosage used for longer than 4 mo

Interactions

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Drug-drug

• Increased CNS depression with alcohol, other CNS depressants, propoxyphene
• Increased effect with cimetidine, disulfiram, omeprazole, isoniazid, hormonal contraceptives, valproic acid
• Decreased effect with carbamazepine, rifampin, theophylline
• Possible increased risk of digitalis toxicity with digoxin
• Decreased antiparkinson effectiveness of levodopa with benzodiazepines
• Contraindicated with ketoconazole, itraconazole; serious toxicity can occur

Drug-food

• Decreased metabolism and risk of toxic effects if combined with grapefruit juice; avoid this combination

Drug-alternative therapy

• Risk of coma if combined with kava therapy
• Additive sedative effects with valerian root

Nursing considerations

CLINICAL ALERT!: Name confusion has occurred among Xanax (alprazolam), Celexa (citalopram), and Cerebyx (fosphenytoin), and between alprazolamand lorazepam; use caution.

Assessment

• History: Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; shock; coma; acute alcoholic intoxication with depression of vital signs; labor and delivery; lactation; impaired liver or kidney function; debilitation
• Physical: Skin color, lesions; T; orientation, reflexes, affect, ophthalmologic examination; P, BP; liver evaluation, abdominal examination, bowel sounds, normal output; CBC, LFTs, renal function tests

Interventions

• Arrange to taper dosage gradually after long-term therapy, especially in epileptic patients.
• Do not administer with grapefruit juice.
• Taper drug slowly; decrease by no more than 0.5 mg every 3 days.

Teaching points

• Take this drug exactly as prescribed; take extended-release form once a day in the morning; place rapidly disintegrating tablet on top of tongue, where it will disintegrate and can be swallowed with saliva.
• Do not drink grapefruit juice while on this drug.
• Do not stop taking drug (in long-term therapy) without consulting health care provider; drug should not be stopped suddenly.
• Avoid alcohol, sleep-inducing, or over-the-counter drugs.
• You may experience these side effects: Drowsiness, dizziness (these effects will be less pronounced after a few days, avoid driving a car or engaging in other dangerous activities if these occur); GI upset (take drug with food); fatigue; depression; dreams; crying; nervousness.
• Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, difficulty voiding, palpitations, swelling in the extremities.

Sources: (1) (2) (3) (4) (5)

Alprazolam Original source at: Nurseslabs

Brand Name: Valium, Trazepam

Action: anti-anxiety, anticonvulsants, sedative/hypnotics

Indication: Preoperative sedation, management of anxiety

Contraindications of Diazepam

Hypersensitivity, comatose patient, pre-existing CNS depression, uncontrolled severe pain, narrow angle glaucoma, pregnancy or lactation

Dosage of Diazepam

2-10 mg, may repeat in 3-4 hrs as needed (1 amp)

Side Effects of Diazepam

CNS: dizziness, drowsiness, lethargy, depression, hangover, headache, paradoxical excitation; EENT: blurred vision; Resp: respiratory depression; CV: hypotension; GI: constipation, diarrhea, nausea, vomiting; Derm: rashes; Local: pain at IM site, phlebitis at IV site, venous thrombosis; Misc: physical dependence, psychological dependence, tolerance

Nursing Considerations of Diazepam

• Monitor BP, pulse, and respiratory prior and periodically throughout therapy.
• Assess IV site during administration.
• Assess degree of anxiety and level of sedation.
• Patient should be kept on bed rest and observe for at least 3 hr.
• Resuscitation equipment should be available.
• Administer slowly at a rate of 5mg over 1 min.
• Provide safety
• It may be addictive to adults: reinforce proper intake and dosage of the drug

Diazepam Drug Study Original source at: Nurseslabs