midazolam (Versed, Buccolam)
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Introduction
Tradename: Versed. DEA-controlled substance: class 4.
Indications
- used in anesthesia for sedation
- management of sedation/agitation (< 24 h) in an ICU setting
- NOT recommended for sedation > 24 h due to active metabolite accumulation, especially in elderly & patients with renal impairment
- status epilepticus
- anxiety[7]
- amnesia[7]
Contraindications
- uncontrolled pain
- pre-existing CNS depression
- shock
- narrow angle glaucoma
Caution:
- increased potential for toxicity in elderly
- congestive heart failure
- renal impairment
- pulmonary disease
- hepatic dysfunction
Dosage
- 5 mg or 0.07 mg/kg IM[1].
- 0.08 mg/kg IM[2].
- conscious sedation:
- 2-4 mg IV every 3-4 hours (1-2 mg if > 60 years of age)
- infusion 2-8 mg/hr (1-4 mg/hr > 60 yr), titrate to effect
- 2.5-10 mg (buccal)
1 mg lorazepam = 4 mg midazolam
Injection: 1 mg/mL (2 mL, 5 mL, 10 mL) 5 mg/mL (1 mL, 2 mL, 5 mL, 10 mL)
Pharmacokinetics
- well absorbed with IM administration
- rapid onset of action
- duration of action 60-90 minutes
- poor systemic absorption after oral administration
- highly lipophilic
- metabolized in the liver by cyt P450 3A4 to active metabolites (hydroxylation)
- principal metabolite is alpha-hydroxymidazolam
- excreted in the urine
- active metabolites accumulate with renal dysfunction
- 1/2life 1.5-3 hours
- metabolite 1/2life 24-36 hours
elimination via liver
1/2life = 1-4 hours
protein binding = 94-97 %
Adverse effects
- common (> 10%)
- decreased respiratory rate, apnea, hypotension, hiccups, pain at site of injection
- less common (1-10%)
- cardiac arrest, bradycardia, drowsiness, ataxia, amnesia, dizziness, paradoxical excitement, sedation, headache, nausea/vomiting, blurred vision, diplopia, laryngospasm, bronchospasm
- uncommon (< 1%)
- other[3]
- withdrawal
- agitation
- anterograde amnesia
- phlebitis
- cardio-respiratory depression
- hallucinations
- relaxation of lower esophageal sphincter (GERD)
- over sedation, especially with renal insufficiency
- tachyphylaxis
- physical & psychologic dependence with prolonged use
- drug adverse effects of benzodiazepines
- drug adverse effects of psychotropic agents
- drug adverse effects of sedatives
Drug interactions
- disulfiram, nefazodone, fluoxetine, fluvoxamine, cimetidine, ranitidine, erythromycin & grapefruit juice decrease metabolism of benzodiazepines
- CNS depressants in combination increase CNS depression
- anticonvulsants, rifampin increase metabolism of benzodiazepines
- flumazenil antagonizes effects of benzodiazepines
- any drug that inhibits cyt P450 3A4 may increase levels of midazolam
- any drug that induces cyt P450 3A4 may diminish levels of midazolam
- drug interaction(s) of methadone in combination with benzodiazepines
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of benzodiazepines with thiazide diuretics
- drug interaction(s) of antipsycotics with benzodiazepines
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists (except atenolol) with benzodiazepines
- drug interaction(s) of alcoholic beverage with benzodiazepines
- drug interaction(s) of benzodiazepine with opiates
Laboratory
Mechanism of action
- potentiates inhibitory effects of GABA by inhibiting neuronal membrane permeability to Cl-
More general terms
Additional terms
References
- ↑ 1.0 1.1 1.2 The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ 2.0 2.1 2.2 Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 7
- ↑ 3.0 3.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S, Choonara I. Safety and efficacy of buccal midazolam versus rectal diazepam f or emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005 Jul 16-22;366(9481):205-10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16023510
- ↑ 7.0 7.1 7.2 Deprecated Reference