Midazolam adverse effects

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Although it is a desirable anesthetic in many respects, ketamine has been associated with postoperative disorientation, sensory and perceptual illusions, and vivid dreams (so-called emergence phenomena). Diazepam, 0.2-0.3 mg/kg, or midazolam, 0.025-0.05 mg intravenously, given prior to the administration of ketamine reduces the incidence of these adverse effects. 

Respiratory depression has been reported as the commonest adverse effect of intravenous diazepam (56), especially at the extremes of age. Midazolam has similar effects (62). All benzodiazepines can cause respiratory depression, particularly in bronchitic patients, through drowsiness and reduction in exercise tolerance (63). Rectal administration of, for example, diazepam can offer advantages in unconscious or uncooperative patients, and is less likely than parenteral administration to produce respiratory depression. 

Diazepam produces less sedation in cigarette smokers, and higher (not lower, as stated in SEDA-20) doses may be required for the same sedative or anxiolytic effect. Owing in part to its continued widespread use, several unusual adverse effects of diazepam continue to be reported. These include cases of urinary retention and compartment syndrome, which are not explicable by its pharmacology. On the other hand, accumulation of diazepam and attendant complications of obtundation and respiratory depression may be understood in terms of its long half-life, particularly in elderly people and medically ill patients. Caution about the intravenous use of diazepam comes from a study that showed cardiac dysrhythmias (mainly ventricular extra beats) in a quarter of oral surgery patients midazolam and lorazepam were much safer (1). 

The pharmacology and adverse effects of midazolam in infants and children have been reviewed (4). 

In a 1-year retrospective survey of the use of intramuscular midazolam in a 30-bed acute inpatient general adult unit in Sydney, Australia, 212 doses of intramuscular midazolam were given, predominantly 5 mg (48%) or 10 mg (50%) (13). An antipsychotic drug was co-adminis-tered in 2.4%. Adverse effects were documented in eight episodes (3.8%), seven cases of excess sedation and one of urinary incontinence. None of the adverse effects required medical intervention. 

In 27 children with refractory generalized convulsive status epilepticus, midazolam 0.2 mg/kg as a bolus followed by 1-5 (mean 3.1) micrograms/kg/minute as a continuous infusion achieved complete control of seizures in 26 children within 65 minutes (14). There were no adverse effects, such as hypotension, bradycardia, or respiratory depression. In one patient with acute meningoencephalitis, status epilepticus could not be controlled. Five patients died of the primary disorders, one with progressive encephalopathy. 

There was a variety of significant nervous system adverse effects in six of 104 patients who underwent transesophageal echocardiography, including aggression, euphoria, depression, and intense hiccups (42). These effects occurred despite careful titration and relatively low doses of intravenous midazolam (mean 4.8 mg), and were generally reversible with intravenous flumazenil 0.25-0.5 mg. 

The pharmacology and adverse effects of midazolam in infants and children have been reviewed (4). The optimal dose of intramuscular midazolam for preoperative sedation has been studied in a double-blind prospective study of 600 patients who were age-stratified (51). The patients received intramuscular atropine 0.6 mg and one of five doses of midazolam 15 minutes before induction of anesthesia. For the age groups 20-39, 40-59, and 60-79 years, the optimal sedative and amnesic effects of midazolam were 0.10, 0.08, and 0.04 mg/kg respectively. The frequency with which the undesirable adverse effects of reduced blood pressure, oxygen desaturation, oversedation, loss of eyelash reflex, and tongue root depression occurred increased with age, and optimal doses for a low incidence of adverse effects were 0.08, 0.06, and 0.04 mg/ kg in the same age groups respectively. 

Several adverse effects have been reported with the combined use of fentanyl and midazolam, including chest wall rigidity, making ventilation with a bag and mask impossible (SEDA-16, 79). In neonates, hypotension can occur (SEDA-16, 80), and respiratory arrest in a child and sudden cardiac arrest have been reported (SEDA-16, 80). However, in one study there were no cardiac electrophy-siological effects of midazolam combined with fentanyl in subjects undergoing cardiac electrophysiological studies (SEDA-18, 80). 

Hughes J, Gill A, Leach HJ, Nunn AJ, Billingham I, Ratcliffe J, Thomington R, Choonara I. A prospective study of the adverse effects of midazolam on withdrawal in critically ill children. Acta Paediatr 1994 83(ll) 1194-9. 

DIAZEPAM, MIDAZOLAM NNRTIs - EFAVIRENZ t efficacy and t adverse effects, e.g. prolonged sedation 1 CYP3A4-mediated metabolism of diazepam and midazolam 1. Monitor more closely, especially sedation levels. May need 1 dose of diazepam or alteration of timing of dose 2. Avoid co-administration with midazolam... 

ALPRAZOLAM, DIAZEPAM, MIDAZOLAM-ORAL GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. sedation, CNS depression Possibly t bioavailability, 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Avoid concomitant use. Be particularly vigilant in elderly patients or those with impaired liver function. Consider alternative, e.g. temazepam... 

Hourigan C, Safih S, Rogers 1, Jacobs I, Lockney A. Randomized controlled trial of midazolam premedication to reduce the subjective adverse effects of adenosine. Emerg Med (Fremantle) 2001 13(l) 51-6. 

Intranasal midazolam 0.2 mg/kg and intravenous diazepam 0.3 mg/kg have been compared in a prospective randomized study in 47 children (aged 6 months to 5 years) with prolonged (over 10 minutes) febrile seizures (55). Intranasal midazolam controlled seizures significantly earlier than intravenous diazepam. None of the children had respiratory distress, bradycardia, or other adverse effects. Electrocardiography, blood pressure, and pulse... 

Several adverse effects have been reported with the combined use of fentanyl and midazolam, including chest wall rigidity, making ventilation with a bag and mask impossible (SEDA-16, 79). 

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