Midazolam (Versed)

A short-acting drug in the benzodiazepine class that is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures.

Therapeutic and adverse effects due to its effects on the GABAA receptors.

Enhances the effect of the neurotransmitter GABA on the GABAA receptors resulting in neural inhibition.

It has potent anxiolytic, amnestic, hypnotic, anticonvulsant, skeletal muscle relaxant, and sedative properties.

Most commonly used benzodiazepine as a premedication for sedation.

Commonly it is used for induction and maintenance of anesthesia.

Flumazenil is a benzodiazepine antagonist drug that can reverse sedation and can be used to treat an overdose of midazolam, but can trigger seizures.

Can be administered by nose or the buccal route for the emergency treatment of seizures in children.

Commonly used for endoscopy pre-procedural sedation and sedation in intensive care.

The anterograde amnesia property inhibits unpleasant memories of surgery.

A benzodiazepine with a rapid onset of action, high effectiveness and low toxicity level.

Adverse properties include drug interactions, tolerance, withdrawal syndrome, cognitive impairment and sedation.

Occasionally associated with paradoxical effects in children, and the elderly.

Utilized for sedation of ventilated patients in critical care units.

Superior to diazepam in impairing memory of endoscopy procedures.

Most common benzodiazepine in the intensive care unit because of its short elimination half life.

Water soluble.

Suitability for continuous infusion therapy.

Propofol has advantages over midazolam when used in the ICU for sedation, such as shorter weaning time and earlier tracheal extubation.

Buccal and intranasal administration effective in the emergency control of seizures.

Used at low doses via subcutaneous injection to alleviate agitation, myoclonus, restlessness or anxiety in the last hours or days of life.

At higher doses during the last weeks of life provides palliative deep sedation therapy to alleviate suffering.

May be used for short term treatment of moderately severe insomnia in patients who have not reacted adequately to other hypnotics.

Because of an extremely short duration, it is not used for patients who have trouble staying asleep.

Decreases delta activity on sleep EEG and the latter is an indicator of depth of sleep within non-REM sleep, with lower levels of delta sleep reflecting poorer sleep.

This drug and other benzodiazepines cause a deterioration in sleep quality.

In combination with an antipsychotic drug is indicated for the acute management of schizophrenia with aggressive or out of control behaviour.

Can be used for the acute management of seizures such as status epilepticus.

Long-term use for the management of epilepsy is not recommended.

Has a high degree of breakthrough seizures, because of its to short half life,in over 50 percent of people treated.

Has a treatment failure rate in 14–18 percent of people with refractory status epilepticus.

With prolonged use, tolerance and tachyphylaxis can occur.

Can be administered intramuscularly, intravenously, intrathecally, intranasally, buccally or orally.

When administered during the third trimester of pregnancy, may cause severe risk to the neonate, including benzodiazepine withdrawal syndrome with possible symptoms including hypotonia, apneic spells, cyanosis, and impaired metabolic responses to cold stress.

Hypotonia and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.

The elderly are more sensitive to the pharmacological effects and are more prone to adverse effects, including drowsiness, amnesia, ataxia, hangover effects, confusion and falls.

Its use require special precaution if used in the elderly, during pregnancy, in children, in alcohol or drug-dependent individuals or individuals with comorbid psychiatric disorders.

Kidney or liver dysfunction may slow down the elimination of the drug, enhancing or ptolonging drug dffects.

Contraindications to use include hypersensitivity, acute narrow angle glaucoma, shock, hypotension or head injury.

After nighttime administration, residual sleepiness and impaired psychomotor and cognitive functions, may persist into the next day.

IV adminstration may be associated with hypotension if given too rapidly.

Paradoxical reactions are associated with intravenous administration, and may manifest with anxiety, involuntary movements, aggressive or violent behavior, uncontrollable crying or verbalization, and other similar effects.

Flumazenil can be administered to inhibit or reverse the effects of midazolam. Antipsychotic medications, such as haloperidol, have also been used for this purpose.

Known to cause respiratory depression.

Withdrawal symptoms range from insomnia and anxiety to seizures and psychosis, which can sometimes resemble the patient’s underlying condition.

Gradual reduction after regular use minimizes withdrawal and rebound effects.

Long-term use can cause changes in the function of the GABAergic neuronal system.

An overdose is considered a medical emergency, and the antidote is flumazenil.

Concentrations of midazolam and/or its major metabolite, 1-hydroxymidazolam glucuronide, may be quantified in plasma, serum or whole blood in order to monitor for safety.

In the presence of renal dysfunction may exhibit prolongation of elimination half-life for both the parent drug and its active metabolite, with accumulation of these two substances.

The metabolism is inhibited by clarithromycin, diltiazem, erythromycin, atorvastatin, fluoxetine, grapefruit juice, HIV protease inhibitors, nefazodone and sertraline.

Enhance drug metabolism with reduced action seen with phenytoin, rifabutin, rifampin, rifapentine and St. John’s wort.

Sedating agents enhance the sedative effects.

Metabolized almost completely by cytochrome P450-3A4.

A short-acting benzodiazepine in adults with an elimination half-life of one to four hours.

In the elderly, as well as young children and adolescents, the elimination half life is longer.

Metabolized into an active metabolite alpha1-hydroxymidazolam.

The active metabolite of midazolam is minor and contributes to only 10 percent of biological activity.

Poorly absorbed orally with only 50 percent of the drug reaching the bloodstream.

Metabolised by cytochrome P450 (CYP) enzymes and by glucuronide conjugation.

Its water solubility allows it to be less likely to cause thrombophlebitis than similar drugs.

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