Lorazepam; Uses, Dosage, Side Effects, Interactions

Lorazepam is a benzodiazepine with anxiolytic, anti-anxiety, anticonvulsant, anti-emetic and sedative properties. Lorazepam enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid on the GABA receptors by binding to a site that is distinct from the GABA binding site in the central nervous system. This leads to an increase in chloride channel opening events, facilitation of chloride ion conductance, membrane hyperpolarization, and eventually inhibition of the transmission of nerve signals, thereby decreasing nervous excitation.

Lorazepam is an orally available benzodiazepine used widely in the therapy of anxiety and insomnia. As with most benzodiazepines, lorazepam therapy has not been associated with serum aminotransferase or alkaline phosphatase elevations, and clinically apparent liver injury from lorazepam has not been reported and must be very rare if it occurs at all.

Lorazepam is an intermediate-duration psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, anti-nausea, depressant and preanesthetic effects.I t affects chemicals in the brain that may be unbalanced in people with anxiety.

Mechanism of Action of Lorazepam 

Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolerization of the neuron.

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Lorazepam is a benzodiazepine with anxiolytic, anti-anxiety, anticonvulsant, anti-emetic and sedative properties. Lorazepam enhances the effect of the inhibitory neurotransmitter gamma-aminobutyric acid on the GABA receptors by binding to a site that is distinct from the GABA binding site in the central nervous system. This leads to an increase in chloride channel opening events, a facilitation of chloride ion conductance, membrane hyperpolarization, and eventually inhibition of the transmission of nerve signals, thereby decreasing nervous excitation.

Indications of Lorazepam 

• Insomnia
• Anxiety
• Cervical Dystonia
• Anxiety Disorders
• Feeling Anxious
• Refractory seizure disorders
• Borderline Personality Disorder
• Panic Disorder
• ICU Agitation
• Dysautonomia
• Light Anesthesia
• Nausea/Vomiting
• Nausea/Vomiting, Chemotherapy Induced
• Sedation
• Status Epilepticus
• For the management of anxiety disorders, and for treatment of status epilepticus.

Contra Indications of Lorazepam 

• Low amount of albumin proteins in the blood
• Having thoughts of suicide
• Alcohol intoxication
• Drug abuse
• Wide-angle glaucoma
• Closed angle glaucoma
• Chronic lung disease
• Liver problems
• Severe liver disease
• Temporarily stops breathing while sleeping
• Pregnancy
• Impaired brain function due to liver disease
• Kidney disease with a likely reduction in kidney function

Dosages of Lorazepam 

Strengths:  0.5 mg;  1 mg; 2 mg; 4 mg/mL; 2 mg/mL; 1 mg/mL

Insomnia

• 2 to 4 mg orally administered at bedtime

Anxiety

Tablets

• Initial dose: 2 to 3 mg orally per day administered 2 to 3 times per day
• Maintenance dose: 1 to 2 mg orally 2 to 3 times a day
• IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Light Anesthesia

• IM: 0.05 mg/kg up to a maximum of 4 mg
• IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Status Epilepticus

• 0.1 mg/kg IV up to 4 mg per dose; may repeat in 5 to 10 minutes
• Maximum dose: 8 mg

Pediatric Dose for Anxiety

12 years or older

• Initial dose: 2 to 3 mg orally per day administered 2 to 3 times per day
• Maintenance dose: 1 to 2 mg orally 2 to 3 times a day.

Pediatric Dose for Insomnia

12 years or older

• 2 to 4 mg orally administered at bedtime

Side Effects of Lorazepam 

The most common

• clumsiness or unsteadiness
• dizziness
• drowsiness
• dry mouth
• false sense of well-being
• increased watering of mouth
• lightheadedness
• constipation;
• vision changes;
• breast swelling (in men or women); or
• decreased sex drive, impotence, or difficulty having an orgasm.
• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• restless muscle movements in your eyes, tongue, jaw, or neck;
• a light-headed feeling, like you might pass out;

Common

• Drowsiness and lightheadedness the day after taking the medicine.
• Confusion.
• Numbed emotions.
• Visual disturbances such as blurred vision or double vision.
• Shaky movements and unsteady walk (ataxia).
• Loss of memory (amnesia).
• Muscle weakness.
• Dizziness.
• Headache.
• Skin rashes.
• Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting or abdominal pain.
• Difficulty in passing urine (urinary retention).
• Changes in sex drive.
• Low blood pressure (hypotension).
• Blood disorders.
• Jaundice.
• Unexpected aggression, restlessness or irritability (tell your doctor if you experience this).
• Nightmares or hallucinations (tell your doctor if you experience this).

Serious

• agitation
• anxiety
• behavioural changes, including aggressiveness, angry outbursts, bizarre behaviour, or decreased inhibitions
• confusion
• increased trouble sleeping
• memory problems
• muscle spasms
• shortness of breath
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• sleepwalking

Drug Interactions of Lorazepam 

Lorazepam may interact with following drug, supplements & may change the efficacy of drugs

• Benzodiazepines,
• Birth control pills
• Barbiturates,
• anticonvulsants (e.g., carbamazepine, gabapentin, levetiracetam, phenytoin, topiramate)
• antihistamines that cause drowsiness (e.g., chlorpheniramine, dimenhydrinate, diphenhydramine)
• antipsychotic medications (e.g., chlorpromazine, clozapine, haloperidol, olanzepine, quetiapine, risperidone)
• aripiprazole
• azole antifungal medications (e.g., fluconazole, ketoconazole)
• baclofen
• barbiturates (e.g., phenobarbital, secobarbital)
• other benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
• birth control pills
• calcium channel blockers (e.g., diltiazem, nifedipine, verapamil)
• carbamazepine
• cimetidine
• gabapentin
• mirtazapine
• muscle relaxants (e.g., cyclobenzaprine, methocarbamol, orphenadrine)
• phenytoin
• proton pump inhibitors (PPIs; e.g., omeprazole, pantoprazole)
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, paroxetine, sertraline)
• tapentadol
• theophylline
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, imipramine)
• Theophylline
• Aminophylline

Pregnancy and Lactation of Lorazepam 

FDA pregnancy category D