Lorazepam chemical structure
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Ativan

Lorazepam (marketed under the brand names Ativan®, Temesta®, Tavor®) is a drug which is a benzodiazepine derivative. Pharmacologically, it is classified as a sedative-hypnotic, anxiolytic and anticonvulsant. more...

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Pharmacology and Pharmacokinetics

Lorazepam is rapidly and nearly completely absorbed after any mode of application (oral, sublingual, i.m., i.v.). The onset of action is several minutes after i.v. injections, 30 to 45 minutes after oral/sublingual administration, and up to 1 hour after i.m. injections.

The duration of action depends on the dose, and is normally 6 to 12 hours. The half-life of lorazepam in patients with normal liver function is 11 to 18 hours. Therefore, 2 to 4 daily doses are often needed.

0.5mg (500µg) of lorazepam is equivalent to 5mg of diazepam.. Other experts estimate a proportion of 1mg lorazepam to 5mg diazepam.

Indications

Lorazepam is indicated for:

  • Treatment of anxiety disorders
  • Short-term treatment of insomnia, particularly if associated with severe anxiety
  • Treatment of symptoms associated with alcohol withdrawal
  • As a premedication,
    • To facilitate unpleasant procedures, such as endoscopies and dental surgery.
    • To augment the action of the primary anaesthetic drug.
    • To produce varying degrees of anterograde amnesia for the duration of the procedure.
  • Long-term treatment of otherwise resistant forms of petit mal epilepsy
  • Acute therapy of status epilepticus
  • Acute therapy of catatonic states alone/or with haloperidol
  • As an initial adjunctive treatment for depressions, mania and psychosis
  • Treatment of acute delirium, preferrably together with haloperidol
  • Supportive therapy of nausea/emesis frequently associated with cancer chemotherapy, usually together with firstline antiemetics like 5-HT3-antagonists

Lorazepam is available in tablets and as a solution for intramuscular and intravenous injections. It is also available as a parenteral patch.

Dosage

Daily doses vary greatly from 0.5 mg bedtime for insomnia and 2.5 mg every 6 hours and more in the acute treatment of mania, before the firstline drugs (lithium, valproic acid) control the situation.

Catatonia with inability to speak is very responsive and sometimes controlled with a single dose of 2 mg oral or slow i.v. injection. Catatonia may reoccur and treatment for some days may be necessary. Sometimes haloperidol is given concomitantly.

The control of status epilepticus requires slow i.v. injections of 2 to 4 (or even 8) mg. Patients should be closely monitored for respiratory depression and hypotensive effects.

In any case, dose requirements have to be individualized especially in the elderly and debilitated patients in whom the risk of oversedation is greater. Safety and effectiveness of lorazepam is not well determined in children under 18 years of age, but it is used to treat serial seizures. With higher doses (preferably i.v.-doses) the patient is frequently not able to recall unpleasant events (anterograde amnesia) such as therapeutic interventions (endoscopies etc.), which is a desirable effect. But in these cases the risk is given that a patient later makes unjustified allegations of sexual abuse during treatment due to poor recall.

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Diary: from a week in practice
From American Family Physician, 7/15/05 by Paul Gross

Monday

How do medical errors happen? In a crowded emergency department, I quickly tell an intern about a patient: "Miguel is a 45-year-old man with debilitating coronary artery disease and congestive heart failure. I sent him here this morning because his wife is leaving him and now he says he wants to die." At the moment, my patient is sleeping off a dose of lorazepam (Ativan) in a tiny, unlit cubicle he's wedged into with another depressed patient who has been awaiting a bed for days. Our psychiatric unit is full. In fact, there isn't an available bed in the entire county, and we decide that admitting Miguel to a medical floor is the only humane option. Hours later, the intern reports that Miguel is settled into his room upstairs, but mentions some odd inconsistencies: "He told me he doesn't have a wife or children," she says, "and that he's been here since Saturday." A light begins to flicker. "Are you sure you admitted the right patient?" I ask. Seems that in the chaos of a busy emergency department, the intern was directed to the wrong man. With my patient fast asleep, she asked his neighbor if he was Miguel. "I'm Michael," the man answered. "Are you 45?" she'd persisted. "Forty-six," he replied. Close enough, she thought, and voila, assigned him a new identity! The intern is horrified. "I've learned my lesson," she says, and I believe her. But boy, this really frightens me.

Tuesday

When the medical examiner pages me at 10:30 p.m., I click worriedly through the names of my sickest patients while dialing her number. But my guesses are off, and it's Bart who has died in his sleep. Bart was a convivial bachelor who served in the merchant marines during World War II. A 290-lb 75 year old with hypertension when I first met him in 1994, he developed diabetes a few years later, then shed 50 lbs in fits and starts. He was a model patient--compliant with medications, enthusiastic about his on-again, off-again diet, and unfailingly cheerful despite arthritis that hobbled his golf game. He had recently come to my office wearing a baseball cap with a leafy green insignia that resembled marijuana. I pointed questioningly. "Gotta tell ya," Bart said, "I was coming out of a store yesterday when a red sports car pulls up. 'Hey pops,' this young gal says, 'are you buying or selling?'" Bart shrugged. "I didn't know what she was talking about. I showed her my grocery bag and said, 'I'm buying!' Do you believe that?" He took off the hat and peered at it. "Now I get it," he said, "but I'm too old for smoking that stuff, don't you think?" Yes, I did think--and we both laughed. Despite his age, I didn't think Bart was ready for the final tee off.

Wednesday

As a family physician who believes that there's more to life than can be measured, I'm delighted by patients who resist high-tech attempts to pinpoint their ailments. Olivia, 27, was admitted to our inpatient service with 10 days of right upper quadrant pain worsened by fatty foods. Gallstones, most likely? Her tenderness included the right upper and lower quadrants and the right flank; her blood work was normal except for a minimally elevated alanine transaminase; and her abdominal ultrasound did not reveal any gallstones. Might this be renal calculi? Appendicitis? An abdominal computerized tomographic scan was clean as a whistle except for a fatty liver, and a gallbladder hepatobiliary scan also was negative. Throughout the next day, Olivia was still nauseated and hurting, and she received another shot of meperidine (Demerol). Today, our radiologist called to say that a reexamination of the gallbladder scan showed a reduced gallbladder ejection fraction, suggesting dysmotility. Might that be the problem? Our gastroenterologist's reaction is ho hum. "That low ejection fraction could be caused by starvation or by the meperidine," he says firmly. "She doesn't have gallbladder disease." And the patient? Despite some residual nausea and tenderness, Olivia's appetite is back and she's eating once again. So after one radiograph, one ultrasound, two scans, and many blood tests, we finally send her home with a diagnosis of ... pain. I love it!

Thursday

I find myself sitting in the waiting room of an ear, nose, and throat specialist with my daughter Nikki, who's 11 and suffering from vertigo. It began last Wednesday when she vigorously tossed her head back while drying her hair. Suddenly, the room began to jerk and spin, and then she threw up. She spent the next day sitting robot-like on the couch, head motionless atop a carefully erect neck. I figured we were home free when she went out to play basketball the following afternoon. But this week, she became congested, and yesterday, the dizziness returned; it got so bad she went to the school nurse, where lying down made it worse. At that point I began to worry: when have I ever seen positional vertigo or labyrinthitis in a child? So today I took Nikki to her doctor, who shared my concern and referred us here, where the specialist now performs a careful examination and, to my relief, is unperturbed. "It's probably a labyrinthitis or traumatic vertigo caused by the head shaking," he says. "But here's something odd: she has some bilateral hearing loss in the higher frequencies. You don't use a jackhammer, do you?" he asks Nikki. No, but she did attend a dance with earsplitting music two weeks earlier. And so, like many patients, we leave the doctor's office happily reassured about our presenting problem, but saddled with something new to fret about.

Friday

In my early days of practice, I often felt overwhelmed whenever someone presented with one too many problems. Over time, the ability to handle simultaneous catastrophes improved, but today, the old feeling returns when Gary presents for results of a blood test. Gary is a jittery 51-year-old cab driver with hypertension, diabetes, and hyperlipidemia. Three weeks ago, he made me the latest in his long line of doctors. When his results crossed my desk a few days later, my breath caught: a blood urea nitrogen level of 71 mg per dl and a creatinine level of 4.3 mg per dl. Gary's kidneys are failing. He needs a nephrologist, and dialysis is on the horizon. I consider what other issues to address with this patient. His uncontrolled blood pressure? (For some reason, he failed to take the atenolol [Tenormin] I added to his regimen.) His one and one half pack a day smoking habit? His hepatitis C infection? (A gastroenterologist recommended a biopsy and possible treatment, "once Gary is able to discontinue alcohol.") "When was your last drink?" I ask. "A week ago," he says, nodding quickly. "I'm attending a program." I get that old familiar feeling of multiple headlights converging on me. Where, exactly, do I begin?

Saturday/Sunday

My daughters, Nikki and Ariel, are 11 and 13, which means that one of them still thinks that I'm funny, and one knows for sure that I'm not. Having read Mary Pipher's Reviving Ophelia many years ago, I anticipated a challenging stretch of road during middle school, and haven't been disappointed. My wife and I hoped to inoculate our family against some of the worst of it by being involved parents, by encouraging athletic and artistic pursuits, and by listening. I'm sure all these tactics helped, but they don't really compare to a Salk vaccine. So now we face provocative clothing, boyfriends, erratic grades, instant messaging, mood swings, and predatory music. I used to listen with pity as parents returned from meetings with middle school guidance counselors. Now, having been there myself, I'm not so smug. I take solace in the catchily titled, Yes, Your Teen Is Crazy! by psychologist Michael Bradley, who explains adolescent excess as a function of brain maturation and offers advice that is gutsy, wise, and funny. I've also been helped by Daughters (http:// www.daughters.com), a thoughtful newsletter for parents that tackles issues like weight- and beauty-obsession, dating, and limit setting. "Having a teenager," a wise colleague once told me, "is like having manic depression externally imposed." Today is a case in point: one daughter's sullen mood inexplicably morphs into a chirrupy "Hi, Daddy!" as she chats easily about her self-image. Parenting, like doctoring, is seldom dull.

For the past 13 years, Paul Gross, M.D., has been on the residency faculty of New York Medical College at St. Joseph's in Yonkers, New York, a city with a population of 196,000. He divides his time between patient care, resident supervision, teaching, and life with his own family--a wife and two daughters.

Address correspondence to Paul Gross, M.D., at pgross@pol.net.

To preserve patient confidentiality, the patients' names and identifying characteristics have been changed in each scenario. Any resemblance to actual persons is coincidental.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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