Molecular structure of pseudoephedrine
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Drixoral

Pseudoephedrine is a sympathomimetic amine commonly used as a decongestant. The salts pseudoephedrine hydrochloride and pseudoephedrine sulfate are found in many over-the-counter preparations either as single-ingredient preparations, or more commonly in combination with antihistamines and/or paracetamol/ibuprofen. more...

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This agent is often referred to by consumers as Sudafed, which is the trademark for a common brand of pseudoephedrine hydrochloride. Other brand names include Afrinol, Novafed, and Cenafed.

Unlike antihistamines, which modify the systemic histamine-mediated allergic response, pseudoephedrine only serves to relieve nasal congestion commonly associated with colds or allergies. The advantage of oral pseudoephedrine over topical nasal preparations, such as oxymetazoline, is that it does not cause rebound congestion (rhinitis medicamentosa). However, the disadvantage of oral pseudoephedrine is that it can cause high blood pressure.

Nomenclature

Pseudoephedrine is the International Nonproprietary Name (INN) of the (1S,2S)- diastereomer of ephedrine (which has 1R,2S- configuration). Equivalent names are (+)-pseudoephedrine and D-pseudoephedrine. (Reynolds, 1989)

(-)-Pseudoephedrine or L-pseudoephedrine then designates the enantiomer of pseudoephedrine.

Chemistry

Pseudoephedrine, a phenethylamine, is a structural isomer of the popular weightloss/energy supplement and asthma medication, ephedrine. Ephedrine is an alkaloid extracted from the Ephedra plant, which produces it naturally as a racemic mixture. That is, ephedrine molecules occur as two "mirror images," inasmuch as a pair of hands do (See the article on entantiomers). The pharmacologic properties of each "reflection" often share similarities and differences. The (-) or levorotatory isomer is a very potent sympathomimetic amine and anorectic, thus responsible for the amphetamine-like stimulation that is characteristic of Ephedra products. The (+) or dextrorotatoryisomer, aka pseudoephedrine, is far less potent as a stimulant. However, it retains much of ephedrine's ability to open airways and nasal passages.

Mode of action

Pseudoephedrine is a sympathomimetic amine - that is, its principal mechanism of action relies on its indirect action on the adrenergic receptor system. Whilst it may have weak agonist activity at α- and β-adrenergic receptors, the principal mechanism is to displace noradrenaline from storage vesicles in presynaptic neurons. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the aforementioned postsynaptic adrenergic receptors.

The vasoconstriction that pseudoephedrine produces is believed to be principally an α-adrenergic receptor response. Whilst all sympathomimetic amines, to some extent, have decongestant action; pseudoephedrine shows greater selectivity for the nasal mucosa and a lower affinity for central nervous system (CNS) adrenergic-receptors than other sympathomimetic amines. (+)-(1S,2S)-pseudoephedrine shows far lower CNS activity than other Ephedra alkaloids, ephedrine, and (-)-(1R,2R)-pseudoephedrine.

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Military quacks - analysis of military medical system
From Washington Monthly, 9/1/98 by Russell Carollo

It's time to repair the military medical system

Leigh Clark, 16, was to undergo a 45-minute laparoscopic procedure to provide physicians with pictures of the inside of her abdomen, where she had complained of sharp pains. But something went wrong and a surgeon's mistake caused her right femoral artery to be severed. Clark was on the verge of bleeding to death when a second surgeon, summoned from his home, saved her life. Loss of blood caused her right leg to wither.

Emily Houck was only a few days old when her mother became concerned about small blisters that had appeared on her head and took her to a clinic. A pediatrician who examined the infant acknowledged later that he suspected a herpes infection. A few days later Emily's temperature rose and she began to lose weight, so her mother took her back. She'll be fine, the mother recalls the doctor telling her. But Emily will never be fine. A herpes infection caused her temperature to rise even more, damaging her brain. Today, a six-year-old, she cannot see, hear, talk, or walk.

Donald McKinley, 67, complained repeatedly to his doctor of chest and shoulder pains, sometimes so severe they kept him awake at night. At the time, McKinley had a medical record that included high blood pressure, diabetes, angina, high cholesterol, an abnormal heart beat, a history of heavy smoking, and a severely occluded aorta. His doctor thought the pains may have come from muscle soreness, even though McKinley could not recall any recent exertion. The doctor prescribed an anti-inflammatory drug. A few weeks later, McKinley's wife found him lying face down in the backyard. He had died of a heart attack.

Leigh Clark, Emily Houck, and Donald McKinley were not unlike victims of medical accidents and misjudgments that occur every day in hospitals, doctors offices, and clinics throughout America, except in one respect: In all three cases, the doctors involved worked for the U.S. military. That meant the patients were treated in an environment not governed by some of the most significant safeguards that help protect civilians from bad medicine.

None of the doctors was licensed in the state where he practiced, and in the Clark surgery, which took place at Fitzsimmons Army Hospital in Denver, the surgeon had been specifically rejected for a medical license by the Colorado Board of Medical Examiners. The doctors did not have to obtain medical malpractice insurance or to maintain a practice record that enabled them to keep it. They were virtually immune from malpractice suits, because in such claims, the government is the defendant. The doctor who treated McKinley was practicing in Texas with an Alabama medical license, and although he has never been sued in either state, the government has quietly paid claims in three different cases in which he failed to correctly diagnose illnesses and the patients subsequently died.

The pediatrician who would later admit he failed to treat Emily Houck with a toothpaste-sized tube of ointment that might have prevented the brain damage that today confines her to specially-built, $5,000 wheelchair, was licensed by the State of New York, although he was practicing in Georgia. The government paid $4.2 million to settle the malpractice claim brought by Emily's mother. But under Defense Department rules, the incident would not be reported to the National Practitioners Data Bank, a nationwide registry created by Congress in the 1980s to track malpractice in the United States. A civilian doctor would have automatically been reported.

Because of hundreds of cases like these, even the people in charge of the military health care system now say their system must be reformed if it is to provide the top-notch medical care every recruit is promised for himself and his family.

License to Kill

Though one would assume that the military would ensure that the men and women who serve in this country's armed forces receive the best medical care available, in many ways the system seems to work toward the opposite effect.

Among other things, the licensing process for military doctors is less stringent than for civilian doctors. Understandably, since military physicians are frequently transferred from one installation to another, it would be unworkable to require them to obtain a new license every time they landed in a new state. As a result, military doctors may practice anywhere so long as they hold a valid license from any state. But so broad was this licensing rule that it encompassed even doctors holding "special licenses" from the State of Oklahoma. These licenses do not require physicians to pass the medical exams Oklahoma and other states require for most licenses. Holders of special licenses are not authorized to practice medicine on civilians in the state, but can practice in prisons, on Indian reservations, and in the military, as well as work in laboratories that handle human organs for transplant purposes. One doctor flunked various state exams 30 times between 1973 and 1992 before obtaining a special license that enabled him to become an Air Force doctor. Another military doctor had failed 14 times; yet another had taken licensing exams 18 times, in Louisiana, Arizona, Alabama, Tennessee, and Oklahoma, before obtaining the Oklahoma special. In previous jobs he had delivered pizza, worked in a furniture store, and made sales pitches as a telemarketer. All told, in our reporting for the Dayton (Ohio) Daily News, we found that at least 77 Army, Navy, and Air Force physicians (out of the more than 15,000 total) held the special licenses.

But the military licensing policy has broader implications. For civilian doctors, state licenses involve more than simply passing a test and opening an office. State boards can discipline physicians, and data compiled by the Public Citizen Health Research Group contain over 16,000 cases of doctors who have been disciplined for everything from repeated cases of malpractice to murder. However, a military doctor who is licensed in Texas and practicing in Alabama is beyond the reach of the Texas state medical board, which does not have the budget to send investigators to another state. And a physician stationed at a military reservation in one state while holding a license from another state is of little interest to the medical board in the state where he practices.

Military officials also acknowledge that the services routinely fail to report doctors to the National Practitioners Data Bank when malpractice claims are paid. In fact, Army medical care providers were accused of malpractice in more than 900 incidents in 1994 and 1995, and the government paid $66 million to settle malpractice claims, according to computerized records. Yet, it reported only one practitioner to the National Practitioners Data Bank.

Most Americans have never heard of the National Practitioners Data Bank; access to the data it contains is strictly limited to hospitals, state medical boards, HMOs, and government agencies that may need to investigate the background of a job applicant. When Congress created it, members acknowledged that having to pay a malpractice judgment or settlement does not necessarily mean a doctor is incompetent. But repeated claims can signal problems. The data bank is searched 8,000 times a day, and one in nine searches matches a name with a stored report.

When the data bank was created, however, Defense Department lobbyists got military hospitals excluded. Instead, the secretary of defense and the secretary of health and human services have signed a "memorandum of understanding" under which each branch of the services decides if a doctor whose action resulted in a malpractice payment by the government should be reported. In the case of Emily Houck, a committee of Navy physicians met behind closed doors and reviewed whether the treatment Dr. Edner C. Monsanto provided satisfied the "standard of care" The committee concluded that Dr. Monsanto's decisions had been proper and, notwithstanding a $4.2 million settlement, he was not reported to the registry. (In an earlier case involving Dr. Monsanto, a committee concluded that his care had not met prevailing medical standards. That case, in which the government paid slightly less than $2 million to settle the claim, was reported to the data bank.)

Of course, even highly qualified doctors sometimes have trouble providing the best care for military patients, in part because of a lack of systems to track patient records. Doctors are frequently required to see patients they've never seen before and who have been passed from doctor to doctor. Some patients don't meet their surgeons until they are in operating rooms or until an operation is over. A perhaps extreme example of how this lack of continuity of care can undercut treatment is the case of Tech. Sgt. Arthur A. Wells, who saw 10 doctors in nearly three years at McChord Air Force Base, just outside Tacoma, Wash. Only five of the 10 doctors reported board certification to the American Medical Association--four in family practice and one in orthopedics. None was a board certified cancer specialist.

That was too bad for Sgt. Wells, who continually complained of stomach pains. His medical records, obtained by his widow, show in part:

Feb. 4, 1992: Doctor notes Wells "has many stressors," including his job as a recruiter, his wife's problems with depression, and their three children. The doctor prescribed 2 tablespoons of Mylanta after meals, along with Tagamet.

June 10, 1992: Doctor notes Wells had picked up an infection from his son, prescribes more fluids and said to avoid dairy products.

Oct. 26, 1992: Doctor says Wells has a sinus problem and prescribes Drixoral, an over-the-counter drug.

March 17, 1993: Doctor gives Wells a physical.

March 22, 1993: Lungs and chest checked; doctor prescribes more Mylanta.

Oct. 28, 1993: "Acute sinusitis" Two antibiotics and a decongestant.

March 8, 1994: A physical exam.

April 18, 1994: Doctor notes that stomach pain came after meals with spices and coffee. "The treatment: decrease the coffee," the doctor wrote.

April 24, 1994: Diagnosis: heartburn.

In January 1995, Wells received a CAT scan at an Army hospital. The scan found four tumors in his abdomen, some the size of a grapefruit. By then, the tumors had spread beyond hope.

Wells died in June 1995, of cancer. "He loved the Air Force," says his wife.

Under-Covered

After the Dayton Daily News published a seven-part series on problems in military medicine last October, officials of the Defense Department Office of Health Affairs appeared before congressional committees and veterans' groups and acknowledged that problems had developed in the 115 hospitals and medical centers and 471 clinics that make up the Military Health Services System. Dr. Edward D. Martin, then the acting assistant secretary of defense for health affairs, appeared before a coalition of military advocacy groups, including the Veterans of Foreign Wars, the Military Family Association, and others, and vowed to correct problems the paper had described. He insisted that problems in military medicine were not dissimilar to the private system but went on to say that this did not relieve the services of correcting the problems. "These are real problems and these are real people," Dr. Martin said.

Among other things, the military is moving to end the practice of allowing its physicians to operate with the special licenses from Oklahoma. Physicians already holding such licenses are being assigned to jobs in which they do not treat patients. But just how successful the overall reform effort will be remains to be seen. For example, after the Daily News disclosed that hundreds of paid malpractice claims had not resulted in reports to the data bank--and that 75 military hospitals and clinics that had been targets of more than 1,000 malpractice suits had never reported a doctor--the Office of Health Affairs conducted its own investigation. Among other things, officials subsequently disclosed to a congressional subcommittee that the Army had a backlog of more than 800 cases in which the secret review committees had never met. In testimony before the House Appropriations Subcommittee on National Security in February, Dr. Martin said he was instituting a system in which civilian doctors would review the conduct of military physicians in cases of alleged malpractice. "We are going to open up the system," he vowed. "There's going to be a lot of sunlight shined on it. A lot of things that used to be kept secret are no longer going to be secret."

New openness rules notwithstanding, the full degree of medical malpractice in the military will never be known because a large portion of the system's patients cannot bring court actions in which incidents are made public. The largest group consists of active duty members of the Army, Navy, Air Force, or Coast Guard. They are barred by a 1946 Supreme Court ruling known as the Feres Doctrine from suing the government for any harm that befalls them as a result of actions that are deemed "incident to service."

The controversial ruling has been interpreted to apply to any medical care provided to an active duty troop by a military hospital or clinic. Although a bill to overturn the Feres Doctrine has passed the House of Representatives three times, it has never passed the Senate. And despite a scathing dissent by Justice Antonin Scalia, the Supreme Court has refused to review the decision. An Air Force sergeant whose hand was mistakenly amputated when he went to a clinic after being bitten by a dog, an Army sprinter who was training for an Olympics tryout when a series of operating room foul-ups left him crippled, a Marine Corps corporal who complained of stomach pains for over a year before Navy surgeons realized they had left a sponge and a felt-tip marker in her abdomen, an Army SPC who died of an overdose of lidocaine following treatment for a bee sting, an Air Force sergeant who lost her ovaries and a fallopian tube because of an operating room error--the list of Feres-barred cases that have come to light, but will never come to court, seems almost endless.

In addition, a law called the Military Claims Act provides that when civilian dependents of active duty personnel are the victims of malpractice while living overseas, they have no access to the courts. They may file a claim with the branch of the service responsible for the alleged malpractice, but if the claim is denied or the claimant is not satisfied with an award, there is no right to appeal to federal courts. At the hearings last fall, Rep. David Hobson (R-Ohio), argued that the Military Claims Act unfairly denied a particular class of American citizens the right to appeal to the courts. "I really have a problem with that," Hobson said. "I think they ought to have the same remedies as people over here. Do you think the code should be amended?" Dr. Martin, flanked by the surgeons general of the Army, Navy and Air Force, replied: "On the family issue, not being lawyers, we believe our dependents ought to be treated the same way when they are living overseas as when they live here." Responded Hobson: "I probably will be doing something about this."

Later, Hobson quietly dropped his plans to introduce a bill changing the Military Claims Act. When asked why, he said Justice Department lawyers had talked him out of it.

Compounding the problem, the military is facing systemic stresses that may make reform even more difficult. Strapped for cash by congressional "deficit neutrality" dictates and slammed by downsizing and hospital closings, the military medical system faces a growing population of increasingly unhappy civilian beneficiaries. It also finds itself caught between ever-changing and often contradictory priorities. Officially, the primary purposes of the military medical system are to provide medical care for active duty troops and prepare military doctors to provide battlefield medical care. Yet the most common medical procedure performed at any military hospital is delivering babies. The second most common is the related care of healthy newborns. "It [shortcomings in military medicine] is an institutional problem that I don't think they can correct," says Walter Boyaki, an El Paso lawyer and one of a growing group of lawyers who specialize in medical malpractice suits against the military. "Patients are by statute entitled to free medical care, so they are treated like welfare patients. Then you overlay on that a military system that protects its own?

Overlay on that overlay a growing move among military retirees to get out of the medical care system, and the prospects for reform become even dimmer. Recent votes in Congress may have opened a valve through which the military system could bleed to death in a few years. Unhappy with the Civilian Health and Medical Plan for the Uniform Services and its successor, TRICARE, military organizations have been lobbying for permission to opt out of the system and into the Federal Employee Health Benefits Plan, or FEHBP, the medical insurance plan for civil service employees and retirees. (See the Monthly's April 1998 issue for details on FEHBP.) Such a change, in which retirees would have the option of buying FEHBP coverage with the Defense Department paying 72 percent of the premiums has been vigorously opposed by the department. Currently, the DoD drops retirees from its population of beneficiaries as soon as they turn 65, leaving them to Medicare. Paying FEHBP premiums for this group alone would be a major additional expenditure--$1 billion a year according to estimates by the Congressional Budget Office. Gary Christopherson, who a few months ago succeeded Dr. Martin as acting head of health affairs, recently told a House subcommittee that such a development could lead to a slippery slope that could destroy the military medical system. In order to come up with the $1 billion and comply with the deficit neutrality mandate, Christopherson explained, the department would have to close more hospitals and cut more services. This could motivate still more civilian beneficiaries to press for the FEHBP option, necessitating further cutbacks, and so on, he warned.

Notwithstanding such warnings, the House, in one of its last actions before recessing for the Memorial Day weekend, voted to extend the FEHBP option to a demonstration group of up to 70,000 Medicare-eligible retirees. The retirees could use the FEHBP coverage to supplement their Medicare benefits. Only one member of the House voted against the bill. A similar, less extensive bill has passed the Senate.

But unless direct steps are taken to correct some of the flaws in the military medical system, we'll continue to see far too many cases like that of Navy Lt. Bryce Campbell. In 1996, Lt. Campbell underwent a brain catheter procedure at Walter Reed Army Medical Center to determine if a malformation that seemed to be causing him sleep disorders and other problems could be corrected. After several hours in surgery, Lt. Campbell was wheeled back to his room and his wife, Mafia, a nurse, was told simply that the procedure had not been successful. "He was whimpering and moaning in pain and saying to me that he was seeing lightning bolts and streaks," she recalls. Later, Mafia was told her husband would be transferred to George Washington University Medical Center where Dr. William O. Bank, an internationally known neuro-radiologist, would attempt to correct the vein malformation. As he prepared for the procedure, Dr. Bank told the Campbells that because of "the problem at Walter Reed," he would be forced to try to insert a catheter into Bryce's brain by way of the left carotid artery, rather than the right--the side where the malformation was located. "Bryce and I looked at each other and said, `The problem? What problem?'" says Maria. It fell to Dr. Bank to inform them that during the procedure at Walter Reed, the left carotid artery, one of the two main avenues of blood to the brain, had been torn and had healed in a way that left it 95 percent occluded. Dr. Bank, a former Navy flight surgeon, declined to comment on the case, saying he did not know what was involved in the Walter Reed procedure. But he notes: "There are two kinds of doctors in the military. They're either fabulous, wonderful doctors, or they're spectacularly incompetent."

RELATED ARTICLE: Who's Who

Although the Clinton administration has at times--take the case of its attempts to fill the job of attorney general--seemed almost embarrassingly eager to place women in top jobs, its dedication has been less evident in selecting members of the White House staff. Sylvia Mathews, who is going from the white House to the OMB, recently hinted at the problem in a memo she wrote on the "advantages" of working at the White House. Number four was "Never a waiting line at the women's bathroom"

Because California is a community property state, such luminaries of the Murdoch media empire as Fred Barnes, William Kristol, and John Podhoretz are said to be just a tad nervous about the turmoil the division of assets Anna Murdoch's divorce might bring to the Fox TV network, The New York Post, the Weekly Standard, and the many other organizations her husband, Rupert, controls. They are not comforted by the disturbing precedent offered by the divorce of Gloria and Herbert Haft that led to the dissolution of that family's financial empire. Their anxieties may be relieved, however, by the news that the lawyer Mrs. Murdoch has hired to represent her, Daniel Jaffe, is described as "not a gung-ho litigator" and has, according to The Washington Post's Paul Farhi, "a reputation for settling his cases out of the public eye."

How do the star Watergate reporters think Clinton's troubles compare with the scandal that made them famous? Bob Woodward says it's "not something of that magnitude." Bernstein adds, "It's as if you have a kind of Nuremberg prosecution for war crimes and you end up with a kind of jaywalking offense."

During Anita Hill's testimony in the hearings on Clarence Thomas' nomination to the Supreme Court, Richard Nixon told his biographer, Monica Crowley: "If I were [George] Bush and Thomas is defeated and I needed to choose another nominee, I'd stick it to all of them and go for a white woman reactionary card-carrying right-to-lifer! That would drive them crazy!" This is, of course, exactly what Nixon did when the Senate rejected Clement Haynesworth in 1970. He immediately named G. Harrold Carswell to the court. Carswell was, to put it as gently as possible, not one of the great legal minds of his era.

If you've wondered who is the source of those leaks from Ken Starr's office to such Starr favorites as ABC's Jackie Judd, Newsweek's Michael Isikoff, and The Washington Post's Susan Schmidt, and Jeff Gerth and Stephen Labaton of The New York Times, the consensus seems to be that it was Starr's deputy Jackie Bennett Jr., and that he was not acting without his boss's knowledge.

The Republicans get more than four times as much campaign money from the tobacco industry as the Democrats. They also got about four times as many trips on corporate jets controlled by the tobacco people--84 to at most 23 in one recent period. Among the beneficiaries: Dick Armey, Tom DeLay, and Trent Lott, who appears to have been treated to 12 of the flights. This is made legal under our somewhat less than stringent election laws by the politician's payment of the equivalent of a first class fare on a regularly scheduled commercial plane. For that he gets a corporate jet all to himself to fly wherever he wants whenever he wants. Does he get frequent flyer miles?

Nina Burleigh, who recently confessed that her interest in Bill Clinton had reached a point where "I had been quite willing to let myself be ravished ... should he have but asked," has a book coming out this fall. We are, of course, not so cynical as to suspect the confession had any relation to the book, but it is true that the book deals with a president's sex life. Must reading for all of us who love to dish dirt, it is about John Kennedy's last mistress, the late Mary Meyer, who was the sister-in-law of Ben Bradlee and the former wife of CIA insider Cord Meyer. It reveals at least one similarity in the way Clinton and Kennedy handled these matters. On the first night of the romance, Kennedy got Meyer into the White House this way: "That night, October 3, at 7:40 p.m., according to the gate log, `Mary Meyers' had an appointment with Evelyn Lincoln, the president's personal secretary, and was authorized by Lincoln to enter the White House"

You've heard about the tie that Monica Lewinsky gave Bill Clinton. But did you know she also presented one to Vernon Jordan?

Speaking of Ken Starr, Timothy Noah, before his untimely departure from U.S. News & World Report in the wake of the James Fallows firing, told the readers of his "Whispers" column about the details of a Start subpoena--the one to Kramerbooks for documentation about Monica Lewinsky's possible gift books for Bill Clinton. Here are excepts from the subpoenas two-page definition of documents: "summaries or records of personal conversations, meetings, or interviews, logs, summaries or records of telephone conversations and/or telefax communications, diaries, forecasts, statistical statements ... voicemail recordings, and all other written, printed or recorded or photographic matter or sound reproductions, however produced or reproduced." All this from a bookstore from which Lewinsky may have bought a book or two.

The next time the Postal Service asks for another rate increase someone should inquire as to whether the agency's cost control procedures are all that they might be. An Atlanta postmaster spent $45,000 of Postal Service money on his swearing in ceremony. Did Postmaster General Marvin Runyon crack down? No, he decided to spend $82,500 on his own farewell parties, one of which, according to The Washington Post's Bill McAllister, "featured a band, cocktails, and dinner with two entrees and wine."

Just in case Hillary Clinton ever loses patience with the leader of the free world and does something the law might frown on, we have the lawyer to defend her. He's Blair Howard, a Virginia attorney who specializes in defending damsels in legal distress. He got Susan Cummings off with 60 days for shooting and killing her man and Lorena Bobbitt off completely for surgically removing the penis of hers.

Russell Carollo is a reporter for the Dayton (Ohio) Daily News and Jeff Nesmith is a reporter in the Washington bureau of Cox newspapers.

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