Friday, October 26, 2007

Urispas Oxybutynin and Tolterodine to Reduce Spasms of The Bladder

 ditropan Both Oxybutynin (Ditropan) and Tolterodine (Detrol) are approved by the FDA to treat urge urinary incontinence (loss of bladder control due to sporadic contractions of the bladder muscle) and frequent urination. The drugs decrease the spasms in the bladder that produce these symptoms and increase the bladder’s ability to hold urine. Although Oxybutynin is used by some doctors to treat disorders of the stomach and intestines, it has not been proved effective for this purpose.

These drugs are in the family known as anticholinergic agents. Such drugs block the effects of acetylcholine, a substance produced by the body that is responsible for certain nervous system (parasympathetic) activities. Drugs with anticholinergic effects (including antidepressants, antihistamines, antipsychotics, drugs for intestinal problems, antiparkinsonians) all inhibit the secretion of acid in the stomach; slow the passage of food through the digestive system; inhibit the production of saliva, sweat, and lung secretions; and increase heart rate and blood pressure. Side effects of these drugs thus include dry mouth, constipation, difficulty urinating, and decreased sweating. Other side effects are described in the box above. Because both the effectiveness and the side effect profile of the drugs are related to their anticholinergic activity, more effective drugs or doses are likely to be more toxic. The drugs are contraindicated in patients with inability to urinate (urinary retention), gastric retention, or narrow-angle glaucoma.

Angioedema and palpitations were observed with Tolterodine in post marketing surveillancc.

Oxybutynin was first approved in 1975. For years it dominated the incontinence market. It is now available as a less expensive generic. In 1998, Tolterodine was approved by the FDA for the same indications. Reflecting the new competition in the market, Pharmacia & Upjohn, Tolterodine’s manufacturer, was twice cited by the FDA for overstating the benefits of the drug.

In clinical trials, both drugs performed better than a placebo, although the extent of the drugs’ effectiveness is disappointing. For example, in one trial comparing short-acting versions of the drugs, after subtracting the effects of the placebo, Tolterodine reduced the number of episodes of incontinence per day by 0.5, compared to a reduction of 0.8 for Oxybutynin. A type of statistical summary of clinical trials known as a meta-analysis found Tolterodine and Oxybutynin to be clinically similar. Oxybutynin was statistically significantly more effective, but Tolterodine was better tolerated. Similarly, the editors of The Medical Letter on Drugs and Therapeutics concluded their review of Tolterodine by saying, “Tolterodine appears to be tolerated better than older drugs for treatment of overactive bladder, but it may be less effective.”

Since the arrival of Tolterodine, we have seen the marketing of extended-release versions of both Oxybutynin (DITROPAN XL) and Tolterodine (DETROL LA), as well as a skin patch (OXYTROL) that delivers Oxybutynin and is applied every three to four days. All seek to improve patient compliance with the drugs by reducing the number of doses per day and to keep drug levels in the blood more stable. This might reduce anticholinergic adverse effects by avoiding the ups and downs associated with intermittent drug dosing. Indeed, clinical trials show that dry mouth, in particular, is less common with the extended-release formulations. However, as The Medical Letter points out, “Both the tolerability and the effectiveness of these drugs are related to their [anticholinergic] activity. The less dry mouth, the less effective they are likely to be. None of them are as effective as advertisements to the public have suggested.”

When the Oxybutynin patch was introduced, The Medical Letter had a similar reaction: “Oxybutynin delivered transdermally may cause less dry mouth than when it is taken orally, but it may be less effective for incontinence, and itching at the application site can be a problem.” Here is why the authors reached that conclusion. In the first of two clinical trials described in the drug’s product labeling, patch Oxybutynin was compared to placebo in patients experiencing about 5.1 episodes of incontinence per day. At the end of 12 weeks, there was an average reduction in incontinence episodes of 3.0 per day in patients using the patch, compared to 2.7 in patients on placebo. In the second study in the labeling, patients who had previously responded to an anticholinergic drug and had approximately 4.9 incontinence episodes per day were studied for 12 weeks. The average daily reduction in incontinence episodes was 2.9 in the patch-treated group, compared to 2.1 in the placebo group. These are not major differences.

There are also effective nondrug treatments available to manage urge urinary incontinence. In our view, a proper trial of these should precede drug treatment whenever possible. The first randomized trial of behavioral treatment compared to a drug (Oxybutynin) was conducted in older women and actually showed the behavioral intervention to be more effective. Behavioral treatment (four treatments including biofeedback on contraction of pelvic muscles) reduced the number of incontinence episodes by 81% compared with 69% for Oxybutynin and 39% for placebo. The authors concluded, “Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.” A follow-up study in which patients were given the option of adding the other treatment (biofeedback for the Oxybutynin group and Oxybutynin for the biofeedback group) suggested that the combination is more effective than either treatment alone. The least invasive or dangerous treatment should be tried first, and for many forms of urinary incontinence this is behavioral treatment rather than drugs.

Thursday, October 25, 2007

Facts About Prozac and Other Antidepressant Drugs

In addition to being approved by the FDA for major depressive disorder, or MDD, various SSRIs are also approved to treat obsessive-complusive disorder, bulimia, panic disorder, social anxiety disorder, and posttraumatic stress disorder. Fluoxetine, better known as Prozac, is also sold as Sarafem to treat a condition known as premenstrual dysphoric disorder. Women taking Prozac should not be taking Sarafem.

The SSRIs may reduce the risk of suicide in depressed adult patients. However, there have been a few reports that Prozac may actually induce suicidal thoughts in selected patients, although this has not been confirmed. Our Research Group petitioned the FDA in 1991 to require a box warning in the professional product labeling prozac for Prozac warning doctors that a small minority of persons taking the drug have experienced intense, violent, suicidal thoughts; agitation; and impulsivity after starting treatment with the drug.  In October 2004 the FDA issued a public health advisory requiring manufacturers to add a black-box warning to its professional product labeling or package insert of all antidepressants. This  black-box warning is shown below. A black-box warning is the strongest type of warning that the FDA can require. The FDA also requires that a Patient Medication Guide be given to patients receiving this drug advising them of the risk and precautions that can be taken. You should not take this drug for mild depression or anxiety, or as a sleeping pill.

The FDA-approved professional product labeling for antidepressant drugs sold in the United States carries the following statement:

Suicide: The possibility of a suicide attempt is inherent in major depressive disorder and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy. Prescriptions for Drug X should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Only Prozac is approved for use in children less than 18 years of age for major depressive disorder.

A review of 64 randomized controlled trials comparing SSRIs to the older tricyclic antidepressants such as imipramine (TOFRANIL) found similar benefit from the new and older drugs. When the results of many clinical trials were pooled, called a meta-analysis, no clear benefit was found for the new drugs over the older antidepressants. The adverse effects of the new and old antidepressants have little in common except for withdrawal symptoms. For example, SSRIs are less likely than the tricyclic drugs to cause sedation, anticholinergic effects, and heart rhythm disturbances. On the other hand, SSRIs’ adverse effects commonly affect the gastrointestinal tract, especially causing nausea and diarrhea, and may also cause insomnia, agitation, extrapyramidal symptoms (drug-induced parkinsonism), and withdrawal effects.

One group of adverse effects is traded for another between the SSRIs and tricyclic antidepressants, and there does not appear to be any difference in the proportion of people who can tolerate these two groups of antidepressants. When the number of people who stopped taking an antidepressant in 58 clinical trials were studied, there was no clinically significant difference between the SSRIs and the tricyclic and related antidepressants.

A large meta-analysis commissioned by the U.S. Department of Health and Human Services through the Agency for Health Care Policy and Research in 1999 found that in general there were no significant differences in the effectiveness of the newer antidepressants such as the SSRIs and the older agents such as the tricyclic antidepressants. In terms of adverse drug reactions, there was no significant difference between the new and old antidepressants in overall discontinuation rates of use of these drugs by patients. Drug discontinuation rates can be used to compare adverse reactions between drugs.

When you take these medicines you may experience some adverse effects. The most frequently reported include nausea, anxiety, headache, and insomnia. These adverse effects tend to be worst at the start of treatment and improve over a few weeks. Akathisia—symptoms of restlessness, constant pacing, and purposeless movements of the feet and legs—may also occur. Dry mouth, sweating, diarrhea, tremor, loss of appetite, and dizziness are also common adverse effects.

The length of time it takes an antidepressant to work can overlap with the time of spontaneous recovery, especially if the depression is situational—caused by a death or other external circumstances. The majority of people lift themselves out of depression with friends, spiritual resources, or activities such as exercise, work, reading, play, art, and travel. If depression is not overcome by these measures, seek help from mental health professionals, such as therapists or psychiatrists. Antidepressant drugs should be reserved for depression that is major and does not respond to psychotherapy alone.

In March 2005, the FDA amended the professional product label of fluvoxamine to include warnings about its use together with tizanidine (ZANAFLEX), a drug used for spasticity, and alosetron (LOTRONEX), a Do Not Use drug used to treat Irritable Bowel Syndrome. Fluvoxamine can increase the amounts of each of these drugs that is present in the bloodstream to dangerous levels.

In July 2006 the FDA notified healthcare professionals and consumers that there may be additional, though rare, risks of taking SSRI medications during pregnancy. This study focused on newborn babies with persistent pulmonary hypertension (PPHN), which is a serious and life-threatening lung condition that occurs soon after birth. Babies born with PPHN have high pressure in their lung blood vessels and are not able to get enough oxygen into their bloodstream.

Additionally, the labeling for paroxetine (PAXIL) was recently changed to add information about findings in an epidemiologic study that suggests that exposure to the drug in the first trimester of pregnancy may be associated with an increased risk of cardiac birth defects.

In July 2006 the FDA also issued a public health advisory warning consumers about the possibility of life-threatening reactions — such as nausea, changes in blood pressure or hallucinations — that may be caused by the interaction of migraine headache drugs, called “triptans,” and certain antidepressants.

When  triptans are taken in combination with antidepressants known as  selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs), a condition called serotonin syndrome may result.

Signs and symptoms of serotonin syndrome include the following:
Restlessness, hallucinations, loss of coordination, fast heart beat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhea, coma, nausea and vomiting.


Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in short term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Antidepressant’s Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Antidepressant’s Name] is not approved for use in pediatric patients except for patients with [Any approved pediatric claims here].

Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving over 4400 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

Friday, October 19, 2007

Proton Pump Inhibitor NEXIUM


Nexium was approved in February 2001 as the fifth member of the proton pump inhibitor (PPI) family of drugs. These drugs are approved for short-term treatment of gastroesophageal reflux disease (GERD) and most are also approved for duodenal and stomach ulcers resistant to treatment with histamine2-blockers and antacids. Most of the PPIs are also used in combination with antibiotics to treat ulcer disease caused by the bacterium Helicobacter pylori (see Ulcers and Gastroesopageal Reflux Disease (GERD)). Most studies do not show a significant difference between the different PPIs for the treatment of GERD, duodenal ulcer, or Heliocobacter pylori. PPIs inhibit the secretion of stomach acid, whereas histamine2-blockers partially prevent production of acid.

Nexium was approved by the Food and Drug Administration (FDA) in 2006 for the treatment of Zollinger-Ellison Syndrome, a rare hormonal disorder characterized by excessive stomach acid production due to tumors in the duodenum or pancreas. PPIs, including Nexium, do not affect the tumors involved in Zollinger-Ellison Syndrome,  but reduce the acid secretion, thereby relieving symptoms and promoting healing of the ulcers.

In fact, patients who have been taking Prilosec (Omephazole) since it was approved in 1989 have been getting Nexium with each dose. Like many drugs, Prilosec is a mixture of two forms that are chemically identical but are “mirror images” of each other. These mirror images are called optical isomers, and Nexium is one of the two that make up omeprazole. Nexium and Prilosec are both produced by the same company, AstraZeneca Pharmaceuticals.

In its application for marketing to the FDA, AstraZeneca claimed that Nexium had important advantages over omeprazole. An FDA Medical Officer was charged with reviewing the veracity of this claim. FDA reviews can be very different from the image that drug companies try to portray about their new drugs because the agency has access to research data that may never be published if it is not in the economic interests of the company. The Medical Officer stated:

nexiumThe sponsor’s [AstraZeneca’s] conclusion that H 199/18 [Nexium] has been shown to provide a significant clinical advance over Prilosec in the first-line treatment of patients with acid-related disorders is not supported by data [emphasis in original].

...Specifically, there are [sic] no scientific basis for the sponsor’s statement that compared to omeprazole, H 199/18 offers a faster and improved resolution of heartburn symptoms and higher rates of healing in the treatment of erosive esophagitis. The two compounds are comparable in their efficacy for this indication.

The Medical Officer’s final recommendation on Nexium was equally clear:

In addition, it is recommended not to allow the sponsor [AstraZeneca] to claim that Nexium magnesium has any significant clinical advantage over Prilosec in the first-line treatment of these acid-related disorders because no data in support of such a claim have been submitted.

Why would an industry that claims it is so innovative engage in such tactics? Prilosec was about to lose its patent protection. The most expedient strategy for AstraZeneca to protect its lucrative share of the PPI market was thus for the company to develop Nexium, a drug that would have patent protection even though it is clearly not an innovation that required much scientific ingenuity, and then get physicians to switch their Prilosec patients to Nexium. The result: AstraZeneca revenues stay up, the price of drugs increases, and Nexium (esomeprazole magnesium) pillspatients derive no clinical benefit whatsoever.

We have listed Nexium as a Do Not Use drug rather than a Do Not Use Until Seven Years After Release drug not because of safety and effectiveness concerns but because there is no significant difference between this drug and omeprazole. Switching from omeprazole, which is available generically, to Nexium will cause the health care system economic harm. Patients with poor or nonexistent drug coverage will foot the bill that ensues from doctors being conned into prescribing Nexium. However, we acknowledge that particular health insurance plans may reimburse for Nexium and not some other PPIs that have longer track records.

Post-marketing reports of myalgia (pain in a muscle) and hepatitis with or without jaundice (liver inflammation with or without the yellowing of the skin and eyes) were reported (very rarely) with the use of Nexium.

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Wednesday, October 17, 2007

Angiotensin Converting Enzyme Inhibitors

These drugs belong to a group of drugs for high blood pressure called angiotensin converting enzyme (ACE) inhibitors. Capoten, Prinivil, and Vasotec are the preferred ACE inhibitors because they have been on the market the longest. 

ACE inhibitors are effective drugs for the treatment of high blood pressure (hypertension) and congestive heart failure in older adults. After a heart attack, treatment with some ACE inhibitors prevents subsequent heart failure and reduces morbidity and mortality (the rate of disease-related sickness and death). The American Heart Association modified secondary-prevention guidelines recommend that ACE inhibitors be "considered for all patients with vascular Prinivildisease."

In people with high blood pressure and kidney disease, ACE inhibitors, along with water pills, slow progressive kidney failure. ACE inhibitors may also be the preferred class of drugs to control blood pressure in those people with kidney damage from diabetes. However, ACE inhibitors can cause dangerous adverse effects such as bone marrow depression and, ironically, kidney disease itself, and therefore should be taken in lower doses by older adults. This may amount to less than one-third the doses used in the past. In general, patients  are more likely to suffer harmful effects from ACE inhibitors if they have decreased kidney function, including dehydration. Since older adults generally have some decrease in kidney function, these drugs may be especially dangerous for them. In older adults, therefore, use of an ACE inhibitor requires a careful balancing of the risks and benefits by the patient with his or her physician.

In addition, patients taking a diuretic (water pill) should be watched carefully or, at their physician’s discretion, be taken off that medication when an ACE inhibitor is started. Vasotec decreases the potassium loss caused by thiazide-type diuretics. Patients using potassium-sparing drugs (see below) should not use ACE inhibitors. Potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium may lead to significant increases in serum potassium, which in extreme cases can be fatal.

The Food and Drug Administration (FDA) issued a public health advisory in 2006 concerning the increased possibility of birth defects in children born to mothers who took angiotensin-converting enzyme (ACE) inhibitors during the first trimester of pregnancy.

Problems with the possibility of birth defects when ACE inhibitors are used in the second and third trimesters are well known. All marketed ACE inhibitors carry a black box warning in their professional product labels, or package inserts, but this is the first study to raise concerns about use in the first trimester.

At times when using ACE inhibitors, the blood pressure goes too low, especially with the first dose. Older people are more likely to be sensitive to low blood pressure. A rare but potentially life-threatening reaction is angioedema, a sudden swelling of the face, lips, and particularly the tongue, which may last three days. While this reaction usually occurs with the first dose, it can occur years later. Once angioedema occurs, all ACE inhibitors should be stopped.In general, if you are over 60, you should be taking less than the usual adult dose. Since Vasotec stays in the body longer than Capoten, its adverse effects may last longer.

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without) nausea and vomiting; in some cases there was no prior history of facial angioedema.

If you have high blood pressure, the best way to reduce or eliminate your need for medication is by improving your diet, losing weight, exercising, and decreasing your salt and alcohol intake. Mild hypertension can be controlled by proper nutrition and exercise. If these measures do not lower your blood pressure enough and you need medication, hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE), a water pill, is the drug of choice, starting with a low dose of 12.5 milligrams daily. It also costs less than other blood pressure drugs.

If your high blood pressure is more severe, and hydrochlorothiazide alone does not control it, the best treatment is a combination of hydrochlorothiazide and a second type of drug called a beta-blocker, such as  propranolol (INDERAL, INDERAL LA). If you can’t take a drug in the beta-blocker family, another family of high-blood-pressure-lowering drugs may be added to your treatment. In either case, your doctor would prescribe the hydrochlorothiazide and the second drug separately, with the dose of each drug adjusted to meet your needs, rather than using a product that combines the drug in a fixed combination.

Whatever drugs you take for high blood pressure, once your blood pressure has been normal for a year or more, a cautious decrease in dose and renewed attention to nondrug treatment may be worth trying, according to The Medical Letter

An editorial in the British Medical Journal stated:

Treatment of hypertension is part of preventive medicine and like all preventive strategies, its progress should be regularly reviewed by whoever initiates it. Many problems could be avoided by not starting antihypertensive treatment until after prolonged observation....Patients should no longer be told that treatment is necessarily for life: the possibility of reducing or stopping treatment should be mentioned at the outset.

Short-Acting Muscle Relaxant Zanaflex

zanaflex Zanaflex is approved by the Food and Drug Administration (FDA) for the management of spasticity in conditions such as multiple sclerosis and spinal cord injury. It has been available in Japan and Europe since 1985 for use as a short-term muscle relaxant.

An April 2007 public advisory issued by the FDA said using Zanaflex together with certain drugs (including fluvoxamine [LUVOX] and ciprofloxacin [CIPRO]), can result in drowsiness and extremely low blood pressure.

Zanaflex is related chemically to the blood-pressure-lowering drug clonidine (CATAPRES). Because Zanaflex can lower blood pressure, patients should be cautious when using this drug in combination with blood pressure-lowering drugs. Even when used alone, patients may experience dizziness, lightheadedness, or fainting when getting up suddenly from a sitting or lying position because of the blood pressure-lowering effect of this drug.

Drowsiness was reported by almost half (48 percent) of patients taking Zanaflex in clinical trials. In 10 percent of these cases, the drowsiness was severe.

A small percentage (about 5 percent) of patients participating in controlled clinical trials experienced liver function test (LFT) results greater than three times the upper limit of what is considered normal. This level of LFT elevation is an early indicator of possible liver toxicity. In postmarketing reports, the use of Zanaflex has been associated with three deaths from liver failure. LFT monitoring should be done before and during the first six months of Zanaflex treatment.


seroquel SEROQUEL (Quetiapine) is approved to treat psychotic disorders such as schizophrenia. It belongs to a class of drugs called atypical or second-generation antipsychotics. While all antipsychotics usually improve symptoms such as agitation, delusions, hallucinations, and suspiciousness, atypical antipsychotics claim to improve “negative” symptoms such as apathy, disorientation, emotional withdrawal, and lack of pleasure more than older antipsychotics. However, there is no clear evidence that atypical antipsychotics are more effective or are better tolerated than the older conventional antipsychotics such as haloperidol (HALDOL)

The Food and Drug Administration (FDA) issued a public health advisory on April 11, 2005, to warn that the drugs known as the atypical antipsychotics are associated with an increased risk of death when used to treat dementia in elderly patients.

The atypical antipsychotics affected by the FDA advisory are aripiprazole (ABILIFY), olanzapine (ZYPREXA), quetiapine (SEROQUEL), risperidone (RISPERDAL), clozapine (CLOZARIL), and ziprasidone (GEODON). None of these drugs, however, are approved for the treatment of behavioral disorders in patients with dementia.

In September 2003, the FDA ordered that the professional product labeling for these drugs warn that patients should be monitored for the symptoms of diabetes mellitus. The drugs requiring the new warning are aripiprazole (ABILIFY), clozapine (CLOZARIL), olanzapine (ZYPREXA), quetiapine (SEROQUEL), risperidone (RISPERDAL), and ziprasidone (GEODON).

Seroquel can have serious adverse effects. These include neuroleptic malignant syndrome (NMS), a condition that includes a dangerously high fever, muscle rigidity, and altered mental states, heatstroke that can be fatal, and tardive dyskinesia, a serious adverse effect that may be reversible in its early stages. Early signs of tardive dyskinesia include unusual movements of the tongue or mouth, or tremor. If progressive, it may lead to uncontrollable movements of the arms, legs, and tongue, for which there is no known effective treatment. Women and older people are more prone to tardive dyskinesia. Extrapyramidal effects, such as drug-induced parkinsonism, may cause a shuffle when walking.

Seroquel can cause dizziness and low blood pressure. Common anticholinergic effects are drowsiness and dry mouth (see the Adverse Effects of Antipsychotic Drugs table in Antipsychotic Drugs: Another Group of Dangerously Overused Drugs). More than 20 percent of people taking quetiapine gained weight, sometimes accompanied by an increase in cholesterol level. A common adverse effect is drowsiness. Generally, older people develop adverse effects more often.

In one species of animal (beagles) but not in any other animals, quetiapine caused cataracts. Until the effect of quetiapine on the eyes of humans is determined, you should have eye exams at initiation of treatment and every six months, such as slit lamp exams, to detect the formation of cataracts.

Tuesday, October 16, 2007

Which Drug to Use to Reduce High Blood Pressure

Regardless of your age, much of the time high blood pressure can be controlled with just one drug. The National Institutes of Health’s National Heart, Lung and Blood Institute recommends beginning treatment with a mild water pill (diuretic) at a low dose. The safest and best studied of the diuretics is  hydrochlorothiazide (ESIDRIX, HYDRODIURIL, MICROZIDE). The starting dose should be low: 12.5 to 25 milligrams per day or even every other day. Confirming the advice we have been giving since 1988 is a large definitive study (named ALLHAT) involving more than 33,000 patients aged 55 or older that found “compelling evidence that thiazide diuretics (such as hydrochlorothiazide or chlorthalidone) should be the initial drug of choice for patients with hypertension.” Thus, the widespread prescribing practice—spurred on by massive advertising—of starting people with newly diagnosed hypertension with calcium channel blockers (such as Norvasc, Cardizem, or Procardia), ACE inhibitors (such as Zestril, Accupril, or Vasotec), or other drugs that are not thiazides lacks any scientific rationale.

For older adults, in general, the rule for treating high blood pressure, as with so many other drug treatments, is “start low and go slow.” According to experts in prescribing for older adults, for mild hypertension (or heart failure) start with half the standard starting dose and increase gradually.

If a second drug is needed the National Heart, Lung, and Blood Institute recommends  beta blockers, although they are not as effective in older adults as they are in younger adults. Because of this, beta-blockers should never be used as the first drug in treating high blood pressure in older adults. ACE inhibitors are also effective drugs to use as a second agent. It is rarely necessary to take more than two drugs to treat high blood pressure. If you are taking more than two, a reassessment is indicated.

Monday, October 15, 2007

Cholesterol-lowering Drugs

Mevacor LovastatinMevacor (Lovastatin), Pravachol (Pravastatin Sodium), Zocor (Simvastatin) and Lipitor (Atorvastatin) are members of the statin family of cholesterol-lowering drugs. The statin drugs work by inhibiting an enzyme that is responsible for the production of cholesterol in the body. Like all cholesterol-lowering drugs, these drugs should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other non-drug treatment measures, including exercise, has been inadequate.

Mevacor, Pravachol, and Zocor are sometimes referred to as “natural statins” because they are similar to chemicals produced naturally by fungi.

The major FDA-approved uses for Mevacor are to reduce the risk in individuals without symptomatic cardiovascular disease, and with moderately elevated cholesterol levels, of heart attack, unstable angina (chest pain), and the need for coronary revascularization procedures such as angioplasty or heart bypass surgery.

Pravachol was approved by the FDA as the primary drug for individuals without clinically evident coronary heart disease to reduce the risks of heart attack, revascularization procedures such as angioplasty and heart bypass surgery, and cardiovascular mortality, without increasingPravachol the risk of death from noncardiovascular causes.

Pravachol is also approved for the secondary prevention of cardiovascular events. Secondary prevention refers to reducing the risk of a serious outcome in individuals who already have clinically evident coronary heart disease. Pravachol is approved to reduce the risk of coronary death, heart attack, coronary revascularization procedures, stroke and stroke/transient ischemic attack (TIA), and to slow the progression of coronary atherosclerosis.

ZocorThe FDA has approved Zocor for use in individuals at high risk of coronary events because of existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke, or other cerebrovascular disease. In this group of patients this statin is approved to reduce the risk of coronary heart disease death, nonfatal heart attack and stroke, coronary and noncoronary revascularization procedures.


Lipitor has been approved for use in adult patients who either have clinically evident coronary heart disease or multiple risk factors for coronary heart disease, to reduce the risk of heart attack (myocardial infarction), stroke, angina, and to reduce the need for certain surgical procedures such as angioplasty or bypass surgery that restore blood flow to the heart or other organs (revascularization). In addition, for patients who have coronary heart disease, the drug is approved to reduce the risk of hospitalization for congestive heart failure.

A Patient Package Insert was added to the Lipitor product label to provide patients with information about taking this drug.

In early 2003, a highly publicized study comparing a high dose of Lipitor to a standard dose of Pravachol (PRAVACHOL) found that Lipitor was better in reducing a combination of adverse cardiovascular events in people who had recently been hospitalized with a heart attack or angina. Although this combination of subsequent events was reduced by Lipitor (compared with Pravachol), there was no significant reduction in the incidence of heart attacks alone or strokes alone.

In 2006, the FDA revised the professional product label of Lipitor to include information from a large study that examined the effects of statin drugs on patients who had a recent stroke. The study showed that patients taking Lipitor who had a hemorrhagic stroke within the six months preceding the study appeared to be at an increased risk for hemorrhagic stroke compared to patients who taking a dummy pill with no medicinal value, known as a placebo.

The consumer’s “gold standard” for knowing the health benefits, if any, of a prescription drug is the FDA-approved professional product labeling for that drug. It is clear from the FDA-approved labeling for the statins that Mevacor, Pravachol, Zocor, and Lipitor should be used in preference to rosuvastatin (CRESTOR) or fluvastatin (LESCOL) because of acceptable scientific evidence of a health benefit, rather than just the ability to lower cholesterol.

The statin drugs appear to share psychiatric risks with other cholesterol-lowering drugs. Aggressive behavior; memory impairment; mood changes; and cognitive, sleep and perception disorders, such as nightmares, have been reported with the use of many drugs used to treat high cholesterol: the statins, fenofibrate (TRICOR), gemfibrozil (LOPID), ezetimibe (ZETIA) , and clofibrate, Though researchers have not yet established a direct link between these reports and the use of the cholesterol-lowering drugs listed, patients should be alert to this possibility and report unexpected changes to their doctor. Potentially, statin-induced memory impairment could be mistaken for other conditions such as early Alzheimer’s disease. This could result in the prescribing of a drug to treat Alzheimer’s when it is not needed.

In the October 2005 issue of the Canadian Adverse Reaction Newsletter, 19 case reports of memory loss or impairment associated with the use of a cholesterol-lowering statin drug were analyzed. Potentially, statin-induced memory impairment could be mistaken for other conditions such as early Alzheimer’s disease. This could result in the prescribing of a drug to treat Alzheimer’s when it is not needed.

Video joke about Abilify


Call your doctor immediately if you experience:

  • anxiety or nervousness
  • blood pressure increases or decreases
  • difficult breathing
  • increased sweating
  • loss of bladder control
  • chest pain
  • confusion
  • convulsions
  • sudden loss of consciousness
  • tiredness
  • unusually pale skin
  • lip smacking
  • puffing of cheeks
  • uncontrolled chewing movements
  • uncontrolled movements of arms and legs
  • dizziness, fainting, lightheadedness
  • facial grimace
  • feelings of depression, euphoria, or suicide
  • fever
  • flulike symptoms
  • faster or slower heartbeats
  • hostility
  • involuntary movements of all extremities, twisting, snakelike movements
  • twitching muscles
  • severe muscle stiffness
  • pneumonia
  • restlessness that is extreme, urgent need of movement
  • blue-black, greenish-brown, or yellow patches on skin
  • difficulty swallowing
  • swelling of ankles or feet
  • thirst
  • tremor
  • blurred vision
  • difficulty walking

Call your doctor if you continue to experience:

  • appetite decrease
  • constipation
  • fear
  • inability to sit still
  • lack of or loss of strength
  • lightheadedness
  • nervousness
  • rash
  • trouble sleeping
  • blurred vision
  • coughing
  • fever
  • runny nose
  • prolonged drowsiness
  • inflamed or irritated eyes
  • headache
  • muscle cramps
  • nausea or vomiting
  • dry or itchy skin
  • profuse sweating
  • undesired weight gain

Other adverse effects are possible. Check with your doctor about any concerns.

Signs of overdose:

  • sleepiness or unusual drowsiness
  • vomiting

Abilify. FDA Approved

Abilify DrugAbilify was approved by the FDA for the treatment of schizophrenia in November 2002. On March 1, 2005, it was approved as a maintenance therapy for Bipolar disorder.

The Food and Drug Administration (FDA) issued a public health advisory on April 11, 2005, to warn that the drugs known as the atypical antipsychotics are associated with an increased risk of death when used to treat dementia in elderly patients.

The atypical antipsychotics affected by the FDA advisory are Aripiprazole (ABILIFY), olanzapine (ZYPREXA), quetiapine (SEROQUEL), risperidone (RISPERDAL), clozapine (CLOZARIL) and ziprasidone (GEODON). None of these drugs, however, are approved for the treatment of behavioral disorders in patients with dementia.

Abilify is a member of a relatively new family of drugs known as atypical antipsychotics. These drugs are also being referred to as second-generation antipsychotics. All antipsychotic drugs usually improve symptoms such as agitation, delusions, hallucinations, and suspiciousness. Atypical antipsychotics additionally tend, more than the older antipsychotics, to improve negative symptoms such as apathy, disorientation, emotional withdrawal, and lack of pleasure. However, there is no clear evidence that atypical antipsychotics are more effective or are better tolerated than the older conventional antipsychotics such as haloperidol (HALDOL).

Three of the five short-term trials submitted to the FDA for Abilify’s approval showed the efficacy of the drug in doses ranging from 10 milligrams to 30 milligrams per day. There appeared to be no therapeutic advantage of the 30 milligram dose over the lower doses. The FDA-approved dose for the drug ranges from 10 milligrams to 15 milligrams per day. Of the two remaining studies, Abilify could not be differentiated from placebo in one, and the other trial failed.One of our reviewers suggests starting with the new 5 milligram dose to minimize the risk of adverse effects.

These trials were not conducted in a way to make direct comparisons between Abilify and haloperidol or risperidone, which were used as comparator drugs. And nothing in these five trials can lead one to believe that Abilify is a meaningful advancement in the treatment of schizophrenia.

The editors of the highly respected Medical Letter on Drugs and Therapeutics concluded in their evaluation of Abilify that “published comparisons with other atypical antipsychotics are needed to determine its relative efficacy and safety.”

We are concerned about the possibility of eye toxicity with the use of Abilify. The studies done in rats before the drug was approved clearly showed degeneration of the retina in animals receiving Abilify. The studies done in mice and monkeys found no retinal degeneration, but they were invalid studies. The company committed to doing additional postmarketing research on retinal degeneration in animals as a condition for the approval of Abilify. These are studies that clearly should have been completed before the drug was approved.

There are additional findings from the FDA’s safety review of Abilify that are important. An alteration in the electrical conduction of the heart known as QT prolongation is an important safety issue with both old and new antipsychotic drugs. QT prolongation can lead to life-threatening heart rhythm disturbance.

There was no evidence of QT prolongation with Abilify at doses up to 30 milligrams per day. However, in a special study that explored doses of the drug up to 90 milligrams per day, there was substantial prolongation of the QT interval at doses of 75 milligrams and 90 milligrams per day.

In February 2005, the French regulatory agency warned of a risk of stroke associated with the use of Abilify. In three 10-week placebo controlled trials of Abilify, strokes and transient ischemic attacks (small strokes caused by a temporary blockage of blood flow to part of the brain) were twice as frequent among patients taking arpiprazole. Two of the patients who had strokes died.

In March 2005, the FDA revised the product package label of apiprazole regarding an increased incidence of cerebrovascular adverse events (stroke and transient ischemic attacks), including fatalities in Abilify-treated patients. Abilify is not approved for the treatment of patients with dementia related psychosis.

Weight gain has also been a problem with the antipsychotic drugs, particularly with the atypical antipsychotics. In the short-term trials, there was a small difference in average weight gain between Abilify and placebo patients. The patients given Abilify gained on average 1.5 pounds, while the placebo patients lost 0.1 pounds on average. The number of patients gaining more than 7% of their body weight who were taking Abilify was equal to 8%, compared to 3% of the placebo patients.

Mizoprostol Cytotec

Mizoprostol Cytotec TabsMisoprostol Cytotec is used to prevent ulcers, especially, stomach, by the action of aspirin, ibuprofen and other analgesics commonly used in arthritis. Analgesics may cause serious harm, even lead to death from bleeding in the stomach or intestine. Misoprostol Cytotec is a synthetic prostaglandin, which can protect the gastric mucosal shell and moderately reduce the formulation of hydrochloric acid in the stomach.

The group of high-risk ulcerous diseases as a result of analgesics side effects includes older patients, whose body weakened by disease and patients suffered particularly from ulcerous diseases. Misoprostol Cytotec should apply only to patients who have previously been observed ulcerous disease. In any case, the appointment of such patients at the same time acting analgesics and Misoprostol Cytotec can be justified only in the event of severe arthritis. Treatment ulcerous illness in smokers has been slower.

For older patients, which represent a group at high risk of complications ulcerous development of the disease, there is also a high risk of developing complications from accepting Misoprostol Cytotec. It was shown that Misoprostol Cytotec affects the metabolism of bone tissue in animals and in the chemical markers of bone metabolism in tissues in humans. Although the drug is intended for implementation of the older patients suffering from arthritis, which form a group of the risk of osteoporosis (bone weakening and depletion), from the manufacturer, there is little information on the effects of Misoprostol Cytotec on the human skeleton, with a lengthy admission of the drug.

Diarrhea is a common side effect of Misoprostol Cytotec and has varying degrees of severity from mild to severe, poses a threat to life. Do the elderly loss of fluids and minerals with diarrhea can lead to the fall of blood pressure or lead to a breach of heart, kidney and impair mental condition. Misoprostol Cytotec causes diarrhea among a significant number of patients are not carrying the drug. In clinical studies diarrhea observed in the 14-40% of cases.

Sunday, October 14, 2007

Medical Parasitology - Neurocysticercosis, Pinworms, Etc.

ALBENDAZOL. New opportunities of the worms infections cure

Albenza. Generic:Albendazole
People familiar with the diseases caused by parasitic worms (de-worming) from the times of great antiquity.Now we have high protivogelmintnye synthesized drugs. Their feature is the low toxicity. Many of these drugs are very important property-polivalentnost action, that is acting on several parasites. One of the most interesting and effective deworming drugs is Albendazole.

Albendazole, marketed as Albenza is a member of the benzimidazole compounds. One of this group of compounds synthesized such a drug, commonly known as Mebendazole issued also called vermoks (vormin). But Albendazole far exceeded Mebendazole both efficiency and breadth spectrum.

Albendazole is effective against most threadworms (pinworms), roundworms, whipworms, tapeworms and hookworms. Perhaps today it is a single deworming drug with such a wide range of actions.