Patients receiving high-dose drug trimethoprim sulfamethoxazole (TMP-SMX, Generic Bactrim®, Women First; Septra®, Monarch) appear to be at higher risk for abnormal muscle contractions such as myoclonus and asterixis. In fact, these side effects might not be as rare as once thought.

A 63-year-old woman with a history of non-Hodgkin’s lymphoma, hypertension, hypercholesterolemia, and transient ischemic attack had recently been in remission for acute myelogenous leukemia. Admitted to the hospital with a Nocardia asteroides infection, she began a regimen of trimethoprim 20 mg/kg per day and canadian sulfamethoxazole 100 mg/kg per day, given intravenously in two doses, along with 2 g of ceftriaxone sodium (Rocephin®, Roche), given twice daily.

Her fever abated, but she began to experience progressively worsening involuntary movements involving her head and her extremities. Neurological examination revealed diffuse, multifocal myo-clonus and bilateral asterixis but no other abnormalities. The TMP-SMX therapy was stopped, and the involuntary movements decreased markedly the next day. By the fourth day, they disappeared.

The physicians knew of only one report describing tremors in an immuno-competent patient.

The complication of tremors is dose-related, not immunological. The physicians suggest that the “rare” effect might actually be underdiagnosed, and they advise stopping TMP-SMX treatment before ordering a costly neurological evaluation.

When opioid therapy does not relieve pain or when it leaves patients with intolerable side effects, a new option might be ziconotide (SNX-111, Pfizer/Elan/ Warner-Lambert/Partner Medtronic).

In experimental studies, the fact that intrathecal ziconotide cleared rapidly suggested that it would also metabolize through the cerebrospinal fluid rapidly. One study involved 24 patients who had chronic pain from cancer, acquired immunodeficiency syndrome (AIDS), and other conditions and who experienced pain control with opioids, even when they were given intrathecally. Of those 24 patients, 19 rated their pain on the Visual Analogue Scale of Pain Intensity as 43% lower in degree and 15 patients were able to reduce their concomitant use of opioids by at least 50%. Central nervous system effects were diminished or resolved when the infusion rate was reduced or stopped.

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Olanzapine (Zyprexa canadian, Eli Lilly), an antipsychotic agent that is often used to calm elderly people with dementia, may increase the risk of strokes and death in those patients, according to a letter sent by Eli Lilly & Co. to physicians on January 15, 2004.

The letter mentioned a “significantly higher” incidence of stroke among these patients and a higher rate of deaths of all types (3.5%) compared with a rate of 1.5% in patients receiving placebo.

Although this drug is not approved for use in elderly patients with dementia (it is indicated for people with schizophrenia and bipolar disorder), over time, olanzapine and drugs like it have become widely used in nursing homes and hospitals to treat verbal outbursts and behavior problems in older patients.

A Lilly spokesperson cautioned that the elderly patients in whom the increased risks were seen often had other serious medical problems, and it was not clear whether medication olanzapine actually played a role in the higher death rates.

Two recent studies have linked a lack of exposure to vitamin D, which is created naturally by sunshine or artificial ultra­violet (UV) light, to the development of multiple sclerosis (MS), an often debili­tating disease that affects 250,000 to 350,000 Americans.

The body makes vitamin D through exposure to sunlight’s UV-B ultraviolet rays. The exact causes of MS remain un­known, but MS becomes more prevalent in people living farther away from the Equator. It is thought that a minimum level of UV exposure throughout the year might be important in conferring protec­tion by influencing the immune system response, possibly through changes in the production of vitamin D and melanin, the substance involved in acquiring a tan.
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A major hindrance to generating suffi­cient vitamin D is living at high latitudes, where exposure to natural sunlight may be insufficient. Some research, including these two new studies, has shown a cor­relation between high latitudes and increases in diseases linked to vitamin D deficiency.

In the National Institutes of Health study of more than 185,000 women, MS was 40% less likely to develop in women who maintained recommended levels of vitamin D than in women who were oth­erwise deficient in vitamin D.

Oxaliplatin for injection (Eloxatin™, Sanofi-Synthelabo/Debiopharm SA), in combination with 5-fluorouracil/leuco-vorin (5-FU/LV), has been approved by the FDA for the first-line treatment of advanced colorectal cancer. Eloxatin™ was approved in 2002 for the second-line treatment of patients with metastatic carcinoma of the colon or rectum.

In a study sponsored by the National Cancer Institute and coordinated by the North Central Cancer Treatment Group (NCCTG), patients treated first with Eloxatin™, combined with infusional 5-FU/LV (the FOLFOX regimen), experienced an overall median survival time of 19.4 months after starting therapy. Patients taking a standard combination of irinotecan (Camptosar®, Pharmacia & Upjohn) plus 5-FU/LV (the IFL regimen) had a median survival time of 14.6 months; therefore, the median survival advantage for the FOLFOX patients was 4.8 months (a 35% improvement). The FOLFOX group reported less severe, more manageable, and more reversible side effects than the IFL group did.)

The survival rate for patients with asystole, the most lethal form of cardiac arrest, has been found to be greatly improved if patients receive an injection of vasopressin (e.g., Pitressin®, King), according to a new study from Europe. A naturally occurring hormone in the human body, vasopressin is a common therapy for frequent urination because of its effect on the kidneys.

In the study, vasopressin was superior to epinephrine in patients whose heart had stopped beating. Patients with asystole cardiac arrest had triple the survival rate when they were given an injection of vasopressin rather than epinephrine, the most common form of treatment in these cases.

Only four of the 262 patients (1.5%) who received epinephrine were eventually able to leave the hospital, whereas 12% of 258 patients (4.7%) who received vasopressin were discharged. Because the long-term survival of patients in cardiac arrest is very poor, the gain from 1.5% to 4.7% is considered significant.
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The patients who received vasopressin were also 40% more likely to reach the hospital alive than those who received epinephrine. The American Heart Association estimates that more than 95% of cardiac arrest patients die before reaching the hospital.

The effects of vasopressin were simi­lar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity; however, vasopressin was superior in patients with asystole. The researchers suggested that vasopressin followed by epinephrine might be more effective than epineph-rine alone in cases of refractory cardiac arrest. The results have been so impressive that meetings are scheduled to be held to determine whether resuscitation guidelines should be quickly revised to include the use of vasopressin.

The ideal sedative for patients who are undergoing cardioversion in the emergency department (ED) might be propofol (Diprivan®, AstraZeneca), according to an experience reported from Hospital Clinic in Barcelona, Spain. The drug offers a fast onset, minimal cardio-pulmonary depression, and a rapid recovery.

When researchers compared propo-fol and etomidate (Ben Venue Laboratories) and midazolam (Versed®, Roche), with or without flumazenil (e.g., Mazicon®, Roche), propofol yielded superior results. Although all four regimens were uniformly effective, patients receiving propofol experienced the shortest recoveries and the fewest adverse effects.
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The midazolam/flumazenil combination was found to be problematic when all patients, except one, became sedated again after flumazenil was discontinued.

Although etomidate offered hemo-dynamic stability, rapid sedation, and rapid recovery, it had adverse effects such as myoclonus, which can interfere with the interpretation of the electrocardiogram.