Talk:Mefloquine
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I'm unfamiliar with the syntax for using wikipedia, but I recently found a US patent for the selective use of the (+)enantiomer of mefloquine, which also references various other papers to the same conclusions. I've put this in the references, albeit probably in the wrong format.
This entry has a great deal of alarmist claims about mefloquine. They are claims based often on anecdotal accounts of side effects, side effects that sometimes accompany the high therapeutic dose levels, or on studies (with rats for example) in which test subjects are given levels much greater than a normal prophylactic or even therapeutic dose. Unfortunately the results of these particular studies are being represented as if they are the expected results of normal prophylactic use and are thus misleading and, as I have said, alarmist. The tone of this account should be a little more sober and balanced. The extreme views should be represented but they should be represented against rigorous mainstream studies for comparison. If not, this page will remain biased. see http://www.rxlist.com/cgi/generic2/mefloq_ad.htm 216.8.121.1 22:54, 29 January 2007 (UTC)
There's quite an emphasis on the side effects. I think the risk of side effects is about 4% with the risk of severe s/e being about 1 in 10000 (i.e. psychiatric disturbance). When I get time I will find some evidence and put them in. Dr prune 11:43, 26 January 2006 (UTC)
The risk is higher: http://www.jpharmtechnol.com/abstracts/volume22/January-February/32.html http://www.journals.uchicago.edu/CID/journal/issues/v33n7/010125/010125.html http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=14604928
Dr. Prune,
The following is an excerpt from a peer reviewd papaer from the drug researchers at Walter Reed Army Institute of Research where the drug was invented. Walter Reed in Table 1 indicates that the neurotoxicity of Mefloquine is 25 µM(Chloroquine is 600 µM and Quinine is 900 µM):
The antimalarial potential of 4-Quinolinecarbinolamines may be limited due to neurotoxicity and cross-resistance in mefloquine-resistant plasmodium falciparum strains. Dow, GS et al., Walter Reed Army Institute of Research (WRAIR), Antimicrobial Agents Chemotherapy, 48(7):2624-2632 (2004). Antimicrobial Agents and Chemotherapy, July 2004, p. 2624-2632, Vol. 48, No. 7.
"Adverse central nervous system (CNS) events have been associated with mefloquine use. Severe CNS events requiring hospitalization (e.g., seizures and hallucinations) occur in 1:10,000 patients taking mefloquinefor chemoprophylaxis (22). However, milder CNS events (e.g., dizziness, headache, insomnia, and vivid dreams) are more frequently observed, occurring in up to 25% of patients (22).
"we recently showed that mefloquine severely disrupts calcium homeostasis in rat neurons in vitro at concentrations in excess of 20 µM, an effect closely related to the acute neurotoxicity of the drug in terms of dose effect and kinetics (10)."
However, the drug crosses the blood-brain barrier and accumulates as much as 30-fold in the central nervous system and mefloquine brain concentrations as high as 50 µM have been reported in human postmortem cases (14, 21). Mefloquine brain concentrations as high as 90 µM have been reported in rats given a therapy-equivalent dose rate, with concentrations in subcompartments in the brain exceeding 100 µM (2). Since it has long been known that a prolonged disruption of neuronal calcium homeostasis may lead to neuronal cell death and injury (6, 13), it is reasonable to suppose that such events may contribute to the clinical neuropathy of the drug."
Essentially, treatment level concentrations can develop in the CNS with prophylactic use.
Additionally, Walter Reed published the following paper in Mar 2006 regardign treatment level brain stem damage in rats:
Mefloquine Induces Dose-Related Neurological Effects in a Rat Model G. Dow,1* R. Bauman,2 D. Caridha,1 M. Cabezas,3 F. Du,4 R. Gomez-Lobo,3 M. Park,2 K. Smith,1 and K. Cannard1 Divisions of Experimental Therapeutics,1 Military Casualty Research,2 Psychiatry and Neuroscience, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland, 20910,3 FD Neurotechnologies, Inc., P.O. Box 785, Ellicott City, Maryland 210414. Antimicrobial Agents and Chemotherapy, March 2006, p. 1045-1053, Vol. 50, No. 3.
It states:
1. "At the time this study was conceived, no formal FDA guidelines for neurotoxicity testing existed. In contrast, first-tier neurological screens, such as those recommended by the U.S. Environmental Protection Agency (EPA), are often employed to detect a broad range of possible neurological effects that may be induced by uncharacterized test compounds (43)."
The FDA "approval" process in 1970 did not require testing for neurotoxicity since no protocol existed at the time. Apparently it still does not exist since the Walter Reed researchers had to use a test protocol from the EPA to write this paper.
2. "It is also important to point out that the mefloquine-induced brain stem injury revealed by silver staining is permanent in nature."
Lastly, Walter Reed recently released a funding document STTR A06-T034 Neurotoxicity Associated with Mefloquine, an Anti-Malarial Drug. (see http://www.acq.osd.mil/osbp/sbir/solicitations/sttr06/army06.htm ) This document calls for the development of a commercially available "safety test" for Mefloquine users.
Proponents of Mefloquine report the drug to be "safe and effective". Then why would it need a "safety test"?
24NOV2006
[edit] Dreams
This drug is crazy, it gives me insane dreams. —Preceding unsigned comment added by 122.167.178.159 (talk) 15:00, 28 April 2008 (UTC)
