High percentage of side effects from Lariam

Not a trip I would recommend, although a little late for some of us. Would it not best to abstain from taking Lariam/Mefloquine? After all, several report taking Lariam and suffering from
Malaria...

Unexpected frequency, duration and spectrum of adverse next term events after therapeutic dose of previous mefloquine next term in healthy adults

Abstract

The frequency and spectrum of previous termadversenext term events associated with the antimalarial therapeutic regimen of previous termmefloquinenext term (MQ) (750 and 500 mg at an interval of 6 h) was assessed in 22 healthy volunteers who were monitored for 21 days following drug administration. An unexpected high frequency of side effects of any grade were reported by all 22 subjects. The most commonly reported symptoms were vertigo (96%), followed by nausea (82%) and headache (73%). Participants suffering from severe (grade 3) vertigo (73%) required bed rest and specific medication for 1 to 4 days. More females than males reported severe previous termadverse reactions.next term The majority (77.3%) of the participants (f: 8/12, m: 9/10) showed symptom resolution within 3 weeks (510 h) after drug administration. Biochemical and haematological findings stayed within the normal range of values, but showed nevertheless a significant rise of Na, Cl, Ca, bilirubin, GGT and LDH. The unexpectedly high frequency and severity of previous termadverse reactionsnext term after normal therapeutic dosage of MQ in healthy subjects may influence future recommendations regarding the use of MQ for stand-by treatment of suspected malaria in travellers.
http://www.sciencedirect.com.proxy.lib.p....38aab3328af18a1

Lariam causes neuronal death

This article clearly show damage causing neuronal death. The author is taking
a cautionary approach, though, implying neurological dysfunction prior to
taking Lariam. We know otherwise.....I suppose, this why I am opposed to
psychotropics. Again, I am not judgemental of those who do, but fear
even more neuronal damage, delaying new neuronal circuitry take place.

Malar J. 2009 Aug 5;8(1):188. [Epub ahead of print]

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis.

Nevin RL.

ABSTRACT: BACKGROUND: Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear. PRESENTATION OF THE HYPOTHESIS: Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis. Testing and implications of the hypothesis Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented. http://tinyurl.com/lcrgwh

Lariam side effects

Through legistlation in 2002, Roche included side effects and adverse reactions to Lariam/Mefloquine for patients inserts. The Department of Veterans also published a list of side effects causing long term damage. This includes, cardiovascular, gastrointestinal, endocrinological, cognitive, neuropsychiatric, sensory system, haematological, kidneys, liver, skin, neurological, mitochondria, ions channels, showing how toxic this chemoprophylaxis can be! Connecting the dots with ChemoProphylaxis??

Note that on all inserts in packaging, side effects are described as "Rare" or "Infrequent" does not reflect some published articles, or what is being reported. More on FDA's and MRHA's reporting system later.

Unfortunately, many symptoms are delayed and can manifest themselves sometimes two or more years after taking it.

Furthermore, taking one pill only, can and do cause listed above damage to many. Medical Doctors are very reluctant to give a diagnosis of Lariam toxicity, making it very difficult for patients to access care, except for psychotropics, if suffering from neuropsychiatric symptoms. These drugs are not helpful long term, are addictive and cause more damage to neuronal circuitry. Overall, Medical Doctors, rarely, if ever, diagnose prescribed drug Adverse Reactions. They are dismissive of correlation of symptoms and side effects!!

Factors involved in side effects and adverse reactions are poorly understood. Extraneous variables include what was eaten on that day, alcohol consumption, the temperature, gender, ethnicity, weight, CPYs in the liver, digestive system, kidneys, detoxification Phase I & Phase II, genetic polymorphisms, and pharmacodynamics/pharmacokinetics of Lariam. In no way, does this mean that there is a genetic malfunction, rather, that Lariam is a very toxic drug, and those who do not react are very lucky. This could be due to the fact that during that period of time, they were able to avoid Lariam reaching toxic level by excreting it more efficiently. It is worth noting that most drugs are only effective for less than 10% fo the general population.

It is not feasible to manufacure any pharmaceutical drugs to suit everybody's unique biochemistry.

Published research focuses on neuropsychiatric and neurological side effects, in particular suicides, but lacking in other long term side effects such as cardiovascular, which can be devastating.

For those of you suffering from side effects from Lariam, please read:

http://tiny.cc/2rKP9
http://tiny.cc/oPnlZ
http://www.lariam.dk/Trial.htm

I have an old pdf format of a document concerning long terms effects of Lariam from the Department of Veterans Affairs, which was not found on their site today. Has it been deleted? Those who wish to have a copy, please register, leave a comment with your email address, requesitng your email address to be deleted before publishing your comments.

For those of you suffering neuropsychiatric symptoms, there is hope. These symptoms will fade in time, specially for those who are able to resist the lure of psychotropics. Do not allow psychiatrists convince you that you had an underlying psychiatric condition which suddenly appeared after taking Lariam. Or that you are personality Type A, driven and ambitious, thriving on stress, etc. Lariam does NOT work that way.

Some medications, in particular Lariam and Fluoroquinolones are known to cause chaos in neuronal circuitry. Moreover, there is little knowledge concerning neuronal circuitry, but sufficient data and research show serious damage to the central nervous system, can and do occur by certain types of medications.

The next post will focus on Lariam pharmacodynamics and pharmacokinetics.

Information and published papers concerning Lariam/Mefloquine were NOT copied from any other Lariam sites, but researched from the orignial source.

Mefloquine - antagonists of 5-HT3

This one of the reasons, I am opposed to anti-depressants. Although, this paper was published in 2007, it is still very relevant!!

The antimalarial drugs quinine, chloroquine and mefloquine are antagonists at 5-HT3 receptors
A J Thompson,1 M Lochner,1 and S C R Lummis1*
1Department of Biochemistry, University of Cambridge, Cambridge, UK
*Author for correspondence:
Received November 1, 2006; Revised January 3, 2007; Accepted January 5, 2007.

Abstract
Background and Purpose:
The antimalarial compounds quinine, chloroquine and mefloquine affect the electrophysiological properties of Cys-loop receptors and have structural similarities to 5-HT3 receptor antagonists. They may therefore act at 5-HT3 receptors.

Experimental Approach:
The effects of quinine, chloroquine and mefloquine on electrophysiological and ligand binding properties of 5-HT3A receptors expressed in HEK 293 cells and Xenopus oocytes were examined. The compounds were also docked into models of the binding site.

Key Results:
5-HT3 responses were blocked with IC 50 values of 13.4 μM, 11.8 μM and 9.36 μM for quinine, chloroquine and mefloquine. Schild plots indicated quinine and chloroquine behaved competitively with pA 2 values of 4.92 (K B=12.0 μM) and 4.97 (K B=16.4 μM). Mefloquine displayed weakly voltage-dependent, non-competitive inhibition consistent with channel block. On and off rates for quinine and chloroquine indicated a simple bimolecular reaction scheme.

Quinine, chloroquine and mefloquine displaced [3H]granisetron with K i values of 15.0, 24.2 and 35.7 μ M. Docking of quinine into a homology model of the 5-HT3 receptor binding site located the tertiary ammonium between W183 and Y234, and the quinoline ring towards the membrane, stabilised by a hydrogen bond with E129. For chloroquine, the quinoline ring was positioned between W183 and Y234 and the tertiary ammonium stabilised by interactions with F226.

Conclusions and Implications:
This study shows that quinine and chloroquine competitively inhibit 5-HT3 receptors, while mefloquine inhibits predominantly non-competitively. Both quinine and chloroquine can be docked into a receptor binding site model, consistent with their structural homology to 5-HT3 receptor antagonists.

Keywords: 5-HT3 receptor, Cys-loop receptor, binding site, ligand docking, malaria, quinine, chloroquine, mefloquine, antagonist.....

Conclusion

Cont/.....

In summary, we have used a combination of electrophysiology, ligand binding, homology modelling and simulated docking to define the mechanisms by which quinine, chloroquine and mefloquine inhibit the 5-HT3 receptor response. Our observations further extend the number of receptors known to be affected by these compounds and the growing diversity of targets may account for the broad spectrum of side effects that have been reported by patients receiving them (Luzzi and Peto, 1993; Palmer et al., 1993; Taylor and White, 2004). Inhibition of the 5-HT3-mediated current could have wide-ranging effects in the nervous system, as 5-HT3 receptors can modulate a variety of neurotransmitter responses such as those to GABA, dopamine and cholecystokinin (Thompson et al., 2006b).http://tinyurl.com/ny2zqv