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» LymeNet Flash » Questions and Discussion » Medical Questions » primer on malarial drugs

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Author Topic: primer on malarial drugs
janet thomas
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http://www.itg.be/evde/02_Malariap12.htm

12.2 Treatment, overview
Broadly speaking, anti-malaria drugs can be divided into four major classes


Blood schizonticides


Antifolates


Antimitochondrials


Redox process-based agents


Blood schizonticides

When the malaria parasite leaves the liver and penetrates an erythrocyte, it can at last begin a haemoglobin diet. However, it cannot use the iron-containing haem group. What is more, released ferriprotoporfyrin IX (syn. = haemin) is toxic for the parasite. It contains trivalent iron (ferric = Fe3+). Normally the parasite polymerises haemin to non-toxic malaria pigment. Chloroquine, quinine, mefloquine and halofantrine interfere with the detoxification of haemin in the digestive vacuole of the parasite. The drugs prevent this detoxification so that haemin can generate free radicals and membrane damage follows. It is therefore logical that the drugs are not active against the parasitic stages which precede the blood forms (sporozoites, liver forms) and which do not consume haemoglobin.


Antifolates

Folic acid is an important metabolic factor. Humans obtain this vitamin from the food they eat. The malaria parasite, on the other hand, must produce it for itself. Para-aminobenzoic acid (PABA) is used at an early stage of the biosynthesis of folic acid by the enzyme dihydropteroate synthetase. This step is inhibited by structural analogues of PABA, such as sulphonamides and sulphones, e.g. sulphanilamide, sulphadoxine and dapsone. The next synthesis step is catalysed by dihydrofolate reductase. This step is prevented by pyrimethamine, trimethoprim and cycloguanil (prodrug = proguanil), to such an extent that tetrahydrofolate - the end product - is not formed. The combination of these two sequential inhibitors forms the basis of Fansidar (similar to cotrimoxazole). Resistance to both antifolates is easily developed, however (a specific point mutation in each gene is sufficient).


Antimitochondrial products

Although artemisinin derivatives and 8-aminoquinolines cause mitochondrial swelling, this organelle is not their chief target. Some antibiotics such as tetracycline and clindamycin prevent protein synthesis by mitochondrial ribosomes (these are similar to the ribosomes found in bacteria). They are slow-acting. Atovaquone is a naphthoquinone which specifically destroys the electron transport chains of Apicomplexa. The molecule is rather similar to ubiquinone (coenzyme Q) which plays a role in the energy transfer between cytochrome B and C1. The enzymes of Plasmodium falciparum are 1000 times more sensitive to atovaquone than the corresponding enzymes in humans. Resistance can easily develop if it is used in monotherapy.


Redox reactions

Primaquine and etaquine exercise their action via redox-active quinone metabolites. They are selectively toxic for the pre-erythrocytic stages and are the only medicaments which kill hypnozoites. Etaquine has in addition a pronounced blood schizonticidal action.

(etaquine=tafenoquine)

--------------------
I am not a doctor and this is not medical advice but only my personal experience and opinion.

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kitty9309
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Thanks! Good to know.
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sammy
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Good find [Smile]
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seibertneurolyme
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Bringing this back to the top.

For those who are worried about drug resistance, I think the best approach is to use meds which work by different means -- combine meds from more than one category.

Blood schizonticides -- includes chloroquine, quinine and mefloquine (larium)

Antifolates -- includes pyrmethamine (daraprim), trimethoprim (bactrim), and proguanil (2nd ingredient in malarone)

Antimitochondrial products -- includes artemesia, artemesinin, coartem/riamet (artemeter ingredient), tetracycline, clindamycin, atovaquone (mepron)

Redox reactions -- includes primaquine

Not sure how flagyl, alinia or ivermectin work -- or even if they do work on babs. Anecdotal evidence that these meds may be beneficial as they are all antiparasitic.

There is little research explaining the mechanisms of how herbs work on malaria -- but there are many many herbs which may be of some use. But in my opinion for them to work the dose would have to be extremely high. Most Western (U.S.) herbalists do not prescribe anywhere near the doses used by Chinese herbalists and personally I think that is one of the reasons herbs often fail.

As for supplements -- lactoferrin may be of use to keep the iron away from the babesia parasites.

Hubby says that the only time he actually thought his dizziness was actually going away was when he treated with an extremely high dose of cryptolepis tincture in combo with lactoferrin.

Bea Seibert

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BoxerMom
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Bea - This is really helpful. Thanks!

--------------------
 - Must...find...BRAIN!!!

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blinkie
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I've been trying to get in touch with Janet-if anyone happens to see her here.
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seibertneurolyme
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Took a lot of searching to find this. Bringing this back to the top as it is very relevant to those treating babs.

New info would include the drug tafenoquine if it is available from a foreign pharmacy -- same group as primaquine.

Note -- Don't remember the year, but unfortunately Janet died from her tickborne illnesses since this original post was made.

Bea Seibert

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Lymetoo
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I remember her well. Made me sad to see her name here, but her legacy lives on. She tried desperately to help others.

(so did her husband)

--------------------
--Lymetutu--
Opinions, not medical advice!

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seibertneurolyme
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Updating this thread to add some potential new med choices.

Tafenoquine

http://flash.lymenet.org/ubb/ultimatebb.php/topic/1/127511

Ribivirin - Antiviral drug for babesia

http://flash.lymenet.org/ubb/ultimatebb.php/topic/1/128230

Albitiazolium - New potential babesia drug

http://flash.lymenet.org/ubb/ultimatebb.php/topic/1/129698

Pentamidine - antifungal

Statin drugs - lovastatin or simvastatin

Above drugs added to discussion at link below.

http://flash.lymenet.org/ubb/ultimatebb.php/topic/1/129674


Bea Seibert

[ 08-09-2014, 06:20 AM: Message edited by: seibertneurolyme ]

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ms dixie
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Thank you lovely lady!
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