Medication Solvency

[dasaltemelosguy]

I try to avoid medications whenever possible but on rare, unfortunate occasions, one can find oneself with virulent outbreaks that require immediate, potent medications that are easily toxic if overdosed.

To that end, I was wondering if anyone has used nitrofurazone or praziquantel with an organic solvent like DMSO?

I use the latter to dissolve medications that are poorly soluble in water prior to introducing it to the tank.

What I was concerned over was that using solvents might alter the dosages in that it may increase the efficacy of solvation such that the dosage may change from the "default in water" to needing less as it's near 100% solubility with DMSO.

If this is the case, it could suggest that "poor solubility" of some medications is factored into the dosing recommendations. Does anyone know if this is true or not?

Insofar as solvents are concerned, DMSO or Dimethyl Sulfoxide is an organic solvent I have used for years to dissolve fish medications with poor water solvency. Alcohol is often used but has a good deal of toxicity. 'Liquid praziquantel products often use oxybispropanol which has lower toxicity than alcohol. Unlike using alcohol (Vodka) or even oxybispropanol-based products, DMSO exhibits even lower toxicity such that it is suitable for very delicate species.

(It's often the only choice for reefers as even oxybispropanol can stress tubeworms and feather dusters and similarly delicate species whereas DMSO is safe even for these and for shrimp).

To quantify it in some measure, praziquantel as an example, will dissolve at a rate of 0.4mg/ml of water. Praziquantel in DMSO dissolves at a rate of 20mg/ml or some 50X the efficacy!

Praziquantel or nitrofurazone form a clear, water soluble liquid when dissolved in DMSO which leaves no particulates or undissolved residue in the tank.

Therein lies my question:

With the solvency increased some 50X (there is no visible residue of the praziquantel nor the nitrofurazone once dissolved in DMSO, it's near 100% solvency) I am concerned that the dosage recommended by the manufacturers is likely based upon "water solubility" (0.4mg/ml) such that;

Might there be an efficacy increase with improved solubility using DMSO (20mg/ml) over solubility in water (0.4mg/ml) such that it would affect the actual dosage?

If yes, does anyone know if this has been quantized anywhere? In particular, if near 100% solvency of either nitrofurazone or praziquantel vs their poor water solvency will affect the total dosage? Sorry to be so verbose.

Thanks all!

 

[coriesinhawaii]

Interesting question. I don’t have any experience with it to say yes or no but would like to hear if anyone else does. Do you have a really large tank you are treating so you’re trying to figure out ways to use less medication for cost reasons? Cuz otherwise seems like it would just be safer to dose the normal way (unless there are sources available that provide precise dosing using DMSO). I agree it seems likely dosing would be affected (perhaps exponentially).

 

[itiwhetu]

Why are you using these medications?. Have you got a commercial operation or just on going problems with fish health.

 

[dasaltemelosguy]

Thank you for responding. I agree, it would be safer to just use water since this is how it's expected to be used!

In my case, the horse is out of the barn if you will. This potential for overdosing just occurred to me after I've medicated two tanks which is when I finally thought to ask.

I actually have been medicating freshwater and marine tanks with solvents for some time (I was a chemical physicist in the 1970's so it's hard to break old habits!) but I recently found myself amidst two separate epidemics such that I had to administer in this case, nitrofurazone dissolved in water and I was surprised by how insoluble it is as I've always used it and other medications with a solvent.

It was then I began to question how essentially 100% solvency might affect the effective dosage?

I have three tanks but two tanks are with new fish in QT/grow-out. One has a school of 13 silver dollars and the other, 8 severums.

The dollars began dying the day they arrived. I noticed the large, flat, dull, white patches on all of the deceased and began nitrofurazone/kanamycin which fortuitously began working literally just 2 days after I began treatment. The patches have cleared up and there have been no more deaths.

Simultaneously but coincidentally, I have 8 severums in another grow-out who had no visible symptoms, all were active and eating well. One morning one gold had the classic hemorrhagic blemishes form on his side and died later that day. I began kanamycin treatment right away. Another developed the blemishes and perished overnight. A third developed the blemishes but he seems to have reacted well to the kanamycin and it cleared up. The rest so far, seem fine.

So my question was really about the efficacy should one need to use medications. I avoid medications whenever possible and I've admittedly been lucky in I've run into few issues until this.

So these two new fish batches really surprised me in that they each manifested symptoms of different but virulent pathogens. This is hardly scientific but I assume I didn't poison them with too high a dosage when using the solvents as they seem to all be recovering well but I do wonder if the near 100% solvency actually changes the effective dosage or if it's a meaningless different such that it's virtue is entirely that of facilitating the solvency of the medications.

IF all else is the same, (& I don't know if it is!) if you must medicate, it certainly makes preparing medications easier.

 

[coriesinhawaii]

After doing a little research I found that DMSO not only makes drugs more soluble in water but also increases the absorption of substances through the skin—in humans….I’m assuming it would do the same for fish. So using DMSO should definitely increase the blood and tissue concentration of medication (as well as anything else in the tank water) in the fish. I would think this effect could be especially marked in scaleless fish. This may give DMSO some usefulness in treating internal infections when the desired treatment is not usually absorbed well through the skin and the fish is no longer eating.

However without having some idea of how much of an absorption difference we’re talking about it would be a challenge to dose it appropriately so I would probably only do it as a last resort. Because DMSO increases the absorption of anything and everything present in the water you would have to consider that before using it when there is anything at all toxic in the water like ammonia, nitrite, or anything but low nitrates.

Apparently DMSO itself, like many things, can be toxic when its concentration exceeds a certain level so you would want to ensure what you’re adding in doesn’t exceed that level.

Interesting to hear that you’ve already tried it out (albeit unintentionally) twice and it appeared to work well without causing any obvious ill effect. Can you tell us the amount of DMSO to medication to volume of water you used for future reference? As well as what form the DMSO comes in (is it a liquid? concentration?) Do you mix it with powder medication and then add the mixture into the tank?

 

[dasaltemelosguy]

Excellent information, thank you!

I did not use DMSO on the kanamycin as it's so water soluble but I do know the amounts I used for nitrofurazone specifically as that was the most recent. It was a 75G with many infected fishes with columnaris. After seeing the 1st fatality, I began this regiment of Day 1-5:

Nitrofurazone/Kanamycin
Nitrofurazone
Nitrofurazone/Kanamycin
Nitrofurazone
Nitrofurazone/Kanamycin

I began dosing them per default instructions when it dawned on me albeit late, that I might be overdosing them. I stopped treatment after the 5th day upon which the columnaris returned after about a week.

Upon seeing it's return, I was beyond frustrated and restarted the above treatment but this time, for 10 days and it seems to be gone as I've seen nothing indicative of it's presence thus far (crossing all fingers and toes!), and it's been several weeks. As I was doing it with DMSO, I continued as it was working and I did not detect any stress in the fishes but I have no idea if the solvent had any effect beyond making it very easily soluble in water!

I wish I had more quantization details to give but for what it's worth, this is what I did and fortuitously it seems to have worked and I've suffered no fatalities since day 2 of the treatments:

The tank was a 75G with about 30 Cardinal Tetras and 13 Silver Dollar juveniles.
It was serving as both a QT for these newcomers and a grow-out for the Dollars.

The dosing suggested for nitrofurazone is 2G/75G as I was treating the entire tank.
The kanamycin was also the default dosages or 1.75g/75G. The kanamycin is so water soluble, I dissolved that directly.

With the nitrofurazone, I used 2G with 5ML of DSMO and it forms a clear, yellow, syrupy liquid.

I have not had the pleasure to need praziquantel yet but there is a far too long video of it being dissolved with DSMO on Humble Fish. As with the nitrofurazone, it forms a clear fluid with virtually no particulate. They site DSMO amounts for several popular, fairly insoluble medications but they do not list nitrofurazone.

However they do use MUCH more DSMO than I needed to dissolve nitrofurazone (they use as much as 1ML/77MG of medication) such that I fear I'm comparing apples and oranges.

But yes, the 5ML/2G fully dissolved the nitrofurazone and I didn't lose any fish (and I think the columnaris has totally cleared). That's hardly enough information to inspire confidence!

I wish I had more quantification but here is the video where you may see the amounts of DSMO Humble Fish uses for three popular, relatively insoluble fish meds: DSMO used with Popular Aquarium Medications

 

[coriesinhawaii]

Thanks for the information. Yes I've heard Columnaris can be very virulent, treatment is often ineffective, and a whole tank can be wiped out once it is introduced to an aquarium. Thankfully I haven't had to deal with it myself. Something like DMSO that increases the amount of medication available at the site(s) of infection just might make a big difference in prognosis for the fish.

 

[Fishmanic]

When I have dosed prazipro (praziquantel), I put the proper dose in a jar filled with tank water and then shake it. The prazipro stays in suspension making the water appear cloudy. - it doesnt precipitate out. I then pour the water from the jar all around the top of the surface of the water and into the hob filter. It gets circulated throughout the tank. I notice a continuous change in the bubble stream as if bubbles are smaller coming out of the top of my sponge filter indicating the prazipro is thoroughly dispersed throughout the tank water. A solvent addition is not necessary in my opinion.

 

[coriesinhawaii]

When I have dosed prazipro (praziquantel), I put the proper dose in a jar filled with tank water and then shake it. The prazipro stays in suspension making the water appear cloudy. - it doesnt precipitate out. I then pour the water from the jar all around the top of the surface of the water and into the hob filter. It gets circulated throughout the tank. I notice a continuous change in the bubble stream as if bubbles are smaller coming out of the top of my sponge filter indicating the prazipro is thoroughly dispersed throughout the tank water. A solvent addition is not necessary in my opinion.

Just to be clear if a medication is in suspension it is pretty much the same as if it were precipitated in that it is in an insoluble form. (You couldn't meaningfully say it was "precipitated" because that is what would happen if the medication were already dissolved in the tank water and you add something else that causes it to come out of solution.) But with that aside I'm pretty sure the manufacturer recommended dosages of medications are such that the amount that does dissolve is sufficient to treat the infection, so I agree that in most cases it shouldn't be necessary to use a solvent. But I still think it could be useful in rare cases where you really need to increase the amount of dissolved medication for the treatment to be absorbed well enough into the fish's body.

 

[itiwhetu]

I don't know why you are playing with this stuff. Before treating fish you need to Know exactly what is wrong. This is one of those situations where the cure is worse than the disease.

 

[coriesinhawaii]

How can the cure be worse than the disease if it’s something like the OP is describing that kills so quickly and is obviously contagious. Without treatment all of the fish would almost certainly die. With treatment at least there’s a chance they will survive. In an ideal world we would be able to get the causative organism identified and do susceptibility testing for medications but that’s just not practical in the home aquarium setting. If you did get the samples cultured it would take forever for the results to come back and all of your fish would be dead by then.

So unfortunately it does come down to best guess a lot of times. But those guesses can be quite educated. Actually this is what physicians do with people who are hospitalized. They make an educated guess at what the infection is, start an antibiotic or two they think would be appropriate and once culture results are back they adjust therapy if needed. They certainly don’t withhold treatment until the organism and appropriate medication is known.

 

[itiwhetu]

I hope the fish survive.

 

[dasaltemelosguy]

How can the cure be worse than the disease if it’s something like the OP is describing that kills so quickly and is obviously contagious. Without treatment all of the fish would almost certainly die. With treatment at least there’s a chance they will survive. In an ideal world we would be able to get the causative organism identified and do susceptibility testing for medications but that’s just not practical in the home aquarium setting. If you did get the samples cultured it would take forever for the results to come back and all of your fish would be dead by then.

So unfortunately it does come down to best guess a lot of times. But those guesses can be quite educated. Actually this is what physicians do with people who are hospitalized. They make an educated guess at what the infection is, start an antibiotic or two they think would be appropriate and once culture results are back they adjust therapy if needed. They certainly don’t withhold treatment until the organism and appropriate medication is known.

I fully agree. Unfortunately, aquariums are a closed system and as such, pathogenic spread can be far more ubiquitous and virulent than it would be in nature. It's a big petri dish if you will.

In this case I probably brought the pathogens in with two new batches of juveniles I planned to grow out. Ironically, I've had tanks since the 70's and prior to this, ich was the worst disease I've encountered!

So when these little guys started dropping dead at a almost regular rate of 1-2/day, and the sores appeared, while I didn't know what the disease was, It certainly appeared that it was going to wipe out the entire tank if left untreated.

BTW you raised an interesting point. Particularly with regard to the columnaris. In my ignorance, I may have inadvertently done something right (go figure). As you stated, the DMSO does increase absorption through the skin in mammals. If this does indeed pass through to fishes, then it may have improved the intimacy of the medication to the external ulcerations.

Again I speak here as a neophyte insofar as columnaris and septicemia are concerned so I don't know if this is typical or not but I was (pleasantly) surprised by how quickly the medications worked. In the 4 days between first noticing the sores and the medications 2nd day, I still lost 40% of the entire tank! Yet in 2 days post-meds, there were no more deaths and the sores began to vanish.

So I have no idea if it did improve medicative intimacy or efficacy or just made it easier to dissolve!

 

[dasaltemelosguy]

This may prove to shed some light on the topic though it may not translate directly to our discussions. It's a study by the Bureau of Sport Fisheries and Wildlife Fish Control Laboratory in WI. of DMSO toxicity and antimycin absorption in fish. It's very old, circa 1966, but with respect to DMSO and antimycin absorbed by the fish, their study suggests it has no effect. In fact, they considered the lack of "absorption augmentation" to be a disappointment as they were seeking to improve medication efficacy in fisheries. But it would suggest it does nothing more than help dissolve the meds:

EFFECT OF DMSO ON TOXICITY
OF ANTIMYCIN - Wayne A. Willford, Chemist
Bureau of Sport Fisheries and Wildlife
Fish Control Laboratory, La Crosse, Wis.(1966)

A preliminary test was performed to determine what, if any, influence DMSO has
on the toxicity of antimycin to bluegill. Various concentrations of antimycin were added
in combination with enough DMSO to produce
1.0 p.p.t. of DMSO in the test vessel. A comparison test was run using only acetone as
solvent for the antimycin.

The 96-hour LC so of antimycin and acetone
alone was 0.089 parts per billion (p.p.b.),
while antimycin in combination with 1.0 p.p.t.
of DMSO produced a 96-hour LC 50 of 0.084
p.p.b.

These results reflect biological variation and indicate that DMSO has no effect on
the toxicity of antimycin at 96 hours. It is
possible that in a bioassay designed to yield
toxicity with shorter exposures, DMSO could
enhance the absorption of antimycin sufficiently to affect toxicity.
Ball (1966) compared the relative toxicity of
0.05 p.p.m. p,p'-DDT to goldfish when used in
combination—with 6 and 18 p.p.t. of either
DMSO or acetone.

His results indicated that
DMSO does not significantly affect the median
survival time of goldfish when compared to
acetone. He further suggested that DMSO may
be a better solvent than acetone for pesticide
toxicity studies.

Summary:
Rabinowitz and Myerson (1966) were unable
to show a significant difference in the uptake
by aquarium fish of radioactive labeled dyes
when used in combination with 1.0 p.p.t. of
DMSO.

All of these results indicate that DMSO,
when used as a diluted constituent, does not
affect the absorption of some chemicals by
fish. It has been shown to be an excellent
solvent, and is worthy of further investigation as such for certain chemicals used in
fisheries. In addition, the potential of DMSO
as a penetrant carrier of certain drugs used
In human medicine suggests investigation of
similar potential in the treatment of fish
disease.

CONCLUSIONS
1. The acute toxicity of DMSO to fish is of a
very low order.
2. When the level of acute toxicity is reached,
DMSO is abruptly and non-selectively toxic
to the nine species tested.
3. Various water qualities at 120 C. have
little effect upon the toxicity of DMSO to
rainbow trout.
4. Increases in temperature cause a definite
increase in the toxicity of DMSO to rainbow
trout.
5. Preliminary results indicate that 1.0 p.p.t.
of DMSO has no effect on the toxicity of
antimycin to bluegill at 96 hours.