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Description

Levamisole Hydrochloride (Levamisole HCl), is an anthelmintic (anti-worm) agent commonly used in large livestock such as cattle, pigs and sheep. In 1971 it was found to have immunostimulatory properties and investigation into its use in humans began to expand. Currently, Levamisole HCl is used in humans for diseases related to imbalances in the regulation of immune responses or deficiencies of the immune system, including autoimmune diseases, chronic and recurrent diseases, chronic infections and cancer. It has beneficial effects on host defense mechanisms and restores depressed immune responses in animals and humans. Another interesting use of levamisole in humans is as a treatment for common warts (verruca vulgaris).

News of its anthelmintic efficacy and immune system benefits has been known among aquatic hobbyists for years. The problem, however, is that there is not much in the way of definitive information on its use and application in the hobby. Anecdotal accounts of how it has worked for those ‘outside the box’ aquarists who first braved its use with fish, and accounts of personal experience with Levamisole in individual aquariums are helpful, but the ‘your mileage may vary’ factor is immense. Word about its usefulness in treating internal parasites in the ornamental fish trade has spread, but information regarding its use is limited and sometimes conflicting. From the information I have found thus far, Levamisole HCl is safe to use in aquaria and effective against many internal parasites, especially nematodes, when used in appropriate dosages. It does not harm the bio-filter, plants, invertebrates or uninfected fish. As an added benefit, it boosts the immune competence of fish, humans, large animals, birds and some reptiles.

Medical Use

Microsurgery

These agents are used commonly by microsurgeons to decrease vascular thrombosis. The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing theirelectronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function. Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarserfibrin[citation needed]). By inhibiting α-2 antiplasmin, dextran serves as a plasminogen activator, so possessesthrombolytic features.

Outside from these features, larger dextrans, which do not pass out of the vessels, are potent osmotic agents, thus have been used urgently to treat hypovolemia. The hemodilution caused by volume expansion with dextran use improves blood flow, thus further improving patency of microanastomoses and reducing thrombosis. Still, no difference has been detected in antithrombotic effectiveness in comparison of intra-arterial and intravenous administration of dextran.

Dextrans are available in multiple molecular weights ranging from 3,000 Da to 2,000,000 Da. The larger dextrans (>60,000 Da) are excreted poorly from the kidney, so remain in the blood for as long as weeks until they are metabolized. Consequently, they have prolonged antithrombotic and colloidal effects. In this family, dextran-40 (MW: 40,000 Da), has been the most popular member for anticoagulation therapy. Close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion, while the remaining 30% are retained for several more days.

Other medical uses

· It is used in some eye drops as a lubricant.and in certain intravenous fluids to solubilize other factors, such as iron (in a solution known as Iron Dextran).

· Intravenous solutions with dextran function both as volume expanders and means of parenteral nutrition. Such a solution provides an osmotically neutral fluid that once in the body is digested by cells into glucose and free water. It is occasionally used to replace lost blood in emergency situations, when replacement blood is not available, but must be used with caution as it does not provide necessary electrolytes and can causehyponatremia or other electrolyte disturbances.

· It also increases blood sugar levels

Laboratory uses

· Dextran is used in the osmotic stress technique for applying osmotic pressure to biological molecules.

· It is also used in some size-exclusion chromatography matrices; an example is Sephadex.

· Dextran has also been used in bead form to aid in bioreactor applications.

· Dextran has been used in immobilization in biosensors.

· Dextran preferentially binds to early endosomes; fluorescent-labelled dextran can be used to visualize these endosomes under a fluorescent microscope.

· Dextran can be used as a stabilizing coating to protect metal nanoparticles from oxidation and improve biocompatibility.

· Dextran coupled with a fluorescent molecule such as fluorescein isothiocyanate can be used to create concentration gradients of diffusible molecules for imaging and allow subsequent characterization of gradient slope.

· Dextran is used to make microcarriers for industrial cell culture

Application

How does Levamisole HCl work as an antiparasitic agent?

Levamisole HCl is absorbed through the gut, can also be absorbed through the skin and is distributed throughout the body. It affects the neurotransmitters within the parasite and paralyzes the worm (spastic paralysis). The fish then passes the inactive worms. Good gravel vacuuming is advised after treatment to remove the paralyzed worms. It is not ovicidal, which means it will not affect eggs already present, but it will affect the larval stage of the worm. To ensure complete eradication of the parasite treat again after remaining eggs have hatched.

How does Levamisole HCl work as an immunomodulator?

The mechanism of action for its immunostimulating effects is not well understood. It is believed that it restores cell-mediated immune function in peripheral T-lymphocytes and stimulates phagocytosis by monocytes. The drug appears to restore depressed immune function rather than to stimulate response to above-normal levels. There are multitudes of medical studies being done with its use in humans and animals, the goal being to attain understanding of its immunomodulating mechanism. The mechanism will be defined, with time. However, at the time of the writing of this article, there is no complete answer to this question. For us, it is enough to know that it does stimulate immune function in fish that are suffering due to parasites or disease.

What if I overdose my fish?

The LD-50 (the lethal dose of a compound for 50% of animals exposed) of Levamisole HCl is 250 mg/l per 24 hours. This level of dosage is much higher than that which is prescribed for use in a freshwater bath, which is the method used in our fish tanks (See "Recommended Dosage" below). Be aware, however, that overdosing with this medication could result indeath to your fish. There have been accounts of adverse side effects in aquaria noted using higher than currently accepted appropriate dosing.

How long will it stay in my fish and how do I get it out of my tank?

Levamisole HCl is rapidly absorbed into the digestive system. Less than 6% of the medication is excreted unchanged in the urine and feces. Half-lives for several species have been recorded:

Cattle: 4 - 6 hours
Swine: 3.5 - 6.8 hours
Dogs: 1.8 - 4 hours

Absorption is systemic within 3 - 4 hours. Within three days 70% of the medication will be gone from the fish via its excretory system. The vast majority of the compound will have been metabolized by your fish. The remainder can be removed by water changes and/or adding activated charcoal to your filtration system.

Side Effects

Carcinogenicity
Adequate studies in animals have not been done. Studies at doses of 5, 20, and 80 mg per kg of body weight (mg/kg) per day for up to 18 months in mice and up to 24 months in rats found no evidence of carcinogenicity; however, these studies were not conducted at the maximum tolerated dose, and there is a possibility that the animals may not have been exposed to a reasonable drug challenge . Chronic administration of high doses (25 mg/kg) in New Zealand Black mice increased the rate and intensity of spontaneous lymphomas . No carcinogenic effect was found in 12- to 18-month studies in dogs.

Mutagenicity
Levamisole was not found to be mutagenic in dominant lethal studies in male and female mice, in an Ames test, and in a study to detect chromosomal aberrations in cultured peripheral human lymphocytes .

Pregnancy/Reproduction
Fertility—
Administration through 3 generations of rats and rabbits did not affect fertility . No adverse effects on male or female fertility were noted in rats given oral doses of 2.5, 10, 40, and 160 mg/kg . In a rat gavage study at doses of 20, 60, and 180 mg/kg, the copulation period was increased, the duration of pregnancy was slightly increased, and fertility, pup viability and weight, lactation index, and number of fetuses were decreased at a dose of 60 mg/kg . No adverse reproductive effects occurred when the offspring were allowed to mate and litter .
Pregnancy—
Adequate and well-controlled studies in humans have not been done.
Studies in rats and rabbits at oral doses up to 180 mg/kg found no evidence of fetal malformations . Embryotoxicity occurred at doses of 160 mg/kg in rats and was significant in rabbits at doses of 180 mg/kg .
FDA Pregnancy Category C.

Breast-feeding
It is not known whether levamisole is distributed into human breast milk; however, it is distributed into cows' milk .

Pediatrics
No information is available on the relationship of age to the effects of levamisole in pediatric patients. Safety and efficacy have not been established

Geriatrics
Appropriate studies on the relationship of age to the effects of levamisole have not been performed in the geriatric population. However, clinical trials were conducted in older patients and geriatrics-specific problems that would limit the usefulness of this medication in the elderly are not expected.

Dental
The leukopenic effects of levamisole may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If leukopenia occurs, dental work should be deferred until blood counts have returned to normal and patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.
Levamisole may also cause mild stomatitis associated with discomfort (severe stomatitis may occur during combination therapy with fluorouracil).

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