Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

DIMETHYL SULFOXIDE, DMSO

Chemistry - DMSO is a clear, colorless to straw-yellow liquid. It is dipolar, aprotic (acts as a
Lewis base) and extremely hygroscopic. It has a melting/freezing point of 18.5°C, boiling point of189°C, and a molecular weight of 78.1. It is miscible with water (heat is produced), alcohol, acetone, chloroform, ether and many organic solvents. A 2.15% solution in water is isotonic with serum.

Storage, Stability, Compatibility

Must be stored in airtight containers and away from light. As
DMSO may react with some plastics, it should be stored in glass or in the container provided by the manufacturer. If DMSO is allowed to contact room air it will self-dilute to a concentration of 66-67%. DMSO is apparently compatible with many compounds, but because of the chances for accidental percutaneous absorption of potentially toxic compounds, the admixing of DMSO with other compounds is not to be done casually.

Pharmacology - DIMETHYL SULFOXIDE, DMSO

The pharmacologic effects of DMSO are diverse. DMSO traps free radical hydroxide and its metabolite, dimethyl sulfide (DMS) traps free radical oxygen. It appears that these actions help to explain some of the anti-inflammatory, cryopreservative, antiischemic, and radioprotective qualities of DMSO.
DMSO will easily penetrate the skin. It also serves as a carrier agent in promoting the percutaneous absorption of other compounds (including drugs and toxins) that normally would not penetrate. Drugs such as insulin, heparin, phenylbutazone, and sulfonamides may all be absorbedsystemically when mixed with DMSO and applied to the skin.
DMSO has weak antibacterial activity when used clinically and possible clinical efficacy whenused topically as an antifungal. The mechanism for these antimicrobial effects have not beenelucidated.
The anti-inflammatory/analgesic properties of DMSO have been thoroughly investigated. DMSOappears to be more effective an anti-inflammatory agent when used for acute inflammation versuschronic inflammatory conditions. The analgesic effects of DMSO has been compared to thatproduced by narcotic analgesics and is efficacious for both acute and chronic musculoskeletal pain.
DMSO decreases platelet aggregation, but reports on its effects on coagulability have beenconflicting, as has its effect on the myocardium. DMSO has diuretic activity independent of themethod of administration. It also provokes histamine release from mast cells, which probablycontributes to the local vasodilatory effects seen after topical administration.
DMSO also apparently has some anticholinesterase activity and enhances prostaglandin E, butblocks the synthesis of prostaglandins E2, F2-alpha, H2, and G2. It inhibits the enzyme alcoholdehydrogenase, which not only is responsible for the metabolism of alcohol, but also themetabolism of ethylene glycol into toxic metabolites.
Uses, Indications - Purported uses for DMSO are rampant, but the only FDA-approved veterinary indication for DMSO is: "...as a topical application to reduce acute swelling due to trauma" (Package Insert - Domoso® ¯ Syntex). Other possible indications for DMSO include: adjunctive treatment in transient ischemic conditions, CNS trauma and cerebral edema, skin ulcers/wounds/burns, adjunctive therapy in intestinal surgeries, and analgesia for post-operative or intractable pain, amyloidosis in dogs, reduction of mammary engorgement in the nursing bitch, enhancement of antibiotic penetration in mastitis in cattle, and limitation of tissue damage following extravasation injuries secondary to chemotherapeutic agents.
DMSO's effect on alcohol dehydrogenase, may make it useful in the treatment of ethylene glycolpoisoning, but this has not been sufficiently studied as of yet. DMSO's attributes as a potentialcarrier of therapeutic agents across the skin and into the systemic circulation and its synergisticeffects with other agents are potentially exciting, but require much more study before they can beroutinely recommended.
While the potential indications for DMSO are many, unfortunately, the lack of well-controlledstudies leave many more questions than answers regarding this drug.

Pharmacokinetics - DIMETHYL SULFOXIDE, DMSO

DMSO is well absorbed after topical administration, especially at concentrations between 80-100%. It is extensively and rapidly distributed to virtually every area of thebody. After IV administration to horses, the serum half-life was approximately 9 hours. DMSO ismetabolized to dimethyl sulfide (DMS) and is primarily excreted by the kidneys, although biliaryand respiratory excretion also takes place.
In cattle, the drug is eliminated quite rapidly and after 20 days no detectable drug or metabolitesare found in milk, urine, blood, or tissues.
Contraindications/Precautions - Wear rubber gloves when applying topically, and apply withclean or sterile cotton to minimize the chances for contaminating with potentially harmful substances. Apply only to clean, dry areas to avoid carrying other chemicals into the systemic circulation.
DMSO may mask existing pathology with its anti-inflammatory and analgesic activity.
At high doses DMSO has been shown to be teratogenic in hamsters and chicks, but not in mice, rats or rabbits; weigh the risks versus benefits when using in pregnant animals.
Because DMSO may degranulate mast cells, animals with mastocytomas should only receive
DMSO with extreme caution. DMSO should be used cautiously in animals suffering from dehydration or shock as its diuretic and peripheral vasodilatory effects may exacerbate these conditions.

Adverse Effects, Warnings

When used as labeled, DMSO appears to be an extremely safe drug.
Local effects ("burning", erythema, vesiculation, dry skin, local allergic reactions) and garlic oroyster-like breath odor are the most likely adverse effects. They are transient and quickly resolvewhen therapy is discontinued. Lenticular changes, which may result in myopia, have been notedprimarily in dogs and rabbits when DMSO is used chronically and at high doses. These effects areslowly reversible after the drug is discontinued.
When DMSO is administered intravenously to horses it may cause hemolysis and hemoglobinuria. These effects can be minimized by using concentrations of 20% or less (not less than 2% in water) and slowly administering.
Reports of hepatotoxicity and renal toxicity have also been reported for various species anddosages. These occur fairly rarely and some clinicians actually believe DMSO has a protectiveeffect on ischemically insulted renal tissue.
Overdosage - The reported LD50's following IV dosage in dogs and cats are: Cats » 4 g/kg, and Dogs » 2.5 g/kg. Signs of toxicity include: sedation and hematuria at non-lethal doses; coma, seizures, opisthotonus, dyspnea and pulmonary edema at higher dosages. Should an acute overdosage be encountered, treat supportively.

Drug Interactions

Because of its anticholinesterase activity, avoid the use of organophosphatesor other cholinesterase inhibitors with DMSO. A fatality secondary to mercury intoxication wasreported when DMSO was mixed with a mercury salt "red blister" and applied topically to theleg of a horse. Because it inhibits alcohol dehydrogenase, DMSO may prolong the effects ofalcohol. Insulin, corticosteroids (including endogenous steroids), and atropine may bepotentiated by DMSO.

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