Trimethoprim - Dihydrofolate Reductase Inhibitors
 |
This article has been peer reviewed but is awaiting expert review. If you would like to help with this, please see more information about expert reviewing. |
|
Trimethoprim is the only dihydrofolate reductase inhibitor currently in veterinary use. It is chemically related to the antimalarial drug pyrimethamine.
Mechanism of Action
Trimethoprim works as an antagonist inhibiting the dihydrofolate reductase enzyme. This means that the bacteria is unable to grow as it is denied it's folic acid source. This means that trimethoprim is a bacteriostatic drug.
Spectrum of Activity
- It is a broad spectrum antibiotic active against aerobic gram positives and negatives.
- It isn't active against anaerobes and Pseudomonas.
- As with sulphonamides it is inhibited by necrotic tissue as this provides an alternative source of growth products for the bacteria. This bypasses the folic acid use and so the effects of the trimethoprim become obselete.
Pharmacokinetic Considerations
It is a lipophilic weak base, that is orally active and fully absorbed by the gastrointestinal tract. It widely distributes throughout the body, reaching quite high concentrations in the kidney, lung, and CSF. It will become ion-trapped in acidic fluid. It is rapidly metabolised by the liver but the rate varies with each species. It's elimination by the kidney will increase with acidic urine due to the basic nature of the drug.
Side Effects and Contraindications
It is a fairly non-toxic drug. It can cause folic acid deficiency if given at high and extended doses. It is less safe in cats as excessive salivation can occur.