Doxycycline

Microbial resistance is always a concern when determining proper antibiotic therapy. The tetracycline class presents a therapeutic alternative for many infections, especially some rarely encountered varieties of advanced diseases involving the skin.

Doxycycline is a semi-synthetic derivative of the antibiotic oxytetracycline and is indicated as adjunctive treatment for a broad spectrum of susceptible infections, including those of the respiratory and urinary tracts and skin, and for severe acne. Doxycycline is available in 50-, 75-, and 100-mg tablet strengths from Ranbaxy Pharmaceuticals.

Pharmacology

Doxycycline is bacteriostatic, inhibiting the binding of transfer-RNA at the ribosomal level of the microbe. The effect is selective for infecting bacteria, since the doxycycline molecule can only reach the cell ribosome by an active transport mechanism that does not exist in human cells.

First-line therapy using doxycycline follows that of the tetracycline class and includes treatment for rickettsial disease, Chlamydia trachomatis, brucellosis, cholera, Mycoplasma pneumoniae, Lyme disease, anthrax, and gastric infections involving Helicobacter pylori. In addition, oral doxycycline is indicated during Grade III acne vulgaris.

General Dosage and Specific Indications

The usual adult dose for doxycycline is 100 mg every 12 hours for the first day, then 100 mg daily given in 1 dose or 2 divided doses. For severe infections, patients may require 100 mg every 12 hours. Children less than 45 kg are dosed by weight, with the first day's dose being 4.4 mg/kg and followed by daily doses of 2.2 to 4.4 mg/kg, depending on the severity of the infection.

Specific infections involve specialized dosing regimens. For rickettsial infections (such as Rocky Mountain Spotted Fever), dosing is continued for at least 3 to 7 days or until the patient is afebrile for 2 to 3 days. Chlamydial infections should be treated for up to 14 days to prevent a relapse. Uncomplicated gonorrhea is treated with 100 mg twice a day for a week, or, as an alternative, with an initial 300-mg dose, followed by a second 300- mg dose 1 hour later. Brucellosis is treated with 200 mg of doxycycline daily for 4 days, followed by a 100-mg daily dose for the next week. For the treatment of cholera, some clinicians suggest a single 300-mg dose. For postexposure prophylaxis to anthrax, the 100-mg twice-daily dose is continued until exposure confirmation, and then continued for 60 days if anthrax has been confirmed. Oral doxycycline even has a role in postexposure prophylaxis for plague and malaria.

For acne vulgaris, treatment with doxycycline can last for 6 to 8 weeks, with a tapering of the dose at the end of therapy. Total duration of treatment for acne vulgaris with doxycycline should not exceed 4 months.

Side Effects and Interactions

Tetracyclines as a class are associated with tooth discoloration when used in patients younger than the age of 8, and photosensitivity reactions can only enhance the discoloration once permanent teeth emerge. Chelation with calcium, iron, aluminum, magnesium, zinc, and lithium are also possible, requiring nonconcurrent dosing. The potential for renal Falconi's syndrome remains possible from ingesting outdated doxycycline, but this reaction is considered very rare.

Unlike other tetracycline antibiotics, doxycycline may be used by patients with renal impairment without an adjustment in dosage.

If necessary, the tablets of doxycycline can be crushed and mixed with food or liquid to mask the taste. Chocolate flavoring, whether in milk or pudding, provides the best coverage, while grape, strawberry, and cherry inadequately cover the bitterness of the crushed tablets. To minimize esophageal irritation, any such formulation should be followed by adequate fluids and should not be administered too close to bedtime.

Clinical Outlook

Doxycycline remains a versatile option for the treatment of a variety of infections. This version is comparable with the brand name product Adoxa (Bradley Pharmaceuticals Inc).

Zonisamide

The treatment for seizure disorders is likened more to an art than a science. With nearly 5 in 1000 afflicted, and with a resistance rate of up to 30%, it often takes a creative mixture of drugs to provide effective seizure control.

Zonisamide is an import from Japan, where it had been used for nearly a decade before its introduction in the United States in 1998. It is available in 25-, 50-, and 100-mg capsules from Mylan Laboratories Inc.

Pharmacology

Zonisamide is a sulfonamide. Its specific mechanism of action, as for many drugs that affect the central nervous system, remains unknown. Control of seizures is postulated to involve slowing the flow of sodium and calcium at the neural membranes. In addition, it may potentiate the effects of dopamine and serotonin but has not shown an effect on the synaptic effects of gamma-aminobutyric acid.

It is currently indicated as combination therapy for managing partial seizures. Like many therapies for seizures, it is also being used as an adjunct in the treatment of intractable neuropathic pain.

Dosing and Administration

Initial adult dosing of zonisamide is 100 mg daily for the first 2 weeks, with 100-mg increases at 2-week intervals. Therapeutic effectiveness is usually reached at daily doses in the range of 100 to 600 mg, with 400 mg being the usual daily maximum. This titration may take longer among patients with hepatic impairment. Discontinuing therapy with zonisamide should be done through gradual tapering to prevent a rebound in seizures.

Side Effects and Interactions

An allergy to sulfonamides is a specific contraindication to the use of zonisamide; and, like many drugs used to treat seizures, zonisamide is associated with fatigue, impaired concentration, and psychiatric symptoms.

Zonisamide should be stopped immediately if symptoms of allergy occur, as deaths have been reported due to Stevens-Johnson syndrome and toxic epidermal necrolysis. In fact, stopping zonisamide should be considered with the emergence of any unexplained rash.

About 4% of patients have experienced kidney stones, with other renal effects being a substantial increase in serum creatinine and blood urea nitrogen. Zonisamide should be avoided when renal failure is present.

Decreases in the ability to sweat along with hyperthermia have been reported in children younger than 17. Some of these cases have required hospitalization for heat stroke. Children requiring zonisamide in addition to their established drug regimen require careful monitoring. Although zonisamide does not affect the clearance of phenytoin or carbamazepine, concurrent use of these drugs increases the clearance of zonisamide.

Clinical Outlook

Seizure disorders continue to represent a great challenge for clinical control, with the traditional treatments involving phenytoin, phenobarbital, and valproic acid being frequently inadequate. Zonisamide represents an additional layer of therapy which, if properly monitored, can afford up to 50% additional relief from the symptoms of partial seizures. Although the drug is effective for some neuropathic pain relief, the strongest effects seen in that category are among cases involving phantom pain or a condition known as reflex sympathetic dystrophy. Diabetic neuralgia appears to be less responsive in the few controlled studies conducted thus far.

Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.