DOXYCYCLINE

J Cyst Fibros. 2005 Mar;4(1):35-40.
Long-term azitromycin treatment of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection; an observational cohort study.
Hansen CR, Pressler T, Koch C, Hoiby N.
Cystic Fibrosis Center, 5003, Department of Pediatrics, Juliane Marie Center, Rigshospitalet, Blegdamsvej 9, DK-2100 Kobenhavn O, Denmark.

BACKGROUND: In cystic fibrosis (CF), chronic endobronchial infection with Pseudomonas aeruginosa is a serious complication. Macrolides can increase lung function and weight in patients, and reduce exacerbations. METHODS: In 2001, we introduced long-term, low-dose azithromycin (AZ) treatment as an integral part of our routine treatment of these patients. Our study is an observational cohort study of all CF patients with chronic P. aeruginosa infection in our CF center comparing clinical parameters of the patients 12 months prior to treatment with the same values during 12 months of treatment. RESULTS: 45 patients (27 men, median age 29 years) completed 1-year treatment. Median weight increased from 63.1 kg in the pre-treatment period to 63.9 kg during treatment (p=0.01). Median slope of decline in lung function increased from pre-treatment FEV(1) -4.1% and FVC -3.0% to +0.8% (p<0.001) and +1.6% (p=0.01), respectively. 90% of sputum samples contained mucoid P. aeruginosa before treatment, decreasing to 81% during treatment (p=0.003). Median CRP decreased from 6.2 mmol/l to 5.8 mmol/l (ns). CONCLUSION: Long-term, low-dose AZ treatment in adult CF patients with chronic P. aeruginosa infection is safe and reduces the decline in lung function, increases weight, and reduces the percentage of mucoid strains of P. aeruginosa in sputum samples.

Ann N Y Acad Sci 1999 Jun 30;878:159-78
MMP inhibition in abdominal aortic aneurysms. Rationale for a prospective randomized clinical trial
Thompson RW, Baxter BT.
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Abdominal aortic aneurysms (AAAs) represent a chronic degenerative condition associated with a life-threatening risk of rupture. The evolution of AAAs is thought to involve the progressive degradation of aortic wall elastin and collagen, and increased local production of several matrix metallo-proteinases (MMPs) has been implicated in this process. We have previously shown that tetracycline derivatives and other MMP inhibitors suppress aneurysm development in experimental animal models of AAA. Doxycycline also reduces the _expression of MMP-2 and MMP-9 by human vascular wall cell types and by AAA tissue explants in vitro. To determine whether this strategy might have a role in the clinical management of small AAA, we examined the effect of doxycycline on aortic wall MMP _expression in vivo. Patients were treated with doxycycline (100 mg p.o. bid) for 7 days prior to elective AAA repair, and aneurysm tissues were obtained at the time of surgery (n = 5). Tissues obtained from an equal number of untreated patients with AAA were used for comparison. By reverse transcription-polymerase chain reaction and Southern blot analysis, MMP-2 and MMP-9 were both found to be abundantly expressed in the aneurysm wall. Preoperative treatment with doxycycline was associated with a 3-fold reduction in aortic wall _expression of MMP-2 and a 4-fold reduction in MMP-9 (p < 0.05 compared to untreated AAA). These preliminary results suggest that even short-term treatment with doxycycline can suppress MMP _expression within human AAA tissues. Given its pleiotropic effects as an MMP inhibitor, doxycycline may be particularly effective in suppressing aortic wall connective tissue degradation. While it remains to be determined whether MMP inhibition will have a clinically significant impact on aneurysm expansion, it is expected that this question can be resolved by a properly designed prospective randomized clinical trial.

J Vasc Surg 1998 Dec;28(6):1082-93
Pharmacologic suppression of experimental abdominal aortic aneurysms: acomparison of doxycycline and four chemically modified tetracyclines
Curci JA, Petrinec D, Liao S, Golub LM, Thompson RW.
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.

BACKGROUND: Matrix metalloproteinases (MMPs) likely contribute to the degradation of medial elastin in abdominal aortic aneurysms (AAAs), and tetracycline antibiotics exhibit MMP-inhibiting properties. The purpose of this study was to compare the effects of doxycycline and several non-antibiotic chemically modified tetracyclines (CMTs) in a rat model of elastase-induced AAA. METHODS: Fifty-two male Wistar rats underwent intraluminal perfusion of the abdominal aorta with porcine pancreatic elastase. The rats then were treated for 7 days with subcutaneous injections of saline solution, different doses of doxycycline, or 1 of 4 different CMTs. The aortic diameters were measured with microcalipers, and the fixed tissues were examined by means of light microscopy. Gelatin zymography was used to assess the MMP activity in the aortic tissue extracts. RESULTS: The mean aortic diameter in the control group increased by 126% +/- 14% on day 7 (from 1.57 +/- 0.04 mm to 3.54 +/- 0.27 mm; P <.05), and 5 of 6 animals (83%) had AAAs. Doxycycline appeared to inhibit aortic dilatation in a dose-dependent manner, and AAAs did not develop in any animals. Half-maximal effects were observed at a dose of approximately 6 mg/kg/day, and maximal effects were noted at greater than 30 mg/kg/day. No AAAs were observed in the animals that were treated with CMTs at 15 mg/kg/day. Each of the following CMTs exhibited an efficacy that was similar to that of doxycycline (percent inhibition of aortic dilatation vs control; all P <.05): CMT-3 (47.6%), CMT-4 (38.9%), CMT-7 (47.6%), CMT-8 (54.0%), and doxycycline (51.6%). Tissues from saline solution-treated controls exhibited a transmural inflammatory response and marked destruction of the medial elastic lamellae. Tetracycline derivatives limited the disruption of medial elastin without appearing to alter either the inflammatory response or the rat aortic wall production of metallogelatinases. CONCLUSION: Tetracycline derivatives suppress the development of AAAs after elastase-induced aortic injury in the rat. The aneurysm-suppressing effects of doxycycline appear to be dose-dependent and distinct from its antibiotic activities, and they coincide with the structural preservation of medial elastin fibers. Further studies are needed to explore the potential of MMP-inhibiting tetracyclines as a novel pharmacologic strategy for the suppression of aortic aneurysms.

GENERIC NAME: doxycycline
BRAND NAME: Vibramycin

DRUG CLASS AND MECHANISM: Doxycycline is a synthetic broad-spectrum antibiotic derived from tetracycline. It is effective against a wide variety of bacteria, such as Hemophilus influenzae, Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydia psittaci, Chlamydia trachomatis, Neisseria gonorrhoea, and many others.

PREPARATIONS: Capsules: 50mg, 100mg; Tablets: 100mg; Suspension: 25 mg/teaspoon; Syrup: 50 mg/teaspoon.

STORAGE: Capsules should be kept below 30°C (86°F). The suspension should be refrigerated and shaken prior to each use.

PRESCRIBED FOR: Doxycycline is used for many different types of infections, including respiratory tract infections due to Hemophilus influenzae, Streptococcus pneumoniae, or Mycoplasma pneumoniae. It also is used for the treatment of nongonococcal urethritis (due to Ureaplasma), Rocky mountain spotted fever, typhus, chancroid, cholera, brucellosis, anthrax, syphilis, and acne.

DOSING: The absorption of doxycycline is not markedly affected by food, and therefore, it can be taken with meals. For most infections, doxycycline is taken once or twice daily for 7 to 14 days. Sometimes, the first dose is given as a "double dose," that is, twice as large as the remainder of the doses.

DRUG INTERACTIONS: It is recommended that doxycycline not be taken at the same time as aluminum-, magnesium-, or calcium- based antacids, such as Mylanta, Maalox, Tums, or Rolaids because, like food, these medications bind doxycycline in the intestine. Similarly, doxycycline should not be taken with minerals (such as calcium or iron), with bismuth subsalicylate (Pepto Bismol).

Doxycycline may enhance the activity of warfarin (Coumadin) and cause excessive "thinning" of the blood, necessitating a reduction in the dose of warfarin. Phenytoin (Dilantin), carbamazepine (Tegretol), and barbiturates (such as phenobarbital) may enhance the metabolism (destruction) of doxycycline thus making it less effective.

PREGNANCY: Tetracycline antibiotics, such as doxycycline, can have toxic effects on development of bone in the fetus. Therefore, tetracyclines are not recommended during pregnancy unless there is no other appropriate antibiotic.

NURSING MOTHERS: Doxycycline is secreted into breast milk. Since tetracyclines can cause decreased bone, the use of tetracyclines in nursing mothers is of concern. The physician must decide whether to recommend that a nursing mother discontinue nursing during treatment with tetracyclines or to choose a different antibiotic.

SIDE EFFECTS: Doxycycline is generally well-tolerated. The most common side effects are diarrhea or loose stools, nausea, abdominal pain, and vomiting. Tetracyclines, such as doxycycline, may cause tooth discoloration if used in persons below 8 years of age. Exaggerated sunburn can occur with tetracyclines; therefore, sunlight should be minimized during treatment.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.
Also, you should read carefully important health information about this drug given here:

www.nlm.nih.gov