Tetrahydrofolate synthesis pathway
Find information on thousands of medical conditions and prescription drugs.

Cotrim

Co-trimoxazole (abbreviated SXT) is a bacteriostatic antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections. The name co-trimoxazole is the International Nonproprietary Name, and has been marketed worldwide under many brand names (GlaxoSmithKline under Septrin®, Hoffmann-La Roche as Bactrim®, and by many other generic pharmaceutical manufacturers). more...

Home
Diseases
Medicines
A
B
C
Cabergoline
Caduet
Cafergot
Caffeine
Calan
Calciparine
Calcitonin
Calcitriol
Calcium folinate
Campath
Camptosar
Camptosar
Cancidas
Candesartan
Cannabinol
Capecitabine
Capoten
Captohexal
Captopril
Carbachol
Carbadox
Carbamazepine
Carbatrol
Carbenicillin
Carbidopa
Carbimazole
Carboplatin
Cardinorm
Cardiolite
Cardizem
Cardura
Carfentanil
Carisoprodol
Carnitine
Carvedilol
Casodex
Cataflam
Catapres
Cathine
Cathinone
Caverject
Ceclor
Cefacetrile
Cefaclor
Cefaclor
Cefadroxil
Cefazolin
Cefepime
Cefixime
Cefotan
Cefotaxime
Cefotetan
Cefpodoxime
Cefprozil
Ceftazidime
Ceftriaxone
Ceftriaxone
Cefuroxime
Cefuroxime
Cefzil
Celebrex
Celexa
Cellcept
Cephalexin
Cerebyx
Cerivastatin
Cerumenex
Cetirizine
Cetrimide
Chenodeoxycholic acid
Chloralose
Chlorambucil
Chloramphenicol
Chlordiazepoxide
Chlorhexidine
Chloropyramine
Chloroquine
Chloroxylenol
Chlorphenamine
Chlorpromazine
Chlorpropamide
Chlorprothixene
Chlortalidone
Chlortetracycline
Cholac
Cholybar
Choriogonadotropin alfa
Chorionic gonadotropin
Chymotrypsin
Cialis
Ciclopirox
Cicloral
Ciclosporin
Cidofovir
Ciglitazone
Cilastatin
Cilostazol
Cimehexal
Cimetidine
Cinchophen
Cinnarizine
Cipro
Ciprofloxacin
Cisapride
Cisplatin
Citalopram
Citicoline
Cladribine
Clamoxyquine
Clarinex
Clarithromycin
Claritin
Clavulanic acid
Clemastine
Clenbuterol
Climara
Clindamycin
Clioquinol
Clobazam
Clobetasol
Clofazimine
Clomhexal
Clomid
Clomifene
Clomipramine
Clonazepam
Clonidine
Clopidogrel
Clotrimazole
Cloxacillin
Clozapine
Clozaril
Cocarboxylase
Cogentin
Colistin
Colyte
Combivent
Commit
Compazine
Concerta
Copaxone
Cordarone
Coreg
Corgard
Corticotropin
Cortisone
Cotinine
Cotrim
Coumadin
Cozaar
Crestor
Crospovidone
Cuprimine
Cyanocobalamin
Cyclessa
Cyclizine
Cyclobenzaprine
Cyclopentolate
Cyclophosphamide
Cyclopropane
Cylert
Cyproterone
Cystagon
Cysteine
Cytarabine
Cytotec
Cytovene
Isotretinoin
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z

Synergistic action

Co-trimoxazole exhibits a synergistic antibacterial effect when compared to each of its components administered singly. This is because trimethoprim and sulfamethoxazole inhibit successive steps in the folate synthesis pathway (see diagram below).

Sulfamethoxazole acts as a false-substrate inhibitor of dihydropteroate reductase. Sulfonamides such as sulfamethoxazole are analogues of p-aminobenzoic acid (PABA) and are competitive inhibitors of the enzyme; inhibiting the production of dihydropteroic acid.

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid.

Folic acid is an essential precursor in the de novo synthesis of the DNA nucleosides thymidine and uridine. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) thus are dependent on their own de novo synthesis - inhibition of the enzyme starves the bacteria of two bases necessary for DNA replication and transcription.

Clinical indications

Co-trimoxazole is more effective than either of its components individually in treating bacterial infections. However the degree of benefit for the additonal of the Sulfonamide, was in most cases marginal, but reponsible for its high association will allergic responses (see below). Its widespread use has been restricted in many countries to very specific circumstances where its improved efficacy is demonstrated. It may be effective in a variety of upper and lower respiratory tract infections, renal and urinary tract infections, gastrointestinal tract infections, skin and wound infections, septicaemias and other infections caused by sensitive organisms.

Specific indications for its use include: (Rossi, 2004)

  • treatment and prophylaxis of pneumonia caused by Pneumocystis jiroveci (P. carinii)
  • infections caused by Listeria monocytogenes, Nocardia spp., Stenotrophomonas maltophilia (Zanthomonas maltophilia)
  • melioidosis
  • shigellosis
  • traveller's diarrhoea
  • prophylaxis of cerebral toxoplasmosis in HIV patients
  • Whipple's disease

Safety

There has been some concern about its use, however, since it has been associated with both frequent mild allergic reactions and rare but serious adverse effects including Stevens-Johnson syndrome, myelosuppression, agranulocytosis, as well as severe liver damage (cholostatic hepatosis, hepatitis, liver necrosis, fulminant liver failure) and renal impairment up to acute renal failure and anuria. These side-effects are seen especially in the elderly and may be fatal. (Joint Formulary Committee, 2004)

Read more at Wikipedia.org


[List your site here Free!]


Do acetaminophen and an NSAID combined relieve osteoarthritis pain better than either alone?
From Journal of Family Practice, 6/1/04 by Jennifer J. Buescher

* EVIDENCE-BASED ANSWER

Combining nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen for short courses provides more relief of pain in osteoarthritis without an increase in side effects (strength of recommendation [SOR]=B). Combining acetaminophen at 4 g/d with an NSAID can also decrease the daily dose of NSAID required for pain relief, thus reducing the potential risk from higher-dose NSAID therapy (SOR=B).

Over the long term, however, this combination may increase the risk of upper gastrointestinal (GI) bleeding more than that conferred by the NSAID alone (SOR=B). If combination therapy is necessary, limiting the dose of acetaminophen to [less than or equal to] 2 g/d minimizes gastrointestinal toxicity. Acetaminophen alone at the lowest dose to provide pain relief is the safest pharmacologic choice for patients with osteoarthritis.

* EVIDENCE SUMMARY

Clinical guidelines for osteoarthritis recommend acetaminophen as first-line therapy followed by an NSAID or cyclooxygenase-2 (COX-2) inhibitor, and many patients are treated with combination therapy.

Several small randomized controlled trials have compared the individual efficacy of NSAIDs and acetaminophen in osteoarthritis and have found that both provide more pain relief than placebo. (1-3) There is a trend toward improved pain relief with NSAIDs compared with acetaminophen in the initial treatment period; however, few long-term studies of efficacy have been reported. One randomized controlled trial comparing 750 mg/d naproxen (Aleve, Naprosyn) with 2600 mg/d acetaminophen for 2 years found similar pain relief for both medications and a dropout rate of 65% in both groups. (2) Similar numbers of persons taking acetaminophen or naproxen dropped out because of adverse effects (20%) or lack of efficacy (19%), and no difference was seen in functional improvement between the 2 groups.

A 6-week randomized double-blind crossover trial of 227 patients comparing 75 mg diclofenac and 200 mg misoprostol (Arthrotec) with acetaminophen 4 g/d found the diclofenac-misoprostol combination provided more pain control than acetaminophen alone. Adverse events were slightly more common in the diclofenac group (54% vs 46%; P=.046). (4)

The COX-2 inhibitors rofecoxib (Vioxx) and celecoxib (Celebrex) have been shown to provide equal pain relief compared with naproxen for patients with osteoarthritis. (5) One industry-sponsored randomized trial found rofecoxib superior to celecoxib, and both superior to acetaminophen in treatment of osteoarthritis pain. (6) There was no difference in the incidence of side effects among the 3 medications. Thirty percent of patients taking 4 g/d acetaminophen discontinued the study because of lack of efficacy, compared with 20% of those taking either celecoxib or rofecoxib. (6)

Few studies have evaluated the safety or efficacy of the combination of NSAIDs and acetaminophen in osteoarthritis. One double-blind, double-dummy crossover trial of 18 patients with osteoarthritis of the hip compared naproxen at doses of 500 mg and 1000 mg, with and without 4 g/d of acetaminophen, and 1500 mg/d of naproxen alone over 5 one-week trial periods. (7) Adding acetaminophen improved patient-reported pain scores compared with naproxen alone. Higher doses of naproxen alone provided less pain relief than a lower dose of naproxen combined with acetaminophen. GI side effects increased with the increase in naproxen dose, but were unaffected by the addition of acetaminophen. Functional ability was not affected during this short study. A similar study by the same researchers of patients with rheumatoid arthritis found similar results. (7)

One randomized, double-blind, crossover trial compared single doses of tolmetin (Tolectin, 100, 150, 200 mg) and acetaminophen (400 mg) alone and in combination with placebo in the control of experimentally induced pain (thermal and electrical stimulation). Acetaminophen alone did not differ from placebo in pain control; however, the combinations of acetaminophen with tolmetin provided similar pain relief to higher doses of tolmetin alone, (8) No studies have evaluated the efficacy or safety of acetaminophen combined with rofecoxib or celecoxib.

Regarding the risks of combining acetaminophen with NSAIDs, 1 nested case-control study based on the entire enrollment panel of the British National Health Service characterized the risk of upper GI side effects among persons taking NSAIDs or acetaminophen alone or in combination. The study evaluated medications in use at the time of an upper GI bleed, controlling for age, sex, and concomitant medications (corticosteroids, [H.sub.2] receptor antagonists, omeprazole, anticoagulants, and others) and excluding patients with varices, alcohol-related disorders, liver disease, and cancer; no attempt was made to control other comorbidities. The relative risk of upper GI perforation or bleeding for patients taking [greater than or equal to] 2g/d acetaminophen or high-dose NSAIDs was 2.4 (95% confidence interval [CI], 1.7-3.5) and 3.6 (95% CI, 2.9-4.3), respectively. Concomitant use of an NSAID with [greater than or equal to] 2 g/d of acetaminophen showed a relative risk of upper GI perforation or bleed of 16.6 (95% CI, 11.0-24.9). Acetaminophen doses <2 g/d conferred no additional risk for serious upper GI side effects. (9)

A systematic review of selective COX-2 inhibitors vs naproxen found fewer endoscopically detected ulcers in patients taking celecoxib but no difference in serious gastrointestinal bleeds. (5) A meta-analysis of randomized controlled trials found a higher incidence of serious thrombotic cardiovascular events among patients taking COX-2 inhibitors compared with naprosyn. (10) The safety profile of rofecoxib and celecoxib in the long-term treatment of pain is not fully understood at this time.

* RECOMMENDATIONS FROM OTHERS

The American College of Rheumatology (ACR) recommends acetaminophen up to 4 g/d as a first-line pharmacologic treatment for osteoarthritis of the hip and knee, and advises NSAIDs be used at the lowest effective dose if they are necessary for pain control. (11) The ACR does not specifically comment on combining NSAID and acetaminophen use.

The American Academy of Orthopaedic Surgeons recommends initial use of an NSAID or acetaminophen, but does not comment on the combination of NSAIDs and acetaminophen. (12)

* CLINICAL COMMENTARY:

Adding acetaminophen may be more desirable than switching NSAIDs Compared with NSAIDs, acetaminophen has a complementary analgesic mechanism of action and can be safely used in many patients. Additive effects of acetamiuophen have not been well described with all NSAIDs (eg, COX-2 inhibitors); however, this combination is inexpensive and overall appears to effectively augment analgesia when combined with NSAIDs. Although observational data demonstrate an increased risk of upper GI bleeding with this combination, selection bias (higher-risk patients being on combination therapy) could reasonably explain this association. Adding acetaminophen may be more desirable than switching NSAIDs for patients with osteoarthritis that have a partial response to their current NSAID therapy

Joseph Saseen, PharmD, FCCP, BCPS, University of Colorado Health Sciences Center, Denver

REFERENCES

(1.) Amadio P Jr, Cummings DM. Evaluation of acetaminophen in the management of osteoarthritis of the knee. Curr Ther Res 1983; 34:59-66.

(2.) Williams HJ, Ward JR, Egger MJ, et al. Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. Arthritis Rheum 1993; 36:1196-1206.

(3.) Bradley JD, Brandt KI), Katz BR Kalasinski LA, Ryan SI. Treatment of knee osteoarthritis: relationship of clinical features of joint inflammation to the response to a nonsteroidal antiinflammatory drug or pure analgesic. J Rheumatol 1992; 19:1950-1954.

(4.) Pincus T, Koch GG, Sokka T, et al. A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen for patients with osteoarthritis of the hip or knee. Arthritis Rheum 2001; 44:1587-1598.

(5.) Decks JJ, Smith LA, Bradley MD. Efficacy, tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials. BMJ 2002; 325:619.

(6.) Geba GR Weaver AL, Polis AB, Dixon ME, Schnitzer TJ; Vioxx, Acetaminophen, Celecoxib Trial (VACT) Group. Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial. JAMA 2002; 287:64-71.

(7.) Seideman P, Samuelson P, Neander G. Naproxen and paracetamol compared with naproxen only in coxarthrosis. Increased effect of the combination in 18 patients. Acta Orthop Scand 1993; 64:285-288.

(8.) Stacher G, Bauer P, Ehn I, Schreiber E. Effects of tolmetin, paracetamol, and of two combinations of tolmetin and paracetamol as compared to placebo on experimentally induced pain. A double blind study. Int J Clin Pharmacol Biopharm 1979; 17:250-255.

(9.) Garcia Rodriguez LA, Hernandez-Diaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res 2001; 3:98-101.

(10.) Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective C0X-2 inhibitors. JAMA 2001; 286:954-959.

(11.) Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on 0steoarthritis Guidelines. Arthritis Rheum 2000: 43:1905-1915.

(12.) AAOS Clinical Guideline on Osteoarthritis of the Knee. Rosemont, IL: American Academy of Orthopaedic Surgeons, 2003. Available at: www.aaos.org/wordhtml/ pdfs_r/guidelin/suprt_oakn.pdf. Accessed on May 11, 2004.

DRUG BRAND NAMES

Amoxicillin * Amoxil, Biomox, Polymox, Trimox, Wymox Cephalexin * Biocef, Keflex Celecoxib * Celebrex Diclofenac/Misoprostol * Arthrotec Ipratropium * Atrovent Labetalol * Trandate Methyldopa * Aldomet Naproxen * Aleve, Anaprox, Naprosyn Nitrofurantoin * Furadantin, Macrobid, Macrodantin Rofecoxib * Vioxx Tiotropium * Spiriva Tolmetin * Tolectin Triamcinalone * Aristocort, Atolone, Kenacort Sulfamethoxazole/Trimethoprim * Bactrim, Cotrim, Septra, Sulfatrim Sulfisoxazole * Gantrisin

Jennifer J. Buescher, MD, Susan Meadows, MLS, Department of Family and Community Medicine, University of Missouri-Columbia

COPYRIGHT 2004 Dowden Health Media, Inc.
COPYRIGHT 2004 Gale Group

Return to Cotrim
Home Contact Resources Exchange Links ebay