Trimethoprim Co-trimoxazole

DIGOXIN TRIMETHOPRIM, CO-TRIMOXAZOLE Trimethoprim may t plasma concentrations of digoxin, particularly in elderly people Uncertain postulated that trimethoprim 1 renal clearance of digoxin Monitor digoxin levels watch for digoxin toxicity... 

USAN] Gantanol ) is a sulphonamide with antibacterial activity, used in the treatment of respiratory and urinary tract infections. It is usually used in conjunction with trimethoprim (co-trimoxazole). sulphamethoxydiazine [ban] (suifametoxydiazine... 

Sarafem fluoxetine Septra sulfamethoxazole, trimethoprim, co-trimoxazole... 

Before penicillin and the other antibiotics became generally available, the sulfonamides were the mainstay of antibacterial chemotherapy. They maintain a significant role, largely due to the use of a combination of sulfamethoxazole and trimethoprim (co-trimoxazole) for the treatment of bacterial respiratory tract infections and gastrointestinal infections. 

Co-trimoxazole refers to the combination of sulfamethoxazole and trimethoprim, which offers synergistic activity. Co-trimoxazole is associated... 

Co-trimoxazole is a folate antagonist and should be avoided in the first and the third trimesters of pregnancy. In the third trimester there is an increased risk of neonatal haemolysis and methaemoglobinaemia, whereas in the first trimester there is a teratogenic risk caused by the trimethoprim (folate antagonist) component. 

Co-trimoxazole consists of trimethoprim and sulphamethoxazole combined because of their synergistic antimicrobial effects. Trimethoprim is a folate antagonist that poses a teratogenic risk. 

Trimethoprim inhibits bacterial DHF reductase, the human enzyme being significantly less sensitive than the bacterial one (rarely bone marrow depression). A 2,4-diaminopyrimidine, trimethoprim, has bacteriostatic activity against a broad spectrum of pathogens. It is used mostly as a component of co-trimoxazole. 

Co-trimoxazole is a combination of trimethoprim and the sulfonamide sulfamethoxazole. Since THF synthesis is inhibited at two successive steps, the antibacterial effect of co-trimoxazole is better than that of the individual components. Resistant pathogens are infrequent a bactericidal effect may occur. Adverse effects correspond to those of the components. 

Trimethoprim (TMP)-Sulfamethmazole (SMX) [Co-Trimoxazole] (Bactrim, Septra) [Antibiotic/Folate Antagonist] Uses un Rx prophylaxis, otitis media, sinusitis, bronchitis Action SMX T synth of dihydro-folic acid TMP T dihydrofolate reductase to impair protein synth Dose Adul. 1 DS tab PO bid or 5-20 mg/kg/24 h (based on TMP) IV in 3-4 doses P. jiroveci ... 

Intermediate-acting sulfonamides include sulfadiazine and sulfamethoxazole. Sulfamethoxazole is combined with trimethoprim in co-trimoxazole. Sulfadiazine shows good penetration into the cerebrospinal fluid and is effective for cerebral Toxoplasmosis. It has an elimination half-life 10-17 hours which prolonged in renal impairment. 

Trimethoprim is a competitive inhibitor of the enzyme dihydrofolate reductase and can thus prevent the formation of tetrahydrofolate thereby blocking the synthesis of purines. The affinity of trimethoprim for the enzyme in microorganisms is 10,000 times higher than for the human enzyme which explains the selective toxicity. Used alone its main indication is acute uncomplicated urinary tract infections. It is then as effective as co-trimoxazole but has the advantage of fewer adverse reactions. 

Note that in addition to the adverse events due to trimethoprim the combination trimethoprim-sulfamethoxazole may cause all of the untoward reactions associated with sulfonamides. In HIV positive patients the incidence of rashes can increase to 50%. Desensibilisation with increasing doses of co-trimoxazole has been successful. 

Reserve for women unable to tolerate or unlikely to comply with 3-day courses of co-trimoxazole or trimethoprim... 

Antibacterials ciprofloxacin hydrochloride co-trimoxazole (sulfamethoxazole/ trimethoprim) doxycycline hyclate mentronidazole vancomycin hydrochloride... 

Trimethoprim-sulfamethoxazole [co-trimoxazole, TMP-SMZ] (generic, Bactrim, Septra, others)... 

Co-trimoxazole has been suggested to have some antithyroid activity. However, whether this effect is due to trimethoprim alone is still unclear (1142,1143). Co-trimoxazole 27-31 mg/kg bd orally substantially altered serum total T4 and TSH concentrations and neutrophil counts in dogs within as short a time as a few weeks (1144), and 14—16 mg/kg orally every 12 hours for 3 weeks reduced total and free T4 concentrations and increased the TSH concentration, conditions that would be compatible with hypothyroidism (1145). 

Trimethoprim 15 mg/kg/day increased urinary uric acid excretion and reduced the plasma uric acid concentration in five healthy volunteers from 333 gmol/l (5.6 mg/dl) to 226 pmol/l (3.8 mg/dl) (1149). In 90 in-patients with hypouricemia co-trimoxazole was identified as the likely cause in four patients (1150). However, since the study was limited to patients with hypouricemia and since exposure rates for co-trimoxazole were not reported for hypouricemic or non-hypouricemic patients, no conclusions about the incidence and the relevance of trimethoprim-associated hypouricemia can be made. 

The sulfas, including co-trimoxazole (sulfamethoxazole plus trimethoprim, see p. 293), are bacteriostatic. These drugs are active against selected enterobacteria, chlamydia, Pneumocystis, and nocardia. Typical clinical applications are shown in Figure 29.3. In addition, sulfadiazine [sul fa DYE a zeen] in combination with the dihydrofolate reductase inhibitor pyrimethamine [py ri METH a meen] is the only effective form of chemotherapy for toxoplasmosis (p. 353). 

Trimethoprim is most often compounded with the sulfa drug, sulfamethoxazole. The resulting combination, called co-trimoxazole, shows greater antimicrobial activity than equivalent quantities of either drug used alone (Figure 29.6). The combination was selected because of the similarity in the pharmacokinetics of the two drugs. 

Typical therapeutic applications of co-trimoxazole (sulfamethoxazole plus trimethoprim). 

The synergistic antimicrobial activity of co-trimoxazole results from its inhibition of two sequential steps in the synthesis of tetrahydro-folic acid sulfamethoxazole inhibits the incorporation of PABA into folic acid, and trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate (see Figure 29.5). Co-trimoxazole exhibits more potent antimicrobial activity than sulfamethoxazole or trimethoprim alone (seed Figure 29.6). 

Administration and metabolism Trimethoprim is more lipid-soluble than sulfamethoxazole and has a greater volume of distribution. Administration of 1 part of trimethoprim to 5 parts of the sulfa drug produces a ratio of the drugs in the plasma of 20 parts of sulfamethoxazole to 1 part trimethoprim. This ratio is optimal for the antibiotic effect. Co-trimoxazole is generally administered orally. An exception involves intravenous administration to patients with severe pneumonia caused by Pneumocystis carinii. or to patients who cannot take the drug by mouth. 

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