Liver penicillin effects

Mechanism of Action A penicillin that acts as a bactericidal in susceptible microorganisms. Therapeutic Effect Inhibits bacterial cell wall synthesis. Bactericidal. Pharmacokinetics Poorly absorbed from gastrointestinal (GI) tract. Protein binding 87%-90%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life 10.5-1 hr (half-life increased with imparted renal function). 

It has an isoxzalyl side chain and has weaker antibacterial activity than benzyl penicillin. It is absorbed after oral administration partially and elimination occurs mainly by kidney and partly by liver. It is devoid of any serious side effect but can cause hypersensitivity reaction in some patients. 

In contrast to local irritants and corrosive acids and alkalis, other chemicals, such as the drug paracetamol (see chap. 7), cause systemic toxicity, damaging the liver, possibly irreversibly and with some delay after an oral overdose. Penicillin can also cause systemic toxicity as a result of an immune reaction, which may be immediate and serious, if it is anaphylaxis (see chap. 7). However, this effect, if not fatal, is reversible. 

Adverse effects Aztreonam is relatively nontoxic, but it may cause phlebitis, skin rash, and occasionally, abnormal liver function tests. Aztreonam has a low immunogenic potential and shows little cross-reactivity with antibodies induced by other p-lac-tams. Thus aztreonam may offer a safe alternative for treating patients allergic to penicillins and/or cephalosporins. 

METHOTREXATE PENICILLINS t plasma concentrations of methotrexate and risk of toxic effects of methotrexate, e.g. myelosuppression, liver cirrhosis, pulmonary toxicity Penicillins 1 renal elimination of methotrexate by renal tubular secretion, which is the main route of elimination of methotrexate. Penicillins compete with methotrexate for renal elimination. Displacement from proteinbinding sites may occur and is only a minor contribution to the interaction Avoid concurrent use. If concurrent use is necessary, monitor clinically and biochemically for blood dyscrasia, liver toxicity and pulmonary toxicity. Do FBCs and LFTs prior to concurrent treatment... 

Adverse effects of the penicillins on the central nervous system include headache, dizziness, somnolence, confusion, tremor, and seizures. The penicillins can also adversely affect the liver, as evidenced by elevated liver enzymes and bilirubin, and the kidney, as evidenced by elevated blood urea nitrogen and creatinine. 

As shown in Table 1, satisfactory recoveries (over 71%) and corresponding coefficients of variation (C.V., less than 8.7%) were obtained for these low concentrations of the penicillins. The detection limit was 0.02 mg/kg for each penicillin in the meat, and those were 0.02 mg/kg for MPIPC, MClPC, and NFPC, 0.03 mg/kg for PCV, 0.04 mg/kg for PCG, and 0.05 mg/kg for MDIPC in the bovine kidney and liver (S/N ratio=3). Fig. 1 shows typical chromatograms of standard solution (a), fortified bovine muscle and liver samples (b and d), their corresponding controls (c and e), and bovine kidney sample (f), respectively. As shown by these chromatograms, satisfactory separation of PCs and cleanup effects were achieved... 

D-Penicillamine (D-/6,/l-dimethylglycine), a metabolite of penicillin, was first isolated in the urine specimens from patients treated with penicillin with liver disease. It is an effective chelator of metals such as copper, zinc, and lead. It is used in the chelation therapy of Wilson s disease, which is characterized by excess copper accumulation leading to hepatolenticular degeneration (Chapter 37). 

Probenecid reduces the hepatic clearance of BSP (B23, B25) as well as inhibiting the renal clearance of penicillin, phenol red, and PAH (M5). Probenecid is also a choleretic (G7) the concentration of both BSP and bilirubin in bile are reduced, but the excretion rate of BSP only is affected (S39). There is an increased reflux of dye from the liver to plasma (G7, S39). The effect of the drug as a choleretic and as an inhibitor of BSP... 

Penetrate cell membranes poorly or not at all limited or no significant absorption from GIT except for acid-stable aminopeni-cillins, which have moderate but species-variable absorption distribution limited mainly to extracellular fluids concentrations in intracellular fluid, CSF, miUc, and ocular fluids low, but effective concentrations may be reached in synovial, peritoneal, and pleural fluids some penicillins actively transported out of CSF into plasma generally excreted, usually in urine, in high concentrations as the parent molecule some drugs actively secreted into urine and/or bUe biotransformation (e.g., in the liver) usually slight or absent... 

Not understood. The interaction between nafcillin and warfarin is possibly due to increases in the metabolism of warfarin by the liver. Dicloxacillin also possibly reduces serum warfarin levels. Other penicillins (ampicillin, benzylpenicillin, carbenicillin, methicillin, ticarcillin ) have caused increased bleeding times when given alone, principally due to platelet inhibition, which might be additive with the effects of oral anticoagulants. Broad-spectrum antibacterials may decrease the gut flora and thereby possibly decrease production of vitamin K. Other factors relating to the disease may be important, see Coumarins -i- Antibacterials p.365. 

The interaction between metronidazole and combined oral contraceptives is not established, and the whole issue of any interaction with broad-spectrum antibacterials remains very controversial. Bearing in mind the extremely wide use of both metronidazole and combined oral contraceptives, any increased incidence of contraceptive failure above that seen in general usage is clearly very low indeed. The Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit has issued guidance on the use of antibacterials with combined hormonal contraceptives. Although they recognise that there is poor evidence for contraceptive failure, they recommend that additional form of contraception, such as condoms, should be used for short courses of antibacterials, see Hormonal contraceptives + Antibacterials Penicillins , p.981, for more detailed information. This applies to both the oral and the patch form of the combined contraceptive. This advice has usually been applied to only broad-spectrum antibacterials that do not induce liver enzymes but the FFPRHC notes that some confusion has occurred over which antibacterials are considered to be broad-spectrum , and thus they recommend that this advice is applied to all antibacterials that do not induce liver enzymes, which would include metronidazole. ... 

Although this advice has previously only been applied to broad-spectrum antibacterials that do not induce liver enzymes the FFPRHC notes that some confusion has occurred over which antibacterials are considered to be broad-spectrum , and thus they recommend that this advice is applied to all antibacterials that do not induce liver enzymes, which would include penicillins. However, others contend that these instructions may confuse patients, and complicate pill taking, and could have the opposite effect of increasing the failure rate of oral contraceptives. ... 

---