Toxicity penicillin causing

Hypersensitivity reactions to antimicrobial drugs or their metabolic products frequently occur. For example, the penicillins, despite their almost absolute selective microbial toxicity, can cause serious hypersensitivity problems, ranging from urticaria (hives) to anaphylactic shock. 

Cation toxicity Penicillins are generally administered as the sodium or potassium salt. Toxicities may be caused by the large quantities of sodium or potassium that accompany the penicillin. Sodium excess may result in hypokalemia. This can be avoided by using the most potent antibiotic, which permits lower doses of drug and accompanying cations. 

Hoigne R, Krebs A. Kombinierte anaphylaktische und embolisch-toxische Reaktion durch akzidentelle intravas-kulare Injektion von Procain-Penicillin. [Combined anaphylactic and embolic-toxic reaction caused by the accidental intravascular injection of procaine penicillin.] Schweiz Med Wochenschr 1964 94 610-14. 

Penicillins (oral) Group toxicity may cause bleeding abnormalities, hvpersensitivitv, seizures ... 

Toxicity. Penicillin is relatively nontoxic to mice, the LDso being greater than 600 mg. per kg. On the contrary, penicillin is quite toxic to guinea pigs, 4 mg. per day for four days being enough to cause death within six days (138a). 

Tetracyclines are used as alternative dnigs in a variety of circumstances when the patient is unable to take the dnig of choice, eg, in patients allergic to penicillin (88,89). Tetracyclines are widely known to cause staining of teeth (and are therefore contra-indicated in children developing permanent teeth), photosensitivity, and, in the case of minocycline, vestibular toxicity. Details of these adverse effects and others associated with administration of tetracyclines have been comprehensively reviewed (96—101). 

Penicillin-allergic patients tolerate aztreonam without reaction. Occasional skin rashes and elevations of serum aminotransferases occur during administration of aztreonam, but major toxicity has not yet been reported. In patients with a history of penicillin anaphylaxis, aztreonam may be used to treat serious infections such as pneumonia, meningitis, and sepsis caused by susceptible gram-negative pathogens. 

Aztreonam Prevents bacterial cell wall synthesis by binding to and inhibiting cell wall transpeptidases Rapid bactericidal activity against susceptible bacteria Infections caused by aerobic, gram-negative bacteria in patients with immediate hypersensitivity to penicillins IV administration renal clearance half-life 1.5 h dosed every 8 h Toxicity No cross-allergenicity with penicillins... 

Because of potential toxicity, bacterial resistance, and the availability of many other effective alternatives, chloramphenicol is rarely used. It may be considered for treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever. It is an alternative to a B-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

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. 

Penicillin and its derivatives are very widely used antibiotics, which are well tolerated and have a low acute toxicity. Doses as high as 1 g kg-1 day-1 can be given by intravenous injection. However, penicillin and related derivative drugs cause more allergic reactions than any other class of drug. The incidence of allergic reactions to such drugs occurs in at least 1% of recipients. 

Hypersensitivity reactions are major problems with penicillins. Frequent manifestations are skin rashes, itching, and urticaria, which may lead to anaphylaxis and eventual death. Parenteral administration causes severe pain. Toxicity to the brain may be manifested as confusion, muscular twitching, convulsions, and coma. Superinfection is rare with penicillin. 

Although cephalosporins are more toxic than penicillin, they are well tolerated. Parenteral injection may cause pain when given intramuscularly and may cause thrombophlebitis when given intravenously. The oral cephalosporin administration causes diarrhea by altering the gut ecology. Hypersensitivity reactions are caused and are similar to those of penicillins. Cephaloridine causes nephrotoxicity, but presently available cephalosporins have less renal toxicity. 

Antistaphylococcal penicillins Methicillin [meth i SILL in], naf-cillin [naf SILL in], oxacillin [ox a SILL in], cloxacillin [klox a SILL in], and dicloxacillin [dye klox a SILL in] are penicillinase-resistant penicillins. Their use is restricted to the treatment of infections caused by penicillinase-producing staphylococci. Because of its toxicity, methicillin is rarely used. Methicillin-resistarft strains of Staphylococcus aureus (MRSA), currently a serious source of nosocomial (hospital-acquired) infections, are usually susceptible to vancomycin, and rarely to ciprofloxacin or rifampin. 

Second, certain nucleotide phosphonates (e.g., adefovir and cidofovir) are effective antivirals, but their use in the clinic is limited by renal toxicity. This is believed to be caused by avid uptake at the basolateral membrane of renal proximal tubule cells followed by slow transport into the urine at the apical membrane, a sequence of events that results in intracellular drug accumulation and thus toxicity. As with penicillin, the OAT family of transporters has been implicated in cidofovir uptake. Co-administration of probenecid with cidofovir has been shown to decrease renal clearance of the antiviral and reduce its nephrotoxicity, presumably through com-... 

Because of its potential toxicity, vancomycin is reserved for serious infections in which less toxic antibiotics are ineffective or not tolerated. Generally, vancomycin is administered intravenously because of poor intestinal absorption. It is the drug of choice for treating infections caused by methicillin-resistant staphylococci and penicillin-resistant Streptococcus pneumoniae. Vancomycin has been used to treat enterococcal infections because of their resistance to the P-lactam antibiotics, but most enterococci are now also resistant to vancomycin. Oral administration of rancomycin is important for treatment of some gastrointestinal infections such as pseudomembranous colitis caused by C. difficile. 

Clinical experience with penicillins, especially penicillin G and the aminopenicillins, is extensive. These substances are rarely toxic, even when they are given in an extended range of dosages, making them invaluable for use in pregnant women and children. Their major limitation is their propensity to cause allergic reactions. 

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