McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

Therapeutic actions and indications The lincosamides react at almost the same site in bacte- rial protein synthesis and are effective against the same strains of bacteria (Figure 9.2). These drugs are used in the treatment of severe infections when a less toxic anti- biotic cannot be used. Pharmacokinetics The lincosamides are rapidly absorbed from the GI tract or from IM injections and are metabolised in the liver and excreted in the urine and faeces. These drugs cross the placenta and enter breast milk (see contraindications and cautions). Clindamycin has a half-life of 2 to 3 hours. It is avail- able in parenteral and oral forms, as well as in topical and vaginal forms for the treatment of local infections. Lincomycin has a half-life of 5 hours. It can be given orally, IM or IV. Contraindications and cautions Use lincosamides with caution in people with hepatic or renal impairment, which could interfere with the metab- olism and excretion of the drug. Use during pregnancy and breastfeeding only if the benefit clearly outweighs the risk to the fetus or neonate. Adverse effects Severe GI reactions, including fatal pseudomembranous colitis, have occurred, limiting the usefulness of lincos­ amides. However, for a serious infection caused by a susceptible bacterium, a lincosamide may be the drug of choice. Some other toxic effects that limit usefulness are pain, skin infections and bone marrow depression. The only monobactam antibiotic currently available for use is aztreonam ( Azactam ) (Table 9.9). Therapeutic actions and indications Among the antibiotics, aztreonam’s structure is unique, and little cross-resistance occurs. It is effective against gram-negative enterobacteria and has no effect on gram-positive or anaerobic bacteria. Aztreonam disrupts bacterial cell wall synthesis, which promotes leakage of cellular contents and cell death in susceptible bacteria (see Figure 9.2). The drug is indicated for the treatment of urinary tract, skin, intra-abdominal and gynaecological infections, as well as septicaemia caused by suscepti- ble bacteria, including E. coli , Enterobacter , Serratia , Proteus , Salmonella , Providencia , Pseudomonas , Citro- bacter , Haemophilus , Neisseria and Klebsiella. MONOBACTAM ANTIBIOTIC

occurs. Ocular preparations are contraindicated for viral, fungal or mycobacterial infections of the eye, which could be exacerbated by loss of bacteria of the normal flora. Use with caution in people with hepatic dysfunction, which could alter the metabolism of the drug , and in those with renal disease, which could inter- fere with the excretion of some of the drug. Also use with caution in breastfeeding women because macro­ lides secreted in breast milk can cause diarrhoea and superinfections in the infant and in pregnant women because of potential adverse effects on the developing fetus ; use only if the benefit clearly outweighs the risk to the fetus or the infant. Adverse effects Relatively few adverse effects are associated with the macrolides. The most frequent ones, which involve the direct effects of the drug on the GI tract, are often uncomfortable enough to limit the use of the drug. These include abdominal cramping, anorexia, diar- rhoea, vomiting and pseudomembranous colitis. Other effects include neurological symptoms such as confu- sion, abnormal thinking and uncontrollable emotions, which could be related to drug effects on the CNS mem- branes; hypersensitivity reactions ranging from rash to anaphylaxis; and superinfections related to the loss of normal flora. Clinically important drug–drug interactions Increased serum levels of digoxin occur when digoxin is taken concurrently with macrolides. People who receive both drugs should have their digoxin levels monitored and dose adjusted during and after treatment with the macrolide. In addition, when oral anticoagulants, theophyl- lines, carbamazepine or corticosteroids are administered concurrently with macrolides, the effects of these drugs reportedly increase as a result of metabolic changes in the liver. People who take any of these combinations may require reduced dose of the particular drug and careful monitoring. Clinically important drug–food interactions Food in the stomach decreases absorption of oral macro­ lides. Therefore, the antibiotic should be taken on an empty stomach with a full, 150 mL glass of water 1 hour before or at least 2 to 3 hours after meals. LINCOSAMIDES The lincosamides (Table 9.9) are similar to the mac- rolides but are more toxic. These drugs include clindamycin ( Cleocin ) and lincomycin ( Lincocin ).