Aminoglycosides, oral

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

Patomomycin This oral aminoglycoside was first shown to be effective as a topical treatment for cutaneous leishmaniasis, and later as a parenteral drug against visceral leishmaniasis. Phase III clinical trials were completed in 2005 in India, 15 years after the potential of this component for treating viscer al leishmaniasis was discovered. It is currently not registered for this use. 

Because the oral aminoglycosides are poorly absorbed, they are useful to suppressing gastrointestinal bacteria The oral aminoglycosides kanamycin (Kantrex) and neomycin (Mycifradin) are used preoperatively to reduce the number of bacteria normally present in the intestine (bowel prep). A reduction in intestinal bacteria is thought to lessen the possibility of abdominal infection that may occur after surgery on the bowel. 

Neurotoxicity (damage to the nervous system by a toxic substance) may also be seen with the administration of the aminoglycosides. Signs and symptoms of neurotoxicity include numbness, skin tingling, circum-oral (around the mouth) paresthesia, peripheral paresthesia, tremors, muscle twitching, convulsions, muscle weakness, and neuromuscular blockade (acute muscular paralysis and apnea). 

The oral aminoglycosides may be given without regard to meals. If there is any doubt about administration of... 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

The in vivo protective activity of rifaximin was studied in mice, infected experimentally by intraperitoneal inoculation of S. aureus Colliva and compared to that of rifampicin (a systemic rifamycin) and gentamicin (a poorly absorbed aminoglycoside) [74]. After oral administration, only rifampicin was effective whereas the other two compounds were inactive at doses up to 10 mg/kg. However, when injected subcutaneously, rifaximin displayed a good therapeutic efficacy (table 2). While confirming its antibacterial activity, these results clearly indicate that rifaximin, like gentamycin, is poorly absorbed after oral administration. 

For penicillin-allergic adults, use a fluoroquinolone (ciprofloxacin 0.5-0.75 g orally every 12 hours or 0.4 g IV every 12 hours levofloxacin 0.5-0.75 g orally or IV every 24 hours or moxifloxacin 0.4 g orally or IV every 24 hours). eGentamicin or tobramycin, 2 mg/kg loading dose, then maintenance dose as determined by serum concentrations, fluoroquinolone or aztreonam 1 g IV every 6 hours may be used in place of the aminoglycoside in patients with severe renal dysfunction or other relative contraindications to aminoglycoside use. 

Complicated coli Proteus mirabiiis Klebisella pneumoniae Pseudomonas aeruginosa Enterococcus faecalis 1. Quinolone x 14 days (B, III)0 2. Extended-spectrum penicillin plus aminoglycoside (B, III)0 Severity of illness will determine duration of IV therapy culture results should direct therapy Oral therapy may complete 14 days of therapy... 

Drugs that may affect penicillins include allopurinol, aminoglycosides (parenteral), aspirin, beta blockers, chloramphenicol, erythromycin, ethacrynic acid, furosemide, indomethacin, phenylbutazone, probenecid, sulfonamides, tetracycline, and thiazide diuretics. Drugs that may be affected by penicillins include aminoglycosides (parenteral), anticoagulants, beta blockers, chloramphenicol, cyclosporine, oral contraceptives, erythromycin, heparin, and vecuronium. 

Pharmacokinetics Oral aminoglycosides are poorly absorbed therefore, use only for suppression of Gl bacterial flora. 

Drugs that may affect methotrexate include oral aminoglycosides, charcoal, chloramphenicol, folic acid, NSAIDs, PCNs, probenecid, salicylates, sulfonamides, TCN, trimethoprim. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

WARNING Systemic absorption of oral route may cause neuro/oto/nephrotox may result resp paralysis possible w/ any route of administration Uses Hepatic coma, bowel prq) Action Aminoglycoside, poorly absorbed PO -1- GI bacterial flora Dose Adults. 3-12 g/24- h PO in 3-4 doses Peds. 50-1 (X) mg/kg/24 h PO in 3-4 doses Caution [C, /-] Renal failure, neuromuscular disorders, hearing impair Contra Intestinal obst Disp Tabs, PO soln SE Hearing loss w/ long-term use rash, NA EMS Use neuromuscular blockers w/ caution, reduced dose may be necessary t bleeding risk w/ concurrent anticoagulant use OD May cause neuromuscular block and kidney failure calcium salts can be used to revise neuromuscular block... 

The aminoglycosides are a closely related family of antibiotics produced almost exclusively by members of the genus Streptomyces and Micromonospora (Table 1.19). Most are polycationic compounds, composed of a cyclic amino alcohol to which amino sugars are attached. They all induce their bacteriocidal effect by inhibiting protein synthesis (apparently by binding to the 30 S and, to some extent, the 50 S, ribosomal subunits). Most are orally inactive, generally necessitating their parenteral administration. 

Once again the defence mechanisms that keep foreign chemicals at bay have succeeded. However, this can be turned around and used to therapeutic advantage. For example, if an aminoglycoside antibiotic is very poorly absorbed from the gut, a large proportion of any oral dose will remain there and may be useful for treating gut infections. 

A good example is neomycin, which is one of the least well absorbed of the aminoglycosides and has a place as an oral drug in the management of hepatic failure - probably because it acts locally and reduces the bacterial load of the large bowel. 

The intravenous curve is, by definition, a representation of 100% bioavailability as the drug was put in its entirety into the vein. The oral curve has an area under it approximately 75% the size of the intravenous curve, and this suggests that 25% of the oral dose failed to get into the circulation. The oral bioavailability of the drug is the proportion getting into the vascular compartment, and can be measured if there is an intravenous dose curve available for the same subject at the same dose. In this example, F (the fraction bioavailable) is 0.75. It might be as high as 1.0 (100%) for some steroids, or as low as 0.1 (10%) or even less for poorly absorbed aminoglycosides. 

The very poorly absorbed aminoglycoside, neomycin, may also induce a malabsorption state which can include other drugs such as oral penicillins. 

The pharmacokinetic behavior of the aminoglycosides is characterized by poor oral absorption. 

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