AminoglycosidesAminoglycosides

The Hashemite University

Faculty of Nursing

Pharma Project

AbdulQadir Nashwan RN .

References

Diane S. Aschenbrenner., et al., 2006. Drug Therapy in Nursing. 2nd Ed, Lippincott’s. USA.

Outlines

Introduction

Gentamycin

Amikacin

Kanamycin

Neomycin

Streptomycin

Introduction

The Aminoglycosides have been in use since 1944. They are extremely effective antibiotics for treating

severe infections. Their general use, however, is limited because of the

potential for serious adverse effects, especially ototoxicity and nephrotoxicity.

Aminoglycosides include gentamicin, amikacin, kanamycin, netilmicin, tobramycin, paromomycin and streptomycin.

Introduction

The most frequently used aminoglycosides are gentamycin, tobramycin and amikacin.

Gentamicin is the most widely used, possibly because of its availability as a generic formulation, and its prototype drug for the aminoglycoside family.

Pregnancy Category C inhibits protein synthesis in susceptible strains of gram-

negative bacteria. Gentamicin must be transported across the cell memb.

in order to enter the cell and disrupt protein synthesis. This process requires oxygen; therefore, gentamicin and other aminoglycosides are ineffective against anaerobes.

Gentamicin

Gentamicin

Action Gentamicin, like all antibiotics, has no direct effect on

the cells of the body. It exerts its effect by entering the bacterial cell and

binding to the 30S ribosomal subunit. This event leads to a misreading of the information

used within the cell to form proteins. The cell then produces amino acids that do not link

correctly.

Gentamicin

The result is a change in metabolic function that in turn prevents bacterial reproduction and weakens the cell wall, leading to cell wall rupture and death.

Many strains of bacteria are resistant to the aminoglycosides and do not allow them to enter the cell.

Because of this, aminoglycosides are often given with synergistic antibiotics to increase their effectiveness or to alter the cell wall so that the aminoglycoside can enter.

Indications Gentamicin is effective in managing infections caused

by gram-negative bacilli. Susceptible organisms include: Pseudomonas

aeruginosa, Proteus mirabilis, Escherichia coli, Klebsiella, Enterobacter, Serratia, and Citrobacter species; and staphylococci (gram+).

Gentamicin

Gentamicin is NOT considered useful in treating meningitis unless it is administered intrathecally.

Gentamicin is also indicated for topical treatment of eye or skin infections caused by susceptible organisms.

Gentamicin

Clinically, gentamicin is useful for urinary tracts infections (UTIs), such as pyelonephritis, gynecological infections, peritonitis, endocarditis, pneumonia, bacteremia and sepsis, respiratory infections, including those associated with cystic fibrosis, osteomyelitis, and foot and other soft tissue infections associated with diabetes.

Gentamicin

Pharmakinetics: Parenteral genta is widely distributed through the body

in ECF; however, it does NOT penetrate appreciably into the CNS.

It crosses the placenta and is secreted in breast milk. Genta concentrates in the kidney, reaching levels 50

times higher than those in serum.

Gentamicin

It is also concentrates in the endolymph and perilymph of the inner ear.

High concentration of genta in these fluids are associated with its major adverse effects “ nephrotoxicity and ototoxicity.

Parenteral genta is excreted unchanged in urine, whereas oral genta is excreted unchanged in feces.

Gentamicin

Because it is poorly absorbed when taken orally, genta is usually reserved for parenteral or topical use.

It may, however, be given orally to exert a local decrease in GIT bacteria before surgical or other invasive procedures.

Gentamicin

o Most Common Adverse Effects:o Nephrotoxicity occurs most frequently in infants or

elderly patients, or with prolonged or high-dose therapy.

o Ototoxicity occurs most frequently when serum trough levels are elevated, in infants or elderly patients, or with prolonged or high-dose therapy.

o Neuromuscular blockade may result in profound respiratory depression. It occurs most frequently in patients with myasthenia gravis and in patients receiving general anesthetics or nondepolarizing skeletal muscle relaxants.

Gentamicin

CNS: confusion, depression, disorientation, numbness, tingling and weakness.

Hemato: leukemoid rxns and depressed bone marrow function.

GI: nausea, vomiting, diarrhea, w.t loss, stomatitis, and hepatic toxicity.

CV: palpitations, hypotension, hypertension.Hypersensitivity rxns.Other: superinfections, fever, apnea, and joint pain may

also occur.

Gentamicin

Contraindications: Pregnancy and lactation Known allergy to any aminoglycoside

Cautions: Renal and Hepatic disease Dehydration Pre-existing hearing loss Myasthenia gravis Parkinsonism Infant botulism

Gentamicin

Maximizing Therapeutic Effects Make sure that patients receive the full course as

prescribed. Coordinate the administration of drugs to decrease

potential drug interactions. Evaluate C/S reports to make sure that genta is the

appropriate drug. Administer extended penicillins, such as carbenicillin

or ticarcillin at least 2 hrs apart to ensure the efficacy of genta.

Gentamicin

Minimizing Adverse Effects:To reduce the occurrence of adverse effects, it is

imperative to maintain blood levels of genta within a therapeutic margin that is very narrow.

To do this, Peak and Trough drug levels are monitored throughout therapy.

Blood for Peak levels is drawn 30 minutes after the completion of IV administration and 1 hr after IM administration.

Bloods for Trough levels is drawn just before the next dose.

Gentamicin

Monitor for signs of ototoxicity. Before administering each dose, assess the patient’s balance and gross hearing.

Monitor for signs of nephrotoxicity. Assess the hydration status of the patient and be alert for dilute urine or proteinuria.

Monitor the patient for gentamicin-induced diarrhea because diarrhea may also cause dehydration.

Gentamicin

If CNS effects occur, safety measures should be instituted to protect the patient.

Small, frequent meals can be arranged for patient with GI effects, and frequent mouth care and ice chips can be offered to relieve stomatitis and sore mouth.

If a patient receiving genta requires surgery, the chart should indicate prominently that genta has been given.

Remember that genta may interact with neuromuscular blocking agents commonly used during surgery.

Gentamicin

Monitor lab. Tests such as renal and hepatic functions ( KFT & LFT ), Peak and Trough levels of genta, and the fluid intake and output status of the patient.

Gentamicin

Memory Chip “ GentamicinGentamicin ”

Used for serious gram-negative infections. Major contraindications: hypersensitivity, pregnancy,

and breast-feeding. Most common adverse effects: nausea, vomiting,

diarrhea, and w.t loss. Most serious adverse effects: nephrotoxicity,

ototoxicity, neuromuscular blockade.

Maximizing therapeutic effects: administer al least 2 hrs before or after extended infusions of penicillins.

Minimizing adverse effects: monitor Peak and Trough levels throughout therapy.

Most important patient education: teach the patient the S&S of both nephrotoxicity and ototoxicity and also the importance of contacting the health care provider immediately if any symptoms should occur.

Memory Chip “ GentamicinGentamicin ”

AmikacinAmikacin

Amikin ® Is a parenteral aminoglycoside with a broader spectrum of

activity than gentamicin for gram-negative bacilli. Amikacin Amikacin is also less likely to induce bacterial resistance. Although some hospitals use AmikacinAmikacin as first-line

treatment of systemic infection because of an increased resistance to gentamicin, may others reserve its use for infections that do not respond to other aminoglycoside antibiotics.

Its contraindications, adverse effects, drug interactions, and patient management are similar to those of gentamicin.

KanamycinKanamycin

Kantrex ®Is used orally to reduce ammonia-forming bacteria in

hepatic coma and as an adjunctive therapy to decrease GI flora.

It use for systemic infections is limited by the number of bacteria that are resistant to it and the availability of genta in its less expensive generic formulation.

Its contraindications, adverse effects, drug interactions, and patient management are similar to those of gentamicin.

NeomycinNeomycin Mycifradin ® Has the highest risk for toxicity of all of the aminoglycosides. Because it is so toxic, it is not administered parenterally. It is available orally to decrease GI flora as a preparation for

bowel surgery and to treat hepatic encephalopathy. Because it is not absorbed from the GI tract, it frequently

causes superinfection within the bowel. Neomycin is also available in OTC drugs as a topical

antibiotic. Its contraindications, adverse effects, drug interactions, and

patient management are similar to those of gentamicin.

StreptomycinStreptomycin

Is a parenteral aminoglycoside. It is used as part of combination therapy for both active

TB and for treating streptococcal or enterococcal endocarditis.

As a single agent, it is used for mycobacterial infections, plague, tularemia, and brucellosis.

In addition to ototoxicity and nephrotoxicity, streptomycin may include neurotoxicity.

The End