Clinical Chemistry (Antibiotics)

Toxicology: Therapeutic Drugs: ANTIBIOTICS

Presented by:Flores, Lanie Grace P.Gongora, Erica Mae S.

What are antibiotics?

•Antimicrobial agents that kill or inhibit the growth of bacteria

•Produced naturally by a bacterium or fungus

How do antibiotics work?

WIS

•Weakening the bacteria’s cell wall until it bursts

•Interfering with the bacteria’s ability to repair its damaged DNA

•Stopping the bacteria’s ability to make what it needs to grow

AMINOGLYCOSIDES• Group of chemically related antibiotics• Treatment of infections with Gram (–) bacteria that are

resistant to less toxic antibiotics• Act synergistically against certain Gram (+) organisms• Used in treatment of:

– Severe infections of abdomen and UT– Bacteremia– Endocarditis

• Require trough and peak measurements

ROUTES OF ADMINISTRATION

Not well absorbed from the GI tract, it is limited to:– Intravenous (IV)– Intramuscular (IM)

Not used in an outpatient setting

GENTAMICIN

• Most commonly used– Low cost– Reliable activity against Gram (-) aerobes

• Isolated from Micromonospora– Breakthrough in the treatment of bacillary

infections ( Pseudomonas aeruginosa)

TOBRAMYCIN

• Has greater in vitro activity against Pseudomonas aeruginosa

AMIKACIN

• Effective against resistant organisms– Its chemical structure makes it less susceptible to

inactivating enzymes• Preferred agent for serious nosocomial

infections caused by Gram (-) bacilli

KANAMYCIN

• Used to treat serious bacterial infections in many different parts of the body

• Short-term use only• Toxic effects more likely to occur in elderly

patients and newborn infants

STREPTOMYCIN

• The first aminoglycoside– Isolated from Streptomyces griseus

• Used for:– Tuberculosis– Infections caused by certain bacteria

NEOMYCIN

• Had better activity than Streptomycin against aerobic Gram (-) bacilli

• Could not safely be used systemically due to its formidable toxicity

• Isolated from Streptomyces fradiae

TOXIC EFFECTS

• Ototoxic effect – Disrupts inner ear cochlear and vestibular membrane

o Hearing and balance impairmento Irreversible

• Nephrotoxic effect– Increase in serum creatinine and BUN– Impairs the function of the PCT

o Electrolyte imbalanceo Possibly proteinuria

TOXIC EFFECTS

• Neuromuscular blockade– Administration of neuromuscular blocking drugs and

anesthetics– Hypocalcemia– Myasthenia gravis

• Hypersensitivity reactions• Superinfections• CNS effects• GI disturbances

ELIMINATION

• Renal filtration– Patients with compromised renal function,

adjustments must be made based on serum concentration

METHODS

• Chromatography• Immunoassay

VANCOMYCIN

• Glycopeptide antibiotic• Effective against Gram (+) cocci and bacilli• Skipping doses may increase risk of further

infection that is resistant to antibiotics• Used against resistant strains of Streptococcus

and Staphylococcus• Only trough levels are monitored to ensure the

serum drug concentration is within the therapeutic range

ROUTE OF ADMINISTRATION

Because of poor oral absorption, it is administered by:– IV infusion

TOXIC EFFECTS

• “Red-man syndrome”– Erythemic flushing of the extremities

• Ototoxic and Nephrotoxic effects are similar to aminoglycosides

ELIMINATION

• Renal filtration• Excretion

METHODS

• Chromatography• Immunoassay

CHLORAMPHENICOL

• Distributes to all tissues• Concentrates in the CSF• Isolated from Streptomyces venezuelae• 50% protein bound; rapidly absorbed in the GIT• No longer drug of choice due to BM toxicity• Used against:– Gram (+) and Gram (-) cocci and bacilli (including

anaerobes)– Ricketssia, Mycoplasma, Chlamydia, and Chlamydophila spp.

ROUTES OF ADMINISTRATION

• Well absorbed orally• Intravenous (IV)

TOXIC EFFECTS

• Blood dyscrasia• “Gray baby syndrome”– Condition that occurs in newborns (especially

premature babies) who are given the drug chloramphenicol

• Cytoplasmic vacuolation– Erythroid cells– Myeloid cells

ELIMINATION

• 68%-99% – Excreted in the urine

• 8% - 12%– Excreted as free chloramphenicol

• Remainder is excreted as inactive metabolites

REFERENCES:

Bishop, Michael (2010). Clinical Chemistry 6th Edition: Techniques, Principles, Correlations.Rodriguez, M.T. (2014). Clinical Chemistry Review Handbook for Medical Technologists.Tortora et al. (1998). Microbiology: An Introduction 6th Edition.

http://www.aafp.org/afp/1998/1115/p1811.htmlhttp://www.drugs.com/cdi/streptomycin.htmlhttp://campus.usal.es/~galenica/clinpkin/Aminoglycosides.htmhttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a604038.htmlhttps://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/chloramphenicolhttp://www.medicinenet.com/chloramphenicol-oral/article.htm