[3S] Aminoglycosides & Spectinomycin PPT Flashcards
MODES OF ANTIBACTERIAL ACTION
Treatment of microbial infection with antibiotics
▪Multiple daily dosing
▪Maintain serum concentration level
above the minimum inhibitory concentration (MIC)
Aminoglycosides
MODES OF ANTIBACTERIAL ACTION
Some drugs and aminoglycosides
▪As the plasma level is increased above
the MIC, the drug kills an increasing
proportion of bacteria at a more rapid
rate
Concentration Dependent
MODES OF ANTIBACTERIAL ACTION
Any antibiotics, including Penicillin and
Cephalosporins
▪Directly related to time above MIC
▪Independent of concentration once the MIC is reached
Time Dependent
MODES OF ANTIBACTERIAL ACTION
Aminoglycosides’ killing action continues when the plasma levels have declined below measurable levels
Postantibiotic Effect
MODES OF ANTIBACTERIAL ACTION
Greater efficacy when administered as a SINGLE LARGE DOSE than when given as multiple smaller doses
Postantibiotic Effect
MODES OF ANTIBACTERIAL ACTION
T/F: Toxicity (in contrast to antibacterial activity)
depends on a critical plasma concentration and
on that time such a level is exceeded
T
MODES OF ANTIBACTERIAL ACTION AMINOGLYCOSIDES
T/F: Time above such threshold is longer with
single large dose
F; shorter
MODES OF ANTIBACTERIAL ACTION AMINOGLYCOSIDES
T/F: Basis for once-daily dosing protocols
T
PKINETICS
- Structurally related amino sugars attached by glycosidic linkages
- Polar compounds
Aminoglycosides
T/F: Aminoglycosides are absorbed orally
F; not absorbed
AMINOGLYCOSIDES PKINETICS
T/F:
- Limited tissue penetration
- Do not readily cross the blood-brain barrier
T
PKINETICS
Aminoglycosides:
- Major mode of excretion
- Plasma levels are affected by changes in
Glomerular filtration
Renal function
AMINOGLYCOSIDES PKINETICS
T/F: Excretion is directly proportional to creatinine clearance
T
AMINOGLYCOSIDES PKINETICS
T/F: Dosage adjustment must be made in renal insufficiency to avoid toxic accumulation
T
AMINOGLYCOSIDES PKINETICS
________________ is needed for safe and effective dosage selection and adjustment
Monitoring plasma levels
MECHANISM OF ACTION
- Bactericidal (irreversible) inhibitors of protein synthesis
- Penetration of bacterial cell wall is partly dependent on O2-dependent active transport
Aminoglycosides
MECHANISM OF ACTION
- Bind to 30S ribosomal unit
- Interfere with protein synthesis
1. Block formation of initiation complex
2. Cause misreading of the code on the mRNA template
3. Inhibit translocation
AMINOGLYCOSIDES
MECHANISMS OF RESISTANCE
- Resistant due to failure to penetrate into the cell
▪Streptococci, including S. pneumoniae
▪Enterococci
AMINOGLYCOSIDES
MECHANISMS OF RESISTANCE
- Plasmid-mediated formation of inactivating
enzymes
▪Primary mechanism of resistance
▪Varying susceptibility to the enzyme
AMINOGLYCOSIDES
MECHANISMS OF RESISTANCE
▪Catalyze the acetylation of amine functions
▪Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside
Group transferases
MECHANISMS OF RESISTANCE
Transferases produced by enterococci can inactivate
▪Amikacin
▪Gentamicin
▪Tobramycin
MECHANISMS OF RESISTANCE
Receptor protein on the 30S ribosomal subunit
may be deleted or altered as a result of a mutation
AMINOGLYCOSIDES
CLINICAL USES
Used for the following but is not the drug of choice
▪H. influenzae
▪M. catarrhalis
▪Shigella species
GENTAMICIN, TOBRAMYCIN, AMIKACIN
CLINICAL USES
- Not effective for gram (+) cocci when used alone
- Combination of aminoglycoside and cell wall synthesis inhibitors
Antibacterial Synergy
CLINICAL USES
Combined with penicillin in the treatment
▪Pseudomonal
▪Listerial
▪Enterococcal infections
ANTIBACTERIAL SYNERGY
CLINICAL USES
- Tuberculosis
- Plague
- Tularemia
- Multi-drug-resistant (MDR) strains of M. tb resistant to streptomycin maybe susceptible to amikacin
Streptomycin
Neomycin ROA
Topical
Kanamycin and paromomycin ROA
IM/IV/PO
CLINICAL USES
• Active against: Gram-positive bacteria, Gram-negative bacteria, some mycobacteria
• Resistant: P aeruginosa, Streptococci
NEOMYCIN, KANAMYCIN, PAROMOMYCIN
Netilmicin ROA
IM/IV/Topical/Ocular/Intrathecal
CLINICAL USES
Reserved for serious infections resistant to other aminoglycosides
Netilmicin
CLINICAL USES
- Aminocylitol related to aminoglycosides
- Back-up drug
Spectinomycin
CLINICAL USES
Intramuscular as single dose for gonorrhea
- NOT recommended for treatment of pharyngeal gonococcal infections
Spectinomycin
OTOTOXICITY
Auditory impairment
Amikacin, neomycin and kanamycin
OTOTOXICITY
Vestibular dysfunction
Gentamicin and tobramycin
Book: Streptomycin & Gentamicin
TOXICITY
- Risk is proportionate to the plasma levels
▪ High if dosage is not modified in renal dysfunction - Increased with the use of loop diuretics
- Contraindicated in pregnancy
Ototoxicity
TOXICITY
Acute tubular necrosis
Reversible
Nephrotoxicity
Most nephrotoxic
Gentamicin, Tobramycin & Neomycin
NEPHROTOXICITY
Patients concurrently receiving
▪ Amphotericin B
▪ Cephalosporins
▪ Vancomycin
Neuromuscular Blockade treatment
▪ Calcium
▪ Neostigmine
▪ Ventilatory support
TOXICITY
Allergic skin reactions like contact dermatitis
Neomycin
