aminoglycosides Flashcards by Carmina Mislang

Flashcards in aminoglycosides Deck (42):

 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

conc dependent

 Any antibiotic, including penicillins and cephalosporins
• Directly related to time above MIC
• Independent of concentration once the MIC is reached

TIME DEPENDENT

 Structurally related amino sugars attached by glycosidic linkages


aminoglycosides

are aminoglycosides polar or not

polar

RoA of aminoglycosides

 Given intramuscularly or intravenously for systemic effects

Are aminoglycosides absorbed orally?

no

tissue penetration of aminoglycosides (full partial limited)

Limited

 Does it readily cross the blood-brain barrier

no

 Major mode of excretion
•

Glomerular filtration

 Excretion is directly proportional to ---- clearance

creatinine

With normal renal function, elimination half-life is

2-3 h

 Peak serum levels
 Measured at

30-60 minutes after administration

 Trough serum levels
 Measured when

just before the next dose

MoA of AG

 Bactericidal (irreversible) inhibitors of protein synthesis

 Penetration of bacterial cell wall is partly dependent on ___________

O2-dependent active transport

 Transport is enhanced by ________

cell wall synthesis inhibitors

 Bind to _____ AND Interfere with protein synthesis

30S ribosomal unit

ag interfere with protein synthesis by

1. Block formation of initiation complex
2. Cause misreading of the code on the mRNA template
3. Inhibit translocation

MECHANISMS OF RESISTANCE

 Failure to penetrate into the cell
 Plasmid-mediated formation of inactivating enzymes

• Primary mechanism of resistance

Plasmid-mediated formation of inactivating enzymes

•
 Catalyze the acetylation of amine functions
 Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside

Group transferases

transferases produced by enzyme can inactivate

• Amikacin
• Gentamicin
• Tobramycin
• Not streptomycin
• Netilmicin is less susceptible and is active against more strains of organisms

for Serious infections caused by aerobic gram (-) bacteria
• E. coli Enterobacter
• Klebsiella Proteus
• Providencia Pseudomonas
• Serratia

GENTAMICIN, TOBRAMYCIN, and AMIKACIN

 Tuberculosis
 Plague
 Tularemia
 Multi-drug-resistant (MDR) strains of M. tb resistant to streptomycin maybe susceptible to amikacin

STREPTOMYCIN

 Used topically
 Locally
• In the GIT
• Eliminate bacterial flora

NEOMYCIN

 Reserved for serious infections resistant to other aminoglycosides

NETILMICIN

 Aminocylitol related to aminoglycosides
 Back-up drug
 Intramuscular as single dose for gonorrhea

SPECTINOMYCIN

A. OTOTOXICITY
 Auditory or vestibular damage (or both) maybe irreversible or reversible?

IRREVERSIBLE

DRUGS RESPONSIBLE FOR
• Auditory impairment

Amikacin and kanamycin

DRUGS RESPONSIBLE FOR
Vestibular dysfunction

Gentamicin and tobramycin

OTOTOXICITY Risk is proportionate to the
• High if dosage is not modified in renal dysfunction

plasma levels

 Increased with the use of loop diuretics
 Contraindicated in pregnancy

OTOTOXICITY Risk

RESPONSIBLE FOR
• Allergic skin reactions like contact dermatitis

Neomycin

C.
 Rare
 Curare-like block may occur at high doses

NEUROMUSCULAR BLOCKADE

is neuromuscular blockade reversible or irre

reversible

neuromuscular blockade causes

respiratory paralysis

treatment of neuromuscular blockade

Calcium
Neostigmine

treatment of neuromuscular blockade requires

Ventilatory support

nephrotoxicity more common in (2)

 Patients concurrently receiving
• Amphotericin B
• Cephalosporins
• Vancomycin
Elderly

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 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

conc dependent

 Any antibiotic, including penicillins and cephalosporins• Directly related to time above MIC • Independent of concentration once the MIC is reached

TIME DEPENDENT

 Structurally related amino sugars attached by glycosidic linkages

aminoglycosides

are aminoglycosides polar or not

polar

RoA of aminoglycosides

 Given intramuscularly or intravenously for systemic effects

Are aminoglycosides absorbed orally?

no

tissue penetration of aminoglycosides (full partial limited)

Limited

 Does it readily cross the blood-brain barrier

no

 Major mode of excretion •

Glomerular filtration

 Excretion is directly proportional to ---- clearance

creatinine

With normal renal function, elimination half-life is

2-3 h

 Peak serum levels  Measured at

30-60 minutes after administration

 Trough serum levels  Measured when

just before the next dose

MoA of AG

 Bactericidal (irreversible) inhibitors of protein synthesis

 Penetration of bacterial cell wall is partly dependent on ___________

O2-dependent active transport

 Transport is enhanced by ________

cell wall synthesis inhibitors

 Bind to _____ AND Interfere with protein synthesis

30S ribosomal unit

ag interfere with protein synthesis by

1. Block formation of initiation complex 2. Cause misreading of the code on the mRNA template 3. Inhibit translocation

MECHANISMS OF RESISTANCE

 Failure to penetrate into the cell Plasmid-mediated formation of inactivating enzymes

• Primary mechanism of resistance

Plasmid-mediated formation of inactivating enzymes

•  Catalyze the acetylation of amine functions  Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside

Group transferases

transferases produced by enzyme can inactivate

• Amikacin• Gentamicin• Tobramycin • Not streptomycin• Netilmicin is less susceptible and is active against more strains of organisms

for Serious infections caused by aerobic gram (-) bacteria • E. coli Enterobacter• Klebsiella Proteus• Providencia Pseudomonas• Serratia

GENTAMICIN, TOBRAMYCIN, and AMIKACIN

 Tuberculosis Plague Tularemia Multi-drug-resistant (MDR) strains of M. tb resistant to streptomycin maybe susceptible to amikacin

STREPTOMYCIN

 Used topically  Locally• In the GIT• Eliminate bacterial flora

NEOMYCIN

 Reserved for serious infections resistant to other aminoglycosides

NETILMICIN

 Aminocylitol related to aminoglycosides Back-up drug Intramuscular as single dose for gonorrhea

SPECTINOMYCIN

A. OTOTOXICITY Auditory or vestibular damage (or both) maybe irreversible or reversible?

IRREVERSIBLE

DRUGS RESPONSIBLE FOR• Auditory impairment

Amikacin and kanamycin

DRUGS RESPONSIBLE FORVestibular dysfunction

Gentamicin and tobramycin

OTOTOXICITY Risk is proportionate to the • High if dosage is not modified in renal dysfunction

plasma levels

 Increased with the use of loop diuretics Contraindicated in pregnancy

OTOTOXICITY Risk

RESPONSIBLE FOR • Allergic skin reactions like contact dermatitis

Neomycin

C.  Rare Curare-like block may occur at high doses

NEUROMUSCULAR BLOCKADE

is neuromuscular blockade reversible or irre

reversible

neuromuscular blockade causes

respiratory paralysis

treatment of neuromuscular blockade

Calcium Neostigmine

treatment of neuromuscular blockade requires

Ventilatory support

nephrotoxicity more common in (2)

 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

 Any antibiotic, including penicillins and cephalosporins
• Directly related to time above MIC
• Independent of concentration once the MIC is reached

 Structurally related amino sugars attached by glycosidic linkages


 Major mode of excretion
•

 Peak serum levels
 Measured at

 Trough serum levels
 Measured when

1. Block formation of initiation complex
2. Cause misreading of the code on the mRNA template
3. Inhibit translocation

 Failure to penetrate into the cell
 Plasmid-mediated formation of inactivating enzymes

•
 Catalyze the acetylation of amine functions
 Transfer of phosphoryl or adenyl groups to the O2 atoms of hydroxyl groups on the aminoglycoside

• Amikacin
• Gentamicin
• Tobramycin
• Not streptomycin
• Netilmicin is less susceptible and is active against more strains of organisms

for Serious infections caused by aerobic gram (-) bacteria
• E. coli Enterobacter
• Klebsiella Proteus
• Providencia Pseudomonas
• Serratia

 Tuberculosis
 Plague
 Tularemia
 Multi-drug-resistant (MDR) strains of M. tb resistant to streptomycin maybe susceptible to amikacin

 Used topically
 Locally
• In the GIT
• Eliminate bacterial flora

 Aminocylitol related to aminoglycosides
 Back-up drug
 Intramuscular as single dose for gonorrhea

A. OTOTOXICITY
 Auditory or vestibular damage (or both) maybe irreversible or reversible?

DRUGS RESPONSIBLE FOR
• Auditory impairment

DRUGS RESPONSIBLE FOR
Vestibular dysfunction

OTOTOXICITY Risk is proportionate to the
• High if dosage is not modified in renal dysfunction

 Increased with the use of loop diuretics
 Contraindicated in pregnancy

RESPONSIBLE FOR
• Allergic skin reactions like contact dermatitis

C.
 Rare
 Curare-like block may occur at high doses

Calcium
Neostigmine

 Patients concurrently receiving
• Amphotericin B
• Cephalosporins
• Vancomycin
Elderly