- -bind PBPs to inhibit cell wall synthesis of peptidoglycan layer - -beta-lactam ring is antibacterial - -side chains dictate spectrum

Antibacterials Flashcards by Tyler Melancon

bacteriostatic

inhibits bacterial growth without causing death. MIC= minimum inhibitory concentration.

How well did you know this?

Not at all

Perfectly

bactericidal

rapidly kills bacteria by disrupting synthesis or integrity of the cell wall. MBC for 99.9% death

How well did you know this?

Not at all

Perfectly

5 bactericidal mechanisms of action

-cell wall synthesis
-protein synthesis
-nucleic acid synthesis
-antimetabolites
-bacterial membrane disruption

How well did you know this?

Not at all

Perfectly

2 classes of antibiotics that inhibit cell wall synthesis

beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) and glycopeptides

How well did you know this?

Not at all

Perfectly

Penicillin mechanism

-bind PBPs to inhibit cell wall synthesis of peptidoglycan layer
-beta-lactam ring is antibacterial
-side chains dictate spectrum

How well did you know this?

Not at all

Perfectly

Penicillin side effects

Results from hypersensitivity

-Morbilliform rash (most common) due to IgM response
-Anaphylaxis (rare) IgE mediated leads to angioedema, bronchospasm, hypotension

How well did you know this?

Not at all

Perfectly

Cephalosporin mechanism

-inhibit peptidoglycan synthesis by binding PBPs

- -compared to penicillin: wider spectrum, can kill many beta-lactamase bacteria, improved pharmacokinetics

How well did you know this?

Not at all

Perfectly

Cephalosporin coverage and side effects

-better coverage of Gram (-) with later generations

- -can be useful for penicillin hypersensitivity unless they have a history of anaphylaxis runs

How well did you know this?

Not at all

Perfectly

Carbapenem mechanism

-inhibit peptidoglycan synthesis by binding PBPs

- -compared to penicillin: wider spectrum, can kill many beta-lactamase bacteria, improved pharmacokinetics

How well did you know this?

Not at all

Perfectly

Carbapenem coverage and side effects

-very wide coverage, antipseudomonal
-seizures is main side effect
-avoid giving to CNS compromised pts.

How well did you know this?

Not at all

Perfectly

Monobactams (aztreonam) mechanism and side effects

-reserved for penicillin allergic patients
-ONLY active against Gram (-) aerobic bacteria
-no major side effects

How well did you know this?

Not at all

Perfectly

Beta-lactam resistance mechanisms

(1) beta-lactamases (degradative enzymes)
(2) PBPs (cell wall resistant transpeptidases)
(3) efflux pumps

How well did you know this?

Not at all

Perfectly

Beta-lactamase inhibitor mechanisms

-weak antibactericidal, must combine with penicillins

- -irreversibly bind/inactivate beta-lactamses of bacteria

How well did you know this?

Not at all

Perfectly

Glycopeptide mechanism

(Vancomycin)

-inhibits cell wall formation by interacting with D-alanine-D-alanine termini of pentapeptide side chains in the cell wall
-no beta-lactam cross resistance
-ONLY active against Gram (+) organisms

How well did you know this?

Not at all

Perfectly

Vancomycin side effects

-**Red Man’s: histamine release from rapid AB infusion –> anaphylaxis
-administer more slowly
-neutropenia & nephrotoxicity

How well did you know this?

Not at all

Perfectly

Vancomycin resistance

-molecule is too large to penetrate outer membrane of Gram (-) bacteria
-also unable to bind to bacteria from changes in pentapeptide side chain terminus

How well did you know this?

Not at all

Perfectly

Protein synthesis inhibitors (30S ribosome)

-aminoglycosides (streptomycin)

- -tetracyclines

How well did you know this?

Not at all

Perfectly

Protein synthesis inhibitors (50S ribosome)

-clindamycin
-macrolides (erythromycin)
-chloramphenicol
-linezolid
-streptogramins (quinupristin/dalfopristin)

How well did you know this?

Not at all

Perfectly

Aminoglycoside mechanism

-Gram (-) rods
-irreveribly bind to 30S ribosomes
-commonly used in syngery with beta-lactam or vancomycin for Gram(+) treatment

How well did you know this?

Not at all

Perfectly

Aminoglycoside side effects

-nephrotoxicity (dose > 1/day or treatment > 3 days)

- -ototoxicity (often irreversible)

How well did you know this?

Not at all

Perfectly

Aminoglycoside resistance

-*mutation of 30S ribosome binding site
-decreased AB uptake
-enzymatic modification of AB
-efflux pump

Tetracyclines mechanism

-**bacteriostatic binding to 30S ribosome

- -effective against variety of typical and atypical organisms

Tetracycline side effects

-teeth discoloration given to children
-brown skin discoloration
-dark melanin deposits on skin

Tetracyclne resistance

-decreased penetration into bacteria
-efflux pump
-*30S ribosome allows binding but protein synthesis continues

Macrolide mechanism

--**bacteropstatic against atypicals, gram (+), and some mycobacteria

Macrolide side effects

- -(enteric like) abdominal cramps, nausea, vomitting, diarrhea - - V tach with QT prolongation

Macrolide resistance

- -*methylation of 50S ribosome binding site - -efflux pump - -enzyme modification of AB - -decreased permeability of outer envelope

Lincosamide mechanism

(Clindamycin) - -**bacteriostatic against Gram (+) AND anaerobes 50S ribosome - -used to prevent toxin formation (TSS)

Lincosamide side effects

(Clindamycin) - -20% diarrhea - -rare C. difficile colitis

Clindamycin resistance

- -alteration of 50S protein receptor - -methylation of 50S subunit binding site (**cross-resistance with macrolides) - -decreased penetration

Oxazolidinones (Linezolid)

--**Bacteriostatic against resistant Gram (+) 50S

Oxazolidinones (Linezolid) side effects

- -lactic acidososis - -neuropathy - -cytopenias

Chloramphenicol mechanism

- -*static or cidal depending on bacteria - -Salmonella - -50S ribosome target

Chloramphenicol side effects

--Disrupts protein synthesis in bone marrow cells

Chloramphenicol resistance

- -*production of chloramphenicol acetytransferase, catalyzes AB - -decreased permeability

Nucleid acid synthesis antibiotics

- -DNA replication: quinolones & metronidazole | - -RNA replication: rifamycins

Quinolone mechanism

- -inhibit DNA gyrases -> breaks in DNA | - -active against Gram (+) and (-)

Quinolone side effects

- -tendonitis with rupture - -headache dizzine, insomnia - -QT prolongation

Metronidazole mechanism

- -bacteria reduce AB nitro groups resulting in toxic compounds that disrupt DNA - -activae against anaerobic bacteria and some parasites

Metronidazole side effects

- -neuropathy | - -ataxia, dysarthria, cerebellar dentae lesions

Metronidazole resistance

- -reduced AB activation | - -elimination of compounds before DNA interaction

Rifamycin mechanism

- -bind to RNA polymerase inhibiting intiation of RNA synthesis - -Gram (+) and mycobacteria - -single-step mutation resistance

Rifamycin side effects

- -1% hepatitis | - -uveitis

Antimetabolite antibiotics

sulfonamides and trimethoprim

Trimethoprim/Sulfonamide mechanism

- -**bacteriostatic that prevents the synthesis of folic acid - -active against Gram + and Gram - and some protozoa - -Resistance occurs through alteration of the folate pathway

TMP-SMX side effects

--Enteric --Hypersensitivity ...

Bacterial membrane disruption

lipopolypeptides and polymyxins

Lipopolypeptide (Daptomycin) mechanism

- -binds to membranes causing rapid depolarization and cell death - -Active against Gram (+) and anaerobes

Lipopolypeptide (Daptomycin) side effects

- -elevated creatine phosphokinase | - -NO PNEUMONIA (binds surfactant)

Polymyxin mechanism, side effect, and resistance

- -acts as a detergent that interacts with phospholipids ad disrupts the cell membrane - -active against many GNRs - -nephro/neurotoxicity - -resistance by decreased permeability