Antimicrobials III Flashcards by Vanessa Nwaokocha

mechanism of vancomycin

binds to D-Ala-D-Ala terminus of nascent peptidoglycan pentapeptide –> inhibition of transglycosylase –> inhibiting further elongation of peptidoglycan and cross-linking –> peptidoglycan and cell wall synthesis inhibition –> cell lysis

pay back 2 D-ALAs for VANdalizing

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how are enterococci resistant against vancomycin

terminal D-Ala is replaced with D-lactate hence vancomycin not being able to bind to its target

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clinical use of vancomycin

against serious gram positive bacteria only – especially those that are beta lactam resistant or allergic
ex: C. difficile pseudomembrane colitis and staph enterocolitis

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when is vancomycin used to treat enterococci

it is used together with aminoglycosides against E. faecalis or E. faecium in enterococcal endorcarditis

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adverse effect of vancomycin

PORN

Phlebitis
Red man or Red neck syndrome: flushing of the face or upper torso due to release of histamine
Ototoxicity and Nephrotoxicity: esp if renal insufficiency or given with aminoglycosides

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mechanism of daptomycin

binds to cell membrane of bacteria via calcium dependent insertion of lipid tail –> depolarization of cell membrane and potassium efflux –> rapid cell death

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clinical applications of daptomycin

vancomycin resistant enterococci and staph aureus

- MRSA, MSSA, VRE

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what do you not use daptomycin to treat and why

not used to treat pneumonia because pulmonary surfactant antagonizes daptomycin

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adverse effects of daptomycin

constipation, nausea, headache, insomnia

-myopathy and possible increase in creatinine phosphokinase

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mechanism of bacitracin

interferes with dephosphorylation in cycling of the lipid carrier that transfers peptidoglycan subunits to growing cell wall –> cell wall synthesis inhibition

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clinical application of bacitracin

topical treatment of mixed bacterial infections of skin, wounds, or mucous membrane

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adverse effect of bacitracin

nephrotoxic if administered systemically hence why used topically

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mechanism of fosfomycin

inhibits enolypyruvate transferase which is a cytoplasmic enzyme used in early stages of cell wall synthesis

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clinical application of fosfomycin

uncomplicated lower urinary tract infections

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what are the protein synthesis inhibitors

TAMGOS [CC FML]

Tetracyclines
Aminoglycosides
Macrolides
Glycylcylines
Other: Chloramphenicol, Clindamycin, Fidaxomicin, Mupirocin, Linezolid
Streptogramins: Dalfopristin/Quinupristin

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what part of the bacteria do protein synthesis inhibitors work on and why is there still adverse effects?

they work on ribosome 70S found only in bacteria (compare to 80S found in mammalians)
adverse effects seen because mammalian ribosome closely resembles bacterial ribosome

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what are the tetracyclines

Tetracycline
Doxycycline
Minocycline

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mnemonic for protein synthesis inhibitors for what does what part of the 70s ribosome

Buy AT 30, CCEL at 50

30S:
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic) (glycylcylines as well since it is derived from tetracyclines)

50S: 
Chloramphenicol (bacteriostatic)
Clindamycin (bacteriostatic)
Erythromycin (all macrolides) (bacteriostatic)
Linezolid (variable)

mechanism of tetracyclines

binds to 30S and prevents attachment of aminoacyl-tRNA –> inhibition of AA to growing peptide

clinical application of tetracyclines (name them)

tetracycline, doxycycline, minocycline

most common: severe acne and rosacea (flushed appearance of cheeks and nose)
Chlamydia, Cholera, Anthrax, Rickettsia, Lyme diseases, Mycoplasma

what cations impair absorption of tetracyclines

Ca2+, Mg2+, Fe2+

adverse effects of tetracyclines (name them)

Tetracycline, Doxycycline, Minocycline

Discoloration and Hyperplasia of teeth and stunting of growth (affects fetus and kids less than 8)
Dizziness and Vertigo
Photosensitization
Nephrotoxicity
Hepatotoxicity
GI disturbances (most common)

first three are more testable

what is the glycylcylines

Tigecycline

mechanism of glycylcyline (name it)

Tigecycline

binds to 30S but more tightly than tetracyclines and overcome resistance associate with acquired efflux pumps and ribosomal protection

what is intrinsically resistant to glycylcyline (name it)

tigecycline Proteus P. aeruginosa

clinical application of glycylcylines (name it)

tigecycline complicated skin, soft tissue, and intra abdominal infections -MRSA, VISA, VRE

adverse effects of glycylcylines (name it)

tigecycline - same as tetracyclines - Discoloration and hyperplasia of teeth and stunting of growth - Photosensitization - Dizziness and Vertigo - Nephrotoxicity and Hepatotoxicity - GI disturbances (also most common here as well)

who are glycylcylines and tetracyclines contraindicated in and why

pregnant women and children under 8 due to discoloration and hyperplasia of teeth and stunting of growth

what are the aminoglycosides

Mean (aMINoglycosides) GNATS caNNOT kill anaerobes -- all bactericidal ``` Gentamicin Neomycin Amikacin Tobramycin Streptomycin ``` NNOT are the adverse effects - Nephrotoxicity, Neuromuscular blockade, Ototoxicity (esp with loop diuretics), and Teratogen

mechanism of aminoglycosides (name them)

GNATS - gentamicin, neomycin, amikacin, tobramycin, streptomycin irreversible inhibition of initiation complex via binding the 30S subunit --> protein wall synthesis inhibition

aminoglycosides initially cross the outer membrane of the bacteria via passive diffusion. how can this step be inhibited

divalent cations anaerobic environment acidic pH increased osmolality

how can resistance to aminoglycosides occur (name them)

GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin - inactivating drug by phosphorylation, adenylylation, and acetylation - receptor protein on 30S can be altered or deleted due to mutation - decreased accumulation of drug by impaired entry into cell or increased efflux

pharmacodynamic property of aminoglycosides (name them)

GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin post antibiotic effect (PAE): suppression of bacterial growth even after drug has been removed concentration dependent killing: higher conc induces more rapid and complete killing of organism hence why a larger, single dose is more effective than smaller, multiple doses

clinical application of aminoglycosides (name them)

GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin - severe gram neg rod infections - gentamicin plus penicillin/vancomycin for infective endocarditis - streptomycin for plague caused by yersinia pestis - neomycin for hepatic encephalopathy (lactulose is first line though)

adverse effects of aminoglycosides (name them)

Mean (aMEANoglycosides) GNATS caNNOT kill anaerobes GNATS: gentamicin, neomycin, amikacin, tobramycin, streptomycin ``` NNOT Nephrotoxicity Neuromuscular blockade Ototoxicity (esp if taken with loop diuretics) Teratogen ```

contraindication of aminoglycosides

``` pregnant women (teratogen) myasthenia gravis (due to neuromuscular blockade) ```

what are the macrolides

Macrolides CEAT Clarithromycin Erythromycin Azithromycin Telithromycin

mechanism of macrolides (name them)

Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin bind to 50S --> inhibition of transpeptidation, translocation, chain elongation, and protein synthesis

mechanism of resistance in macrolides (name them)

Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin - reduced membrane permeability or active efflux - makes esterase --> hyrolyzation of drug - modification of ribosomal binding site via chromosomal mutation or methylase

clinical application macrolides (name them)

Macrolides CEAT: clarithromycin, erythromycin, azithromycin, telithromycin - erythromycin: whooping cough - infection by by Hemophilus, Strep pneumo, staph, enterococci

of all the macrolides, which one is only one available as an IV

azithromycin

safest macrolide for pregnancy

erythromycin

drug interactions of macrolides

- CET (clarithromycin, erythromycin, telithromycin) leads to increase in plasma conc of drugs that are metabolized by CYP3A4, theophylline, anticoagulants, carbamazepine - erythromycin increases plasma levels of digoxin

adverse effects of macrolides (name them)

Macrolide CEAT: clarithromycin, erythromycin, azithromycin, telithromycin ``` MACRO Motility issues Arrhythmias due to long QT interval Cholestatic hepatitis Rash eOsinophilia ``` Steven Johnson Syndrome