Aminoglycosides Flashcards
Aminoglycoside Examples
Streptomycin
Gentamicin
Tobramycin
Amikacin
Aminoglycoside MOA
inhibit protein synthesis by inhibiting 30S subunit of bacterial ribosome
inhibit protein synthesis
Resistance to Aminoglycosides
Mutation or methylation of 16S rRNA-binding site
Enzymatic destruction of the drug
Lack of permeability to the drug molecule –> drug cannot get into the organism
Active efflux (or lack of active transport)
CHANGE to BINDING SITE
Aminoglycoside Spectrum
aerobic gnb bacilli
Aminoglycosides are synergistic with….
penicillins for enterococci and streptococci
Streptomycin can be used for…
- TB
Aminoglycoside Route of Admin
- IV/IM
Aminoglycosides absorbtion
Penetrate tissues relatively poorly; not CNS
Aminoglycoside Adverse Effects
Nephrotoxicity
Ototoxicity
Neuromuscular blockade
Allergies rare
Aminoglycosides Drug Interactions
Other nephrotoxic drugs
Other ototoxic drugs
Neuromuscular blocking agents
Fluoroquinolone Examples
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
Fluoroquinone MOA
- inhibit DNA gyrase or topoisomerase II & IV
Bacteriocidal; concentration dependent killing
Inhibit DNA replication
Fluoroquinone Resistance
alteration of the A or B subunit of DNA gyrase
-
Mutation in ParC or ParE of topoisomerase IV
Change in outer membrane permeability –> cannot get in to act at DNA
Efflux pumps
In general, fluoroquinones spectrum is
highly active against gnb, Haemophilus sp, neisseriae, chlamydiae, etc
Ciprofloxacin Spectrum
most active against .P aeruginosa
Levofloxacin Spectrum
activity against S. pneumoniae –> gram positive cocci
Moxifloxacin Spectrum
activity against anaerobes
Fluoroquinone Uses
urinary tract infections, STIs due to chlaymdia, lower respiratory tract infections, enteritis/travellers diarrhea, drug resistant mycobacterial infections
Fluroquinones Elimination
Ciprofloxacin and levofloxacin – renal elimination; moxifloxacin has a biliary pathway
Adverse Effects of Fluoroquinolones
Nausea, vomiting, diarrhea
Insomnia, headache and dizziness
Other CNS effects including seizures
Skin rashes
Impaired liver function
-
Tendinitis/tendon rupture –> tends to occur more in elderly (can occur I. young) –> risk factors –> age over 60, being on corticosteroids, and female –> Counsel –> If develop tenderness, stop and see healthcare professional right away
-
Prolongation of QTc interval
Hypo/hyperglycemia
C. difficile
Peripheral neuropathy –> tingling, prickling,
Drug Interactions of Fluoroquinolones
Bind di and tri-valent cations –> Mg, Ca, Zinc, Iron –> Lower serum inf
QTc prolongation
CYP 1A2 inhibition can result in increased levels of many drugs ( e.g. clozapine, duloxetine, methotrexate, quinapril, rasagiline, ropinirole, varenicline,etc)
Increased INR with warfarin
Fluroquinolones exception uses… C.I.
Many toxicities
Many have been removed from the market
Reserve for resistant organisms and situations where you cannot use the DOC
Not used in children <18 years of age ( some exceptions)
Exceptions –> Pseudomonas, resistant infections
–> Cystic Fibrosis in Children –> Seen
Sulfamethoxazole MOA
structural analogue of PABA; competitively inhibits dihydrofolic acid synthesis
Inhibit folic acid synthesis
Trimethoprim MOA
binds to dihydrofolate reductase therefore inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid
- Inhibit folic acid synthesis
Sulfamthoxazole and Trimethoprim mainly found as….
Most commonly combined as TMP/SMX or
co-trimoxazole
Sulfonamides and Trimethoprim Killing Mechanism
Bacteriostatic but together bacteriocidal
Sulfonamides and Trimethoprim Resistance
ability of cell to use preformed folic acid (don’t have to make it)
Sulfonamides and Trimethoprim Spectrum
Spectrum – wide spectrum of gp, gn, chlamydiae, nocardiae and protozoa
No activity against anaerobes
Staphylococci – including MRSA
Streptococcus pneumonia; NOT Group A Strep
S. maltophilia
Moraxella
H. influenza
Enterobacteriaciae
Brucella
Pneumocystis jirovecii
Sulfonamides and trimethoprim Uses
Urinary tract infections
Skin and soft tissue infections- MRSA
PJP –> can be seen in other immunocompromised states but mainly HIV
Many others
Drug Interactions of TMP/SMX
2C9 inhibitor; 3A4 substrate – increased levels of carvedilol, digoxin, phenytoin
Increased INR and bleeding with warfarin
Hypoglycemic agents – increased risk of hypoglycemia
Contraindications of TMP/SMX
CI in first and 3rd trimester of pregnancy
Caution in renal dysfunction excaberates higher K+ levels, hypoglycemic risk
Metronidazole MOA
unknown but possible inhibition of nucleic acid synthesis and disruption of DNA
Metronidazole Resistance
–> Do not know –> Susceptibility testing is extremely difficult
Metronidazole Spectrum
anaerobes including C. difficile
Protozoa – trichomonas, Giardia (diarhhea from drinking H2O out of streams), etc
Propionibacterium are resistant –> acne –> Not used in this situation
Metronidazole Adverse Effects
gi
Metallic taste
Headache
Dark urine
Peripheral neuropathy –> usually not until later (weeks, often not used for long durations)
Disulfiram-like reaction with alcohol (N, V, D, Headache, Chest Pain)
Insomnia
Stomatitis mouth sores
Metronidazole Drug Interactions
Alcohol – disulfiram reaction
Warfarin – increased INR and bleeding
Linezolid MOA and KIlling
MOA – inhibits protein synthesis
Usually bacteriostatic; bactericidal against Streptococci
LInezolid Spectrum
Streptococci, Enterococci (including VRE), Staphylococci (including MRSA)
Linezolid is reserved for….
multi-drug resistant organisms
Linezolid Adverse Effects
Headache
Nausea, vomiting diarrhea
Rash
Increased LFT’s
Myelosuppression (Bone Marrow) –> Causes neutropenia, low platelets, anemia –> dose and duration dependnent
Optic/peripheral neuropathy –> nerve damage in eye –> Sight problems
Lactic acidosis
Decreased seizure threshold
Linezolid Drug Interactions
Increased serotonin syndrome risk with SSRIs and MAOIs (other drugs that cause serotonin syndrome)
Rifampin decreases linezolid levels
