Antibiotics Flashcards
Beta lactam structure
Analogs of D-alanyl-D-alanine
Beta lactam cidal and or static
Cidal - inhibits cell wall synthesis and more susceptible to lysis
Mechanism of Beta Lactams
Inhibit Transpeptidases (PBPs) that remove one alanine from a peptidoglycan polymer and cross link other alanine to antoher adjacent polymer
Form covalent bonds
Can’t form rigid 3D sturcutre
Regular, ES, anti staph, Anti psueod penicillins and routes
Penicillin G (I)
Amoxicillin (O)
Nafcillin (I)
Peperacillin (I)
Resistance to Beta lactam and example of each
beta lactamases cleave lactam ring (Staph aureus)
Mutated PBPs have decreased binding affinities (MRSA)
Each lactamase
Hydrolyzes a different set of beta-lactams
Penicillin spectrum
Braod
+,-, anaerobes, spirochetes
Regular pen coverage
Good for anaerobes and spirochetes but not gram -
ES penicillins coverage
Improved gram - coverage
Anti staph penicillins coverage
Best for Non-MRSA staph
Only strand resistant to some beta-lac
Anti pseudo pen coverage
Improved of P aeruginosa and other gram - bacilli
How to ES and anti pseudo penicillins get into gram negative bacteria
Have side chains that can go through porins…these are + charged chains
Pen absorption
Oral bioavailability is poor
Amoxicillin is good for oral
Pen distribtuion
Do not enter bone or CNS
G used for neurosyphilis
Pen elimination
Rapid renal elimination so short duration
Pen dosing
Most in milligrams
G in IUs
V in either mg or IUs
Adverse effects of penicillins
Rare
Superinfections (more likely with broader)
Serizures (at very high levels, caution with epileptics)
Skin rashes (ES can cause non-allergic rash with mono)
What is common is penicillins
Hypersensitivity reactions…most serious being anaphylaxis and least being skin rashes
All penicillins cross react
With each other and at a lower frequency with other beta lactams
Cephalosporins we need to know and generation
1 - cefazolin (I)
3 - Ceftiaxone (I)
4 - Cefepime (I)
Ceph spectrum and how different than penicillins
+, - , anaerobes, spirochetes
better at gram - than pen
More stable against lactamases
Cefazolin use
Highest against gram + and anaerobes
Wound infections and surgicial prophylaxis
Ceftriaxone use
More serious gram - bacilli
Cefepime use
Similar to ceftriaxone but more psuedomonas activity
Ceph resistance
Lactamases (decreased with later generations)
ESBLs
On some strains of gram - bacilli…resistant to 3rd gen cephalosporins
Ceph absorption
Oral are there for 1-3 gen
Ceph elimination
Most are short and secreted by kidney
Ceftriaxone undergoes biliary elimination and longer T1/2
Ceph deistribtuoon
Moves to restricted better than pen
Ceph toxicity
Hypersensitivity (can use with pts who have a delayed penicillin reaction)
Superinfections (with broader spect)
Nephrotoxicity (rare)
Carbapanems we need to know
Meropenem
Carbapenems are improvement because
Very broad spectrum and insentivie to lactamases that destroy cephs and pens
Most important use for carbapenems
Difficult to treat gram negative bacteria (entero, klebsiella)
Carbapenems spectrum
+, -, anaerobes
Carb resistance
Typically due to non-lactamase mechanism
Recent spread of metallo beta lactamases in Klebsiella pneumoniae
Cilastatin
Used with imipenem to decreased effect of renal dehydropeptidase
Absorptions Carb
Only injection
Distributon Carb
Go to bone, CNS, restricted compartments well
Adverse effects of Carb
Seizures…decrease valproate levels, whcih is important anti-epileptic drug
Beta lactamase inhibitors
Clavulanic acid
Bind to catalytic site and extend spectrum of beta lactams
Augmentin
Amox and clavulanic acid
Augmentin example useful in
Beta-lactamase producing strands of gram-negative bacteria
Glycopeptide example and route
Vancomycin (I,O)
Vancomycin strucutre
Large and hydropihlic
Vancomycin mechanism
Inhibits transglycosylase that attaches new monomers to polymer…earlier step than beta-lactams
Vanco spectrum
+ and anaerobes…totally insensitive to lactamases and PBPs
Vancomycin used for
MRSA…pen still preferred for other S aureus strains
Severe C dif induced diarrhea
Resistance to vancomycin
High level - D-lactate replaces bidning sites D-alanine
Low level - Vancomycin creep due to increased production of peptidoglycan
Vancomycin absorption
Oral form not absorbed but used for GI infections
Vanco elimination
Renal
Distribution of Vanco
Penetrates BBB when inflamed
Vanco adverse effect
Nephrotoxicity
Red Man Syndrome
Histmaine release during infusion of Vancomycin…prevent by slow infusion and pre-admin of antihistamines
Hypotension and vasodilation
Protein suppression is normally
Bacteriostatic…can survive by going dormant
Which bind to 30S and 50S subunits
30 - aminoglycosides
50 - lincosamides and oxazolidinones
Linezolid inhibits
Assembly of 70S complex
Aminoglycosides inhibit
Early elongation of new amino acid binding to the A site
Lincosamides inhibit
Late elongation - bond formed between existing peptide at P site and new amino acid at A site
Aminoglycoside example and form
Gentamicin (I,T)…bactericidal
Aminoglycoside structure
Polycations…sugars with glycosydic links
Aminoglycoside mechanism
Binds to and changes conformation of the 30S subunit and causes miscoding…miscoded protein disrupt membrane
aminoglycoside type of killing
Concentration dependent killing with a long post-antibiotic effect
Resistance to aminoglycoside
Acetylase inactivates
Aminoglycoside scope
Some positive, more negative
No anaerobes because transport dependent on membrane potential
Aminoglycoside absorp
Not absorbed orally
Aminoglycoside distribution
Dont enter restricted well
Aminoglycoside elimination
Renal so short T1/2
Main use of aminoglycosides
Hospital setting for serious
Often combined with beta lactams
Aminoglycoside adverse effects
Nephrotoxicity (reversible)
Ototoxicity (partially reversible)
Vestibular toxicity (partially reversible at best)
How can you elimate nephrotoxicity of aminoglycoside
Keep trough concentrations low and avoid other nephrotoxic drugs
Dosing of aminoglycosides
Once daily allows peaking of the concentration so more killing and saturation of renal uptake
3 times daily is other way
Lincosamide example and route
Clindamycin (I, O, T, vaginal)
Clindamycin routes and why
Oral and injection dosage for systemic
Topical for acne vulgaris
Vaginal for bacterial vaginosis
Clindamycin spectrum
Gram positive and anaerobes…especially anaerobes
Clindamycin absorp
Very good oral
Clindamycin distribution
Very good except CNS…good for bone
Clindamycin elimination
Hepatic oxidation…in feces for long time
Clindamycin adverse effects
Diarrhea, thrombocytopenia…most likely to cause C dif
Clindamycin most useful as
Beta lactam alternative for treating anaerobic infections…also for some S aureus infection
Oxazolidinone example and route
Linezolid (I,O) - cidal or static depnding
Resistance to Linezolid
Binding site mutation or methylation
Linezolid spectrum
Gram positive only…good for multi drug resistant gram + cocci
Linezolid side effects
Mild to moderate thrombocytopenia
Peipheral neurotixicity sometimes
Serotonin syndrome
Linezolid absorption
Excellent oral
Distribution of linezolid
Well distributed including CNS
Linezolid elimination
Mostly through non-enzymatic hepatic oxidation
Sulfonamides example, route, and what they mimic
Sulfamethoxazole (I,O)…mimics PABA
Trimethoprim (I, O, T) - acts on DHFRs…mimics Folate
Human vs bacteria - folate
Bacteria only have dihydropteroate synthase that sulfonamides inhibit
Both have DHFR that trimethoprim acts on
Folates needed for
Synthesis of nucleosides and nucleic acids
Why use SMX-TMP
Similar kinetics and less reistance
Cidal when given together
SMX-TMP spectrum
+, -, intracellular
Uses of SMX-TMP
Urinary tract and community acquired MRSA
Resistance to SMX-TMP
Mutated sulfonamide binding site
Sulf absorp
Good oral
Sulf elimination
Both hepatic and renal…get concentrations in urine
Sulf distribution
Good into restircted compartments like CNS
Some bind to albumin
Sulfonamides and pregnancy
Neonates have large amounts of bilirubin…sulfonamides compete with binding to albumin freeing bilirubin…leads to encephalopathy
Sulfonamides toehr side effects
Crystal in urine…prevent with fluids
Hemolytic anemia
Hypersensitivity
Don’t use trimethoprim if
Patient has folate definiciency induced anemia
Stevens-Johnson syndrome
Most serious reacton to SMX-TMP
