Ab Flashcards
Cell Wall Synthesis Inhibitors
β-lactam drugs: Penicillins, Cephalosporins, Carbapenems, Monobactams
Beta-lactamase inhibitors: NOT antibiotics but are used in a combination with extended-spectrum PCN
Non-β-lactam drugs
All bactericidal since cell lyses without wall.
Classical PCNs
gram (+), bactericidal, relatively narrow spectrum (mostly active against Gram-positive such as Staphylococcus) Penicillin G (IV) Penicillin V (oral) Procaine penicillin G (IM) Benzathine penicillin G (IM)
b-lactamase-resistant (anti-Staphyloccocal)
PCNs
gram (+), b-lactamase resistant (resistant to hydrolysis by beta-lactamase (penicilinase) found in many Staphylococcus aureus), bactericidal,
- -bacteria sensitive to this class of PCNs are called methicillin-sensitive SA (MSSA).
- -bacteria that are resistant to this class of PCNs are called methicillin-resistant SA (MRSA)
Methicillin (Don’t use since toxic to kidney-nephritis) Nafcillin Oxacillin Cloxacillin Dicloxacillin
Extended-Spectrum
PCNs
gram (+) and (-), bactericidal, more active against gram-negative bacteria compared to penicillin G/V
AMINOpenicillins: AMipicillin, AMoxicillin
Anti-pseudomonal PCNs:
CARBOXYpenicillins: CARbenicillin, TiCARcillin
UREIDOpenicillins: Piperacillin, Mezlocillin
-often used in a combination with beta-lactamase inhibitors to treat infections caused by Pseudomonas aeruginosa
Cephalosporins
gram (+): 1st gen gram (-): 2nd, 3rd b-lactamase resistant: 3rd/4th/5th broad spectrum: 4th, 5th bactericidal
Carbapenems
gram (+), gram (-), b-lactamase resistant, broad spectrum, bactericidal
Monobactams
gram (-), bactericidal, only aztreonam
Non-b-lactams
gram (+), bactericidal
Penicillins structure and MOA
D-Ala-D-Ala analogs, belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
three sub groups of drugs that are of different antibacterial spectrum
Pros and Cons of Classical PCNs
penicillin G, penicillin V
pros: Active against G(+), some G(-) cocci and anaerobes
cons: Inactive against G(-) rods; hydrolyzed by β-lactamase
- -narrow spectrum and are often used to treat infections caused by gram-positive bacteria such as Staphylococcus aureus
- -penicillin G remains the drug of choice for treating syphilis which is caused by a spirochete
Pros and Cons of b-lactamase resistant PCNs (Anti-Staphylococcal PCN)
methicillin, nafcillin, cloxacillin, dicloxacillin
- -not broad spec. just good for beta lactam resistant bugs
- -even narrower spectrum than classical PCNs
pros: Resistant to Staphylococcal β-lactamase
cons: Inactive against G(-), anaerobes, enterococci
Pros and Cons of Extended-spectrum PCNs
ampicillin, amoxicillin, carbenicillin, ticarcillin, piperacillin, mezlocillin
pros: Improved activity against G(-) organisms
cons: Hydrolyzed by β-lactamase
- -can be used in fixed combinations with beta-lactamase inhibitors to broaden their antibacterial spectrum
Cephalosporins and Cephamycin
Structure: D-Ala-D-Ala analogs, belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
Same MOA and major side effects as all beta-lactams
-Different spectrums
-Cross-allergenicity with PCN
-Most are renally cleared
-Many 3rd generation cephalosporins are also more likely to cross BBB to reach CNS and are thus useful for treating CNS infections.
-4th and 5th aren’t called broad spectrum since it kills many positive and negatives but not all.
-Covers even anaerobes.
-5th generation ceftobiprol is active against MRSA
1st generation Cephalosporins
Cefazolin (Inj.)
Cephalexin
Cephalothin
Cephradine
–more active against G(+), but less effective against most G(-)
Structure: D-Ala-D-Ala analogs belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
Same MOA as all beta-lactams
Different spectrums
Cross-allergenicity
Most are renally cleared
2nd generation Cephalosporins and Cephamycin*
Cefaclor Cefprozil Loracarbef Cefuroxime Cefoxitin* Cefotetan* Cefonicid
–more active against G(-), but less active against G(+) compared to 1st generation
Structure: D-Ala-D-Ala analogs belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
Same MOA as all beta-lactams
Different spectrums
Cross-allergenicity
Most are renally cleared
3rd generation Cephalosporins
Cefoperazone Cefotaxime Ceftazidime Ceftizoxime Ceftriaxone Cefixime Cefpodoxime Cefdiner Cefibuten --more active against G(-), but less effective against most G(+) --Many are also more likely to cross BBB to reach CNS and are thus useful for treating CNS infections. Structure: D-Ala-D-Ala analogs belong to beta-Lactams MOA: Bind to PBP, inhibit transpeptidation Same MOA as all beta-lactams Different spectrums Cross-allergenicity Most are renally cleared
4th generation Cephalosporins
cefepime most active against both G(+) and G(-) Structure: D-Ala-D-Ala analogs belong to beta-Lactams MOA: Bind to PBP, inhibit transpeptidation Same MOA as all beta-lactams Different spectrums Cross-allergenicity Most are renally cleared
5th generation Cephalosporins
Ceftaroline
Structure: D-Ala-D-Ala analogs belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
Same MOA as all beta-lactams
Different spectrums
Cross-allergenicity
Most are renally cleared
Other b-lactams: Carbapenems
Imipenem*
Ertapenem
Meropenem
Structure: D-Ala-D-Ala analogs belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
–broad-spectrum beta-lactams that are useful for treating mixed infections
*Imipenem + cilastatin (inhibits renal dehydropeptidase: prolongs imipenem’s bioavailability)
Imipenem inhibited by dehydropeptidase
Other b-lactams: Monobactams
Aztreonam
Structure: D-Ala-D-Ala analogs belong to beta-Lactams
MOA: Bind to PBP, inhibit transpeptidation
–is active against gram-negative only
–does not share drug resistance with PCNs and is therefore useful for treating PCN-resistant infections.
Other b-lactams: β-lactamase inhibitors*
Clavulanic acid
Sulbactam
Tazobactam
- -Little/no antibiotic activity: are beta-lactams but are NOT antibiotics
- -MOA: inh. b-lactamase)
- -Used only in fixed combination with specific extended-spectrum penicillins to broaden their antibacterial activity
Non-b-lactam Cell Wall Syn. Inh. - Fosfomycin
Spectrum/Use: G(+), G(-) MOA: Inh. enolpyruvate transferase --blocks NAM --"F" for first step --good for uti when other drugs don’t work
Non-b-lactam Cell Wall Syn. Inh. - Cycloserine
Spectrum/Use: TB
MOA: Inh. alanine racemase, blocks synthesis of linking pentapeptide (PEP)
Non-b-lactam Cell Wall Syn. Inh. - Vancomycin
Spectrum/Use: G(+)
MOA: Binds to D-Ala-D-Ala
–not orally absorbed since it is a glycopeptide
–doesn’t get in through gut easily since it is charged
–so not orally bioavailable
–used in general as injection/infusion except for C. diff colitis (overgrowth from too much ab)
Non-b-lactam Cell Wall Syn. Inh. - Bacitracin
Spectrum/Use: G(+), topical
MOA: Inh. recycling of lipid carrier BPP (Bactoprenol phosphate). NAM and NAG need a carrier through the lipid membrane
–Used in antibiotic ointment since it’s too toxic if taken internally.
Non-b-lactam Cell Wall Syn. Inh. - Daptomycin
Spectrum/Use: G(+)
MOA: Binds to and depolarize cell membrane
–Lipophilic drug (make pores in membrane so contents spill out)
Severe Side Effects/Toxicities: b-lactams
Hypersensitivity, renal toxicity
–don’t give if have seizures beause it binds gaba receptor so more likely to have a seizure if the drug is not released properly
Severe Side Effects/Toxicities: Amoxicillin
Non-allergic rash (nonhistamine (IgE) mediated)
GI toxicity
–Most orally bioavailable drug
Severe Side Effects/Toxicities: Cephalosporins –MTT (cefoperazone, cefotetan)
Disulfiram-like rx (w/alcohol)
- -Disulfiram: treatment of chronic alcoholism by producing an acute sensitivity to ethanol by inhibiting the enzyme acetaldehyde dehydrogenase
- -Mtt ring gives additional side effects
Severe Side Effects/Toxicities: Vancomycin
Ototoxicity
renal toxicity
red man syndrome (caused by histamine release)
–injected
Severe Side Effects/Toxicities: Cycloserine
CNS toxicity
Severe Side Effects/Toxicities: Daptomycin
Muscle pain, liver toxicity
linezolid MOA
Protein translation: Initiation inhibited
tetracyclines MOA
Protein translation: Elongation - attachment of aa-tRNA is inhibited
macrolides, clindamycin, and chloramphenicol MOA
Protein translation: Peptidyl transfer from P to A site inhibition
–chloramphenicol blocks peptide bond formation
aminoglycosides MOA
Protein translation: Translocation of peptidyle-tRNA from A site to P site inhibited
–also block mRNA proofreading
Protein Synthesis Inhibitors
inhibit 30S ribosomal subunit
Tetracyclines: Chlortetracycline Oxytetracycline Tetracycline Demeclocycline Methacycline Doxycycline Minocycline Tigecycline --Broad spectrum --Bacteriostatic (except for tigecycline, which is bactericidal)
Aminoglycosides: Streptomycin Gentamicin Neomycin Kanamycin Amikacin Tobramycin Paromomycin --G(-) and some G(+) --Bactericidal --big and charged so cant be absorbed in gut membrane --becomes ionized even more in acidic stomach, so use as injection
Protein Synthesis Inhibitors
inhibit 50S ribosomal subunit
Relatively Broad spectrum:
Macrolides: Erythromycin, Clarithromycin, Azithromycin
–use erytho is allergic to PCN
–Azithro and claritho have bad drug interaction
Ketolides: Thelithromycin
Broad spectrum:
Clindamycin, Chloramphenicol
–Clinda for acne. Patient can develop C. diff colitis since kills too much bacteria and this outgrows. Diarrhea too
Streptogramins: Quinupristin-dalfopristin (combo)
G(+), Bactericidal
Oxazolidones: Linezolid
G(+)
Severe Side Effects/Toxicities: Tetracyclines
Teeth/bone damage, photosensitivity, liver/kidney/GI toxicities
–Tetracyclines are avoided in pregnancy and <8 yr old.
Avoid dairy products and antacids (cations). Binds to calcium. Cant kill bacteria effectively if calcium is bound.
Severe Side Effects/Toxicities: Aminoglycosides
Ototoxicity, renal toxicity
–inj only and against gram (-)
Severe Side Effects/Toxicities: Macrolides
Liver toxicity
Severe Side Effects/Toxicities: Clindamycin
Pseudomembraneous colitis (c diff overgrowth)
Severe Side Effects/Toxicities: Chloramphenicol
Aplastic anemia, Grey baby syndrome
Severe Side Effects/Toxicities: Streptogramins
Arthralgiamyalgia (muscle pain)
Severe Side Effects/Toxicities: Linezolid
Hematological toxicity
p450 inhibitors
erythromycin, clarithromycin, chloramphenicol, fluoroquinolones
DNA Synthesis Inhibitors: Antifolates
Sulfonamide: inhibits DHPS, Broad Spectrum, Bacteriostatic Sulfacytine Sulfisoxazole Sulfamethizole Sulfadiazine Sulfamethoxazole Sulfapyridine Sulfadoxine Sulfasalazine
Pyrimidines: Broad Spectrum, Bacteriostatic
Trimethoprim - inhibits DHFR
Pyrimethamine - protozoa-specific
DNA Synthesis Inhibitors: DNA Gyrase Inhibitors
Fluoroquinolones: inhibits Topoisomerase IV, DNA gyrase (Topo II), G(+) & G(-), Bactericidal
Norfloxacin Ciprofloxacin (drug of choice for anthrax), better against (-) Levofloxacin (better for (+)) Enoxacin Ofloxacin Pefloxacin Lomefloxacin Moxifloxacin Gemifloxacin
Severe Side Effects/Toxicities: Sulfonamides
Urinary tract disturbance (drink tons of water otherwise crystallize in urinary tract)
SJS: Stevens–Johnson syndrome, a form of toxic epidermal necrolysis
Severe Side Effects/Toxicities: Trimethoprim
Hematological toxicity
Severe Side Effects/Toxicities: Fluoroquinolones
QT-prolongation (arrhythmias), photosensitivity, tendonitis, tendon rupture, arthropathy, avoid cations (dairy products, antacids), avoided in patients <18 yr old
Empirical therapy: Acute bacterial endocarditis
Vancomycin + Gentamicin
Empirical therapy: Acute Otitis Media, sinusitis
Amoxicillin
Empirical therapy: Cellulitis
b-lactamase-resistant penicillin, 1st generation cephalosporin
Empirical therapy: Meningitis (child & adult)
cefotaxime (3rd) + vancomycin
Empirical therapy: Meningitis (neonate)
Ampicillin + cephalosporin (3rd)
Empirical therapy: Community-acquired pneumonia
Macrolide, amoxicillin, tetracycline (outpatient)
Macrolide+ cefotaxime (inpatient)
Empirical therapy: Septicemia
Vancomycin+ cephalosporin (3rd) or piperacillin/tazobactam or imipenem
Empirical therapy: Uncomplicated Cystitis
TMP-SMZ (trimethoprim and sulfamethoxazole synergy), Nitrofurantoin, (Fluoroquinolone for resistant strains)
G(+) only
Bacitracin, Vancomycin, Daptomycin, Streptogramins, Linezolid
Mostly used for G(+)
PCNs
G(-) only
Aztreonam
Mostly used for G(-)
Extended-spectrum PCNs, 3rd gen cephalosporins, Aminoglycosides
Broad-spectrum
Carbapenems, Tetracyclines, Macrolide, Chloramphenicol, Clindamycin, anti-folates, Quinolones
Bactericidal
Cell wall inhibitors, Tigecycline, Aminoglycosides, Streptogramins, TMP/SMZ, Quinolones
