Review - Antibiotics Flashcards
Tetracyclines
- Rx: GramPos
- MOA: Bacteriostatic
- Binds to 30S (Thirty S) subunit
- Prevents Aminoacyl-tRNA attachment
- Limited CNS penetration
- Avoid milk, antacids, iron
- Resistance: Transport pumps (plasmid encoded) decrease uptake into cells or increase efflux out of cells
- Side Effects:
- Tummy problems
- Can’t get Taller
- Terrible Vision (photosensitivity)
Tetracyclines Clinical Use
- Borrelia Burgdorferi
- Mycoplasma Pneumoniae
- Rickettsia (intracell accum)
- Chlamydia (intracell accum)
Doxycycline
Hepatic excretion
Demeclocycline
- ADH antagonist
- Can be used as diuretic in SIADH
Minocycline
Effective for acne (Mi-NO like acne!)
Aminoglycosides
- Rx: GramNeg
- MOA: Bacteriocidal
- Block Initiation Factor II @ 30S (A = 1st letter → initiation)
- Cause mRNA misreading
- Require O2
- Low CNS penetration
- Resistance: Transferases inactivate via APA
- Acetylation
- Phosphorylation
- Adenylation
- Side Effects: (ami-NOT-glycosides)
- Nephrotoxicity, esp w/Cephalosporins
- Ototoxicity, esp w/Loop Diuretics
- Teratogen
Aminoglycosides Clinical Use
- Severe GramNeg Rod infections (ami-NOT)
- Synergistic w/ß-lactams
- Monitor peak & trough
Examples of Aminoglycosides
- Gentamycin
- Streptomycin
- Neomycin
- Amikacin
Examples of Tetracyclines
- Doxycyline
- Demeclocycline
- Minocycline
Gentamycin
- Aminoglycoside
- Marketed longest
- Most Side Effects
Streptomycin
- Aminoglycoside
- Rx:
- TB
- Tularemia
Neomycin
- Aminoglycoside
- Bowel Sx
Amikacin
Only hepatically-excreted aminoglycoside
Penicillins
- Rx: GramPos Cocci & Rods, GramNeg Cocci, Spirochetes
- MOA: Bacteriocidal – Interfere w/Cell Walls
- Bind PBPs
- Block Transpeptidase cross-linking of peptidoglycan
- Activate Autolytic Enzymes
- Resistance: ß-lactamases cleave ring
Penicillins Clinical Use
- Bacteriocidal for:
- GramPos cocci & rods
- GramNeg cocci
- Spirochetes
- Clincal:
- Strep Pneumo
- Strep Pyogenes
- Actinomyces
- Syphilis
Penicillins Side Effects
- Hemolytic Anemia
- Hypersensitivity
Oral Penicillin
Penicillin V
IV Penicillin
Penicillin G
Penicillinase-Resistant Penicillins
- Rx: Staph Aureus (not MRSA)
- MOA: Same as penicillins
- Bind PBPs
- Inihibt Transpeptidase cross-linking of peptidoglycans
- Activate autolytic enxymes
- Narrow Spectrum
- Penicillinase Resistant → bulkier R group
Penicillinase-Resistant Penicillins Clinical Use
Staph Aureus (but not MRSA)
Penicillinase-Resistant Penicillins Side Effects
- Interstitial Nephritis – Methicillin
- Hypersensitivity
This penicillin can cause interstitial nephritis
Methicillin (Penicillinase-Resistant)
Examples of Penicillinase-Resistant Penicillins
- Methicillin
- Nafcillin
- Dicloxacillin
Aminopenicillins
- MOA: same as penicillins
- bind PBPs
- block Transpeptidase cross-linking of peptidoglycans
- activate autolytic enzymes
- Wider spectrum
- Usually combined w/Clavulanic Acid (ß-lactamase inhibitor)
Aminopenicillins Clinical Use
Extended Spectrum good for:
- H. Influenzae
- E. Coli
- Listeria Monocytogenes
- Proteus Mirabilis
- Salmonella
- Shigella
- Enterococci
Aminopenicillins Side Effects
- Pseudomembranous Colitis
- Rash - Ampicillin
- Hypersensitivity
This tetracycline is hepatically excreted
Doxycycline
This tetracycline can be used as a diuretic in SIADH
Demeclocycline
This tetracycline is used for acne
Minocycline
This aminoglycoside is hepatically excreted
Amikacin
This penicillin can cause a rash
Ampicillin (Aminopenicillin)
This type of penicillin can cause pseudomembranous colitis
Aminopenicillins
Examples of Aminopenicillins
- Ampicillin
- Amoxicillin
Ampicillin
- Aminopenicillin
- Can cause rash
Amoxicillin
- Aminopenicillin
- Greater Oral bioavailability (amOxicillin → Oral)
This aminopenicillin has greater oral bioavailability
Amoxicillin
Anti-Pseudomonals
- Rx: GramNeg rods, Pseudomonas
- MOA: same as penicillins
- bind PBPs
- block Transpeptidase cross-linking of peptidoglycans
- activate autolytic enzyme
- Extended Spectrum
- Susceptible to Penicillinase
- Usually combined w/Clavulanic Acid (ß-lactamase inhibitor)
Anti-Pseudomonals Clinical Use
- Pseudomonas
- GramNeg Rods
Anti-Pseudomonals Side Effects
Hypersensitivity
Examples of Anti-Pseudomonals
- Ticarcillin
- Carbenicillin
- Piperacillin
Take Care of Pseudomonas!
ß-lactamase inhibitors
- Added to penicillins to prevent destruction by penicillinase / ß-lactamase
- Include:
- Clavulanic Acid
- Sulbactam
- Tazobactam
ß-lactamase
- aka penicillinase
- breaks down ß-lactam ring → penicillin resistance
Cephalosporins
- MOA: ß-lactams that inhibit Cell Wall Synthesis
- Less susceptible to penicillinase
Cephalosporins Side Effects
-
VItamin K Deficiency
- Clotting Factors 10, 9, 7, 2 + Proteins C & S
- bleed into cavities
- Cross-Hypersensitivity w/Penicillins in 5-10% of pts
- Increase Nephrotoxicity of Aminoglycosides
- Disulfiram-like rxns w/EtOH
1st Gen Cephalosporins
- Drugs: “Jeremy Lin is #1 and Drives a Lexus”
- Cefazolin
- Cephalexin
- Rx: “ 1 PEcK”
- Proteus Mirabilis
- E. Coli
- Klebsiella Pneumoniae
2nd Gen Cephalosporins
- Drugs: “2 Fake Fox Furs”
- Cefaclor
- Cefoxitin
- Cefuroxime
- Rx: “2 HEN PEcKS”
- H. Influenzae
- Enterobacter Aerogenes
- Niesseria Spp
- Proteus Mirabilis
- E. Coli
- Klebsiella Pneumoniae
- Serratia Marcescens
3rd Gen Cephalosporins
- Drugs: “T for Three”
- Ceftriaxone
- Cefotaxime
- Ceftazidime
- Rx: Serious GramNeg
this cephalosporin is good for Rx meningitis and gonorrhea
Ceftriaxone (3rd gen)
“TRI meningitis and gonorrhea”
this 3rd gen cephalosporin is good for Rx pseudomonas
Ceftazidime
“TAZe that pseudomonas!”
4th Gen Cephalosporins
- Drug: “Fe for Four”
- Cefepime
- Rx:
- Pseudomonas
- GramPos
5th Gen Cephalosporins
- Drug:
- Ceftaroline
- Rx:
- MRSA
First beta-lactam approved for Rx MRSA
Ceftaroline (5th gen cephalosporin)
Chloramphenicol
- MOA: blocks peptide bond formation at 50S subunit (chloramFENicol at FIFTY)
- Resistance: Acetyltransferase (plasmid-encoded) inactivates drug
- Rx: Meningitis
Chloramphenicol Clinical Use
MENingitis
(→ ChloraMphENicol)
Chloramphenicol Side Effects
- Dose-DEpendent Anemia
- Dose-INdependent Aplastic Anemia
- Gray Baby Syndrome
Clindamycin
- MOA: blocks peptide bond formation at 50S subunit (like chloramFENicol at FIFTY)
Clindamycin Clinical Use
- Anaerobic Infections above diaphragm
- Aspiration Pneumonia
- Lung Abscess
Clindamycin Side Effects
- Pseudomembranous colitis
- Fever
- Diarrhea
These two drugs can cause pseudomembranous colitis
- Aminopenicillins
- Clindamycin
Macrolides
- MOA: bacteriostatic protein synthesis inhibitors
- block translocation at 50S subunit
- MacroSLIDE → translocation
- Resistance: Methylation of rRNA binding site at 23S of 50S subunit
- Methylation → Macrolide resistance
Macrolides Clinical Use
- Atypical Pneumonias
- Mycoplasma (walking pneumonia – Xray looks way worse than symptoms)
- Chlamydia
- Legionella (silver stain, standing water)
- URI
- STDs
- GramPos Cocci
- Strep when pt allergic to penicillin
- Neisseria
Examples of Macrolides
- ErythROmycin
- AzithROmycin
- ClarithROmycin
(macROlides)
Macrolides Side Effects
- Prolonged QT interval (Erythro) → arrhythmia
- Acute Cholestatic Hepatitis
- Dysgeusia (Clarithro)
-
Increased serum conc of:
- Theophyllines
- Oral anticoagulants
- GI discomfort
- Eosinophilia
- Skin Rashes
this macrolide can prolong QT interval
Erythromycin
(erythro sounds like arrhythmia)
This macrolide can cause dysgeusia
Clarithromycin
This macrolide is safe to use in pregnancy
Azithromycin
Fluoroquinolones
- MOA: Bacteriocidal DNA Gyrase inhibitors
- aka Topoisomerase II
- DNA can’t separate → no replication
- Resistance: DNA gyrase mutation (chromosome-encoded)
- Renal excretion
Fluoroquinolones Clinical Use
- GramNeg rods in Urinary & GI tracts
- Pseudomonas
- Neisseria
- Some GramPos organisms
Fluoroquinolones Side Effects
- Superinfections
- Tendonitis / Tendon Rupture
- Leg Cramps, Myalgias in kids
-
C/I kids, pregnancy → cartilage/bone damage
- likes to steal calcium
- GI Upset
- Skin rash
- Headache
- Dizziness
Examples of Fluoroquinolones
- Ciprofloxacin
- Any-floxacin!
- Enoxacin
- Nalidixic Acid
Fluoroquinolones for Gonorrhea
- Ofloxacin
- Moxifloxacin
- Gatifloxacin
“Oh My God - I have gonorrhea!”
Metronidazole
- MOA: Bacteriocidal and Antiprotozoal
- form free radicals
- pyruvate oxidoreductase → ferredoxin → reacts w/free radicals → anaerobe death
Metronidazole Clinical Use
- Infections below diaphragm:
- Giardia
- Entamoeba
- Trichomonas
- Gardenerella
- Anaerobes
- H. Pylori
GET GAP on the Underground Metro!
Metronidazole Side Effects
-
Disulfiram-like rxn w/EtOH
- Inhibits aldehyde dehydrogenase → EtOH not metabolized → aldehyde buildup
- Metallic Taste / Dysgeusia
- Flushing
- Sweating
- Nausea
- Headache
- Hypotension
Aztreonam
- Monobactam
- MOA: Binds to PBP3 → prevents peptidoglycan cross-linking
Aztreonam Clinical Use
- GramNeg Rods
- Pts w/Penicillin Allergy
- Pts w/Renal Insufficiency who can’t take Aminoglycosides
Carbapenems
- Beta-lactamase resistant
- Imipenem + Ciliastatin to help drug stay in body longer (decrease inactivation in renal tubules)
- Gram + cocci
- Gram – rods
- Anaerobes
- CNS toxicity (seizures)
- GI distress
Examples of Carbapenems
- Imipenem (+cilistatin)
- Meropenem
Vancomycin
- binds D-ala-D-ala to inhibit cell wall peptidogycan formation
- Gram +
- Resistant organisms
- C. diff
- MRSA
- Enterococci
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- Red Man Syndrome
Sulfonamides
- bacteriostatic
- inhibit Dihydropteroate Synthase via PABA antimetabolites
- Use for:
- Gram +
- Gram –
- Nocardia
- Chlamydia
- Simple UTI
- Resistance:
- altered enzyme
- decreased uptake
- increased PABA synthesis
Examples of Sulfonamides
- Sulfamethoxazole (SMX)
- Sulfisoxazole
- Sulfadiazine
Sulfonamide Side Effects
- Hypersensitivity
- Nephrotoxicity
- Photosensitivity
- Kernicterus (high bilirubin) (infants)
- Hemolysis (if G6PDH deficient)
TMP-SMX
- Bactrim
- Trimethoprim-Sulfamethoxazole
- UTI
- Shigella
- Salmonella
- Pneumocystis jirovecii
Trimethoprim
- inhibits dihydrofolate reductase
- usually combined w/SMX
- Megaloblastic anemia
- Leukopenia
- Granuloycytopenia
- Leucovorin can alleviate S/E by replenishing folate
Rifampin
- inhibits DNA-dependent RNA polymerase
- Rapid resistance if used by itself
- Rx:
- TB
- Leprosy
- Meningococcal prophylaxis
- Red-orange secretions
- Hepatotoxicity
(Rifampin for RNA and Red-orange)
Isoniazid
- Activated by KATG bacterial catalase-peroxidase (INH-KATG)
- Inhibits Mycolic Acid synthesis
- Can cause B6 deficiency (heme, GABA)
- anemia
- seizures
- Hepatotoxicity
Pyrazinamide
- Unknown MOA
- Rx: TB
- Hyperuricemia
- Hepatotoxicity
Ethambutol
- Blocks arabinosyltransferase
- decreases carb polymerization of cell wall
- Rx: TB
- Red-green colorblindness
- Optic neuropathy
Rx for TB?
RIPES
- Rifampin
- INH
- Pyrazinamide
- Ethambutol
- Streptomycin
Rx Regimen for TB
- First 2-9mos: INH + Rifampin + Pyrazinamide + Ethambutol
- Continuation: INH + Rifampin
- Completion determined by total # doses (not total therapy time)
Resistant TB
- MDR TB: resistant to at least INH and Rifampin
- Rx: at least 5-7 drugs
- XMDR TB: resistant to isoniazid, rifampin, any fluoroquinolone, and either capreomycin, kanamycin, or amikacin
- Treatment continued for 18-24 months, or 12-18 months after culture becomes negative