Antimicrobial Flashcards
Block Peptidoglycan Crosslinking
- Penicilin, cephalosporin, azotreonam, imipenim
- Bind to PBP and prevent crosslinking
Block peptidoglycan Synthesis
Vancomycin
Block Nucleotide production
- Trimethoprim blocks DHFR
- Sulfamethoxazole blocks PABA sythase
Block Topoisomerase
-Flouroquinolones
Block RNA polymerase
-Rifampin
Damage DNA
-Metronidazole
Block 50S ribosome
- CELL
- Macrolides, Clindamycin, Chloramphenicol, Lincosamide, linzolid, streptogrammins
Block 30S
-Aminoglycosides and tetracyclines
Penicilin
- Binds to PBP and prevents crosslinking
- Effective against gram positive and some gram negative
- Treponema, GAS, Strep Pneumo, Actinomyces
- SE: Hapten mediated hypersensitivity (hemolysis)
- Susceptible to beta lactamase
Methiciln, oxacilin etc
- Bulky side group means lower risk of peniclinase
- Used specifically for MSSA
- Mutation in PBP
Ampicilin
- INcreased effectivness against gram negatives
- H Flu, Listeria, E Coli, Salmonella, SHhigella, etc
- Give with clauvulonate to reduce beta lactamases
- S/E: Pseudomembrane colitis
Piperacilin, ticracilin
- Used for pseudomonas
- GIve with tazobactam a beta lactamase inhibitor
Beta Lactamase inhibitors
-Suicide inhibitors
Cephalosporins
-Beta lactams that are wider spectrum and less vulnerable to beta lactamases
Cefazolin (1st gen)
-Used as prophylaxis against MSSA and for surgical procedures
Cefoxitin
-INcreased use for H flu etc, replaced by 3rd gen
Ceftriaxonem ceftazadime
- Used for NIsseria, and serious gram negative infections
- Crosses BBB and is part of meningitis prophylaxis
Cefepime 4th gen
-Used against pseudomonas
Ceftaroline
-Can be used for MRSA
Azotreonam
- Gram negative rods only
- Resistant to beta lactams
- Given to pen allergic patietns who can’t take aminoglycosides because of renal failure
Imipenem/Cilastatin, meropenam
- Wide spectrum and effective
- Resistant to beta lactamases
- Always give with cilastatin to prevent destruction in kidney
- Usually saved for severe life thretening infections
- Causes siezures and has seen limited use because of this
Vancomycin
- Inhibits peptidoglycan synthesis
- Gram positive only, MRSA or C Dif not given metronidazole
- S/E: Oto and nephrotoxicity. Red mann’s syndrome (Avoid with anti-histamines), thrombophlebitis,
- Resistance due to mutations of Ala-Ala to Ala-Lactate
Protein Synthesis Inhibitors
- 30S are aminoglycosides and tetracyclines
- 50s are Clindamycin, macrolides, chloramphenicol, linezolid, lincosamide, Streptogrammins (Dalfoprastone, quinipristin)
- Majority of resistance is by acetylation or methylation of ribosomes
Aminoglycosides
- Inhibit initation and cause misreading of early protein synthesis
- Cidal and synergistic with beta lactams
- Ototoxicity (worse with loop diuretics)
- Nephrotoxicity (worse with cephalosporins)
- Can also cause neuromuscular blockade and is a teratogen
- Must be taken up with oxygen and are not effective agatinst anaerobes
Tetracyclines
Bind to 30S and prevent attachment of aminoacyl tRNA
- Static activity
- Highly effective against bone and intracellular organisms because of tendency to accumulate intracellularl
- Zoonotics, ricketsia, chlamydia, Borellia, etc
- Cause discoloration and disformation of bones teratogen
- Most cannot be given to renally impaired, but doxyxlycine can
- Can’t be taken with divalent cations or else absorption will be messed up
- Photosensitivity is also a S/E
- Resistance by efflux pumps
Macrolides
- Bind to 50s subunit and prevent translocation
- Static
- Used against atypical Pneumonias, STD’s and gram positives that are allergic to penicilin
- Motilin agonist causes GI problems including cholestatic hepatitis
- Also inhibits P450s and can cause elevations in warfarin
- Prolonged QT
- Methylation of Ribosime is resistance
Chloramphenicol
- Binds 50s and prevents translocation
- Rarely used because of risk of aplastic anemia and gray baby syndrome (decreased UDP gluconyrl transerase)
- Used only as last resort against atypical meningitis
- Resistance by acetylation
Clindaymycin
- Used against anaerobes only not active against aerobes
- Used to treat infections above diaphragm, metronidazole below (oral infections and aspiration pneuonias)
- Can cause pseudomembranous colitis
Sulfonamides
- Block Dihydroberopterin synthesis leading to decreased PABA, competitive inhibitors
- Use is mainly for UTI’s and PCP
- PRevent Thymidine synthesis
- Sulfa reactions,
- Also displace bilirubin, warfarin etc from albumin and can cause kernicterus
- Resistance by increasig PABA production
Trimethoprime
- Inhibits DHFR
- Used for PCP etc
- Can cause megaloblastic anemia and BM supression
- Leucovarin can rescue
Flouroquinilones
- Inhibit toposimerase II and IV
- Bacteriocidal activity
- Absorption will be inhibited by divalent cations
- Can cause tendonous rupture and impaired collagen synthesis in fetus
Metronidazole
- Generates free radicals that damage and destroy DNA
- Bacteriocidal
- Used for anaerobes and protozoal infections below diaphragm
- Disulfaram reaction and metallic taste
TB Drugs
- MTB is RIPE
- MAI is atypical pneumonia treated with azythromycin, prophylax once CD4 drops low
- Leparae is Daptomycin, Rifampin, and clofroinox (guanosine)
INH
- Prevents synthesis of mycolic acids
- Can be used alone as prophylaxis
- Causes depletion of vitamin B6
- Neurotox (supplement B6 to minimize)
- Hepatotox
Rifampin
- Inhibits RNA polymerase in bacteria
- Not used as monotherapy for TB
- Can be used to prophylax against H Flu and Meningitids
- Causes red orange body fluids and reduces T1/2 of other drugs (increases P450s)
Pyrazinamide
- May cause acidity in phagolysosomes
- Minimal S/E with Hypeuricemia and hepatotox
Ethambutol
- Impairs arabinotransferase and inhibits sugar incorporation into wall
- Caues red Green Color blindness
VRE
-Streptogrammins and linezolid
MRSA
-Vanco and ceftaroline
Amphoteracin B
- Binds ergosterol in membrane and creates pores causing cell death
- Strong with severe painful chills and nephrotoxicity, give with Mg, K, and fludis to minimize kidney damage.
- Doesn’t cross BBB, give intrathecally
Azoles
- Prevent ergosterol synthesis P450 enzyme
- Gynecomastia and inhibit steroid synthesis
- Block P450 and increase drug concentraions of others
- Prophylax in HIV
Nystatin
-Same as amphoteracin by applied topically
Flucytosine
- Converted to 5-FU intracellularly, strong and given for severe infections
- Causes BM supression by inhibiting Thymidine synthesis at thymitidylate synthase
Caspofungin
- Inhibits D glucan insertion into cell wall
- Weaker and more mild
Terbenafine
- Squalene epoxidase inhibits
- Minimal S/E, can be used chronically for dermatophytes
Griseofulvin
- Inhibits MT polymerization
- Activator of P450s
- Teratogen, Carcinogen
Chloroquine
- Used for malaria, prevents heme breakdown to hemazolin and thus accumulates to toxic levels inside RBC and kills malaria
- Give primaquine for ovale/vivax
- Quinidine for serious infections
- Resistance because of efflux pump
- S/E: Retinopathy
Zanamavir, oseltamavir
-Inhibit viral neuraminidase and prevent release of Flu A and B
Ribairan
- Inhibits IMP dehydratase leading to decreaed guanine production and dereased synthesis
- Paraflu, RSV, Hep C
IFN B
-MS
INF A
-Hep C, increase MHC, increase DNAase, decrease translation machinery
IFN gamma, IL-8
Increase intracellular killing by macrophages in CGD
Acyclovir
ACtivated by TK, inhibits viral DNA pol
Minimal S/E
-HSV and VZV
Ganciclovir
Activated by CMV kinase
- Inhibits DNA pol
- Nephrotoxicity and BM supression
Foscarnet
- Non kinase activated inhibitor of DNA pol
- Nephrotox
- Used in refractory cases
Cidofivir
- Non kinase activated inhibitor of DNA pol
- Nephrotoxicity, give with probenacid
HARRT
2 NTRIs and then 1 (NNTRI, Prtoease, or integrase inhibitor)
NTRI
Need to be phosphprylated to work (Except for tenofivir)
-BM supression and nephrotoxicity
Zidovudine can be used as prophylaxis to babies
NNTRI
Do not need to be phosphorylated and bind at different site than NTRI
Protease inhibtiors
- end in Navir
- Metabolic syndrome and lipdystrophy
Ralteravir
Integrase inhibitor
-S/E is hypercholesterolemia
Marivaroc
CCR5 inhibtitor
