Pharm antibacterial Flashcards
Which drugs target ?
folic acid synth (DNA methylation: Cell wall synth (peptidoglycan synth): Cell wall synth (peptidoglycan cross linking): The 30S subunit: 50S subunit: mRNA synth: Damages DNA: DNA topoisomerases:
folic acid synth (DNA methylation: sulfonamides, trimethoprim
Cell wall synth (peptidoglycan synth): glycopeptides (bacitracin, vancomycin)
Cell wall synth (peptidoglycan cross linking): penicillins, antipseudomonals, cephalosporins, carbapenems, monobactams
The 30S subunit: aminoglycosides, tetracyclines
50S subunit: chloramphenicol, clindamycin, linezolid, macrolides, and streptogramins
mRNA synth: Rifampin
Damages DNA: Metronidazole
DNA topoisomerases: Fluoroquinolones
What type of drug penicillin G, V? Mechanism? Toxicity? Resistance?
Beta lactam penicillinase sensitive penicillin
Binds PBPs, preventing them from crosslining peptidoglycan in cell wall
HSR
hemolytic anemia
Penicillinase in bacteria (beta lactamase)
What type of drugs are amoxicillin and ampicillin? How do they differ from other drugs in that category? Mechanism? What are they paired with? Why? Toxicity? Mechanism of resistance?
Penicillinase sensitive penicillins
Same as penicillin, but have wider spectrum
Clavulanic acid to protect against destruction by beta lactamase
HSR
Rash
Pseudomembranous colitis
Same as penicillin
What type of drugs are dicloxacillin, nafcillin, and oxacillin? Mechanism? Spectrum? clinical use? toxicity?
penicillinase resistant penicillins
same as penicillin; narrow spectrum
S. aureus
HSR, interstitial nephritis
What type of drugs are piperacillin and ticarcillin? mechanism? Clinical use? What is it used with? Why? Toxicity?
antipseudomonals
Same as penicillin
Pseudomonas and gram negative rods
Susceptible to penicillinase, must be used with beta lactamase inhibitors
HSR
What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?
Beta lactamase inhibitors
used with penicillin antibiotics to protect from destruction by beta lactamase
What type of drug penicillin G, V? Mechanism? Toxicity? Resistance? Organisms covered?
Beta lactam penicillinase sensitive penicillin
Binds PBPs, preventing them from crosslining peptidoglycan in cell wall
Gram positive, N. meningitidis, T. pallidum
HSR
hemolytic anemia
Penicillinase in bacteria (beta lactamase)
What type of drugs are amoxicillin and ampicillin? How do they differ from other drugs in that category? Mechanism? What are they paired with? Why? Toxicity? Mechanism of resistance? Organisms?
Penicillinase sensitive penicillins
Same as penicillin, but have wider spectrum
Clavulanic acid to protect against destruction by beta lactamase
HHELPSS kill enterococci
H. flu, H. pylori, E. coli, LIsteria, Proteus, Salmonella, Shigella, enterococci
HSR
Rash
Pseudomembranous colitis
Same as penicillin
What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?
Beta lactamase inhibitors
used with penicillin antibiotics to protect from destruction by beta lactamase
What is mechanism of cephalosporins? How do they differ from penicillin? What organisms typically arent covered? Toxicity? Mechanism of resistance?
beta lactam drugs that inhibit cell wall synth
Less susceptible to penicillinases
Bactericidal
LAME Listeria Atypicals MRSA Enterococci
HSR AIHA Disulfiram like RXN Vit. K defic Cross reactivity with penicillins Incr. nephrotoxicity with aminoglycosides
What type of drugs are cefazolin (1) and cephalexin? Clinical use? Organisms covered?
1st generation ceph
1=Used prior to surgery to prevent staph infection
PEcK Gram positive Proteus E. coli Klebsiella
What type of drugs are cefoxitin, cefaclor? Organisms covered?
2nd generation ceph
gram positive cocci
HEN PEcKS
H. flu Enterobacter Neisseria Proteus E. coli Klebsiella Serratia
What type of drugs are ceftriaxone (1), cefotaxime (2), and ceftazidime (3)? Organisms covered?
3rd generation ceph
Serious gram negative infections resistant to other beta lactams
1=meningitis, gonorrhea, disseminated lyme disease
3=pseudomonas
What type of drug is cefepime? Organisms?
4th generation ceph
Gram negative, with incr. activity against pseudomonas and gp organisms
What type of drug is ceftaroline? Organisms?
5th generation ceph
Broad gram positive and gran negative coverage
No pseudomonas
What is mechanism of cephalosporins? How do they differ from penicillin? What organisms typically arent covered? Toxicity? Mechanism of resistance?
beta lactam drugs that inhibit cell wall synth
Less susceptible to penicillinases
Bactericidal
LAME Listeria Atypicals MRSA Enterococci
HSR AIHA Disulfiram like RXN Vit. K defic Cross reactivity with penicillins Incr. nephrotoxicity with aminoglycosides
Structural change in PBPs
What type of drug is ceftaroline? Organisms?
5th generation ceph
Broad gram positive and gran negative coverage
No pseudomonas
What type of drug penicillin G, V? Mechanism? Toxicity? Resistance? Organisms covered?
Beta lactam penicillinase sensitive penicillin (2)
Binds PBPs, preventing them from crosslining peptidoglycan in cell wall
Gram positive, N. meningitidis, T. pallidum
HSR
hemolytic anemia
Penicillinase in bacteria (beta lactamase)
What type of drugs are amoxicillin and ampicillin? How do they differ from other drugs in that category? Mechanism? What are they paired with? Why? Toxicity? Mechanism of resistance? Organisms?
Penicillinase sensitive penicillins (2)
Same as penicillin, but have wider spectrum
Clavulanic acid to protect against destruction by beta lactamase
HHELPSS kill enterococci
H. flu, H. pylori, E. coli, LIsteria, Proteus, Salmonella, Shigella, enterococci
HSR
Rash
Pseudomembranous colitis
Same as penicillin
What type of drugs are dicloxacillin, nafcillin, and oxacillin? Mechanism? Spectrum? clinical use? toxicity?
penicillinase resistant penicillins (3)
same as penicillin; narrow spectrum
S. aureus
HSR, interstitial nephritis
What type of drugs are piperacillin and ticarcillin? mechanism? Clinical use? What is it used with? Why? Toxicity?
antipseudomonals (2)
Same as penicillin
Pseudomonas and gram negative rods
Susceptible to penicillinase, must be used with beta lactamase inhibitors
HSR
What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?
Beta lactamase inhibitors (3)
used with penicillin antibiotics to protect from destruction by beta lactamase
What type of drugs are cefazolin (1) and cephalexin? Clinical use? Organisms covered?
1st generation ceph (2)
1=Used prior to surgery to prevent staph infection
PEcK Gram positive Proteus E. coli Klebsiella
What type of drugs are cefoxitin, cefaclor? Organisms covered?
2nd generation ceph (2)
gram positive cocci
HEN PEcKS
H. flu Enterobacter Neisseria Proteus E. coli Klebsiella Serratia
What type of drug is ceftaroline? Organisms?
5th generation ceph
Broad gram positive and gran negative coverage
No pseudomonas
What type of drugs are imipenem (1), meropenem, ertapenem, and doripenem? Mechanism? What drug is “1” administered with? Why? Organisms? Clinical use? Toxicity?
Carbapenems (4)
Broad spectrum, beta lactamase resistant
Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decr. inactivation in renal tubules
GP cocci, GN rods, anaerobes; wide spectrum
Limited to life-threatening infections or after other drugs have failed due to side effects.
GI distress, skin rash, CNS toxicity (seizures) at high plasma levels.
What type of drug is aztreonam? Mechanism? What is it synergystic with? What does it not have a cross allergy with? Clinical use? Organisms? Toxicity?
Monobactam
Less susceptible to beta lactamases
Prevents peptidoglycan cross linking by binding to PBP3
Synergistic with aminoglycosides
No cross allergy with penicillins
Gram negative rods only
Use for penicillin allergic patients and those who cannot tolerate aminoglycosides (renal)
What is the mechanism of vancomycin? Clinical use? Organisms? Toxicity? prevention of toxicity? Mechanism of resistance?
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
Bactericidal
Not susceptible to beta lactamases
GP bugs only
use for serious, multi drug resistant organisms (MRSA, S. epidermidis, enterococcus (if sens), and C. diff (oral)
Well tolerated generally, but NOT trouble free
Nephrotoxicity, Ototoxicity, thrombophlebitis, diffuse flushing.
Red Man Syndrome
Pretreatment with antihist and slow infusion rate
Modification of D-ala D-ala to Dala D-lac.
“pay back 2 D-alas for vandalizing
What is the mechanism of vancomycin? Clinical use? Organisms? Toxicity? prevention of toxicity? Mechanism of resistance?
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
Bactericidal
Not susceptible to beta lactamases
GP bugs only
use for serious, multi drug resistant organisms (MRSA, S. epidermidis, enterococcus (if sens), and C. diff (oral)
Well tolerated generally, but NOT trouble free
Nephrotoxicity, Ototoxicity, thrombophlebitis, diffuse flushing.
Red Man Syndrome
Pretreatment with antihist and slow infusion rate
Modification of D-ala D-ala to Dala D-lac.
“pay back 2 D-alas for vandalizing
Which protein synth inhibitor drugs?
30S inhibitors:
50S inhibitors:
Irreversibly inhibit initiation complex by binding 30S:
Bind to 30S and prevent attachment of aminoacyl t-RNA at A subunit:
Block peptidyltransferase (transfer peptide to chain) at 50S subunit:
Block peptide transfer (translocation) at 50S:
Prevent formation of initiation complex by binding to 50S:
Inhibit protein synth by blocking translocation by binding to 23S rRNA of the 50S ribosomal subunit:
Static:
Cidal:
buy AT 30, CCEL at 50
30S inhibitors: Aminoglycosides, Tetracyclines
50S inhibitors: Chloramphenicol, Clindamycin, Erythromycin, Linezolid
Irreversibly inhibit initiation complex by binding 30S: Aminoglycosides
Bind to 30S and prevent attachment of aminoacyl t-RNA at A subunit: Tetracyclines
Block peptidyltransferase (transfer peptide to chain) at 50S subunit: Chloramphenicol
Block peptide transfer (translocation) at 50S: Clindamycin
Prevent formation of initiation complex by binding to 50S:
Linezolid
Inhibit protein synth by blocking translocation by binding to 23S rRNA of the 50S ribosomal subunit: Macrolides
Static: Macrolides, Clindamycin, Chloramphenicol, Tetracyclines
Cidal: Aminoglycosides
Which protein synth inhibitor drugs?
30S inhibitors:
50S inhibitors:
Irreversibly inhibit initiation complex by binding 30S:
Bind to 30S and prevent attachment of aminoacyl t-RNA at A subunit:
Block peptidyltransferase (transfer peptide to chain) at 50S subunit:
Block peptide transfer (translocation) at 50S:
Prevent formation of initiation complex by binding to 50S:
Inhibit protein synth by blocking translocation by binding to 23S rRNA of the 50S ribosomal subunit:
Static:
Cidal:
buy AT 30, CCEL at 50
30S inhibitors: Aminoglycosides, Tetracyclines
50S inhibitors: Chloramphenicol, Clindamycin, Erythromycin, Linezolid
Irreversibly inhibit initiation complex by binding 30S: Aminoglycosides
Bind to 30S and prevent attachment of aminoacyl t-RNA at A subunit: Tetracyclines
Block peptidyltransferase (transfer peptide to chain) at 50S subunit: Chloramphenicol
Block peptide transfer (translocation) at 50S: Clindamycin
Prevent formation of initiation complex by binding to 50S:
Linezolid
Inhibit protein synth by blocking translocation by binding to 23S rRNA of the 50S ribosomal subunit: Macrolides
Static: Macrolides, Clindamycin, Chloramphenicol, Tetracyclines
Cidal: Aminoglycosides
What kind of drugs are gentamicin, neomycin, amikacin, tobramycin, and streptomycin? Mechanism? What do they require for uptake? Implications? Organisms? Clinical use? Toxicity? Mechanism of resistance?
Aminoglycosides
Bactericidal
Irreversible inhibition of initiation complex by binding 30S subunit. Misreading RNA. Block translocation.
Require O2 for uptake. Don’t work against anaerobes.
Severe gram negative rod infections.
Synergistic with beta lactam antibiotics
Neomycin for bowel surgery
nephrotoxic, NM blockade, ototoxicity, teratogen
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation
What kind of drugs are tetracycline (1), doxycycline (2), minocycline (3) ? Mechanism? What should they not be taken with? Why? Organisms? Clinical uses? Clinical use of 2? Toxicity? CIs? Mechanism of resistance?
Tetracyclines
Bacteriostatic
Bind to 30S and prevent attachment of aminoacyl tRNA
Limited CNS penetration
Do not take with milk or antacids or iron containing preparations (divalent cations prevent gut absorption)
Borrelia Borgdorferi, M. pneumoniae, Rickettsia, Chlamydia
2=Fecally eliminated; good in renal failure
Used to treat acne
GI distress
Discoloration of teeth and inhibition of bone growht in children
Photosensitivity
CI in pregnancy
Decr. uptake or incr. efflux out of bacterial cells by plasmid encoded transport pumps.
What kind of drugs are tetracycline (1), doxycycline (2), minocycline (3) ? Mechanism? What should they not be taken with? Why? Organisms? Clinical uses? Clinical use of 2? Toxicity? CIs? Mechanism of resistance?
Tetracyclines
Bacteriostatic
Bind to 30S and prevent attachment of aminoacyl tRNA
Limited CNS penetration
Do not take with milk or antacids or iron containing preparations (divalent cations prevent gut absorption)
Borrelia Borgdorferi, M. pneumoniae, Rickettsia, Chlamydia
2=Fecally eliminated; good in renal failure
Used to treat acne
GI distress
Discoloration of teeth and inhibition of bone growht in children
Photosensitivity
CI in pregnancy
Decr. uptake or incr. efflux out of bacterial cells by plasmid encoded transport pumps.
What is mechanism of chloramphenicol? Clinical use/organisms? Toxicity? Mechanism of resistance?
Blocks peptidyltransferase at 50S
Static
Meningitis (H. flu, N. men, S. pneumo) and rocky mountain
Limited use due to toxicities, but still used in developing countries due to low cost
Anemia and aplastic anemia (dose dependent)
Gray baby syndrome (in premature infants b/c they lack liver UDP glucuronyl transferase)
Plasmid encoded acetyltransferase that inactivates the drug.
What is the mechanism of clindamycin? Clinical uses/organisms? Toxicity?
Blocks peptide transfer at 50S ribosomal subunit.
Static
Anaerobic infections (C. perfringens, Bacteroides spp) in aspiration pneumo, lung abscesses, and oral infections (above diaphragm). Also gainst invasive group A strep
Pseudomembranous colitis
fever
Diarrhea
What is the mechanism of linezolid? Clinical use/organisms? Toxicity? Mechanism of resistance?
Inhibit protein synth by binding 50S subunit and preventing formation of the initiation complex
GP including MRSA and VRE
Bone marrow suppression (especially thrombo)
periph neuro
Serotonin syndrome
Point mutation of Ribo RNA
Type of drug azithromycin, clarithromycin (1), erythromycin (2)? Mechanism? Clinical use/organisms? Toxicity? Drug interactions of 1/2? of all? Mechanism of resistance?
Macrolides
Inhibit protein synth by blocking translocation; bind to 23S rRNA of the 50S subunit
Static
Atypical pneumonias (mycoplasma, chlamydia, legionella)
STIs (chlamydia)
B. pertussis
MACRO GI motility issues Arrhythmia due to prolonged QT Cholestatic hepatitis (acute) Rash eOsinophilia
Increases serum conc. of theophyllines, oral anticoag
1/2 inhibit cytochrome P450
Methylation of 23S rRNA binding site prevents binding of drug.
Type of drug azithromycin, clarithromycin (1), erythromycin (2)? Mechanism? Clinical use/organisms? Toxicity? Drug interactions of 1/2? of all? Mechanism of resistance?
Macrolides
Inhibit protein synth by blocking translocation; bind to 23S rRNA of the 50S subunit
Static
Atypical pneumonias (mycoplasma, chlamydia, legionella)
STIs (chlamydia)
B. pertussis
MACRO GI motility issues Arrhythmia due to prolonged QT Cholestatic hepatitis (acute) Rash eOsinophilia
Increases serum conc. of theophyllines, oral anticoag
1/2 inhibit cytochrome P450
Methylation of 23S rRNA binding site prevents binding of drug.
What is the mechanism of trimethoprim? What drug is it used with? Clinical use/organisms? Toxicity?
inhibits DHFR
Static
Used with sulfonamides (TMP-SMX), sequential block of folate synth
Combination used for UTIs, Shigella, salmonella, PJP treatment and prophylaxis, and toxoplasmosis prophylax
Megaloblastic anemia, leukopenia, granulocytopenia
What type of drugs are sulfamethoxazole, sulfisoxazole, and sulfadiazine? Mechanism? What is a closely related drug? Clinical use/organisms? Toxicity? Mechanisms of resistance?
Sulfonamides
Inhibit folate synth (dihydropteroate synthase)
Static
Dapsone
GP, GN, Nocardia, chlamydia
Triple sulfas or SMX for simple UTI
HSR
Hemolysis if G6PD defic
nephrotoxicity (tubulointerstitial nephritis)
photosens
kernicterus in infants
displace other drugs from albumin (warfarin)
Altered enzyme (bacterial dihydropteroate synthase), decr. uptake, or incr. PABA synth (substrate in reaction)
What type of drugs are ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin? Mechanism? What can’t they be taken with? Clinical use/organisms? Toxicity? CIs? Mechanism of resistance?
Fluoroquinolones
Inhibit prokaryotic enzymes topoisomerase II (gyrase) and topo IV
Cidal
Can’t be taken with antacids
GN rods of urinary and GI tract infections (including pseudomonas)
Neisseria
Some GP organisms
GI upset Superinfections Rashes Headache Dizziness Leg cramps and myalgias
Pregnant women, nursing mothers, children under 18 (damage to cartilage)
Long QT
Tendonitis or tendon rupture in people > 60 and those taking prednisone
Chromosome encoded mutation in DNA gyrase, plasmide mediated resistance, efflux pumps.
What is the mechanism of daptomycin? Clincal use/organisms? What isn’t it used for? Why? Toxicity?
Lipopeptide that disrupts cell membrane of GP cocci
S. aureus skin infections (MRSA)
Bacteremia
Endocarditis
VRE
Not used in pneumonia (inactivated by surfactant)
Myopathy, rhabdomyolysis
What is the mechanism of daptomycin? Clincal use/organisms? What isn’t it used for? Why? Toxicity?
Lipopeptide that disrupts cell membrane of GP cocci
S. aureus skin infections (MRSA)
Bacteremia
Endocarditis
VRE
Not used in pneumonia (inactivated by surfactant)
Myopathy, rhabdomyolysis
Mechanism of metronidazole? Clinical use/organisms? Toxicity?
Forms free radical metabolites in the bacterial cell that damage DNA
Cidal
Antiprotozoal
Giardia, entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. diff), in triple therapy for H. pylori
Disulfiram like rxn with alcohol
headache
metallic taste
What drug is used as prophylaxis in M. tuberculosis? Treatment? M. avium-intracellulare? M. leprae?
TUBER
P: Isoniazid
T: Rifampin, Isoniazid, pyrazinamide, ethambutol
MAC
P: Azithromycin, rifambutin
T: more resistant than tuberc. Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin
LEP
P: N/A
T: Long term treatment with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.
What kind of drug are rifampin and rifabutin? Mechanism? Clinical use/organisms? Toxicity? Mechanism of resistance?
rifamycins
Inhibit DNA dependent RNA polymerase
M. tuber
Delay resistance to dapsone in leprosy
Prophylaxis in meningococcal, chemoprophylaxis in contacts of children with HiB
Minor hepatotoxicity P450 stim (less with butin, preferred in HIV pts) Orange body fluids (non hazardous)
Mutations reduce drug binding to RNAP
Monotherapy quickly leads to resistance
What is mechanism of isoniazid? Clinical use? Toxicity? Prevention? Mechanism of Resist?
Decr. synth of mycolic acids
Must be activated by bacterial catalase peroxidase (KatG)
M. tuber (prophylaxis and treatment)
Neurotoxicity
Hepatotoxicity
Pyridoxine can prevent neurotoxicity
Mutations leading to underexpression of KatG
What ist he mechanism of pyrazinamide? Clinical use? Toxicity?
Mechanism uncertain
Prodrug (pyrazinoic acid)
M. tuber
Hyperuricemia, hepatotoxicity
What is mechanism of ethambutol? clinical use? Toxicity?
Decr. carbohydrate polymerization of mycobacterium cell by blocking arabinosyltransferase
M. tuber
Optic neuropathy (red green color blindness) (eyethambutol)
