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Step One > Pharm antibacterial > Flashcards

Pharm antibacterial Flashcards

1
Q

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:
A

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

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2
Q

What type of drug penicillin G, V? Mechanism? Toxicity? Resistance?

A

Beta lactam penicillinase sensitive penicillin

Binds PBPs, preventing them from crosslining peptidoglycan in cell wall

HSR
hemolytic anemia

Penicillinase in bacteria (beta lactamase)

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3
Q

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?

A

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

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4
Q

What type of drugs are dicloxacillin, nafcillin, and oxacillin? Mechanism? Spectrum? clinical use? toxicity?

A

penicillinase resistant penicillins

same as penicillin; narrow spectrum

S. aureus

HSR, interstitial nephritis

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5
Q

What type of drugs are piperacillin and ticarcillin? mechanism? Clinical use? What is it used with? Why? Toxicity?

A

antipseudomonals

Same as penicillin

Pseudomonas and gram negative rods

Susceptible to penicillinase, must be used with beta lactamase inhibitors

HSR

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6
Q

What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?

A

Beta lactamase inhibitors

used with penicillin antibiotics to protect from destruction by beta lactamase

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7
Q

What type of drug penicillin G, V? Mechanism? Toxicity? Resistance? Organisms covered?

A

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)

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8
Q

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?

A

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

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9
Q

What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?

A

Beta lactamase inhibitors

used with penicillin antibiotics to protect from destruction by beta lactamase

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10
Q

What is mechanism of cephalosporins? How do they differ from penicillin? What organisms typically arent covered? Toxicity? Mechanism of resistance?

A

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
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11
Q

What type of drugs are cefazolin (1) and cephalexin? Clinical use? Organisms covered?

A

1st generation ceph

1=Used prior to surgery to prevent staph infection

PEcK
Gram positive
Proteus
E. coli
Klebsiella
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12
Q

What type of drugs are cefoxitin, cefaclor? Organisms covered?

A

2nd generation ceph

gram positive cocci
HEN PEcKS

H. flu
Enterobacter
Neisseria
Proteus
E.  coli
Klebsiella
Serratia
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13
Q

What type of drugs are ceftriaxone (1), cefotaxime (2), and ceftazidime (3)? Organisms covered?

A

3rd generation ceph

Serious gram negative infections resistant to other beta lactams

1=meningitis, gonorrhea, disseminated lyme disease
3=pseudomonas

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14
Q

What type of drug is cefepime? Organisms?

A

4th generation ceph

Gram negative, with incr. activity against pseudomonas and gp organisms

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15
Q

What type of drug is ceftaroline? Organisms?

A

5th generation ceph

Broad gram positive and gran negative coverage
No pseudomonas

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16
Q

What is mechanism of cephalosporins? How do they differ from penicillin? What organisms typically arent covered? Toxicity? Mechanism of resistance?

A

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

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17
Q

What type of drug is ceftaroline? Organisms?

A

5th generation ceph

Broad gram positive and gran negative coverage
No pseudomonas

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18
Q

What type of drug penicillin G, V? Mechanism? Toxicity? Resistance? Organisms covered?

A

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)

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19
Q

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?

A

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

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20
Q

What type of drugs are dicloxacillin, nafcillin, and oxacillin? Mechanism? Spectrum? clinical use? toxicity?

A

penicillinase resistant penicillins (3)

same as penicillin; narrow spectrum

S. aureus

HSR, interstitial nephritis

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21
Q

What type of drugs are piperacillin and ticarcillin? mechanism? Clinical use? What is it used with? Why? Toxicity?

A

antipseudomonals (2)

Same as penicillin

Pseudomonas and gram negative rods

Susceptible to penicillinase, must be used with beta lactamase inhibitors

HSR

22
Q

What kind of drugs are clavulanic acid, sulbactam, and tazobactam? Clinical use?

A

Beta lactamase inhibitors (3)

used with penicillin antibiotics to protect from destruction by beta lactamase

23
Q

What type of drugs are cefazolin (1) and cephalexin? Clinical use? Organisms covered?

A

1st generation ceph (2)

1=Used prior to surgery to prevent staph infection

PEcK
Gram positive
Proteus
E. coli
Klebsiella
24
Q

What type of drugs are cefoxitin, cefaclor? Organisms covered?

A

2nd generation ceph (2)

gram positive cocci
HEN PEcKS

H. flu
Enterobacter
Neisseria
Proteus
E.  coli
Klebsiella
Serratia
25
Q

What type of drug is ceftaroline? Organisms?

A

5th generation ceph

Broad gram positive and gran negative coverage
No pseudomonas

26
Q

What type of drugs are imipenem (1), meropenem, ertapenem, and doripenem? Mechanism? What drug is “1” administered with? Why? Organisms? Clinical use? Toxicity?

A

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.

27
Q

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?

A

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)

28
Q

What is the mechanism of vancomycin? Clinical use? Organisms? Toxicity? prevention of toxicity? Mechanism of resistance?

A

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

29
Q

What is the mechanism of vancomycin? Clinical use? Organisms? Toxicity? prevention of toxicity? Mechanism of resistance?

A

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

30
Q

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:

A

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

31
Q

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:

A

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

32
Q

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?

A

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

33
Q

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?

A

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.

34
Q

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?

A

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.

35
Q

What is mechanism of chloramphenicol? Clinical use/organisms? Toxicity? Mechanism of resistance?

A

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.

36
Q

What is the mechanism of clindamycin? Clinical uses/organisms? Toxicity?

A

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

37
Q

What is the mechanism of linezolid? Clinical use/organisms? Toxicity? Mechanism of resistance?

A

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

38
Q

Type of drug azithromycin, clarithromycin (1), erythromycin (2)? Mechanism? Clinical use/organisms? Toxicity? Drug interactions of 1/2? of all? Mechanism of resistance?

A

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.

39
Q

Type of drug azithromycin, clarithromycin (1), erythromycin (2)? Mechanism? Clinical use/organisms? Toxicity? Drug interactions of 1/2? of all? Mechanism of resistance?

A

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.

40
Q

What is the mechanism of trimethoprim? What drug is it used with? Clinical use/organisms? Toxicity?

A

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

41
Q

What type of drugs are sulfamethoxazole, sulfisoxazole, and sulfadiazine? Mechanism? What is a closely related drug? Clinical use/organisms? Toxicity? Mechanisms of resistance?

A

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)

42
Q

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?

A

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.

43
Q

What is the mechanism of daptomycin? Clincal use/organisms? What isn’t it used for? Why? Toxicity?

A

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

44
Q

What is the mechanism of daptomycin? Clincal use/organisms? What isn’t it used for? Why? Toxicity?

A

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

45
Q

Mechanism of metronidazole? Clinical use/organisms? Toxicity?

A

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

46
Q

What drug is used as prophylaxis in M. tuberculosis? Treatment? M. avium-intracellulare? M. leprae?

A

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.

47
Q

What kind of drug are rifampin and rifabutin? Mechanism? Clinical use/organisms? Toxicity? Mechanism of resistance?

A

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

48
Q

What is mechanism of isoniazid? Clinical use? Toxicity? Prevention? Mechanism of Resist?

A

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

49
Q

What ist he mechanism of pyrazinamide? Clinical use? Toxicity?

A

Mechanism uncertain
Prodrug (pyrazinoic acid)

M. tuber

Hyperuricemia, hepatotoxicity

50
Q

What is mechanism of ethambutol? clinical use? Toxicity?

A

Decr. carbohydrate polymerization of mycobacterium cell by blocking arabinosyltransferase

M. tuber

Optic neuropathy (red green color blindness) (eyethambutol)

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