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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
What type of drug is ceftaroline? Organisms?
5th generation ceph Broad gram positive and gran negative coverage No pseudomonas
26
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.
27
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)
28
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
29
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
30
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
31
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
32
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
33
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.
34
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.
35
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.
36
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
37
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
38
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.
39
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.
40
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
41
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)
42
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.
43
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
44
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
45
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
46
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.
47
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
48
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
49
What ist he mechanism of pyrazinamide? Clinical use? Toxicity?
Mechanism uncertain Prodrug (pyrazinoic acid) M. tuber Hyperuricemia, hepatotoxicity
50
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)

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