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Antibacterial Drugs Flashcards

1
Q

What is Prophylaxis?

A

A decrease in pathogens most likely to cause infection. * 1/4 to 1/2 of antibacterial drugs use is for prophylaxis.

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2
Q

What is Empiric Therapy?

A

So you have an infection, but don’t know who is responsible so you use an agent know to be effective against the most likely pathogen.

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3
Q

Gram + bacteria includes many _______.

A

Lactamases *Not many in gram - bacteria

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4
Q

What is MIC?

A

Minimum inhibitory concentration = lowest concentration of drug which completely inhibits growth at 24hrs. * 5-10x MIC is desired as systemic concentration.

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5
Q

What are the Common Mechanisms of action of antibacterials? (5 ways)

A
  1. Inhibition of Nucleic Acid synthesis
  2. DNA Damaging Agents
  3. Inhibition of cell wall synthesis
  4. Damaging cell Membrane
  5. Inhibitors of Protein synthesis (Ribosomal protein binding 30S or 50S)
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6
Q

Tell me about Sulfonamides….

A

Ultimately: They inhibit Nucleic Acid Synthesis
Mechanism: Competitive inhibitor of Dihydorpteroate synthase require to make FOLIC ACID.
* Considered BACTERIOSTATIC
Spectrum of use: Gram positive and Gram negative

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7
Q

Sulfa drugs displace albumin bound bilirubin, why is this significant?

A

Kernicterus can occur = Bilirubin can cross BBB in newborn leading to Encephalopathy. * This is Dose related

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8
Q

What are Dose unrelated effects of Sulfadrugs?

A
  • Hypersensitivity = rash/ stevens-johnsons syndrome

- Photosensitivity

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9
Q

What are Dose Related effects of sulfa drugs?

A
  • Crystalluria = why you should take plenty of water with these drugs.
  • Hemolytic anemia
  • Kernicterus = Encephalopathy
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10
Q

Tell me about Trimethoprim….

A

Ultimately: It inhibits Nucleic Acid synthesis
Mechanism: Inhibits Dihydrofolate Reductase
* BACTERIOSTATIC
* Require much higher concentration to inhabit human compared to bacterial DHFR so it has good selectivity.
Spectrum: Broad spectrum against gram negative and positive.

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11
Q

What are the toxicity concerns with Trimethoprim?

A

Blood dycrasias

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12
Q

Tell me about Rifampin…..

A

Ultimately: it inhibits Nucleic acid synthesis
Mechanism: binds to and inhibits RNA polymerase
*BACRIOCIDAL
* Resistance induction is rapid so its not used by itself.
*Doesn’t bind to Human RNA polymerase = good selectivity.
Spectrum: Potent against M. TUBERCULOSIS!

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13
Q

Tell me about the toxicity of Rifampin….

A

Liver damage (jaundice)

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14
Q

What is the Mechanism of Quinolones?

A

(ULTIMATELY: DNA DAMAGING AGENT) These agents inhibit DNA replication through “poisoning” of DAN Gyrase A ahead of the replication fork. Quinolone also inhabit separation of newly replicated strands of DNA though inhibition of DNA Topoisomerase IV.
*Bactericidal

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15
Q

What is the Antibacterial spectrum of Quinolones?

A

Effective against Gram Positive or Gram negative Bacteria.

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16
Q

What are the major clinical uses of Quinolones?

A

UTI’s
Respirtory tract infections
Anti-tubercular
*Ciproflaxin and levofloxacin are effective against PSEUDOMONAS AERUGINOSA (gram negative)

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17
Q

What is the mechanism of Nitrofurans?

A

(Ultimately: DNA DAMAGE) caused by the formation of oxygen free radicals subsequent to reduction of nitro group.

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18
Q

What is the antibacterial spectrum of Nitrofurans?

A

Broad spectrum against gram positive and negative bacteria, but not EFFECTIVE AGAINST P. AERUGINOSA (gram negative)

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19
Q

What are the clinical uses of Nitrofurans?

A

only used for renal tract infections

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20
Q

What is the mechanism for Methenamine?

A

(ULTIMATELY: DNA DAMAGE) It gets hydrolyzed at acid pH to form formaldehyde, so it denatures proteins and damages DNA. BACTERICIDAL

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21
Q

What are the clinical uses for Methenamine?

A

Gram negative spectrum lower urinary tract infections (rarely used though).
*Not effective against pseudomonas, proteus due to their ability to metabolize ureas resulting in a rise in pH and prevention of formaldehyde generation.

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22
Q

What is the mechanism for Metronidazole?

A

(DNA DAMAGE) via Reductive activation of nitro group specifically in ANAEROBIC bacteria leads to free radical species and reactive intermediates that bind to and affect DNA function. Also activates DNA damage is some Protozoa.

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23
Q

What is the antibacterial spectrum of Metronidazole?

A

Bactericidal against most OBLIGATE ANAEROBIC gram positive and negative bacteria. *not effective against facultative anaerobes. *works on some protozoa.

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24
Q

What are the clinical uses of Metronidazole?

A

Anaerobic bacterial infections and some protozoal infections

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25
Inhibitors of bacterial cell wall synthesis are only bactericidal when?
When cells are growing.
26
Why L-forms of bacteria and mycoplasma resistant to inhibitors of cell wall synthesis?
They lack cell walls!
27
What is the mechanism of Cycloserine?
It inhibits L-ala to D-ala and the linkage of two D-ala in cell wall synthesis.
28
What is the Mechanism of Bacitracin?
It binds to isopropyl phosphate so it can't be used as a carrier (in cell wall synthesis)
29
What is the Mechanism of Vancomycin?
It prevents the transfer of Sugar-pentapeptide form carrier molecule to growing peptidoglycan chain. (Inhibition of Peptidoglycan synthase in cell wall synthesis) *IN GRAM POSITIVE BACTERIA!
30
What is the GENERAL Mechanism of Beta-Lactams (Penicillin, Cephalosporins, Monobactams, Carbapenems, B-lactamase inhibitors)?
Act by binding to various penicillin-binding proteins and inhibiting transpeptidation reaction (in Cell wall synthesis)
31
What is the antibacterial spectrum of Vancomycin?
Gram postive bacteria
32
What is the Mechanism of Penicillin?
Mimics D-ala D-ala structure of pentapeptide on peptidoglycan and ties up transpeptidase. BACTERICIDAL *GRAM POSITIVE
33
What is the selectivity of all Beta-Lactams?
Well, eukaryotic cells do not contain cell walls so there is no direct cytotoxic effects to host!
34
What are the clinical uses of Penicillins (There are a bunch of types)?
Streptococcus Pneumonia = Pneumonia, Meningitis otitis meda, Bacteremia. STD's UTI's Haemophilus influenza.
35
Penicillins are _____ dependent Drugs.
Time dependent = conc. must be maintained for sufficient time period to inhabit cell wall synthesis and kill all bacteria.
36
What is the mechanism for Cephalosporins?
Same as penicillin (BACTERICIDAL) except
37
What is the antibacterial spectrum for Cephalosporins?
1st gen = CEFAZOLIN Gram positive only 2nd gen = Some gram negative activity 3rd and 4th Gen = all have greater effectiveness against gram negative but effectiveness against gram positive decreases!
38
What are the 3rd and 4th Gen Cephalosporins?
3rd = Ceftazidime & Ceftriaxone 4th = Cefepime & Ceftolozane *All effective against gram negative, not as much against gram positive.
39
What are the only 2 Cephalosporins effective against Pseudomonas?
Ceftazidime (3rd gen) | Cefepime (4th Gen)
40
What is the antibacterial spectrum of Carbapenems (Imipenem)?
Broad spectrum against gram negative and positive. * Binds with high affinity to PBP-1 and 2 of gram negative bacteria. * USE is reserved for serious nosocomical infections "restricted drug".
41
What is the antibacterial spectrum of Monobactams (aztreonam)?
Effective against AEROBIC GRAM NEGATIVE including P. Aeruginosa. *No gram positive activity!
42
What is the Mechanism of Vancomycin?
Binds to Carboxy terminus of D-ala-D-ala and inhibits peptidoglycan synthase and transpeptidation reaction. *CONSIDERED MORE BACTERIOSTATIC
43
What is the major clinical problem of Vancomycin?
RESISTANCE! S. Aureus and Enterococcus faecium strains can have altered D-ala D-ala peptide structures so Vancomycin doesn't bind as readily. *Toxicity has shown hearing loss as a dose related effect, and some renal toxicity.
44
What is the antibacterial spectrum of Vancomycin?
Narrow spectrum = active against GRAM POSITIVE Staphylococci, streptococci, E. Faecalis. *LARGE SIZE of vancomycin means it can't penetrate outer membrane of gram negative bacteria!
45
What is a common clinical use of Vancomycin?
Often used to treat methicillin resistant staphylococci (MRSA-Type)
46
What is the Mechanism of Bacitracin?
It binds to Isoprenyl-posphate lipid carrier, inhibits Dephosphorlyation and utilization.
47
What is the antibacterial spectrum of Bacitracin?
Mostly against gram positive, some activity against gram negative though.
48
What are the clinical uses of Bacitracin?
Superficial skin and ophthalmic infections
49
What is the Mechanism of Polymyxins?
(CELL MEMBRANE DAMAGING) acts as bacterial cationic detergent and disrupts cell membrane (pokes holes in it) BACTERIOCIDAL.
50
What is the antibacterial spectrum of Polymyxins?
GRAM NEGATIVE
51
What are the clinical uses of Polymyxins?
Good against Pseudomona infection in ears and eyes by topical administration. *also against acinetobacter *NEPRHOTOXICITY NOTED!
52
What is the mechanism of Daptomycin?
(CELL MEMBRANE DAMAGING) Insertion of lipophilic tail into cell membranes cause membrane depolarization, K+ efflux and disruption of DNA, RNA and protein synthesis. *BACTERICIDAL
53
What is the antibacterial spectrum of Daptomycin?
For gram positive ONLY because it binds to LPS layer in gram negative upon insertion of lipophilic tail and can't get to plasma membrane.
54
What are the clinical uses of Daptomycin?
Not effective in lung infections (inactive pulmonary surfactants) but is good against methicillin resistant staphylococcus aureus (MRSA)
55
What is the Mechanism for Aminoglycosides?
(INHIBITOR OF PROTEIN SYNTHESIS) Bind to proteins in interface between 30s and 50S. - Interfere with tRNA attachment - Block activity of initiating complex - Distortion of mRNA triplet condon - Polysome breakdown to monosomes. * BACTERICIDAL
56
What is the mechanism of Tetracylines?
(INHIBITOR OF PROTEIN SYNTHESIS) Bind to 30s and blocking binding of RNA to mRNA. BACTERIOSTATIC
57
What is the mechanism of Chloramphenicol?
(INHIBITOR OF PROTEIN SYNTHESIS) Binds to 50s, inhibits Peptidyl transferase by preventing attachment of AA end of aminoacyl-tRNA to the A site. BACTERIOSTATIC
58
What is the mechanism of Clindamycin?
(INHIBITOR OF PROTEIN SYNTHESIS) binds to 50s (can be displaced by Chloramphenicol since it binds to same target site) BACTERIOSTATIC
59
What is the mechanism of Erythromycin?
(INHIBITOR OF PROTEIN SYNTHESIS) Binds to 50s close to clindamycin, inhibits translocation, causes release of oligo-peptidyl-tRNA *BACTERIOSTATIC
60
What is the Mechanism of Quinupristin?
(INHIBITOR OF PROTEIN SYNTHESIS) Binds to 50s, stimulates dissociation of the Peptidyl- tRNA * BACTERICIDAL
61
What is the Mechanism of Dalfopristin?
(INHIBITOR OF PROTEIN SYNTHESIS) Binds 50s, prevents binding of aa-tRNA to acceptor site. *BACTERICIDAL
62
___ and _____ are only used in combination.
Quinupristin and Dalfopristin
63
What is the mechanism of Linezolid?
(INHIBITOR OF PROTEIN SYNTHESIS) Binds 50s, block formation of the initiation complex. * BACTERIOSTATIC
64
None if these Inhibitors of protein synthesis cause problems with hosts because ______ with the exception of______.
They dont bind to mammalian ribosome (80S) except for tetracyline.
65
What is the spectrum of Aminoglycosides?
Effective against gram negative bacteria, especially pseudomonal species
66
Which drugs are concentration dependent?
Aminoglycosides, Quinolone and Daptomycin
67
Which drugs are Time dependent?
B-lactams, Vancomycin and Quinolones
68
What is the spectrum of Tetracycline?
Broad spectrum, gram negative and positive. Effective against Rickettsiae, Mycoplasma, Chlamydia, Protozoa... *RESISTANCE VIA: increased efflux pump, decreased binding to ribosomes.
69
What is the spectrum of Tigecycline?
Broad spectrum against gram positive and negative bacteria, including ANAEROBES!
70
What is spectrum of Chloramphenicol?
Broad spectrum gram positive and negative (effective against rickettsial infection when tetracycline is not) *EXTREMELY LIMTED USE DUE TO POETICAL FATAL SIED EFFECT KNOW AS APLASTIC ANEMIA!
71
What is the Spectrum of Macrolides (Erythromycin, Acithromycin, Clarithromycin)?
Bacteriostatic and Bactericidal against mostly gram positive bacteria. Effective against M. Pneumonia and ear and sinus infections in children. (PRETTY SAFE)
72
What is the spectrum of Ketolide (Telithromycin)?
Treatment of respiratory tract infections. Effective against gram positive and gram negative bacteria that cause CAP. (Strep., Staph. Aureas and Haemophilus Influenza) *also effective against macrolide resistant strains
73
What is the toxicity of Ketoglide?
Liver toxicity
74
What is the Spectrum of Clindamycin?
Gram positive bacteria Staph and Strep (but not Enterococci) and anaerobes!
75
What is the toxicity of Clindamycin?
Pseudomembranous colitis caused by toxin from C. diff!
76
What is the spectrum of Quin/Dalfopristin?
Mainly against gram positive MRSA Vancomycin resistant E. Faecium * Toxicity includes phlebitis and myalgias
77
What is the spectrum of Linezolid?
Broad activity against gram positive isolates | *Toxicity = myelosupression
78
What is the Mechanism of Mupirocin?
Inhibits isoleucyl tRNA synthase
79
What is the Spectrum of Mupirocin?
Topical gram postive and gram negative bacteria
80
Tell me about Aminoglycoside Toxicity....
Ototoxicity = cochlear (Irreversible) Nephrotoxicity = relates to proximal tubular cell accumulation of aminoglysosides. (Reversible) Neuromuscular blockade = skeletal weakness, respiratory depression.
81
What are the Gram positive bacteria?
Staphylococcus, Streptococcus, Enterococci, Clostridium, Bacillus, Cornyebacterium, listeria. (SSCCBL)

Pharm Final (1 decks)

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