Antimicrobial 1: Agents that Target the Bacterial Cell Wall or Folic Acid Metabolism Flashcards

1
Q

what are antivirals?

classification?

A

Describes drugs that kill viruses
• Antivirals are not considered antimicrobials

Bactericidal
- agents that interfere with bacterial cell wall
synthesis or inhibit crucial enzymes that kill bacteria

Bacteriostatic
- agents that inhibit protein synthesis and prevent
bacterial growth and/or replication

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2
Q

what different conditions/disorders (both acute and chronic) are the result of bacterial infections

A
– Food Poisoning
– Sexually Transmitted Infections (STIs)
– Whooping Cough
– Pneumonia
– Tuberculosis
– Respiratory Tract Infections
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3
Q

Name 2 classes of antibiotics Targeting Folate Synthesis

A

– Sulfonamides (sulfa antibiotics)

– Folic acid antagonists (trimethoprim, pyrimethamine)

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4
Q

Sulfonamides

drugs

A
– Sulfanilamide
– Sulfamethoxazole
– Sulfasalazine (GI, RA)
– Sulfadiazine
– Sulfadoxine (Anti-Malarial)
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5
Q

Sulfonamides

MOA?

A
  • Are structural analogs of PABA and competitively inhibit dihydropteroate synthetase which turns PABA to dihydropteroic acid and later dihydrofolic acid
  • Folic acid is required to synthesize purines & pyrimidines, which are required by bacteria to synthesize DNA and RNA
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6
Q

Sulfonamides

AE? (4)

A
– *Hepatitis
– Hypersensitivity reactions (Stevens-Johnson syndrome)
– *Bone marrow depression
– *Acute renal failure
– *Cyanosis
– Nausea, Vomiting, Headache
– Depression
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7
Q

Folic acid antagonists

name 2

A

– Trimethoprim

– Pyrimethamine

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8
Q

Folic acid antagonists

MOA

A
  • Are folate antagonists that structurally resemble the pteridine moiety of folate, thereby inhibiting the bacterial dihydrofolate reductase
    – When combined with sulfonamides you get potentiated actions on decreasing bacterial DNA/RNA synthesis
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9
Q

Folic acid antagonists

AE

A
– *Folate deficiency
– *Megaloblastic anemia
– Nausea, Vomiting
– Blood disorders/dyscrasias
– Rashes
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10
Q

β-Lactam Antibiotics

4 classes

A

target peptidoglycan synthesis

– Penicillins
– Cephalosporins
– Carbapenems
– Monobactams

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11
Q

β-Lactam Antibiotics

MOA

A

inhibit bacterial transpeptidase and thereby inhibit
peptidoglycan cross-linking/synthesis

  • Are selective and irreversible inhibitors of the enzymes (penicillin binding proteins
    (PBPs)) processing the developing peptidoglycan layer.
    – This enzyme is one of the PBP (carboxypeptidase, endopeptidase, transpeptidase), normally reside in inner membrane and perform construction,
    repair and housekeeping.
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12
Q

β-Lactam Antibiotics

how does resistance occur

A
  • β-lactamase are enzyme produced by the bacteria that catalyze the hydrolysis of β-lactam ring and inactivate the β-lactam antibiotic before they reach the PBPs.
  • They resemble in function and somewhat structure to the cell wall transamidases
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13
Q

β-Lactam Antibiotics

Penicillins
prototype?
narrow, extended, broad spectrum?

A

– Prototype (Penicillin G, Penicillin V)
– Narrow-spectrum (Cloxacillin, Oxacillin, Nafcillin)
– Extended-spectrum (Ampicillin, Amoxicillin)
– Broad-spectrum (Piperacillin, Ticarcillin)

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14
Q

β-Lactam Antibiotics

Penicillins
indications?

A
– Bacterial meningitis
– Bone and joint infections
– Skin/soft tissue infections
– Pharyngitis
– Bronchitis
– Pneumonia
– Urinary tract infections
– Sexually transmitted infections (e.g. gonorrhea, syphilis)
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15
Q

β-Lactam Antibiotics

Penicillins
AE? (1)
MOA?

A

– Hypersensitivity reactions
– Skin rashes & fever
– Anaphylactic shock
– GI disturbances and infection via penicillin-insensitive microorganisms
– *Proconvulsant effect (if penicillin G given intrathecally)

  • Irreversible inhibition of the PBPs
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16
Q

β-Lactam Antibiotics

Cephalosporins
how many generations?
what is it isolated from?

  • Irreversible inhibition of the PBPs
A
β-lactam antibiotics isolated from fungi
– Cephalexin, Cefazolin (1st generation)
– Cefaclor, Cefuroxime (2nd generation)
– Cefotaxime, Cefexim (3rd generation)
– Cefepim (4th generation)
– Ceftarolin (5th generation)
17
Q

β-Lactam Antibiotics

Cephalosporins
Indications

A
– Septicemia
– Pneumonia
– Meningitis
– Biliary tract infection
– Urinary tract infection
– Sinusitis
18
Q

β-Lactam Antibiotics

Cephalosporins
AE? (3)

A

– Hypersensitivity reactions (some cross sensitivity with penicillin sensitive
individuals)
– *Nephrotoxicity (especially with cefradine)
– *Drug-induced alcohol intolerance
– *Bone marrow suppression
– Diarrhea
– Contraindicated in those who experience anaphylaxis in response to
penicillins

19
Q

Β-Lactamase inhibitors

name 2

A

These agents are sometimes added to other β-lactam antibiotics (e.g. amoxicillin) to overcome resistance due to β-lactamases
– Clavulanic acid (added to amoxicillin)
– Tazobactam (added to piperacillin)

Clav can bind beta lactamase first and amox can get into peptidoglycan to destroy bac

20
Q

Β-Lactamase inhibitors

MOA?

A
  • Irreversible inactivation of β-lactamase
  • Contain a β-lactam ring but are not toxic to the bacteria
  • Bind to β-lactamase and protect other β-lactam antibiotics
21
Q

Other β-Lactam Antibiotics
Carbapenems

name 3
MOA?

A

– Imipenem
– Meropenem
– Ertapenem

  • Very broad spectrum of antimicrobial activity.
  • Functional features of best β-lactam antibiotics as well as β-lactamase inhibitors.
  • Striking structural differences from penicillins/cephalosporins; binds differently to
    PBPs.
22
Q

Other β-Lactam Antibiotics
Carbapenems

AE (1)

imipenum activated by renal dipeptidases (w/ cilastatin)

A

– Nausea & vomiting

– *Neurotoxicity (seizures with imipenem)

23
Q

Other β-Lactam Antibiotics
Monobactams

name 1
MOA?
AE?

A

Aztreonam

  • Spectrum of activity is almost exclusively devoted to Gram negative microorganism.
  • Irreversible inhibitor of the PBP3.
  • Side effects are infrequent and cross reactivity are not reported
24
Q

Glycopeptides & Lipopeptides

name 3
indications?

A
  • Vancomycin
  • Teicoplanin
  • Daptomycin
  • Vancomycin is often a last resort for the treatment of
    methicillin-resistant Staphylococcus aureus (MRSA)
  • Bacteria are rarely able to develop resistance
  • Very unstable, Mostly IV (PO for Clostridium Difficile)
25
Q

Glycopeptides & Lipopeptides

MOA?

A

Bacterial cell wall biosynthesis inhibitors

  • Attach to the end of the peptidoglycan precursor units D-ALA-D-ALA terminus through 5 hydrogen bonds
  • Inhibit transglycosylase and transpeptidase enzyme that cross links between NAM and NAG
  • Act like a peptide receptor and interrupt bacterial cell wall synthesis
26
Q

Glycopeptides & Lipopeptides

how does resistance occur?

A
  • Alteration of the target D-ala-D-ala to D-ala-D-lac
  • Vancomycin-resistant entrocccous (VRE)
  • Vancomycin-resistant staphylococcus aureus (VRSA)
27
Q

Glycopeptides & Lipopeptides

AE? (4)

A
Fever
– Rashes
– Phlebitis (at site of infusion)
– *Ototoxicity
– *Nephrotoxicity
– *Flushing (Redman syndrome)
– *Neutropenia
– Hypersensitivity reactions
28
Q

Polymixin antibiotics
name 2
AE?

A
  • Polymixin B
  • Colistimethate (polymyxin E)
  • Clinical use is limited by their toxicity, with serious adverse effects including neurotoxicity and nephrotoxicity
29
Q

Polymixin antibiotics

MOA?

A

e cationic detergent properties and disrupt the bacterial outer cell membrane of Gram-negative bacilli

  • Bind to phosphate group of cytoplasmic membrane and disrupts Its integrity
  • Gram-negative bacilli (esp. pseudomonas)
  • Not absorbed from the GI tract and used for gut sterilization, and topical treatment of ear, eye, or skin infections
30
Q

Fosfomycin

MOA, indication?

A
  • Broad spectrum
  • Inhibits peptidoglycan synthesis by inactivating the enzyme MurA
  • Only for UTI (E. Coli, E. Faecalis, P. mirabilis