Antimicrobial 1: Agents that Target the Bacterial Cell Wall or Folic Acid Metabolism Flashcards
what are antivirals?
classification?
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
what different conditions/disorders (both acute and chronic) are the result of bacterial infections
– Food Poisoning – Sexually Transmitted Infections (STIs) – Whooping Cough – Pneumonia – Tuberculosis – Respiratory Tract Infections
Name 2 classes of antibiotics Targeting Folate Synthesis
– Sulfonamides (sulfa antibiotics)
– Folic acid antagonists (trimethoprim, pyrimethamine)
Sulfonamides
drugs
– Sulfanilamide – Sulfamethoxazole – Sulfasalazine (GI, RA) – Sulfadiazine – Sulfadoxine (Anti-Malarial)
Sulfonamides
MOA?
- 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
Sulfonamides
AE? (4)
– *Hepatitis – Hypersensitivity reactions (Stevens-Johnson syndrome) – *Bone marrow depression – *Acute renal failure – *Cyanosis – Nausea, Vomiting, Headache – Depression
Folic acid antagonists
name 2
– Trimethoprim
– Pyrimethamine
Folic acid antagonists
MOA
- 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
Folic acid antagonists
AE
– *Folate deficiency – *Megaloblastic anemia – Nausea, Vomiting – Blood disorders/dyscrasias – Rashes
β-Lactam Antibiotics
4 classes
target peptidoglycan synthesis
– Penicillins
– Cephalosporins
– Carbapenems
– Monobactams
β-Lactam Antibiotics
MOA
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.
β-Lactam Antibiotics
how does resistance occur
- 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
β-Lactam Antibiotics
Penicillins
prototype?
narrow, extended, broad spectrum?
– Prototype (Penicillin G, Penicillin V)
– Narrow-spectrum (Cloxacillin, Oxacillin, Nafcillin)
– Extended-spectrum (Ampicillin, Amoxicillin)
– Broad-spectrum (Piperacillin, Ticarcillin)
β-Lactam Antibiotics
Penicillins
indications?
– Bacterial meningitis – Bone and joint infections – Skin/soft tissue infections – Pharyngitis – Bronchitis – Pneumonia – Urinary tract infections – Sexually transmitted infections (e.g. gonorrhea, syphilis)
β-Lactam Antibiotics
Penicillins
AE? (1)
MOA?
– 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
β-Lactam Antibiotics
Cephalosporins
how many generations?
what is it isolated from?
- Irreversible inhibition of the PBPs
β-lactam antibiotics isolated from fungi – Cephalexin, Cefazolin (1st generation) – Cefaclor, Cefuroxime (2nd generation) – Cefotaxime, Cefexim (3rd generation) – Cefepim (4th generation) – Ceftarolin (5th generation)
β-Lactam Antibiotics
Cephalosporins
Indications
– Septicemia – Pneumonia – Meningitis – Biliary tract infection – Urinary tract infection – Sinusitis
β-Lactam Antibiotics
Cephalosporins
AE? (3)
– 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
Β-Lactamase inhibitors
name 2
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
Β-Lactamase inhibitors
MOA?
- 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
Other β-Lactam Antibiotics
Carbapenems
name 3
MOA?
– 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.
Other β-Lactam Antibiotics
Carbapenems
AE (1)
imipenum activated by renal dipeptidases (w/ cilastatin)
– Nausea & vomiting
– *Neurotoxicity (seizures with imipenem)
Other β-Lactam Antibiotics
Monobactams
name 1
MOA?
AE?
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
Glycopeptides & Lipopeptides
name 3
indications?
- 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)
Glycopeptides & Lipopeptides
MOA?
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
Glycopeptides & Lipopeptides
how does resistance occur?
- Alteration of the target D-ala-D-ala to D-ala-D-lac
- Vancomycin-resistant entrocccous (VRE)
- Vancomycin-resistant staphylococcus aureus (VRSA)
Glycopeptides & Lipopeptides
AE? (4)
Fever – Rashes – Phlebitis (at site of infusion) – *Ototoxicity – *Nephrotoxicity – *Flushing (Redman syndrome) – *Neutropenia – Hypersensitivity reactions
Polymixin antibiotics
name 2
AE?
- Polymixin B
- Colistimethate (polymyxin E)
- Clinical use is limited by their toxicity, with serious adverse effects including neurotoxicity and nephrotoxicity
Polymixin antibiotics
MOA?
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
Fosfomycin
MOA, indication?
- Broad spectrum
- Inhibits peptidoglycan synthesis by inactivating the enzyme MurA
- Only for UTI (E. Coli, E. Faecalis, P. mirabilis
