Chapter 7 anti-infective agents - fluoroquinolones and metronidazole + sulfonamides and other antimetabolites

Question 1

Nalidixic acid (negGram)

quinolones

Answer 1

• blocks a subunit of DNA gyrase
• Bactercidal – prevents supercoiling l/t inhibition of DNA synthesis
• Effective against on gram neg bacteria… BUT NOT PSUEDOMONAS

effects
* Hypersen
* seizures
* photosensitive
* dizziness, headache
* displace oral anticoagulants

contra
* not recommended for children (stop growth plate)

pharmcokinetics
does not penetrate prostate

Question 2

norfloxacin (noroxin)

fluoroquinolones

Answer 2

• disrupts DNA gyrase (supercoiling) and DNA topoisomerase activity (topological problems resulting from replication, transcription, recombination, and reorganization of the chromatin.)

Good gram negative coerage’

interactions
* Cartilage damage in studies.. not used in hildren

Primarily used for prostatitis or UTIs

Question 3

lomefloxacin (maxaquin)
ofloxacin (Floxin)
cipofloxacin (cipro)

fluoroquinolones

Answer 3

• disrupt DNA gyrase (supercoling) and DNA topoisomerase activity (relax the supercoiling in DNA strands)
• Great for gram negative, some gram pos

interaction
* cartilage damage — not for children

Ciprofloxacin and ofloxacin — available as IV
Good tissue penetration, only ofloxacin has good CSF penetration

Question 4

moxifloxacin (avelox)

fluoroquinolones

Answer 4

• does not cover psedumonas aeruginosa

reduce dose with renal prob

Question 5

gemifloxacin (factive)

fluoroquinolones

Answer 5

• indicated for atue bacterial exacerbation of chronic bronchitis and mild-moderate pneumonia

reduce dose w/ renal impairment

Question 6

levofloxacin (levaquin)

fluoroquinolones

Answer 6

• disrupts DNA gyrase and DNA topoisomerase activity
• great gram neg ccoverage and improevd staph coverage
• Tx legionella (Gram neg) and chlamydia (gram neg) atyipcal pneumonia

interaction
* cartilage damage

Good tissue penetration

Question 7

metronidazole (flagyl)

other

Answer 7

• enters bacteria or protozoan and activated via reduction of nitro group
• ACTIVATED intermediates bind to DNA and inhibit its synthesis
• Against obligate anaerobes (bacetriodes (gram neg), clostridium (gram pos), peptococcus (gram positive)
• Plus against protozoans (entamoeba histolytica, trichomonas, giardia)

effects
* disulfiram-like rxn w/ ETOH — flushing, vomiting, headache
* CNS - seizure, ataxia (no coordination), dizziness
* n/v
* anorexia

PO/IV
penetrates well into tissues + abcesses (buildup of a pus that can affect any part of your body), empyemas (pockets of pus in a body cavity – pleural space..?!)

majority of drug eliminated in urine

Question 8

nitrofurantoin (macrodantin)

other

Answer 8

• mechanism unclear
• may damage DNA
• kills many urinary pathogens BUT not pseudomonas, klebsiella (gram - ), proteus (gram - ), and serratia (gram neg), plus acinetobacter (gram neg)

effets
* hepatotoxic
* pulmonary fibrosis (scars and thickens lung tissues)
* neuropathy

do not administer if creatine clearance < 40 ml/min

Question 9

sulfadiazine

sulfonamides

Answer 9

• both gram pos and neg
• tx for uncomplicated UTIS
• nocardiasis ( disease caused by bacteria found in soil and water. It can affect the lungs, brain, and skin)
• chancroid (highly contagious yet curable sexually transmitted disease (STD) caused by the bacteria Haemophilus ducreyi)
• prophylaxis against rheumatic fever
• combined with pyrimethamine (antiparasitic prescription medicine) for tx of toxoplasmosis (an infection with a parasite called Toxoplasma gondii. People often get the infection from eating undercooked meat. You can also get it from contact with cat feces.)
• sulfapyridine — chronic, intensely itchy, blistering skin manifestation of gluten-sensitive enteropathy, commonly known as celiac disease.

effects
* bone marrow depression
* renal toxicity
* hepatotoxicity
* hemolysis
* hypersen (fever + rash)
* stevens-johnson syndrome (serious skin conditions that cause your skin to develop rashes, blisters, and then peel. Your mucus membranes, including your eyes, genitalia and mouth, are also affected)
* kernicterus ( bilirubin encephalopathy, is bilirubin-induced neurologic damage, typically in infants) – slfas compete with billrubin for albumin sites => result in elevated free billrubin that is deposited in brain nuclei!

resistance
* bacteria that use exogenous folic acid are resistant
* PO readily penetrates CNS, joints, eyes
* encourage fluid to prevent renal stone

Question 10

antimetabolites

Answer 10

• inhibit DNA, RNA, and protein synthesis via blocking folate pathway
• sulfonamides compete with PABA (para-amino benzoic acid or vitamin B10) — synthesized and utilized as a substrate for the synthesis of folic acid in many bacterial species
• trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate (FAH4) by binding to dihydrofolate reductase (FAH4 — needed to synthesize puriens, pyrimidines and some amino acids

Question 11

sulfisoxazole (gantrisin)

sulfonamides

Answer 11

• both gram pos and neg
• tx for uncomplicated UTIS
• nocardiasis ( disease caused by bacteria found in soil and water. It can affect the lungs, brain, and skin)
• chancroid (highly contagious yet curable sexually transmitted disease (STD) caused by the bacteria Haemophilus ducreyi)
• prophylaxis against rheumatic fever
• combined with pyrimethamine (antiparasitic prescription medicine) for tx of toxoplasmosis (an infection with a parasite called Toxoplasma gondii. People often get the infection from eating undercooked meat. You can also get it from contact with cat feces.)
• sulfapyridine — chronic, intensely itchy, blistering skin manifestation of gluten-sensitive enteropathy, commonly known as celiac disease.
• prophylaxis of recurrent otitis media and UTI

effects
* bone marrow depression
* renal toxicity
* hepatotoxicity
* hemolysis
* hypersen (fever + rash)
* stevens-johnson syndrome (serious skin conditions that cause your skin to develop rashes, blisters, and then peel. Your mucus membranes, including your eyes, genitalia and mouth, are also affected)
* kernicterus ( bilirubin encephalopathy, is bilirubin-induced neurologic damage, typically in infants) – slfas compete with billrubin for albumin sites => result in elevated free billrubin that is deposited in brain nuclei!

resistance
* bacteria that use exogenous folic acid are resistant
* PO readily penetrates CNS, joints, eyes
* encourage fluid to prevent renal stone
* higher urine solubility than other sulfonamides

Question 11

trimethoprim/sulfamethoxazole (TMP/SMZ, septra, bactrim)

sulfonamides

Answer 11

• Enteric gram-negatives (proteus, e coli, klebsiella, enterobacter)
• H influenzae (gram neg)
• shigella (gram neg) - enteric
• serratia (gram neg) - enteric
• salmonella (gram neg) - enteric
• pneumocystis carinii (yeast like fungus)
• inexpensive choice for:
  1) UTI
  2) acute otitis media
  3) traveler’s diarrhea
• used for pneumocsitis carinii prophylaxis/tx in immunocompromised hosts

effects
* bone marrow depression
* renal toxicity
* hepatotoxicity
* hemolysis
* hypersen (fever + rash)
* stevens-johnson syndrome (serious skin conditions that cause your skin to develop rashes, blisters, and then peel. Your mucus membranes, including your eyes, genitalia and mouth, are also affected)
* kernicterus ( bilirubin encephalopathy, is bilirubin-induced neurologic damage, typically in infants) – slfas compete with billrubin for albumin sites => result in elevated free billrubin that is deposited in brain nuclei!

resistance
* bacteria that use exogenous folic acid are resistant
* PO readily penetrates CNS, joints, eyes
* encourage fluid to prevent renal stone

PO/IV; high plasma protein binding