Antibiotics: Antimetabolites and DNA disruptors

Sulfonamides: Sulfamethoxazole, Sulfisoxazole, and Sulfadiazine

• Most common uses

– Gram-positive – Gram-negative bacteria – Chlamydiae – Nocardia – Commonly used to treat infections of the urinary and lower respiratory tracts: MRSA pneumonia, Otitis media and some cases of gonorrhea – Trimethoprim is often combined with sulfamethoxazole for bactericidal effects TMP/SMX, aka, Bactrim.

• Mechanism of Action

– Sulfonamides competitively bind dihydropteroate synthase (in place of para-aminobenzoic acid ((PABA)) Inhibit early steps in folic acid synthesis – Trimethoprim inhibits dihydrofolate reductase

• Mechanism of Resistance

– Enzyme modification – Reduction of drug uptake – Increased drug efflux – Increased PABA synthesis

• Adverse effects of Sulfonamides

– Hypersensitivity, with potential for Stevens-Johnson syndrome or toxic epidermal necrolysis – Drug-induced hemolytic anemia, which is more likely in individuals with G6PD deficiencies – Nephrotoxicity – Aseptic meningitis, specifically associated with TMP/SMX Dapsone

• Most common uses

– Mycobacteria: Leprosy, dermatitis herpetiformis, and some other skin conditions.

• Mechanism of Action

– Inhibits Mycobacteria folic acid synthesis via inhibition of dihydropteroate synthase.

• Adverse effects of Sulfonamides

– Hemolytic anemia, particularly in individuals with G6PD deficiencies. para-aminosalicyclic acid (PAS)

• Most common uses

– Mycobacterium tuberculosis

• Mechanism of Action

– Inhibits folic acid synthesis

• Adverse effects

– Gastrointestinal upset – Hypersensitivity Quinolone: Nalidixic acid

• Most common uses

– Gram-negative bacteria Was particularly useful against urinary tract infections prior to widespread resistance.

• Mechanism of Action

– Inhibits DNA replication via inhibition of topoisomerase type II (aka, gyrase) in Gram-negative bacteria

• Adverse effects

– Nausea and vomiting – Visual changes – Headache – Rash Fluoroquinolones: Ciprofloxacin, Levofloxacin, and Moxifloxacin

• Most common uses

– Gram-negative infections of the urinary and gastrointestinal tracts. – Moxifloxacin has activity against some Gram-positive bacteria and anaerobes, and is used to treat respiratory infections caused by Haemophilus influenzae and Streptococcus pneumoniae.

• Mechanism of Action

– Halt DNA replication by inhibiting topoisomerase type II (in Gram-negative bacteria) or topoisomerase type IV (in Gram-positive bacteria)

• Mechanism of Resistance

– Modification of these enzymes – Increases in efflux pumps

• Adverse effects

– Gastrointestinal upset – Rash – Headache – QT prolongation – Tendinopathy or rupture can occur – Colitis – They should not be taken with antacids, or during pregnancy. – They should not be administered to children, due to the possibility of cartilage or bone tissue erosion. Metronidazole

• Most common uses

– Anaerobes Helicobacter pylori Gardnerella vaginalis Clostridium difficile – Also used to treat some parasitic infections

• Mechanism of Action

– Produces free radical metabolites that damage bacterial DNA

• Adverse effects

– Gastrointestinal upset – Metallic taste – Disulfiram-like reaction when combined with alcohol Rifamycins: Rifampin and Rifabutin

• Most common uses

– Mycobacteria – Rfabutin is particularly active against [Myocbacterium avium

• Mechanism of Action

– Inhibit bacterial RNA synthesis

• Mechanism of Action

– Resistance appears more likely to develop with monotherapy

• Adverse effects

– Reddish-brown hue to the urine, saliva, tears, and other bodily fluids. – Gastrointestinal upset – Rash – Headache