Pharmacology of Antibacterial Drugs II

altered dihydrojpterate synthase enzyme

ß-Lactam cell wall inhibitors

Inhibit the crosslinking in the peptidoglycan wall (causes cells to swell and lyse)

Almost all bactericidal drugs

Inhibits transpeptidase and blocks cross-linking of cell wall polymers

First discovered was penicillin

ß-lactam is a four membered ring functional group

Two families of ß-lactams (same mechanism)

Penicillins

Cephalosporins

Wide range of spectrums

Adverse effects

Allergic reactions

Superinfectins

it is a hapten (it's too small to react by itself, but when it binds to something else it can serve as an antigen

Penicillin G and V

Penicillinase resistant penicillins

Narrow spectrum (gram + organisms)

Pen G is unstable (not good for oral)

Subject to inactivation by ß-lactamase producers

Also has short half life (<1h)

Sustained release was figured out by binding with Benzathine (Benthazine Pen G)

Dicloxacillin

Narrow spectrum (gram+ organisms)

Resistant to ß-lactamase (methicillin like)

unfortunately made the drug less reactive to make it resistant

Extended spectrum penicillins

Ampicillin

Amoxicillin

Extended spectrum (gram+ and some gram- organisms)

Are inactivated by ß-lactamase

This is overcome by adding clavulanic acid

Clavulanic acid + amoxicillin = augmentin

Clavulanate basically sacrifices itself to the ß-lactamse because there is higher affinity binding than to the amoxicillin

Used for broad spectrum infections (gram+ and gram-)

Gotta be aware of hypersensitivity and adverse effects

The first generation was narrow spectrum (gram+)

The following generations were broader spectrum (gram+ and gram-)

Cephalasporinases have appeared

Vancomycin (cell wall inhibitor)

Binds the D-ala-D-ala to keep it from forming the peptidoglycan wallq

Narrow spectrum (gram+) - same as pen G and V

Not given orally (is parenterally given)

Not sensitive to ß-lactamase

Used for treatment of serious gram+ infections

Methicillin resistant gram+

C. diff

can be used in those with penicillin allergy

Anaphylactoid reaction if administered too quickly (red-man syndrome)

Folate Synthesis Inhibitors

Sulfamethoxazole (is a sulfonamide)

Trimethoprim

Folic acid is necessary to make amino acids and neucleotides

Bacteria need to make own folic acid from PABA (p-aminobenzoic acid)

Humans don't need PABA as much

Inhibits Dihydropteroate synthase (can't make purines, can't make DNA)

Inhibits Dihydropholate reductase (can't make purines, can't make DNA)

Broad spectrum (gram+ and gram-)

Bacteriostatic (inhibiting DNA won't kill them, just stop them from multiplying

Sulfamethoxazole and Trimethoprim are synergistic

This allows for lower likelyhood of toxicity because lower concentrations are needed

Used very frequently for UTIs, ear infections, bronchitis

Resistances

Sulfonamides

altered dihydrojpterate synthase enzyme

Decresased accumulation of drug in bacteria

Trimethoprim

altered dihydrofolate reductase enzyme

Adverse effects

Hypersensitivity reaction (Stevens-Johnson syndrome)

Hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency

Kernicturus - brain damage in newborns due to high levels of unconjucated bilirubin

Renal toxicity - drug precipitation in renal tubules

Drug interactions - can potentiate action of other drugs

inhibit metabolism other drugs (CYP450)

Displaces drugs from albumin (increasing free-drug concentration of other drug)