Antibiotics

Question 1

Penicillins

Answer 1

• Bind to penicillin binding proteins (PBPs) and inhibit transpeptidase rxn and cross-linking of peptidoglycans
• Enters inflamed meninges
• Can produce hypersensitivity rxns: hives, SOB, anaphylactic shock (severe), and skin rash (mild)
• Other adverse effects: diarrhea, superinfections
• Penicillins (ampicillin), cephalosporins, or vancomycin with aminoglycoside (gentamicin): synergistic effect that enhances bactericidal functions
• Ampicillin/cephalosporin or vancomycin makes pores in the bacterial cell wall through which amino glycosides can enter the bacteria
• Aminoglycoside dose is decreased to minimize its toxicity

Question 2

Narrow spectrum penicillins

Answer 2

• Penicillin G (IM or IV). Effective against strep and meningococci. Not effective against staph, pneumococci or gonococci
• Mostly effective against GP bacteria (outer membrane limits entry of drug in GN)

Question 3

Penicillinase resistant

Answer 3

• Nafcillin (oral/PA, biliary excretion) and dicloxacillin (oral): only for GP (bulky hydrophobic group cannot pass through porin), used to treat strains of staph that express penicillinase
• Treats endocarditis, osteomyelitis, and cellulitis
• Staph resistant to these are MRSA (methicillin-resistant)

Question 4

Aminopenicillins

Answer 4

• Amoxicillin (oral) and ampicillin (oral/PA, biliary excretion): can be used to treat both GP and GN
• Amoxicillin: is the drug choice to treat otitis media, may be combined w/ penicillinase inhibitor (clavulanate)
• Ampicillin: treats meningitis and other infections from listeria, may be combined w/ penicillinase inhibitor (sulbactam)

Question 5

Cephalosporins

Answer 5

• Inhibit cross-linking of peptidoglycan by binding to PBPs
• Low cross-rxn w/ penicillin allergies (severe penicillin allergies may elicit some run to cephalosporins)
• Penicillins (ampicillin), cephalosporins, or vancomycin with aminoglycoside (gentamicin): synergistic effect that enhances bactericidal functions
• Ampicillin/cephalosporin or vancomycin makes pores in the bacterial cell wall through which amino glycosides can enter the bacteria
• Aminoglycoside dose is decreased to minimize its toxicity

Question 6

1st generation cephalosporins

Answer 6

• Effective against GP cocci

- Cefazolin (IV): surgical prophylaxis against staph

Question 7

2nd generation cephalosporins

Answer 7

• Effective against both GP cocci and GN bacilli

- Cefprozil (oral): treats otitis media from H influenzae (resistant to amoxicillin), also community acquired pneumonia

Question 8

3rd generation cephalosporins

Answer 8

• Effective against GN bacilli
• Ceftriaxone (PA, biliary excretion) and cefotaxime (PA): both are used to treat meningitis
• Ceftriaxone is drug of choice for gonorrhea

Question 9

Vancomycin

Answer 9

• Irreversibly binds to peptidoglycan precursor (not to PBP), not a beta-lactam and is resistant to penicillinase. GP bacteria only
• Given via slow IV infusion, can cause red man syndrome (infusion-related toxicity due to histamine release)
• Enters inflamed meninges
• Can enhance nephrotoxicity of other drugs, can cause ototoxicity at high levels
• Used to treat patients w/ penicillin allergies, MRSA patients w/ medical devices, enterococcal endocarditis
• Pseudomembraneous colitis from C difficile

Question 10

Aminoglycosides

Answer 10

• Binds to 30S subunit and interferes w/ initiation of proteins synthesis. Also causes misreading of genetic code. Results in post-antibio effect
• Not orally absorbed, does not enter CSF, dose is adjusted based on creatinine clearance
• Once daily dose to minimize renal toxicity
• Includes gentamicin and neomycin
• Gentamicin used against enterococcal and staph infections

Question 11

Side effects and drug interactions of aminoglycosides

Answer 11

• Can cause renal toxicity and ototoxicity, both cochlear toxicity (irreversible) and vestibular toxicity (reversible)
• Penicillins (ampicillin), cephalosporins, or vancomycin with aminoglycoside (gentamicin): synergistic effect that enhances bactericidal functions
• Ampicillin/cephalosporin or vancomycin makes pores in the bacterial cell wall through which amino glycosides can enter the bacteria
• Aminoglycoside dose is decreased to minimize its toxicity

Question 12

Tetracyclines

Answer 12

• Blocks tRNA binding to 30S subunit, preventing addition of new AA
• Bind to calcifying teeth and bones (mostly in children, pregnant and nursing mothers, stunts growth and discolors teeth), absorption is decreased if metal products are ingested (dairy, antacids)
• Cause hepatitis in pregnant women
• Cause nephrotoxicity and photoxicity

Question 13

Tetracycline drugs

Answer 13

• Tetracycline and doxycycline (biliary excretion): broad spectrum bacteriostatic
• Used to treat rickettsia (rocky mountain spotted fever), lyme disease (borrelia burgdurferi), chlamydia trachomatis, shorten cholera therapy, acne

Question 14

Macrolides

Answer 14

• Bind to 50S subunit and prevents translocation of peptide from A to P site (blocks peptidyl transferase)
• Does not enter CSF, can cause ototoxicity at high doses
• Erythromycin can cause epigastric distress, cholestatic jaundice
• Erythromycin inhibits Cyp450, which metabolizes cyclosporin (CSA) and warfarin, leading to increased plasma levels of CSA and warfarin
• Causes excess immune suppression and renal toxicity of CSA
• Cause increased prothrombin time and bleeding from warfarin
• Replace erythromycin w/ azithromycin (does not inhibit CYP450), decrease warfarin/CSA doses

Question 15

Macrolide drugs

Answer 15

• Erythromycin and azithromycin (both biliary) used for therapy and prevention of pneumonia
• Also treats chlamydia pelvic infection, H influenzae otitis media
• More for GP bacteria

Question 16

Sulfonamides

Answer 16

• Inhibit dihydropteroate synthesis, decreasing folic acid
• Acetylated forms excreted in urine, can cause crystalluria
• Displaces other drugs from albumin (class II). This causes class I drugs (methotrexate, warfarin) to be displaced from albumin and increased their plasma levels (reduce dose of class I drug)
• Also inhibits Cyp450 when used w/ trimethoprim (TMP-SMX), preventing metabolism of warfarin/CSA
• TMP-SMX not given to neonates, pregnant women, nursing women (displaces bilirubin form albumin and causes kernicterus)
• Also causes skin rashes/stevens-johnson syndrome (hypersensitivity rxn)

Question 17

Sulfonamide drug

Answer 17

-Sulfamethoxazole (SMX): used to treat UTI

Question 18

Fluoroquinolones

Answer 18

• Inhibits DNA gyrase, preventing replication
• Chelates metals, long half lives, post antibio effect
• Once a day oral administration
• Can cause CNS problems at high doses or w/ coffee (inhibits CYP1A, which metabolizes caffeine)
• Can cause photo toxicity, arthropathy in children (not given to children under 18 or pregnant/nursing mothers)

Question 19

Fluoroquinolone drugs

Answer 19

• Ciprofloxacin, levofloxacin: broad-spectrum, treats UTI, prostatitis, traveller’s diarrhea
• Levofloxacin treats pneumonia

Question 20

Isoniazid

Answer 20

• Inhibits synthesis of mycolic acid
• Acetylation inactivates it, dose is reduced in liver disease
• Can cause hepatitis necrosis (increased in elderly and alcoholics), peripheral neuropathy
• Enters CSF
• Induces Cyp450, increasing metabolism of warfarin, CSA
• First line defense against TB (Tx is: Rifampin, Isoniazid, pyrazinamide, ethambutol, or RIPE)

Question 21

Rifampin

Answer 21

• Binds to beta-subunit of RNA polymerase and inhibits transcription
• Deacetylation retains activity but enhances biliary excretion
• Induces Cyp450, increasing metabolism of warfarin, CSA
• Can cause hepatitis necrosis (increased in elderly and alcoholics)
• Can cause discoloration of bodily fluids
• Treats TB (Tx is: Rifampin, Isoniazid, pyrazinamide, ethambutol, or RIPE)

Question 22

Ethambutol

Answer 22

• Blocks arabinosyl transferases involved in cell wall synthesis
• Can cause acute gout, and optic neuritis (cannot discriminate red/green)
• Treats TB (Tx is: Rifampin, Isoniazid, pyrazinamide, ethambutol, or RIPE)