For evaluation of the risk for breast cancer in women, which of the following factors is least

important?

(A) Age at menarche

(B) Family history of breast cancer
(C) Age at menopause
(D) Age at first pregnancy
(E) Cigarette smoking

(E) Cigarette smoking, diet, drug use, and obesity are not well-established factors that
influence the risk for breast cancer. All others listed are known risk factors.

Exam Questions:
o DOC for syphillis (benzathine penicillin),
o DOC in strep infections, especially to prevent rheumatic fever
o DOC for susceptible pneumococci

Antibiotics:
1. All cell wall inhibitors are β –lactms except Vancomycin.
 Β-lactams: Monobactam, cephalasporin, carbapenem, penicillin
 Mechanism of Action
i. All beta-lactams bind penicillin-binding proteins (PBP’s)
ii. All beta-lactams block transpeptidase cross-linking of cell wall
iii. Activate autolytic enzymes, causing osmotic damage (bactericidal)
 Mechanism of resistance
i. β lactamase production (S. aureus)
ii. Change their structure of PBPs (e.g. MRSA, thus must use vancomycin)
iii. Efflux pump or change in porin structure (gram-negatives ie pseudomonas)
 First Generation Penicillin G and V
i. Narrow spectrum (mainly gram positives)
ii. Sensitive to β –lactamases – thus never use for Staph
 Second Generation  Methicillin (made to overcome β –lactamse resistance..but
became so specific, its only used against staph..and thus created the famous MRSA)
 Third Generation  Aminopenicillins e.g. Ampicillin, Amoxicillin
i. Clinical use: broad spectrum (gram positives and negatives, but NOT β –
lactamase resistant)
ii. H.flu, listeria, Lyme Disease in children and pregnant women, Enterococci
 Cluvanic acid is now used to protect the aminopenicillins from β –lactamases.
 Fourth Generation  anti-pseudomonal penicillins.
i. Synergistic effect when combined with aminoglycosides.
ii. Parenteral penicillins usually combined with beta-lactamase inhibitors
 Rule: all penicillins are water soluble, except nafcillin. Thus excreted by kidneys –
potentially renal toxic. Can’t cross BBB,  no good for meningitis.
 Rule: penicillins cause allergies
 First generation: Cephalasporins  cephalexin, cephradine, cefazolin
i. Clinical use: gram positives and few gram negatives PEcK (proteus, e.coli,
kelbsiella)
ii. Cannot enter CNS
 Second Generation Cephalasporins
i. HEN PEcKS
ii. Gram negatives: H. flu, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella,
Serratia
iii. Cannot enter CNS except cefuroxamine.
 Third Generation Cephalasporins
i. Cephtriaxone, cefotaxime, ceftazidime
ii. 1st generation + 2nd generation = 3rd generation (gram positive and
negative) +anaerobes
iii. Ceftriaxone is lipid soluble, thus can enter CNS, metabolized by p450 and
excreted into bowel.
iv. Ceftazidime for pseudomonaz
v. Ceftriaxone for gonorrhea and meningitis
 Fourth Generation Cephalasporins – Cefepime, Cefpirome
i. Clincal use: 3rd Generation + more beta-lactamase resistance

 Monobactam - Aztreonam
i. Same MOA as penicillins
ii. Synergistic with aminoglycosides
iii. Resistant to β –lactamases
iv. Clinical use: gram neg rods only (pseudomonas)
v. Toxicity: no cross-allerginicity with penicilins
 Carbapenems – imipenem, meropenem
i. β –lactamase resistant
ii. Works on anything
iii. BUT can cause CNS toxicity (seizures)
 Vancomycin
i. Inhibits cell wall mucopeptide formation by binding D-ala-D-ala portion of
cell wall precursors. Resistance occurs when changed to D-ala D-lac.
ii. Clinical use: gram positive multidrug resistant organisms e.g. MRSA, C.Diff
iii. Toxicity: kidney and ears, red man syndrome with rapid infusion
2. Rule: All protein synthesis inhibitors are bacteriostatic, except for the aminoglycosides

 Tetracyclines: e.g. doxycycline

o MOA: reversibly bind to 30S
o Clinical use
 Very broad spectrum
 Important use for spirochetes and intracellular bugs
 Rickettsial Infections
 Chlamydia
o Toxicity
 Collect divalent ions
 Means they deposit in bones and teeth
 Means contraindicated in pregnancy and in kids who are still growing
 Means can’t take with antacids or iron.
 GI distress
 Fanconi’s syndrome
 Photosensitivity
o Boards:
 Doxycycline is lipid soluble; means good STD’s and prostatitis
 Minocycline is very water soluble and enters all secretions, especially saliva; means
useful for meningococcus prophylaxis
 Demeclocycline inhibits the release of ADH; means can be used for SIADH

 Aminoglycosides e.g. Gentamycin, neomycin, streptomycin

o MOA: Taken up by an oxygen dependent pump and bind to the 30S ribosomal unit and Induce
the binding of the “wrong” t-RNA-AA complex, resulting in the synthesis of false proteins.
(Bactericidal)
o Clinical use
 Gram negative aerobes only! (pseudomonas)
 Synergistic w/ beta-lactams
 Neomycin for bowel surgery
 Tobramycin for Pseudomonas
 o Toxicity
 Amino (NH3) + glycoside (OH) makes extremely polar
 Means membrane penetration in a bacteria is dependent on a
special oxygen pump and only covers gram negative aerobes
 Means renally excreted and renal toxic
 Means can be trapped in inner ear and is ototoxic
 Neuromuscular blockade
 Macrolides e.g. erythromycin, clarithromycin
o MOA: inhibits protein synthesis by blocking translocation, binding to 50S. resistance
is via methylation at binding site.
o Clinical use
 Same broad coverage as tetracyclines
 URI’s and atypical pneumonias (Mycoplasma, Legionella, Chlamydia)
 Neisseria
 Alternative for penicillin allergic patients
o Toxicities
 Stimulate motilin receptor (erythromycin) causing GI upset
 Lipid soluble, except azithromycin
 Means P450 interactions (erythromycin is a famous inhibitor) and
liver problems (acute cholestatic hepatitis)
 Clindamycin
o MOA: blocks formation of peptide bond at 50S (bacteriostatic)
o Clinical use:
 Gram pos and anaerobes (thus can easily cause C.Diff colitis)
 Good bone penetration (can be used for S.aureus osteomyelitis)
 Linezolid
o Mechanism
 Linezolid binds on the 23S portion of the 50S subunit close to the peptidyl
transferase and chloramphenicol binding sites.
o Clinical
 Famous for treating gram-positive drug resistant bugs (MRSA, and multidrug
resistant pneumococcus)
o Toxicity
 Usually well tolerated
 Thrombocytopenia
 MAOI (avoid tyramine containing food)

3. Inihibitors of DNA synthesis – fluoroquinolones, Rifampin, Sulfonamides

 Fluoroquinolones e.g. Ciprofloxacin, Gatifloxacin, Levofloxacin, Moxifloxacin,
Ofloxacin

o MOA: Inhibits DNA gyrase (topoisomerase II) (Bactericidal)

o Clinical use
 Gram-negative rods of UTI and diarrhea
 Were 1st oral treatment of gram-negative sepsis
 Means were overused, leading to resistance
  Distributes into all tissues and fluids (including bones)
 Means can inhibit cartilage and tendon damage leading to
tendonitis and tendon rupture in adults
 Means can be used for Salmonella osteomyelitis
 Means contraindicated in pregnancy and in children
 Respiratory fluoroquinolones (levofloxacin) for drug resistant
pneumococcus
 Anthrax (ciprofloxacin)
o Toxicity
 QT prolongation and arrhythmias
 Hypo/hyperglycemia
 Achilles tendon rupture or tendinitis has occurred rarely
 Rifampin
o Mechanism
 Inhibits DNA-dependent RNA polymerase
o Clinical use
 TB (in combo and in prophylaxis)
 Famous for prophylaxis of meningococcus and H. flu
o Toxicity
 Hepatotoxic
 Revs up P-450
 R’s:
 RNA polymerase inhibitor
 Revs up P-450
 Red/orange body fluids
