Antibiotics- Nucleic acid synthesis inhibitors

Question 1

DNA damaging drugs

Answer 1

METRONIDAZOLE

NITROFURANTOIN

Question 2

METRONIDAZOLE

Answer 2

MOA:
toxic metabolites that damage DNA

USE: 
both anaerobs ( Clostridium sp., treat pseudomembranous collitis caused by Cl. difficile) & aerobs (H.pylori, to replace AMOXICILLIN if patient has penicillin-allergy)
protozoal infections (trichomoniasis-> cervicitis & vaginitis) , amoebiasis->amoebic dysentery: diarrhea/abdominal pain , giardiasis-> liver abscess)
prophylaxis before intraabdominal surgery

PHARMACOKINETICS:
good oral absorption & good tissue penetration

SE:
GI prob
alcohol intolerance
dizziness

Question 3

NITROFURANTOIN

Answer 3

MOA:
damage of bacterial DNA & enzymes

PHARMACOKINETICS:
poor tissue penetration, excreted by kidney

USE:
against gram + (enterococci) & gram - (E.coli)
prophylaxis & treatment of uncomplicated infections of the lower UT

SE:
GI prob
acute pulmonary Rx (rare)
liver damage
neuropathy

CONTR.:
last month of pregnancy
newborns (4 weeks of age)

Question 4

Fluoroquinolones

Answer 4

inhibitors of DNA Gyrase (topoisomerase II) and topoisomerase IV -> inhibition of DNA replication

Question 5

Fluoroquinolone drugs

Answer 5

I Gen: NALIDIXIC ACID (against gram-), non-fluorinated
II Gen: a.NORFLOXACIN (against gram - rod -> E.coli)
b.CIPROFLOXACIN, OFLOXACIN (against gram - -> enterococci, H.infl.,Pseudomonas, Gonococcus, Chlamydia)
III Gen: LEVOFLOXACIN (like II Gen + higher activity against gram + & intracellular microbes (Mycoplasma, Legionella))
IV Gen: MOXIFLOXACIN (like III Gen + anaerobs)

Question 6

Pharmacokinetics of fluoroquinolones

Answer 6

I & IIa Gen.: not absorbed by GIT , used only for UTI’s & intestine
IIb & IV Gen: good oral abs. (IV also possible), good tissue penetration, some metabolized in liver, excreted by kidney
III & IV: longer half life

Question 7

SE of Fluoroquinolones

Answer 7

GI prob
teratogenecity in pregnancy
eldery and steroid therapy people cause damage to cartilage, arthropathy, tendinopathy
CNS symptoms 
prolonged QT interval (MOXIFLOXACIN)
Allergic Rxs

Question 8

Interactions of Fluoroquinolones

Answer 8

antacids, iron salts, food -> decreased abs.

CIPROFLOXACIN & OFLOXACIN inhibit CYP1A2 -> inhibit metabolism of theophylline

Question 9

Use of fluoroquinolones

Answer 9

UTI's
GI infections (Salmonella, Shigella, E.coli)
Pseudomonas
Pyelonephritis
Prostatitis acute
Atypical pneumonia (caused by Mycoplasma & Legionella)
osteomyelitis (caused by Salmonella)
anthrax (caused by Basillus Anthrax)

Question 10

Contraindications of fluroquinolones

Answer 10

pregnancy
children under 12 yo
arrhythmias (MOXIFLOXACIN)

Question 11

RNA polymerase inhibitors drugs

Answer 11

RIFAMPICIN (bactericidal, against gram + &- cocci, against Mycobacterium TB)
RIFAXIMIN (intestinal gram- eg E.coli)
FIDAXOMICIN (gram + anaerob rods eg Cl. Difficile)

Question 12

RNA polymerase inhibitors MOA

Answer 12

MOA: inhibit bacterial RNA polymerase -> inhibit nucleic acid synthesis

Question 13

RNA polymerase inhibitors pharmacokinetics

Answer 13

good oral abs. & tissue distr.
penetrate BBB
after metabolism excreted in urine & bile
enterohepatic re-circ.

Question 14

RNA polymerase inhibitors SE

Answer 14

RIFAMPICIN: hepatotoxicity, orange discoloration of body fluids, GI prob, rashes, inducer of CYP450

Question 15

RNA polymerase inhibitors use

Answer 15

RIFAMPICIN: TB, prophylaxis H.infl. & Neisseria Mening.
RIFAXIMIN: diarrhea
FIDAXOMICIN: pseudomembrane collitis (Cl. Difficile)

Question 16

Sulfonamides MOA

Answer 16

bacteriostatic
inhibit folic acid synthesis
PABA analogues-> inhibition of dihydropterate synthetase -> inhibit dihydrofolate synthesis -> inhibition of DNA synth.

Question 17

TRIMETHOPRIM MOA

Answer 17

bacteriostatic

inhibit dihydrofolate reductase -> inhibit tetrahydrofolate synthesis -> inhibit DNA synthesis

Question 18

SMX- TMP combo MOA

Answer 18

synergetic effect
bactericidal
broaden spectrum
less chance of resistance

Question 19

inhibition of folate synthesis steps

Answer 19

PABA-> dihydropteroic acid -> dihydrofolate -> tetrahydrofolate -> purines for DNA
1st step enzyme: dihydropterate synthetase
3rd step enzyme: dihydrofolate reductase

Question 20

antibacterial spectrum of folate inhibitors

Answer 20

gram - -> UTI’s eg E.coli,
aerob gram + like strep.pneumoniae
and protozoa like taxoplasma which cause toxoplasmosis, nocardia

Question 21

resistance of folate inhibitors

Answer 21

increased synth. of PABA
altered affinity to target enzymes
reduced penetration of antibiotics to bacterial cell

Question 22

pharmacokinetics of folate inhibitors

Answer 22

abs. from GI, bind to plasma proteins, good tissue penetration, cross BBB, metabolized by acetylation oxidation, excreted by kidney

Question 23

interactions of folate inhibitors

Answer 23

may increase effects of oral anticoag (eg warfarin), Sulfanylurea, Phenytoin, antidiabetics, Methotrexate
CYP450 INHIBITOR

Question 24

SE of folate inhibitors

Answer 24

CNS
Allergy
Steven-Johnsons Syndrome
Renal tubular acidosis type 4 -> hyperkalemia
interstitial nephritis
photosensitivity
teratogenicity
hepititis
GI prob

Question 25

Clinical use of folate inhibitors

Answer 25

UTI's
RTI's
traveller's diarrhea
infections of immunocompromised patients (toxoplasmosis, norcardiosis, pneumocystis pneumonia)
topical eye/ skin inf. (sulfonamides)

Question 26

contraind. of folate inhibitors

Answer 26

pregnancy

newborns (can cause kernicterus)