Quinolones, Folic Acid (Folate) Antagonists and Urinary Tract Antiseptics

Question 1

4th generation; anaerobic and gram pos activity

Answer 1

Moxifloxacin

Question 2

Avoid ingestion of dairy, sucralfate, aluminum / magnesium containing antacids, iron, zinc, calcium (2 hours before / 3 hours after taking)

Answer 2

Fluoroquinolones

Question 3

Adjust dosages for renal impairment.

Answer 3

Quinolones

Question 4

Dyspnea, chest pains, chills, fever, cough

Hematologic - especially in G-6-PD

Peripheral Neuropathy
Hepatotoxicity
Birth defects
CNS Effects

Answer 4

Adverse effects of Nitrofurantoin

Question 5

Generally well tolerated
N/V/D , headache, dizziness, lightheadedness, confusion, Phototoxicity

Use caution in CNS disorders, Peripheral neuropathy, Glucose dysregulation (Hypo/hyperglycemia)
Prolongation of QT interval.

Increases serum concentrations of Theophylline, Warfarin, Caffeine,Cyclosporine

Answer 5

Adverse Effects / Drug Interactions of Fluoroquinolones

Question 6

Sulfonamides, trimethoprim and cotrimoxazole are all …

Answer 6

Folate antagonists

Question 7

(Birth defects possible, especially it taken during the first trimester and near term)
Secreted in breast milk (<2 months old can cause kernicterus)

It is a preferred drug for UTIs and is the drug of choice for PCP in patients with AIDs and other immunodeficiencies.

Answer 7

Cotrimoxazole (bactrim, TMP/SMZ)

Question 8

Fluoroquinolones are commonly considered as …

Answer 8

alternatives for patients with documented SEVERE B-lactam allergies

Question 9

Folic acid deficiency: You can ____ it by giving folic acid to patients.

1 mg/day folic acid with prenatal vitamin regimen (at a min)

Answer 9

reverse

Question 10

Shows improved gram-pos coverage, maintains gram-neg activity and gains ANAEROBIC coverage.

Answer 10

Fourth generation of Fluoroquinolones

Question 11

The first drugs available for systemic treatment of bacterial infections. Introduced in the 1930s.

Usage declined once PCN was introduced in the 1940s.

Older agents had low solubility which caused urine crystallization and kidney injury. Newer agents are more water soluble which decreases renal risk.

Primarily used and often preferred for acute UTIs (90% are due to Escherichia coli)

Answer 11

Sulfonamides

Question 12

Resistance of fluoroquinolones comes from an ____ in DNA gyrase and topoisomerase 4.

Answer 12

Alteration

Question 13

Achieves high levels in bone, urine (except which quinolone…?), kidney, prostatic tissue, lungs. Low CSF penetration except _____ (low urine levels, not for UTI).

Answer 13

ofloxacin

Question 14

Avoid _____ with decreased renal fxn.

Answer 14

Nitrofurantoin

Question 15

Enhanced activity against gram + (S. pneumoniae) + excellent activity against many anaerobes

Poor activity against P. aeruginosa, resistant to Bacteroides fragilis

CAP, nosocomial pneumonia

Not indicated for UTIs due to poor concentration in the urine*

Answer 15

Moxifloxacin (respiratory quinolone)

Question 16

Most quinolones are excreted renally.

Adjust dosage in renal impairment (except _____, which is excreted by the liver)

Answer 16

moxifloxacin

Question 17

Accumulates and has activity against intracellular organisms (effective against _____ and mycobacteria)

Answer 17

chlamydia

Question 18

These are less used today, have moderate gram-negative, minimal serum concentrations, restricted to the treatment of UNCOMPLICATED UTIs.

Answer 18

First generation of Fluoroquinolones

Question 19

What enzyme does Sulfonamides inhibit? dihydropteroate ______.

Answer 19

synthase

Question 20

precedes all fluoroquinolones and are not clinically used

Answer 20

Naldixic Acid

Question 21

Retain expanded gram-negative activity and show improved activity against atypical organisms and specific gram-pos bacteria.

Answer 21

Third generation of Fluoroquinolones

Question 22

____ is required by all cells to make DNA, RNA, and proteins

Folate antagonists inhibit sequential steps in the synthesis of tetrahydrofolic acid. In the absence of _____, bacteria are unable to synthesize DNA, RNA and proteins

Answer 22

Folate; tetrahydrofolate

Question 23

Ampicillin and Gentamicin

Answer 23

Infant UTI tx

Question 24

Resistance is due to an alteration in dihydrofolate reductase that has a lower affinity for trimethoprim+ efflux pumps and decreased drug permeability.

Rapidly absorbed after oral administration.

High concentrations are achieved in prostatic and vaginal fluids and CSF.

Can produce effects of folic acid deficiency:

• Megaloblastic anemia
• Leukopenia
• Granulocytopenia

Answer 24

Trimethoprim

Question 25

If breast feeding, avoid ____. Avoid Trimeth/Sulfa also in early stages of infancy.

Answer 25

Nitrofurantoin

Question 26

What enzyme does Trimethoprim inhibit? dihydrofolate _____.

Answer 26

reductase

Question 27

Sulfamethoxazole + Trimethoprim = greater activity together than each working individually.

Answer 27

Cotrimoxazole (bactrim, TMP/SMZ)

Question 28

Respiratory quinolones

Answer 28

Levo and Moxi (also against anaerobes)

Question 29

Genetic disorder in african, asian, middle eastern

Answer 29

G-6-PD

Question 30

End in "oflxacin" "collateral damage" Used for direct inhibitors of DNA synthesis.

Answer 30

Fluoroquinolones

Question 31

Given twice daily in capsule form, and more costly than Nitrofurantoin (given q6hrs, available in capsules/suspension).

Answer 31

Microbid

Question 32

Used for protozoal infections, anaerobic infections, bacterial vaginosis/vaginitis, Intra-abdominal infections and Trichomoniasis

Answer 32

Metronidazole

Question 33

Use off-label for C. diff, Sexual assault prophylaxis + ceftriaxone and azithromycin or doxycycline) and skin and soft tissue necrotizing infections

Answer 33

Metronidazole

Question 34

These are the only fluoroquinolones approved in children but generally should be avoided in this population due to tendonitis

Answer 34

Cipro and Levo

Question 35

2nd generations Double A (aerobic gram neg, atypicals) Double M (mycoplasma and mycobacteria) Chlamydia

Answer 35

Cipro and Norfloxacin

Question 36

Infrequently prescribed due to poor oral bioavailability (what reaches circulation is poor) and a short half-life Nonsystemic infections UTI, prostatitis, infectious diarrhea (unlabeled use)

Answer 36

Norfloxacin

Question 37

N/V, epigastric distress, abdominal cramps, unpleasant metallic tastes, yeast infections of the mouth Avoid use of alcohol during therapy or within 3 days of therapy discontinuation – disulfiram-like reaction

Answer 37

Adverse effects and contraindications for Metronidazole

Question 38

Bactericidal, Man Made antibiotics, Broad-Spectrum (than other abx), Use has been closely associated with Clostridium difficile and the spread of antimicrobial resistance

Answer 38

Fluoroquinolones

Question 39

Stevens-Johnson syndrome: Rare reaction with a 25% mortality rate. Widespread lesions of the skin and mucous membrane Fever, malaise, toxemia Discontinue ________ immediately if any type of skin rash is observed. Do not give to any patient with a history of hypersensitivity reactions to other drugs like, thiazide diuretics, loop diuretics, sulfonylurea-type oral hypoglycemics.

Answer 39

Sulfonamide

Question 40

Avoid antacids Not used for upper UTIs (pyelonephritis). GI distress is the major side effect. At higher doses – albuminuria, hematuria, rashes. Contraindicated in renal insufficiency. Avoid sulfonamides which react with formaldehyde and increases crystalluria risk and mutual antagonism.

Answer 40

Methenamine

Question 41

Nitrofurantoin and Methenamine are used for UTIs ONLY. These are considered _______ (class). Both concentrate in the urine and neither drug achieves effective antibacterial concentrations in the blood/tissues.

Answer 41

Urinary Tract Antiseptics/Antimicrobials

Question 42

IV, PO, Opthalmic, Otic = CLM

Answer 42

Quinolone Pharmacokinetics Cipro, Levo, Moxi

Question 43

Suppresses synthesis of tetrahydrofolic acid. Similar antibacterial spectrum to sulfonamides. 20 – 50 fold more potent than the sulfonamides. Most often compounded with sulfamethoxazole to = cotrimazole (Bactrim). Can be used alone in the treatment of UTIs and bacterial prostatitis (although quinolones are preferred)

Answer 43

Trimethoprim Folate Antagonist

Question 44

Avoid sulfonamide/trimethoprim use in infants < 2 months due to ______ which can be fatal.

Answer 44

kernicterus

Question 45

3rd generation; has increased gram pos activity

Answer 45

Levofloxacin

Question 46

Hypersensitivity reactions Rash, drug, fever, photosensitivity Especially with topical agents. Blood dyscrasias, hemolytic anemia Kernicterus in newborns* Bilirubin induced Yellow baby syndrome Crystalluria (renal damage)

Answer 46

Adverse side affects of sulfonamides

Question 47

These are well absorbed orally and when used topically may cause systemic effects. Readily crosses the placenta and can achieve antimicrobial effects and toxicity in the fetus (yellow babies). Metabolized in the liver by acetylation Excreted by the kidneys.

Answer 47

Sulfonamides

Question 48

Less resistance with the combination than to either drug alone, but still significant resistance has been encountered to E. coli, and MRSA. Generally administered orally, IV for patients with severe pneumonia caused by PCP. Readily crosses the BBB. Adverse effects include: N/V, Hyperkalemia with higher doses. Megaloblastic anemia, leukopenia, thrombocytopenia (possibly fatal).

Answer 48

Cotrimoxazole (bactrim, TMP/SMZ)

Question 49

1st Choice in uncomplicated cystitis. Broad-spectrum antibacterial. Bacteriostatic at low concentrations / Bactericidal at high concentrations. Therapeutic levels are achieved only in urine. Injures bacteria by damaging DNA after enzymatic conversion to an active form. Used for acute infections of the lower urinary tract and for prophylaxis of recurrent lower UTI* Avoid with significant renal failure. Category B(pregnancy) but contraindicated at term (38+ weeks) .

Answer 49

Nitrofurantoin

Question 50

Fluoroquinolones MOA is inhibition of 2 bacterial enzymes involved in DNA replication.

Answer 50

DNA gyrase, Topoisomerase 4

Question 51

Fluoroquinolones, including _____ , are associated with an increased risk of ____ and ____ rupture in all ages. This risk is further increased in older patients (usually older than 60 years), in patients taking corticosteroid drugs, and in patients with kidney, heart, or lung transplants.

Answer 51

ciprofloxacin, tendonitis, tendon

Question 52

Inhibits sequential steps in bacterial folic acid synthesis. Treats UTIs and respiratory tract infections to include Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis. Activity against MRSA* Particularly community-acquired skin and soft tissue infections caused by MRSA.

Answer 52

Cotrimoxazole (bactrim, TMP/SMZ)

Question 53

Decomposes under acidic conditions and breaks down into ammonia and formaldehyde. Formaldehyde acts locally and is toxic to most bacteria. Bacteria do not develop resistance to formaldehyde which is an advantage of this drug. Frequently formulated with a weak acid (mandelic acid or hippuric acid) to keep the urine acidic. Very important: Used for chronic suppressive therapy (not treatment) to reduce the frequency of UTIs**

Answer 53

Methenamine

Question 54

Sulfonamides are used primarily for _____.

Answer 54

UTIs

Question 55

In many micro-organisms, dihydrofolic acid is synthesized from PABA, p-aminobenzoic acid. Sulfonamides are synthetic analogs of PABA and therefore ____ ____ ___ for the bacterial enzyme, dihydropteroate synthetase

Answer 55

compete with PABA

Question 56

Effective in the treatment of many systemic infections caused by gram neg bacilli Not useful for S. pneumoniae Complicated and Uncomplicated UTIs Traveler’s diarrhea (E.coli) Typhoid fever (Salmonella typhi), Tuberculosis (2nd line) Anthrax (Drug of choice, post exposure prophylaxis) Best activity against P. aeruginosa (commonly used in cystic fibrosis)

Answer 56

Ciprofloxacin

Question 57

Resistance of fluoroquinolones comes from a ____ accumulation of the drug intracellularly.

Answer 57

decreased

Question 58

Have expanded gram-negative activity and also some activity against gram-positive and atypical organisms, mycoplasma, chlamydia

Answer 58

Second generation of Fluoroquinolones

Question 59

After diffusing into the organism, it interacts with DNA to cause a loss of helical DNA structure resulting in inhibition of protein synthesis and cell death

Answer 59

MOA of Metronidazole

Question 60

Avoid fluoroquinolones and nitrofurantoin (in the 3rd trimester) for the tx UTIs during _____.

Answer 60

Pregnancy

Question 61

Ciprofloxacin, Levofloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin (ophthalmic, more than systemic)

Answer 61

Fluoroquinolones

Question 62

1st generation quinolone? Very narrow.

Answer 62

Naldixic acid

Question 63

Sulfonamides suppress ___ ___ by inhibiting the synthesis of dihydrofolic acid and the formation of tetrahydrofolate (folic acid derivative)

Answer 63

bacterial growth

Question 64

Decreased accumulation of fluoroquinolone intracellularly is due to a decreased number of ____ ____ to the outer membrane of the resistant cell which impairs access to the topoisomerases. And Efflux Pumps – Pumps drug out of the cell

Answer 64

porin proteins

Question 65

Excellent activity against S. pneumoniae (unlike Cipro) Complicated and Uncomplicated UTIs Prostatitis, Skin infections, CAP, nosocomial pneumonia

Answer 65

Levofloxacin (respiratory quinolone)

Question 66

Fluoroquinolones, including ciprofloxacin, may exacerbate muscle weakness in persons with ___ ___. Avoid ciprofloxacin in patients with known history of ____ ____.

Answer 66

myasthenia gravis

Question 67

Gram negative (E. coli, P. aeruginosa, H. Influenzae) Atypicals (Legionella, Chlamydiaceae) Gram positive (streptococci) Some mycobacteria (Mycobacterium tuberculosis)

Answer 67

Antimicrobial spectrum for Fluoroquinolones

Question 68

Narrow-spectrum quinolone antibiotic, used only for | UTIs, Some GI infections

Answer 68

Naldixic Acid