Lec. 9: Fluoroquinolones

Question 1

What exhibits inhibition of bacterial DNA gyrase, inhibits DNA synthesis, and is bactericidal?

Answer 1

Fluoroquinolones

Question 2

A mutation in what can lead to resistance to fluoroquinolones?

Answer 2

Mutation in the quinilone resistance determining region (QRDR) of DNA gyrase enzyme.

Question 3

Fluroquinolones decrease with ? containing Al+++ or Mg++ and decrease with ? containing Fe++ or Zn++.

Answer 3

1. Antacids

2. Dietary supplements

Question 4

What generation of fluoroquinolones has increased gram-negative and systemic activity, improved pharmacokinetics, and fewer side effects? Give five examples.

Answer 4

2nd generation

1. Ciprofloxacin
2. Enoxacin
3. Lomefloxacin
4. Norfloxacin
5. Ofloxacin

Question 5

What generation of fluoroquinolones has extended activity against gram-positive organisms and has broad gram-negative coverage? Give three examples

Answer 5

3 generation

1. Grepafloxacin
2. Levofloxacin
3. Sparfloxacin

Question 6

Fluoroquinolones inhibit P450 system, cause photosensitivity reactions, and causes prolongation of QT interval. Which drug causes a definite risk of QTc prolongation?

Answer 6

Sparfloxacin

Question 7

Are fluoroquinolones a broad or narrow spectrum drug?

Answer 7

Broad spectrum

Question 8

Pteridine + PABA to Dihydropteroid acid is blocked by ? and conversion of Dihydrofolic acid to Tetrahydrofolic acid is blocked by? These are sites of inhibition in folic acid synthesis

Answer 8

1. Sulfonamides

2. Trimethoprim

Question 9

What inhibits utilization of p-amino-benzoic acid (PABA) in the synthesis of folic acid?

Answer 9

Sulfonamides

Question 10

Sulfonamides can develop resistance by what four methods?

Answer 10

1. Alteration in enzyme requiring PABA
2. Increased inactivation of drug
3. Alternative metabolic pathway
4. Increased production of PABA

Question 11

T or F. Sulfonamides distribute to all body tissue, including CSF and pass the placental barrier and into great milk.

Answer 11

True

Question 12

Sulfonamides can be used to treat what three things?

Answer 12

1. Urinary tract infectoins
2. Susceptible infections of the eye
3. Chronic inflammatory bowel disease

Question 13

What has the following adverse effects?

1. Crystalline aggregates in urinary tract
2. Hematologic disorder with G6PD deficiency
3. Hypersensitivity
4. Drug potentiation (it will bind serum albumin)

Answer 13

Sulfonamides

Question 14

What inhibits the reduction of dihydrofolate to tetrahydrofolate, is highly selective for bacterial enzyme, and resistance occurs with alteration in enzyme affinity?

Answer 14

Trimethoprim

Question 15

Where does trimethoprim tend to concentrate in the body?

Answer 15

Prostate and vaginal fluids

Question 16

What combination makes up Co-trimoxazole?

Answer 16

Trimethoprim-Sulfamethoxazole

Question 17

What are two advantages of trimethoprim-sulfamethoxazole combination?

Answer 17

1. Synergistic activity

2. Low toxicity

Question 18

What is commonly used to treat uncomplicated lower urinary tract infections, genital infections, bacterial respiratory tract infections, nocardiosis, and infection due to pneumocystis carinii?

Answer 18

Trimethoprim-sulfamethoxazole combination

Question 19

What are the four main categories of anti fungal drugs?

Answer 19

1. Polyenes
2. Flucytosin
3. Azoles
4. Caspofungin

Question 20

Polyene antifungals are characteristic of what two traits?

Answer 20

Amphotericin B and Nystatin

Question 21

What binds to ergosterol in fungal cell membrane and resistance is rare?

Answer 21

Polyene antifungals

Question 22

Amphotericin B is fungicidal or fungistatic?

Answer 22

Fungicidal

Question 23

Nystatin is fungistatic or fungicidal?

Answer 23

Can be either

Question 24

T or F. Amphotericin B and Nystatin exhibit both hydrophilic and hydrophobic portions.

Answer 24

True

Question 25

What is the action of polyene agents?

Answer 25

To form pores in the fungal cell membrane through which K+ and Mg++ can leak out.

Question 26

What is primarily used IV, has greater than 90% bound to beta-lipoprotein, and is has one non-lipid based form (deoxycholate) and three lipid-based forms (abelcet, ambisome, amphotec), and is not metabolized?

Answer 26

Amphotericin B

Question 27

What are five adverse effects of amphotericin B?

Answer 27

1. Nephrotoxicity 2. Thrombophlebitis 3. Fever an dchills 4. Hypersensitivity reaction 5. Shock-like hypotension

Question 28

Amphotericin B is preferred for treatment against ? infections and it should not be used during pregnancy.

Answer 28

Deep fungal infections

Question 29

Nystatin should never be given ? b/c of unacceptable systemic toxicity. Only administer it either ? or ?.

Answer 29

1. Paraenterally 2. Topically 3. Orally

Question 30

What is often used to treat candidal infections of the mucosa, skin, and intestinal tract?

Answer 30

Nystatin

Question 31

Mammalian cells do not have ?, which converts 5-Flucytosine to 5-FU.

Answer 31

Cytosine Deaminase

Question 32

What drug is used to stop thymidylate synthase from converting dUMP to dTMP?

Answer 32

5-Flucytosine

Question 33

What is can be fungicidal or static, inhibits thymidylate synthase and DNA synthesis, is deaminated to 5-fluorouracil, is "almost always used in combination with Amphotericin B?"

Answer 33

5-Flucytosine

Question 34

T or F. 5-Flucytosine does not penetrate the CSF.

Answer 34

False. 5-Flucytosine does penetrate the CSF.

Question 35

What is the effect of clearance on 5-flucytosine when given with Amphotericin B?

Answer 35

Clearance is reduced

Question 36

What is a broad spectrum anti fungal agent that inhibits synthesis of ergosterol (necessary sterol for fungal cell membrane)?

Answer 36

Imidazole Antifungal agent

Question 37

What drug inhibits P450 enzyme (causing potential increase in serum levels of concurrent drugs), but does not inhibit P450 isozyme use for androgen synthesis, and is used to treat candidiasis, coccidiomycosis, and cryptococcal meningitis?

Answer 37

Fluconazole

Question 38

What anti fungal drug is used to treat histoplasmosis, blastomycosis, aspergillus, and cryptococcus, and is a potent inhibitor of CYP3A4?

Answer 38

Itraconazole

Question 39

What drug exhibits genetic polymorphism (CYCP2C19 deficiency = increased concentration), is contraindicated with drugs that induce P450 (rifampin, rifabufin, carbamazapine, long acting barbiturates), and is used to treat invasive aspergillosis, scedosporium, fusarium, and invasive fluconazole-resistant candida?

Answer 39

Voriconazole

Question 40

What are three pharmacological properties of oral azole agents? Name the drug which fits each property.

Answer 40

1. Easily crosses to CSF (Fluconazole) 2. Hepatic elimination (Itraconazole and Voriconazole) 3. Renal elimination (Fluconazole)

Question 41

What is an anti fungal drug that is given as a topical application for mucosal and cutaneous fungal infections, and if swallowed can increase hepatic enzymes in the plasma?

Answer 41

Clotrimazole

Question 42

What inhibits alpha (1,3) D-glucan synthesis, which are integral components of fungal cell WALL?

Answer 42

Caspofungin

Question 43

Metronidazole with lithium leads to what?

Answer 43

It inhibits renal excretion of Li++, leading to elevated blood levels and Li++ toxicity

Question 44

What effect is produced when metronidazole interacts with alcohol?

Answer 44

Disulfiram effect

Question 45

Erythromycin, clarithromycin, or metronidazole with warfarin or anisindione lead to what?

Answer 45

An increased risk of bleeding in anti coagulated patients.