Lec. 9: Fluoroquinolones Flashcards
What exhibits inhibition of bacterial DNA gyrase, inhibits DNA synthesis, and is bactericidal?
Fluoroquinolones
A mutation in what can lead to resistance to fluoroquinolones?
Mutation in the quinilone resistance determining region (QRDR) of DNA gyrase enzyme.
Fluroquinolones decrease with ? containing Al+++ or Mg++ and decrease with ? containing Fe++ or Zn++.
- Antacids
2. Dietary supplements
What generation of fluoroquinolones has increased gram-negative and systemic activity, improved pharmacokinetics, and fewer side effects? Give five examples.
2nd generation
- Ciprofloxacin
- Enoxacin
- Lomefloxacin
- Norfloxacin
- Ofloxacin
What generation of fluoroquinolones has extended activity against gram-positive organisms and has broad gram-negative coverage? Give three examples
3 generation
- Grepafloxacin
- Levofloxacin
- Sparfloxacin
Fluoroquinolones inhibit P450 system, cause photosensitivity reactions, and causes prolongation of QT interval. Which drug causes a definite risk of QTc prolongation?
Sparfloxacin
Are fluoroquinolones a broad or narrow spectrum drug?
Broad spectrum
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
- Sulfonamides
2. Trimethoprim
What inhibits utilization of p-amino-benzoic acid (PABA) in the synthesis of folic acid?
Sulfonamides
Sulfonamides can develop resistance by what four methods?
- Alteration in enzyme requiring PABA
- Increased inactivation of drug
- Alternative metabolic pathway
- Increased production of PABA
T or F. Sulfonamides distribute to all body tissue, including CSF and pass the placental barrier and into great milk.
True
Sulfonamides can be used to treat what three things?
- Urinary tract infectoins
- Susceptible infections of the eye
- Chronic inflammatory bowel disease
What has the following adverse effects?
- Crystalline aggregates in urinary tract
- Hematologic disorder with G6PD deficiency
- Hypersensitivity
- Drug potentiation (it will bind serum albumin)
Sulfonamides
What inhibits the reduction of dihydrofolate to tetrahydrofolate, is highly selective for bacterial enzyme, and resistance occurs with alteration in enzyme affinity?
Trimethoprim
Where does trimethoprim tend to concentrate in the body?
Prostate and vaginal fluids
What combination makes up Co-trimoxazole?
Trimethoprim-Sulfamethoxazole
What are two advantages of trimethoprim-sulfamethoxazole combination?
- Synergistic activity
2. Low toxicity
What is commonly used to treat uncomplicated lower urinary tract infections, genital infections, bacterial respiratory tract infections, nocardiosis, and infection due to pneumocystis carinii?
Trimethoprim-sulfamethoxazole combination
What are the four main categories of anti fungal drugs?
- Polyenes
- Flucytosin
- Azoles
- Caspofungin
Polyene antifungals are characteristic of what two traits?
Amphotericin B and Nystatin
What binds to ergosterol in fungal cell membrane and resistance is rare?
Polyene antifungals
Amphotericin B is fungicidal or fungistatic?
Fungicidal
Nystatin is fungistatic or fungicidal?
Can be either
T or F. Amphotericin B and Nystatin exhibit both hydrophilic and hydrophobic portions.
True
What is the action of polyene agents?
To form pores in the fungal cell membrane through which K+ and Mg++ can leak out.
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?
Amphotericin B
What are five adverse effects of amphotericin B?
- Nephrotoxicity
- Thrombophlebitis
- Fever an dchills
- Hypersensitivity reaction
- Shock-like hypotension
Amphotericin B is preferred for treatment against ? infections and it should not be used during pregnancy.
Deep fungal infections
Nystatin should never be given ? b/c of unacceptable systemic toxicity. Only administer it either ? or ?.
- Paraenterally
- Topically
- Orally
What is often used to treat candidal infections of the mucosa, skin, and intestinal tract?
Nystatin
Mammalian cells do not have ?, which converts 5-Flucytosine to 5-FU.
Cytosine Deaminase
What drug is used to stop thymidylate synthase from converting dUMP to dTMP?
5-Flucytosine
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?”
5-Flucytosine
T or F. 5-Flucytosine does not penetrate the CSF.
False. 5-Flucytosine does penetrate the CSF.
What is the effect of clearance on 5-flucytosine when given with Amphotericin B?
Clearance is reduced
What is a broad spectrum anti fungal agent that inhibits synthesis of ergosterol (necessary sterol for fungal cell membrane)?
Imidazole Antifungal agent
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?
Fluconazole
What anti fungal drug is used to treat histoplasmosis, blastomycosis, aspergillus, and cryptococcus, and is a potent inhibitor of CYP3A4?
Itraconazole
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?
Voriconazole
What are three pharmacological properties of oral azole agents? Name the drug which fits each property.
- Easily crosses to CSF (Fluconazole)
- Hepatic elimination (Itraconazole and Voriconazole)
- Renal elimination (Fluconazole)
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?
Clotrimazole
What inhibits alpha (1,3) D-glucan synthesis, which are integral components of fungal cell WALL?
Caspofungin
Metronidazole with lithium leads to what?
It inhibits renal excretion of Li++, leading to elevated blood levels and Li++ toxicity
What effect is produced when metronidazole interacts with alcohol?
Disulfiram effect
Erythromycin, clarithromycin, or metronidazole with warfarin or anisindione lead to what?
An increased risk of bleeding in anti coagulated patients.
