True or false, first generation quinolones are only used to treat systemic infections.
False, the second generation quinolones are used only for systemic infections
Nalidixic acid and Cinoxacin are ________ generation quinolones.
Ciprofloxacin, Enoxacin, Lemofloxacin, and Norfloxacin are ________ generation quinolones.
Widely distributed in the body
Not recommended for pregnant women and children <16
Fluroquinolones (second generation quinolones)
True or false, fluroquinolones have a higher affinity for DNA Gyrase than Bacterial Topoisomerase IV.
What is the MOA for quinolones in gram negative bacteria?
Inhibit DNA synthesis by inhibiting DNA Gyrase
What is the MOA for quinolones in gram positive bacteria?
Inhibit DNA synthesis by inhibiting Bacterial Topoisomerase IV
True or false, quinolones can inhibit mammalian type II DNA topoisomerase at the clinical dose.
False, at the clinical dose it will NOT inhibit this enzyme but at very high concentrations it will inhibit that enzyme
What are the 2 mechanisms for microbial resistance to the quinolones?
- 1- Expression of an altered DNA gyrase or topoisomerase IV (target modification)
- 2- active efflux
Which quinolone causes serious liver injuries and has been resitricted by the FDA for use in only life-threatening infections?
Quinolones are _______ of cyt P450 and will ________ levels of theophylline, digoxin, caffeine, wafarin, and cyclosporine.
What 4 toxicities can be caused by quinolones?
- 1- Chelation
- 2- Cartilage malformations (arthropathy)
- 3- Tendonitis or tendon rupture
- 4- Phototoxicity
Which 2 quinolones are the most phototoxic?
- 1- Sparfloxacin
- 2- Lomefloxacin
What 2 drugs can reduce the bioavailabilty of quinolones?
- 1- sulcralfate (aluminum ions)
- 2- didanosine (magnesium and aluminum)
What polypeptide antibiotics disrupt cell membrane permeability?
- 1- polymixins
- 2- gramicidin
True or false, polypeptide antibiotics are neutral and gramicidins are basic.
False, polypeptides are basic and gramicidins are neutral
Nephrotoxic and neurotoxic
NOT absorbed in the GI-tract
What are the 2 polymixins on the market?
- 1- polymixin B
- 2- polymixin E (colistin)
True of false, polymixins are not active against Gram positive bacteria
True or false, the polymixins penetrate the CSF, synovial fluid, aqueous humor or the eye, or across the placenta.
False, polymixins DO NOT penetrate these areas
Polymixins have a ____ affinity for bacterial and mammalian cell membranes and there is _______ systemic absorption folowing topical administration
True or false, polymixin can be administered parenterally or orally.
False, it can only be administered parenterally
Why are polymixins rarely used systemically?
Due to their toxicity
What is the MOA for polymixins?
They bind ionically to phospholipids and penetrate into the structure of the cell membrane disrupting the cell membrane permeability
Which antibiotics are amphipathic, surface active agents and act like cationic detergents?
Activity of the polymixins is _______ by the presence of divalent cations like ____ which interfere with binding.
What is the cyclic lipopeptide antibiotic?
Treats gram positive bacteria
Admisitered via IV
Cyclid Lipopeptides (Daptomycin)
What is the MOA (2 total) of Daptomycin?
Inhibits the biosynthesis of lipoteichoic acid in gram-positive bacteria
Depolarizes the membrane potential
What are the toxicities (2) associated with daptomycin?
- 1- superinfection
- 2- peripheral/cranial neuropathy
Sulfonamides belong the the _________ class.
What are 4 ways to minimize the risk of crystalluria in sulfonamides?
- 1- Use sulfanilamides with lower pKa values
- 2- increase the pH of urine
- 3- increase urine flow
- 4- avoid any decrease in the pH of urine
How can you increase the pH of your urine?
Taking sodium bicarbonate
What pKa do the sulfonamides have?
Sulfonamides are structural analogs AND _______ antagonists of ________
PABA (p-aminobenzoic acid)
True or false, sulfonamides do affect mammalian cells.
False, they DO NOT affect mammalian cells
What is the MOA for sulfonamides?
It is a competive inhibitor with PABA to inhibit dihydropteroate synthesis
What happens if PABA has a higher concentration than the sulfonamides?
Dihydropteroate synthase will not be inhibited
True or false, human cells do not use PABA therefore sulfonamides do not inhibit human cells.
What are the 4 mechanisms of resistance to sulfonamides?
- 1- expression of an altered dihydropteroate synthase (target modification)
- 2- decreased bacterial permeablilty/active efflux
- 3-developing an alternative metabolic pathway for the synthesis of THF
- 4- Increased production of PABA
Cross resistance among the sulfonamides is _____%
True or false, sulfonamides are rarely used as single agents.
What are the toxicities associated with sulfonamides? (5)
- 1- hypersensitiviy
- 2- hemolytic anemia
- 3- aplastic anemia
- 4- agranulocytosis
- 5- crystalluria
True or false, sulfonamides are not well distributed in the body.
False, they are well distributed and are absorbed in the GI-tract and CSF, they also cross the placenta
The sulfamethoxazole-trimethoprim is _______ at the clinical dose and is ________.
What is the trimethoprim MOA?
It is a competive inhibitor of dihyrofolate reductase which prevents the conversion of dihydrofolic acid ototetrahydrofolic acid
What is the benefit of using Bactrim?
The drugs are synergistic and will block sequential steps in the pathway inhibiting DNA synthesis
Does trimethoprim have a higher affinity for binding to the bacterial dihydrofolate reductase of the mammalian one?
The bacterial DHFR
What is the most synergistic concentration of sulfamethoxazole/trimethoprim?
What is the most common resistance mechanism for Bactrim?
A plasmid that cosed for an altered DHFR (target modification)
What are the toxicities associated with bactrim?
- 1- leukopenia
- 2- megaloblastosis
- 3- thrombocytopenia
in patients with folate deficiency due to inhibition of DHFR
What are the first line antituberculosis agents? (6)
- 1- Isoniazid
- 2- Rifampin
- 3- Rifabutin
- 4- Ethambutol
- 5- Pyrazinamide
- 6- Streptomycin
What are the second line antituberculosis agents? (8)
- 1- p-aminosalicylic acid
- 2- ethionamide
- 3- cycloserine
- 4- capreomycin
- 5- kanamycin
- 6- amikacin
- 7- moxifloxacin
- 8- linezolid
Which 2 anti-TB drugs are bactericidal?
- 1- isoniazid
- 2- pyrazinamide
What is the MOA for p-Aminosalicylic acid?
Inhibits folic acid synthesis
What is the MOA for Isoniazid?
inhibits the synthesis of mycolic acids in the cell wall of mycobacteria
What is the MOA for Ethambutol?
Inhibits the synthesis of mycolic acids
What is the MOA for Ethionamide?
Inhibits bacterial protein synthesis
Which 2 anti-TB drugs have an unknown MOA?
- 1- Pyrazinamide
- 2- Capreomycin