Quinolones, Folic Acid Antagonists & Urinary Tract Antiseptics ABX med Class- Quiz 2 Flashcards
Fluoroquinolones
*Usually a second line antibiotic
-Overuse has caused resistance and has increased the amount of C. diff infections, and lot of ADEs
-MOA: Bind to enzymes and interfere with DNA ligation, causing chromosal breaking and cell lysis.
-Quinolones have different targets:
-Gram – pathogens—DNA gyrase
-Gram + pathogens—topoisomerase IV
-Ciprofloxacin=PROTOTYPE drug
-Ex: Delafloxacin, Gemifloxacin, Levofloxacin, Moxifloxacin, Ofloxacin
First Generation Quinolones
-Narrow spectrum
-Covers Gram – bacilli
-Ex: -Naladixic acid
-Mainly used for: enterobacteriaee
Second Generation Quinolones
-Improved intracellular penetration and broader coverage against gram -
-Ex: Cipro
Mainly used for: Anthrax, UTI, GI infections, traveller’s diarrhea, typhoid fever (NOT FOR RESP INFECTIONS)
-High dose therapy should be used to treat Pseudomonas
“Below the waist medication”
Third Generation Quinolones
- Cover the same pathogens as the
2nd generation drugs (gram -), but with expanded coverage of Strep
-Ex. Levofloxacin
-Mainly used for: respiratory infections (first line for CAP)
Fourth Generation Quinolones
-Enhanced Gram + and more Staph and Strep
-These drugs cover atypical bacteria (TB)
-Ex. Moxifloxacin, Gemifloxacin, Delafloxacin
Mainly used for: Anaerobes (atypical organisms)
-Can be used for CAP, but not for hospital acquired pneumonia
Causes of Quinolone resistance?
-High-level resistance is primarily from chromosomal mutations within topoisomerases
-Altered target binding
-Decreased accumulation from efflux pumps
-Degradation
Quinolone Pharmacokinetics
-Well absorbed after oral dosing (Sucralfate, Aluminum or Magnesium
containing antacids, Ca, dairy, Zinc or Iron reduce absorption)
-These agents distribute well into all
tissues and body fluids
-Penetration into the CNS is good
-Good coverage against intracellular pathogens—
Listeria, Chlamydia, Mycobacterium
-Excreted renally (need renal dosing)
Quinolone ADE’s
-Nausea, Vomiting, Headache, Dizziness, Photosensitivity (need sunscreen)
-Also, hepatotoxity, low blood sugar, prolonged QTC, lot of drug-drug interactions (warfarin–> HIGH INR)
-Arthralgia and arthritis is often
reported in the pediatric patient (Use in pediatrics should be limited to specific scenarios—CF exacerbations)
-BLACK BOCK WARNING: tendinitis, tendon rupture, peripheral neuropathy and CNS effects (hallucinations, anxiety, insomnia, confusion, seizures)
NOTE* Cold turkey stop these meds with severe ADE’s*
Folate Antagonists
-Sulfonamides and TrimethoPRIM ;)
-Folic acid is a coenzyme essential in synthesis of RNA, DNA
-In the absence of folate, cells cannot grow and divide
-Sulfonamides and Trimethoprim interfere with the ability of the pathogen to perform DNA creation
and allow essential cellular functions
-Combining Sulfamethoxazole with Trimethoprim provides a synergistic effect
Sulfonamides
-Are seldom prescribed alone—except in developing countries
(are inexpensive and effective)
-MOA: Inhibit the genesis of bacterial dihydrofolic acid (prevent the growth of bacteria don’t necessarily kill it)
-Have in vitro activity against gram - and +
- Sulfadiazine [with Pyrimethamine] is DOC for Toxoplasmosis
-Pathogens that get folate from the
environment are naturally resistant
to Sulfa drugs
-Mainly used for:
UTI’s
Sulfonamides Pharmacokinetics
-Well absorbed after oral dose
-IV use is reserved for those who cannot take oral dosages or who have severe infection
-Because of risk of sensitization, Sulfa drugs are usually not given topically (exception for BURNS)
-Widely distributed in body tissues
-Penetrate well into CSF
-Conjugated in liver
-Eliminated via glomerular filtration and secretion
-Dose adjustments are
needed in renal disease
-Are eliminated in breast
milk
Sulfonamides ADE’s
-Crystalluria (Adequate hydration and alkalization of the urine prevent this)
-Hypersensitivity (greatest risk of rash, stevens-johnsons, toxic necrosis of ANY abx)
-Hematological Effects (Fatal reactions)
-Kernicterus in neonates
-Significant drug-drug interactions
CI: Do not give to newborns/ infants less than 2 months of age
-Do not give to pregnant women
-Do not give to patients taking Methenamine, since they can crystallize
-NOTE* DO NOT PRESCRIBE SULFONAMIDES to patients on
Warfarin—unless there are NO OTHER ALTERNATIVES, and in that case, the Warfarin dose must be reduced by 50 PERCENT*
TrimethoPRIM :)
-MOA: Potent inhibitor of bacterial dihydrofolate reductase (interferes with normal bacterial cell functions)
-Most commonly used in combination with Sulfamethoxazole
-Trimethoprim is 20 – 50 fold
more potent than the Sulfonamides
-Rapidly absorbed after oral dose
-Widely distributed in the body
tissues and fluids—including CSF
-ADE’s: Can produce folic acid deficiency (Anemias) but can give folinic acid; hyperkalemia (potassium-sparing)
-Mainly used in:
-UTI’s
-Prostatitis
Cotrimoxazole
-Trimethoprim + Sulfamethoxazole
-Shows greater coverage than either drug used alone
-Synergistic activity and similar ½ lives to each of its components
-MOA: Synergistic activity is
from the inhibition of 2 steps in the
synthesis of tetrahydrofolic acid
-Broader coverage than the sulfa drugs
-Used to treat UTIs, respiratory infections, skin infections (MRSA)
-Usually given orally
-ADE’s: N/V, Skin rash, Hematological
toxicity, Elevated K+
Urinary Tract Antiseptics/Antimicrobials
-Methenamine
-Nitrofurantoin-PROTOTYPE
-Used to use quinolones and Trimethoprim-Sulfa 1st line for UTIs but resistance has increased and as a result, these older antimicrobials must be considered in suppression of UTIs
