Pharmacology - Quinolones, Folic Acid Antagonists, Urinary Antiseptics, Metronidazole Flashcards
List the fluoroquinolones.
Ciprofloxacin, Levofloxacin, Moxifloxacin
What is the mechanism of action of the fluoroquinolones?
Targets DNA gyrase in Gram-negatives and topoisomerase IV in Gram-positives to inhibit DNA replication - inhibition of DNA replication results in bacterial lysis
How far should fluoroquinolones be spaced from consumption of dairy products or substances that contain divalent cations?
2h before or 6h after
How can fluoroquinolones be administered?
PO/IV/Opthalmic
What is the spectrum of action of ciprofloxacin?
Most active against Gram-negatives and enteric coliform (incl penicillin, cephalosporin and aminoglycoside resistant strains)
Highly effective against P.aeruginosa (only oral agent available)
Traveller’s diarrhoea caused by E.coli, food poisoning caused by all Enterobacteriaceae and Campylobacter jejuni
Typhoid fever caused by Salmonella typhi
Prostatitis
Anthrax caused by Bacillus anthracis
Uncomplicated UTI, but not recommended as first-line (mainly for penicillin allergy)
Avoid in MSSA/MRSA - is thus not considered a respiratory quinolone
What is the spectrum of action of levofloxacin?
Better Gram-positive coverage than ciprofloxacin - Streps and S.pneumoniae
(use for MSSA/MRSA coverage w caution)
Active against Gram-negatives - H.influenzae, E.coli, Klebsiella spp, Proteus mirabilis, Pseudomonas aeruginosa
Better coverage against Atypicals than ciprofloxacin
Useful against respiratory infections
NOT FIRST LINE FOR TB
What is the spectrum of action of moxifloxacin?
Better Gram-positive coverage than ciprofloxacin, esp S.pneumoniae, Finegoldia magna
(use for MSSA/MRSA coverage w caution)
Only used for H.influenzae amongst the gram negatives (no breakpoints from CLSI)
Better coverage against Atypicals than ciprofloxacin
Useful against respiratory infections
NOT FIRST LINE FOR TB
Are the fluoroquinolones used for CSF?
No
How are the fluoroquinolones excreted?
Renal - cipro, levo
Hepatic - moxi
All need adjustment in respective organ failures
Can fluoroquinolones be used in G6PD deficiency?
No
What are the adverse reactions associated with the fluoroquinolones?
- GI Sx - N/V/D
- Dysglycaemia risk, esp in DM
- Aortic dissections (rare)
- Inc C.diff colitis risk, esp w ciprofloxacin
- Headache and dizziness - treat CNS disorder pts carefully
- Phototoxicity
- Tendonitis risk
- QTc prolongation
- Peripheral neuropathy (can be reversible or irreversible)
What drugs interact w the fluoroquinolones?
The fluoroquinolones interact w warfarin and cyclosporine
What groups of patients are fluoroquinolones contraindicated in?
Children <18yo
Pregnancy
What is the mechanism of action of sulfamethoxazole?
Competitive inhibitors of dihydropteroate synthase, which stops dihydropteroic acid synthesis (immediate precursor of folic acid) - only active against microorganisms that solely synthesise their own folic acid
What is the mechanism of action of trimethoprim?
Inhibits reduction of dihyrofolic acid by dihydrofolate reductase to its active form, dec purine, pyrimidine & aa synthesis
What is the spectrum of action of co-trimoxazole?
MSSA, MRSA, E.coli, Klebsiella spp, Proteus mirabilis
Use w caution for S.pneumoniae, H. influenzae, ESBL producing E.coli, Enterobacter
Sulfonamides are only effective in bacteria that synthesize their own __________?
folic acid
How should co-trimoxazole be taken by oral route?
Take with a full cup of water
What are the adverse reactions associated with co-trimoxazole?
- Hypersensitivity: can range from mild rash to SJS
- GI Sx: N/V, CDAD also possible
- Can cause haemolytic anemia in G6PD deficient patients
- Can impair haematopoiesis due to folate antagonism - admin folinic acid tgt to prevent
- Hyperkalaemia
How is co-trimoxazole excreted?
Sulfamethoxazole - metabolised hepatically (acetylation and conjugation), excreted renally
Trimethoprim - 60-80% renally as unchanged drug
What groups of patients is co-trimoxazole contraindicated for?
- G6PD deficient
- Folate deficient
- Pregnant women (G6PD deficiency concern + sulfamethoxazole causing kernicterus)
- Infants <2months (G6PD deficiency concern)
What can be given to patients on trimethoxazole/co-trimoxazole for folic acid deficiency?
Simultaneous admin of folinic acid
What is the mechanism of action of nitrofurantoin?
Nitrofurantoin sensitve bacteria reduce the drug to a highly active intermediate that inhibits various enzymes and disrupt the synthesis of proteins, DNA, RNA and metabolic processes
How is nitrofurantoin administered?
PO
What is the spectrum of action of nitrofurantoin?
Active against many strains of E.coli & Enterococci
Most species of Proteus and Pseudomonas, as well as many species of Enterobacter and Klebsiella are resistant
How is nitrofurantoin excreted?
~40% excreted unchanged into urine
(is targeted at the urinary tract)
What are the adverse effects associated with nitrofurantoin?
- GI Sx: N/V/D
- Hypersensitivity: chills, fever
- Leukopenia, hemolytic anemia from G6PD deficiency
- Cholestatic jaundice and hepatocellular damage - rare, but nitroreductive metabolism produces oxidative free radicals that can damage hepatocytes
- Elderly esp susceptible to pulmonary & hepatic toxicities, peripheral neuropathies (risk increases w impaired renal function and long-continued Tx)
What is a side effect of nitrofurantoin to counsel on?
urine will turn brown
What groups of patients is nitrofurantoin contraindicated in?
- G6PD deficient
- Patients with impaired renal function (CrCl<40ml/min)
- Pregnant women (at term > 37 weeks)
- Infants <1 mth of age
What is G6PD, and why is it important in red blood cells?
The glucose-6-phosphate dehydrogenase (G6PD) enzyme is the central factor of the antioxidant defense system in red blood cells, which helps maintain high levels of reduced glutathione (GSH) and nicotine adenine dinucleotide phosphate (NADPH), to protect the RBC from oxidative damage caused by reactive oxygen species.
What is nitrofurantoin indicated for?
uncomplicated lower UTI
What is the mechanism of action of metronidazole?
Metronidazole possesses a nitro group that serves as an electron acceptor from the electron transport proteins in amoebas. This results in formation of cytotoxic free radicals that result in protein and DNA damage, & death of E. histolytica trophozoites
How is metronidazole administered?
PO
What is the spectrum of action of metronidazole?
Mainly anaerobes - eg C.diff, Bacteroides fragilis, Finegoldia magna
Amoebic infections as well - Entamoeba histolytica, Trichomonas vaginalis (vaginitis), Giardia lamblia etc
Can metronidazole be used for CSF?
Yes - can reach therapeutic levels
How is metronidazole excreted?
Hepatic metabolism, affected by CYP450 inducers/inhibitors, will accumulate in severe hepatic disease
Parent drug and metabolites excreted in urine
What are the adverse reactions associated w metronidazole?
- GI Sx: N/V, epigastric distress, abdominal cramps
- Commonly has unpleasant metallic taste
- Oral moniliasis (yeast infection of mouth)
- Central and Peripheral Nervous System Effects: Convulsive seizures, optic and peripheral neuropathy - rare but must discontinue if it happens
What DDIs does metronidazole have?
potentiates the effect of warfarin
How is the distribution of metronidazole like?
Distributes well throughout body tissues and fluids, therapeutic levels can be found in vaginal and seminal fluids, saliva, breast milk and CSF
