Urinary Antiseptics & Metronidazole Flashcards
MOA of Fluoroquinolones?
Targets…
i) DNA gyrase (Gram -ve)
ii) Topoisomerase IV (Gram +ve)
Administration of Fluoroquinolones
Oral/IV (2h before/6h after food, best on empty stomach)
Oral bioavailability of Fluoroquinolones
Good, generally well absorbed after oral administration
Clearance of Fluoroquinolones
Renal (Moxifloxacin - Hepatic)
Use of Ciprofloxacin
Most active: Gram -ve & enteric coliform
1) P. aeruginosa (HIGHLY ACTIVE)
2) Traveller’s diarrhoea due to E.Coli
3) Typhoid fever due to Salmonella typhi
4) Bacillus anthracis
5) Protstatitis
Use of Levofloxacin & Moxifloxacin
Better coverage for Gram +ve & Aytipicals
“Respiratory quinolones”
1) S. pneumoniae (HIGHLY ACTIVE)
2) 2nd line M.TB
(don’t give if suspicious of TB, can mask symptoms)
Adverse Drug Effects of Fluoroquinolones
1) Aortic dissections
2) Increased risk of C. diff colitis (especially w cipro)
3) Phototoxicity
4) Arthropathy
5) QTc interval prolongation
6) Tendinitis
7) GIT (Most common)
8) Risk of dysglycaemia
9) HA, dizziness
10) Peripheral neuropathy
Contraindications for Fluoroquinolones
Pregnancy (breastfeeding not recc)
< 18yo
Myasthenia gravis
What are the Anti-Folate drugs?
Sulfonamides, Trimethoprim, Cotrimoxazole
MOA of sulfonamides
Competitive inhibitors of dihydropteroate synthase
ADE of sulfonamides
1) Crystalluria - Hydrate well/alkanise urine
2) Hypersensitivity
3) Hemolytic anaemia with G6PD Deficiency
4) Kernicterus
Contraindications for sulfonamides
Pregnant women at term & newborns < 2months
MOA of trimethorpin
Inhibits reduction of dihydrofolic acid by dihydrofolate reductase to its active form
Use of trimethorpin
Bacterial prostatitis (ciprofloxacin preferred)
Resistance for trimethorpin?
1) Altered dihydrofolate reductase with lower affinity for trimethorpin
2) Efflux pumps
Administration of Cotrimoxazole
Oral (take with full cup of H2O)/ IV
Distribution of Cotrimoxazole
Good bioavailability & CSF penetration
Clearance of Cotrimoxazole
Renal
Use of Cotrimoxazole
1) 1st line for UTI (E.coli)
2) RTI caused by Haemophilus sp, Klebseilla penumonia
3) MRSA & community-acquired skin & soft tissue infections
4) Pneumocystis pneumonia caused by Pneumocystis jiroveci
ADE of Cotrimoxazole
1) Photosensitivity
2) Hemolytic anaemia
3) Megaloblastic anemia, leukopenia, thromocytopenia
(Give folinic acid for FA deficiency)
4) Skin reactions, N/V
USE WITH CAUTION in pregnancy (1st & 3rd trimester)
MOA of Nitrofurantoin
Bacteria reduces nitrofurantoin to highly active intermediate -> Inhibits various enzymes -> Disrupt synthesis of proteins, DNA, RNA & metabolic processes
Administration of Nitrofurantoin
Oral (Very good F)
Distribution of Nitrofurantoin
Achieves high [urinary] while limiting systemic exposure
Use of Nitrofurantoin
- *1st line for UTI**
1) E.coli
2) Enterococci
ADE of Nitrofurantoin
1) Leukopenia, hemolytic anaemia (G6PD Deficiency)
2) Cholestatic jaundice & hepatocellular damage
3) Elderly more susceptible to pulmonary toxicity of nitrofurantoin
4) N/V, Diarrhoea
5) Hypersensitivity reaction
Which agent causes urine discolouration?
Nitrofurantoin - Brown
Rifampicin - Orange
Which of the Urinary antiseptics can be administered orally?
Fluoroquinolones, FA synthesis inhibitors, Nitrofurantoin, Fosfomycin
MOA of polymyxins
Disrupt structure of c.m phospholipids & increase cell permeability
Use of polymyxins
- *MDR-Gram -ve bacteria**
1) Inhaled CMS (Pseudomonas)
2) Resp infections & severe pneumonia
Polymixin B - UTI & Blood Infections due to P.aeruginosa
Antimicrobial spectrum of polymyxins
MDR Gram -ve organisms
Administration of Polymyxin B
IV
CMS - Inhalation therapy for cystic fibrosis
Elimination of Polymyxins
Renal
Colistin - dosing adjustments
polymyxin B - NIL
ADE of Polymyxins
1) Neuro & nephrotoxicity
2) DO NOT use with neuromuscular blockage agents & in myasthenia gravis
Aerosolised CMS: Sore throat, cough, bronchoconstriction, chest tightness
Which agents will cause phototoxicity?
Fluoroquinolones
Tetracyclines
Which agents will cause ototoxicity?
Vancomycin
Aminoglycosides
Macrolides (Azithromycin)
Which agents will cause nephrotoxicity?
Vancomycin
Aminoglycosides
Polymyxins
MOA of Fosfomycin
Bacteriacidal antibiotic
- Interferes with c.w synthesis by inhibiting initial step involving phosphoenolpyruvate synthase
Spectrum of Fosfomycin
Broad
(+): Staphylococcus aureus, Enterococcus
(-): Pseudomonas aeruginosa, Klebsiella pneumoniae
Use of Fosfomycin
1) UTI (E.coli / Enterococcus faecalis)
2) (+) Other antibiotics for nosocomial infections due to resistant Gram (+)/(-) strains
3) Additive/synergistic effects with B-lactams
Administration of Fosfomycin
Oral (Fosfomycin tromethamine -> Fosfomycin), take on empty stomach
Distribution of Fosfomycin
Widely distributed in CSF & Bile
Elimination of Fosfomycin
Renal (30-60%)
Adverse effects of Fosfomycin
1) GI (Nausea, diarrhea)
2) Headache
3) Vaginitis
Urinary antiseptic for Pregnancy?
B-lactams (1st gen ceph)
Amoxicillin-CA (Augmentin)
Nitrofurantoin (not if at term)
Cotrimoxazole (not for 1st & last trimester)
Contraindications for Nitrofurantoin
Pregnancy at term
Infants < 1 months
Impaired renal function
Therapeutic agents for Amebiasis
Luminal - Parasite in lumen of bowel
Systemic - Amoebas in the intestinal wall & liver
Mixed - Effective against both, though [luminal] too low for single-drug treatment
MOA of Metronidazole
Nitro group serves as electron acceptor, forming cytotoxic free radicals that results in protein & DNA damage
Use of Metronidazole
- *Anaerobes & Protozoa**
1) Anaerobes such as Bacteroides species & Clostridium difficle (2nd line)
2) Amebic infections due to Protozoa - Entamoeba histolytica, Trichomonas vaginalis, Giardia lamblia
3) H.Pylori
4) Surgical prophylaxis
Administration of Metronidazole
Oral
Distribution of Metronidazole
Distributes well, CSF fluid
Metabolism & Excretion of Metronidazole
Metabolism:
Hepatic (Accumulates in severe hepatic disease)
Excretion:
Parent drug & metabolites in urine
Adverse effects of Metronidazole
1) GIT
2) Oral moniliasis (yeast infection of mouth)
3) Central & peripheral nervous system effects
Unpleasant metallic taste
Is Metronidazole safe for pregnancy?
Yes, but avoid in 1st trimester
