Urinary Antiseptics (Chapter 15) PDF

[email protected] [email protected] [email protected] CHAPTER 15...

[email protected] [email protected] [email protected] CHAPTER 15 Chapter 15 Urinary antiseptics Definition: they are oral agents that its antibacterial activity is restricted to urine with no systemic effects (their level in circulation is not sufficient for an- tibacterial effects), so they are effective against lower urinary tract infections Include: Nitrofurantoin-Methenamine-Fosfomycin ‫ﻣﺤﻤﺪ ﺣﻤﺪﻯ ﺍﺑﻮﺍﻟﻌﻼ ﺍﺑﻮﺍﻟﻌﻼ ﺍﻟﻘﻤﺎ‬ Nitrofurantoin I. Pharmacokinetics: Absorption is rapid and complete orally Metabolism and excretion are rapid so no plasma levels or sys- temic actions Excreted in kidney by glomerular 2023/2024 filtration and tubular secretion 2023/2024 2023/2024 II. Pharmacodynamics: Mode of action: bacterial enzymatic reduction of nitrofurantoin to intermediates which destruct bacterial DNA Spectrum: effective against E-coli and enterococci, BUT, Porteous, pseudomonas, Enterobacter and klebsiella are resistant NO cross resistance between nitrofurantoin and other antimi- crobials so it is a good alternative in case of cotrimoxazole and quinolones resistant E- coli infections Acidic pH of urine is important to its antibacterial activity 149  [email protected] [email protected] [email protected] CHAPTER 15 III. Uses: 1. lower urinary tract infections (not recommended in prostatitis or pyelonephri- tis) 2. prevention of recurrent urinary tract infections Dose: 50-100mg/6hours with meals and bedtime, 100mg/12h for 7 days for macrocrystalline preparations, course should not exceed 14 days ‫ﻣﺤﻤﺪ ﺣﻤﺪﻯ ﺍﺑﻮﺍﻟﻌﻼ ﺍﺑﻮﺍﻟﻌﻼ ﺍﻟﻘﻤﺎ‬ IV. Adverse effects 1. Nausea, vomiting and diarrhea 2. Brown urine discoloration 3. Polyneuropathy especially in renal impairment and chronic therapy 4. Hypersensitivity reactions: chills, fever, leukopenia, hepatocellular dam- age 2023/2024 2023/2024 2023/2024 5. Hemolytic anemia is G6PD deficiency and in newborn 6. Acute pneumonitis, cough, dyspnea, chest pain. Pulmonary infiltration and fibrosis (chronic use) V. Contraindications 1. Pregnant women at term, during, labor, delivery or imminent delivery to avoid possible hemolytic anemia. 2. Patients with renal impairment to avoid systemic toxicity Methenamine I. Pharmacokinetics: Absorbed orally, it is unstable in gastric secretion unless coated Excreted in urine 150  [email protected] [email protected] [email protected] CHAPTER 15 II. Pharmacodynamics: Mode of action: it is a prodrug that generate formaldehyde at acidic pH, formaldehyde is antibacterial Spectrum: ◦ All bacteria are sensitive to free formaldehyde ‫ﻣﺤﻤﺪ ﺣﻤﺪﻯ ﺍﺑﻮﺍﻟﻌﻼ ﺍﺑﻮﺍﻟﻌﻼ ﺍﻟﻘﻤﺎ‬ ◦ NO microorganism resistance NB: urea splitting microorganisms as proteus raise urine pH and inhibit release of formaldehyde acidification increase activity, so it is formulated with mandelic or hippuric acid or acidification of urine with acidifying agent e.g. ascorbic acid III. Uses: 2023/2024 2023/2024 2023/2024 Used in chronic suppression of urinary tract infections caused by E-coli, most gram negative, staph aureus and epidermises Not used in treatment of acute infections IV. Adverse effects: 1. GIT distress 2. Painful and frequent micturition, hematuria and albuminuria (at high doses) V. Contraindications: 1. Hepatic encephalopathy due to ammonia production 2. Renal failure is NOT contraindication of methenamine alone, but acids formulated with methenamine may be harmful in these patients so should be avoided 151  [email protected] [email protected] [email protected] CHAPTER 15 VI. Drug interactions: released formaldehyde binds to sulfonamides and form insoluble compound so not given at the same time Fosfomycin It is phosphoric acid derivative I. Pharmacokinetics: Available as a powder formulation dissolved in water and administrated orally, bioavailability 40%, half-life 6-8h ‫ﻣﺤﻤﺪ ﺣﻤﺪﻯ ﺍﺑﻮﺍﻟﻌﻼ ﺍﺑﻮﺍﻟﻌﻼ ﺍﻟﻘﻤﺎ‬ Attain high urinary concentration and low serum concentration after oral administration II. Pharmacodynamics: Mode of action: it inhibits initial steps of bacterial cell wall synthesis Spectrum: E. coli, Proteus, Enterococcus, and Staphylococcus saphrophyticus. Variable activity against Klebsiella, Enterobacter, and Serratia spp. Pseudomonas and Acinetobacter are typically resistant 2023/2024 2023/2024 2023/2024 III. Uses: 1. Prevention and treatment of urinary tract infections 2. 3 g single dose for acute uncomplicated urinary tract infections 3. 3 g every 10 days for urinary tract infections prophylaxis IV. Adverse effects: it is well tolerated but GIT distress, vaginitis, headache, dizziness may occur 152  [email protected] [email protected] [email protected] CHAPTER 15 Drugs that alter Urine pH Urine acidifiers Urine alkalizers Vitamin C, mandelic and hippuric Na or K bicarbonate acid Na and K Citrate: metabolized via Ammonium chloride: rarely used the Krebs cycle and generate bicarbonate which is excreted in urine Na or K Acetate ‫ﻣﺤﻤﺪ ﺣﻤﺪﻯ ﺍﺑﻮﺍﻟﻌﻼ ﺍﺑﻮﺍﻟﻌﻼ ﺍﻟﻘﻤﺎ‬ Carbonic anhydrase inhibitors Uses: Uses: Acidification of urine: to enhance Treatment of metabolic acidosis excretion of weak basic drugs Alkalinize urine to enhance Potentiate urinary antiseptics as secretion of weak acid drugs as methenamine salicylates Na channels blocker toxicity 2023/2024 2023/2024 2023/2024 (NaHco3) Dissolve uric acid and help excretion Used in cysteine stones Prevent crystalluria of sulfonamides Decrease dysuria (common symptom of infections) Contraindicated in liver and kidney disease Table 15.1: Drug that alter Urine pH 153