PHARMACOTHERAPY OF URINARY TRACT INFECTIONS AND INFECTIOUS DIARRHEAS PharmDr. Ondřej Zendulka, Ph.D. MUDr. Alena Máchalová, Ph.D. Mgr. Jana Merhautová Notes for Pharmacology II Practicals This study material is exclusively for students of general medicine and stomatology in Pharmacology II course. It contains only basic notes of discussed topics, which should be completed with more details and actual information during practical courses to make a complete material for test or exam studies. Which means that without your own notes from the lesson this presentation IS NOT SUFFICIENT for proper preparation for neither tests in practicals nor the final exam.

Pharmacotherapy of UTI Antibiotics – acute infection: Drugs of 1 st choice: ‒ nitrofurantoin ‒ co-trimoxazole ‒ cephalosporins of 1 st a 2 nd generation – e.g. cefuroxime- axetil ‒ amoxicillin, co-amoxicillin Drugs of 2nd choice: ‒ fluoroquinolones – ofloxacin, ciprofloxacin, prulifloxacin ‒ trimethoprim ‒ cephalosporins of 3 rd generation

Pharmacotherapy of UTI Secondary prevention treatment – chronic recurrent infections: long-lasting administration of low doses of ATB ‒ nitrofurantoin, fluoroquinolones immunotherapy ‒ bacterial lysate of E. coli (activates T lymphocytes, ↑ IgA) ‒ autovaccines – p.o., inj. dosage forms Adjuvant therapy: Species urologicae (urological herbal mixture) Artostaphylos uva-ursi (bearberry) Tropaeolum majus (garden nasturtium, Indian cress) cranberries, D-mannose acidification of urine (ascorbic acid) – only if there is no contraindication

Renal Infections Non-complicated pyelonephritis: used ATB: ‒ co-amoxicillin ‒ cephalosporins of 2 nd generation – cefuroxime-axetil, cefprozil ‒ fluoroquinolones – ciprofloxacin, ofloxacin ‒ co-trimoxazol complicated pyelonephritis – ATB according to cultivation and local resistance, ATB as above + e.g. aminoglycosides

Therapy of Diarrheas Rehydration – water, mineral water (non-carbonated), tea, oral rehydration therapy – solutions: ‒ WHO rehydration solution: H 2 O 1.0 L, NaCl 3.5 g, NaHCO g, KCl 1.5 g, glucose 20.0 g ‒ Valík‘s rehydration solution – for children: H 2 O 1.0 L, NaCl 2.4 g, NaHCO g, KCl 1.1 g, glucose 27.0 g ‒ home-made rehydration solution: 1 L of boiled water (tepid), 8 teaspoons of sucrose (glucose, fructose), 1 teaspoon of salt, juice from 2 oranges: adults 250 – 500 mL/h, children 125 – 250 mL/h Diet, realimentation

Therapy of Diarrheas Eubiotics ‒ prebiotics – oligo- and polysaccharides, B-vitamins ‒ probiotics – living microorganisms (Lactobacillus, Bifidobacterium, some G+ cocci and Saccharomycetes) ‒ RMP: ‒ preparation with defined content of Sacharomyces boulardii siccatus, Lactobacillus sp. ‒ concentrate of metabolic products of E. coli, Streptococcus faecalis, Lactobacillis acidophillus, L. helveticus non-specific treatment of ID – adsorbents, antiseptics etc. specific treatment – ATB

Diarrheas Caused by ATB ATB with broad spectrum prevention: eubiotics pseudomembranous colitis ‒ Clostridium difficile ‒ ileus, toxic megacolon, sepsis ‒ therapy: metronidazole, vancomycin ‒ most frequent after the administration of lincosamides, aminopenicillins, cephalosporines, fluoroquinolones

Intestinal Adsorbents adsorption of undesirable substances from GIT to active surface of an adsorbent potential interaction with co-administered drugs activated charcoal (Carbo medicinalis, C. activatus) diosmectite (aluminium-magnesium silicate) Adstringents denaturation of intestinal wall proteins, formation of hydrophobic layer, which↓ secretion into the intestine black tea, herbal mixtures (medical plants rich in tannins) diosmectite, bismuth subsalicylate, bismuth subgallate

Antimotility Agents intestinal opioid receptors agonists ↓ peristaltic propulsion, ↑ smooth muscle tone, ↑ resorption of water and electrolytes slow down passage of GIT content contraindication: infections with invasive pathogens, poisoning diphenoxylate – Rx. loperamide – OTC

Intestinal Antiseptics minimal or no absorption from GIT traveler‘s diarrheas chloroxine nifuroxazide rifaximin

ATB in the Treatment of Diarrheas We use ATB only in the case of: severe and complicated infectious diarrheas, or positive blood cultures immunodeficiency of the patient traveler‘s diarrheas typhus and paratyphoid fever pseudomembranous colitis Salmonella – cotrimoxazole, quinolones, amoxicillin Campylobacter – macrolides, quinolones (resistance) Shigella – amoxicillin, quinolones, cotrimoxazole traveler‘s diarrhea – metronidazole, intestinal antiseptics parasitic diarrhea – mebendazol, albendazol (antiparasitics)

Antispasmodics (Spasmolytics) of GIT neurotropic antispasmodics – act via VNS musculotropic antispasmodics – directly influence myocytes Neurotropic Antispasmodics PARASYMPATOLYTICS atropine substances with N + ‒ otilonium, trospium, fenpiverinium…

Musculotropic Antispasmodics various mechanisms of action, mainly blockade of L-type Ca 2+ channels, activation of K + channels, interference with muscle contraction biochemistry papaverine drotaverine, alverine, mebeverine, pitofenone combinations of neurotropic, and musculotropic antispasmodics, and analgesics spasms of GIT, bile duct, or gall bladder, UT spasms, irritable bowel syndrome, spasmodic dysmenorrhea, migraine… spasmo-analgesia