SEMINAR REPORT SEMINAR REPORT ON ON

CHEMOTHERAPY OFCHEMOTHERAPY OFURINARY TRACT URINARY TRACT

INFECTIONINFECTION

URINARY TRACT URINARY TRACT INFECTIONINFECTION

DEFINATIONDEFINATION: : UTI can be defined as the presence of micro UTI can be defined as the presence of micro organisms in the urinary tract, that can be accounted organisms in the urinary tract, that can be accounted for contamination and can invade deep in the tissues of for contamination and can invade deep in the tissues of the urinary tract and adjacent structures. UTI can the urinary tract and adjacent structures. UTI can spread upwards and causes severe kidney damage .UTI spread upwards and causes severe kidney damage .UTI is caused by gram negative bacteria i.e.. E.COLI is caused by gram negative bacteria i.e.. E.COLI depending upon the infection it may be acute or depending upon the infection it may be acute or chronicchronic..

ACUTE INFECTIONACUTE INFECTION:: It is localised to urethra and bladderIt is localised to urethra and bladder..

CHRONIC INFECTIONCHRONIC INFECTION:: Polyuria is common and there is no lost in Polyuria is common and there is no lost in weight anemia and hypertension is frequently seenweight anemia and hypertension is frequently seen..

UTI IS CARRIED OUT IN 3 STEPSUTI IS CARRIED OUT IN 3 STEPS:: 1.ROUTE OF INFECTION 1.ROUTE OF INFECTION (a) ASENDING(a) ASENDING (b) HEMATOGENOUS(b) HEMATOGENOUS (c) LYMPHATIC(c) LYMPHATIC 2.HOST DEFENCE MECHANISM2.HOST DEFENCE MECHANISM 3.BACTERIAL VIRULENCE FACTOR3.BACTERIAL VIRULENCE FACTOR

ROUTES OF INFECTIONROUTES OF INFECTION::(a) ASENDING:(a) ASENDING: It occurs usually due to spermiside and of spermiside and It occurs usually due to spermiside and of spermiside and diaphram as method of contraception. Female urethra is short diaphram as method of contraception. Female urethra is short length which makes colonisation for bacteria. Urethra is colonised length which makes colonisation for bacteria. Urethra is colonised by a bacteria believed to orginate from fecal flora.by a bacteria believed to orginate from fecal flora.(b) HEMATOGENOUS:(b) HEMATOGENOUS: This type occurs by primary infection in the body. Organism This type occurs by primary infection in the body. Organism responsible for stafelo coccus, candida, salmonella, species.responsible for stafelo coccus, candida, salmonella, species.(c) LYMPHATICS:(c) LYMPHATICS: Cause unknown.it is through lymphatic system kidneys are Cause unknown.it is through lymphatic system kidneys are effectedeffected..

2.HOST DEFENCE MECHANISM2.HOST DEFENCE MECHANISM::Normally urinary tract is resistant to invasion of bacteriaNormally urinary tract is resistant to invasion of bacteria

urine is capable of inhibiting & killing micro organism due to low urine is capable of inhibiting & killing micro organism due to low (ph)(ph)

tamm-horse fall protein is a glyco protein produced by asending tamm-horse fall protein is a glyco protein produced by asending limb of henly which contains mannose residue. Binds to e-coli.limb of henly which contains mannose residue. Binds to e-coli.

Polymorpho nuclear are primary responsible for limiting tissue Polymorpho nuclear are primary responsible for limiting tissue invasion and spread of infection in kidney and bladderinvasion and spread of infection in kidney and bladder..

3. 3. BACTERIAL VIRULENCE FACTORBACTERIAL VIRULENCE FACTOR::Divided into two types:Divided into two types:

1) Haemolysin1) Haemolysin

2) Aerobacterin2) Aerobacterin

1) 1) HAEMOLYSIN:HAEMOLYSIN:

It is a cytotoxin protein produced by bacteria that It is a cytotoxin protein produced by bacteria that lysis a wide range of cells including erythrocytes, monocyteslysis a wide range of cells including erythrocytes, monocytes..

2)2) AEROBACTERINAEROBACTERIN:: It facilitates the binding and uptake for iron It facilitates the binding and uptake for iron

by E.coliby E.coli..

CLASSIFICATION OF DRUGS USED IN CLASSIFICATION OF DRUGS USED IN UTIUTI::

1)Bacteriostatic agents:1)Bacteriostatic agents:

Ex: nitrofurantoin, sulfonamides, tetracylcinesEx: nitrofurantoin, sulfonamides, tetracylcines

2) Bacteriocidal agents: 2) Bacteriocidal agents:

Ex:contimoaxozle, ampiclin,extenede specrtum pencillins.Ex:contimoaxozle, ampiclin,extenede specrtum pencillins.

DRUGSDRUGS::

NITROFURANTOINNITROFURANTOIN:: It is a bacteriostatic compound and may be bactericidal at It is a bacteriostatic compound and may be bactericidal at

high concentrastion. In acidic urine its activity is inhanced high concentrastion. In acidic urine its activity is inhanced at lower ph. It in inhibits many gram –ve bacteria. Its at lower ph. It in inhibits many gram –ve bacteria. Its activity is now restricted largely to E.coli. This resistance activity is now restricted largely to E.coli. This resistance develops slowly.develops slowly.

MECHANISMMECHANISM::The anti microbial activity of nitrofurantoin is partly due to the The anti microbial activity of nitrofurantoin is partly due to the

significant contribution made by the bacterial enzymes in significant contribution made by the bacterial enzymes in catalysing the reductoin of drugs.once inside the bacterial cell, catalysing the reductoin of drugs.once inside the bacterial cell, certain enzymes referred to as nitrofuran reductase act upon the certain enzymes referred to as nitrofuran reductase act upon the drug and convert it into highly reactive intermediate and drug and convert it into highly reactive intermediate and nitroanion superoxides. The generates products intern exerts nitroanion superoxides. The generates products intern exerts deleterious effects on the essential bacterial processes such as deleterious effects on the essential bacterial processes such as RNA synthesis, DNA synthesis, metabolism of pyruvate and also RNA synthesis, DNA synthesis, metabolism of pyruvate and also impair the function of ribosomal proteins and other impair the function of ribosomal proteins and other macromolecules this results in anti bacterial effect .macromolecules this results in anti bacterial effect .

moreover, the drug also exhibits its moreover, the drug also exhibits its antibacterial activity by interfering with the synthesis of an antibacterial activity by interfering with the synthesis of an acetyl CoA. This eventually impairs the metabolism, cell wall acetyl CoA. This eventually impairs the metabolism, cell wall synthesis etc.synthesis etc.

PHARMACOKINETICSPHARMACOKINETICS:: Well absorbed orally, rapidly metabolised in liver and Well absorbed orally, rapidly metabolised in liver and

other tissues, less than half excreted unchanged in urine. other tissues, less than half excreted unchanged in urine. Plasma T1/2 is 30-60 minutes. Antibacterial concentration Plasma T1/2 is 30-60 minutes. Antibacterial concentration not attained in blood or tissuesnot attained in blood or tissues..

PHARMACOLOGYPHARMACOLOGY::

Each nitrofurantoin monohydrate/macrocrystals capsule Each nitrofurantoin monohydrate/macrocrystals capsule contains two forms of nitrofurantoin. Twenty-five contains two forms of nitrofurantoin. Twenty-five percent is macrocrystalline nitrofurantoin, which has percent is macrocrystalline nitrofurantoin, which has slower dissolution and absorption than nitrofurantoin slower dissolution and absorption than nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend which, upon monohydrate contained in a powder blend which, upon exposure to gastric and intestinal fluids, forms a gel exposure to gastric and intestinal fluids, forms a gel matrix that releases nitrofurantoin over time. Based on matrix that releases nitrofurantoin over time. Based on urinary pharmacokinetic data, the extent and rate of urinary pharmacokinetic data, the extent and rate of urinary excretion of nitrofurantoin from the 100 mg urinary excretion of nitrofurantoin from the 100 mg nitrofurantoin monohydrate/macrocrystals capsule are nitrofurantoin monohydrate/macrocrystals capsule are similar to those of the 50 mg or 100 mg nitrofurantoin similar to those of the 50 mg or 100 mg nitrofurantoin monohydrate/macrocrystals capsule. Approximately 20 monohydrate/macrocrystals capsule. Approximately 20 to 25% of a single dose of nitrofurantoin is recovered to 25% of a single dose of nitrofurantoin is recovered from the urine unchanged over 24 hours.from the urine unchanged over 24 hours.

Plasma nitrofurantoin concentrations after a single oral Plasma nitrofurantoin concentrations after a single oral dose of the 100 mg nitrofurantoin dose of the 100 mg nitrofurantoin monohydrate/macrocrystals capsule are low, with peak monohydrate/macrocrystals capsule are low, with peak levels usually less than 1 mcg/mL. levels usually less than 1 mcg/mL.

ADVERSE EFFECTS: ADVERSE EFFECTS: GIT intolerance.GIT intolerance.

Nausea.Nausea.

Epigastric Pain.Epigastric Pain.

Diarrhoea.Diarrhoea.

DOSE:DOSE:50-100 mg for 5 to 10 days.50-100 mg for 5 to 10 days.

USES:USES:The indication for nitrofurantoin is UTI acute infection of The indication for nitrofurantoin is UTI acute infection of

E.coli can be treated with 50-100mg.E.coli can be treated with 50-100mg.

SULFONAMIDES:SULFONAMIDES:

Sulfonamides are effective against most of the common Sulfonamides are effective against most of the common urinary pathogens including E.coli.They produce effective urinary pathogens including E.coli.They produce effective urine and tissue levels.They can eradicate uncomplicated urine and tissue levels.They can eradicate uncomplicated E.coli infections but are relatively ineffective in chronic E.coli infections but are relatively ineffective in chronic cases,complicated cases or in the presence of mixed cases,complicated cases or in the presence of mixed infection.Development of bacterial resistance is the major infection.Development of bacterial resistance is the major problem with these drugs.problem with these drugs.

PHARMACOLOGY:PHARMACOLOGY:Most sulfonamides are readily absorbed orally and, when Most sulfonamides are readily absorbed orally and, when

applied to burns, topically. Sulfonamides are distributed applied to burns, topically. Sulfonamides are distributed throughout the body. They are metabolized mainly by the throughout the body. They are metabolized mainly by the liver and excreted by the kidneys. Sulfonamides compete liver and excreted by the kidneys. Sulfonamides compete for bilirubin-binding sites on albuminfor bilirubin-binding sites on albumin

MECHANISM:MECHANISM:Normally folic acid is synthesized in Normally folic acid is synthesized in

two steps in bacteria by the two steps in bacteria by the reaction to the right. If A sulfa reaction to the right. If A sulfa drug is used, the first enzyme is drug is used, the first enzyme is not to specific and can use the not to specific and can use the sulfonamide in the first reaction. sulfonamide in the first reaction. This reaction produces the product This reaction produces the product containing pteridine and the sulfa containing pteridine and the sulfa drug.drug.

The next and final step is the reaction The next and final step is the reaction PABA + with glutamic acid to make PABA + with glutamic acid to make folic acid. If the sulfa drug has folic acid. If the sulfa drug has been substituted for the PABA, been substituted for the PABA, then the final enzyme is inhibited then the final enzyme is inhibited and no folic acid is produced.and no folic acid is produced.

DOSE:DOSE:Sulfonamides can be used in patients with renal insufficiency, Sulfonamides can be used in patients with renal insufficiency,

but peak plasma levels should be measured and but peak plasma levels should be measured and

sulfamethoxazole levels should not exceed 120 μg/mLsulfamethoxazole levels should not exceed 120 μg/mL..

TREATMENT:TREATMENT:(A) Fluid intake more than 2litres per day to maintain high (A) Fluid intake more than 2litres per day to maintain high

urine flow.urine flow.

(B) Regular complete bladder emptying.(B) Regular complete bladder emptying.

(C) Antibiotic therapy.(C) Antibiotic therapy.

(D) Amino glycoside should be used for gram –ve organism.(D) Amino glycoside should be used for gram –ve organism.

.THANK YOU..THANK YOU.