4.QUINOLONES AND FOLIC ACID ANTAGONISTS

BYBY

Dr. Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM

M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD

ANTIBIOTIC (QUINOLONES, FOLIC ACID

ANTAGONISTS)

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NUM CONTENT SLIDE 1 INTRODUCTION TO QUINOLONES 42 ADVANTAGES OF QUINOLONES 53 CHEMICAL STRUCTURES OF QUINOLONES 64 CLASSIFICATION OF QUINOLONES 75 ANTIMICROBIAL SPECTRUM OF QUINOLONES 86 THERAPEUTIC APPLICATIONS OF CIPROFLOXACIN 97 MECHANISM OF QUINOLONES 10-138 SOME ADVERSE REACTIONS TO FLUOROQUINOLONES 149 INTRODUCTION TO SULFONAMIDE 15

10 CLASSIFICATION OF SULFONAMIDE 16,1711 CHEMICAL STRUCTURES OF SULFONAMIDE 1812 MECHANISM OF SULFONAMIDES AND TRIMETHOPRIM 19,2013 SYNERGISM OF TRIMETHOPRIM AND

SULFAMETHOXAZOLE21

14 SOME ADVERSE REACTIONS OF SULFONAMIDES 2215 THERAPEUTIC APPLICATIONS OF CO-TRIMOXAZOLE 2316 MECHANISM OF METHENAMINE 24

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LEARNING OUTCOME

1. Able to understand the quinolones and folic acid antagonists.

2. List the common quinolones and folic acid drug classification.

3. Abele to demonstrate the general mechanism of quinolones and folic acid antagonists.

4. Able to describe the common quinolones and folic acid antagonists adverse effects.

5. Able to understand the therapeutic application of quinolones and folic acid antagonists.

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1. INTRODUCTION TO QUINOLONES

• The quinolones are a family of synthetic broad – spectrum antibacterial drugs.

• The first generation of quinolones began with the introduction of nalidixic acid in 1962 for treatment of urinary tract infections in humans.

• Nalidixic acid was discovered by George Lesher.

• More than 100,000 quinolone compounds have been synthesized and screened their pharmacological activities. Currently, there are more than 20 quinolones used in clinic.

Dr.K.Saminathan.M.Pharm(Ph.D) , M.B.A (Ph.D)

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1) Effective against many organisms.

2) Well-absorbed orally.

3) Well-distributed in tissues.

4) Relatively long serum half-lives and minimal toxicity.

5) Deep-tissue and cell penetration.

6) Urinary tract infections, prostatitis.

7) Infections of the skin and bones.

8) Penicillin-resistant sexually transmitted diseases.

9) lower cost in synthesis with the excellent activities.

2. ADVANTAGES OF QUINOLONES


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Basic structure QUINOLONE

First-generationNALIDIXIC ACID Second-generation

CIPROFLOXACIN

Third-generationLEVOFLOXACIN

Fourth-generationMOXIFLOXACIN

3. CHEMICAL STRUCTURES OF QUINOLONES


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FIRST-GENERATION CINOXACIN NALIDIXIC ACID OXOLINIC ACID PIROMIDIC ACID PIPEMIDIC ACID ROSOXACIN

THIRD-GENERATION

BALOFLOXACIN GREPAFLOXACIN LEVOFLOXACIN PAZUFLOXACIN SPARFLOXACIN TEMAFLOXACIN TOSUFLOXACIN

SECOND-GENERATION

CIPROFLOXACIN FLEROXACIN LOMEFLOXACIN NADIFLOXACIN NORFLOXACIN OFLOXACIN PEFLOXACIN RUFLOXACIN

FOURTH-GENERATION

CLINAFLOXACINGATIFLOXACIN GEMIFLOXACIN MOXIFLOXACIN SITAFLOXACIN TROVAFLOXACIN PRULIFLOXACIN

4. CLASSIFICATION OF QUINOLONES


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5. ANTIMICROBIAL SPECTRUM OF QUINOLONES


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6.THERAPEUTIC APPLICATIONS OF CIPROFLOXACIN


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The fluoroquinolones inhibit the replication of bacterial DNA by interfering with the action of DNA gyrase (topoisomerase II) and topoisomerase IV during bacterial growth and reproduction.

7.MECHANISM OF QUINOLONES


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7. MECHANISM OF QUINOLONES

Con…Dr.K.Saminathan.M.Pharm(Ph.D) , M.B.A (Ph.D)

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Con…


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8.SOME ADVERSE REACTIONS TO FLUOROQUINOLONES


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Sulfonamide drugs were the first antimicrobial drugs.

The first sulfonamide began in 1932.

The first official communication not published until 1935.

Cotrimoxazole was introduced in the mid-1970s, there was a renewed interest in the sulfonamides.

The Sulfonamide drugs are seldom prescribed alone except in developing countries, where they are still employed because of their low cost.

Sulfa drugs differ from each other not only in their chemical and physical properties but also in their pharmacokinetic.

9. INTRODUCTION TO SULFONAMIDE


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10.CLASSIFICATION OF SULFONAMIDE


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1. SHORT ACTING SULFONAMIDE:A. SULFADIAZINEB. SULFADIMIDINEC. SULFAMETHIZOLED. SULFAMETHOXAZOLEE. SULFISOXAZOLEF. SULFISOMIDINE OR SULFAISODIMIDINE

2. INTERMEDIATE ACTING SULFONAMIDE:A. SULACETAMIDEB. SULFADOXINE

3. LONG ACTING SULFONAMIDE:A. SULFADOXINEB. SULFAMETHOXY-PYRIDAZINEC. SULFAMETOPYRAZINED. SULFAPHENAZOLE

10. CLASSIFICATION OF SULFONAMIDE


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11. CHEMICAL STRUCTURES OF SULFONAMIDE


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12. MECHANISM OF SULFONAMIDES AND TRIMETHOPRIM

Con…Dr.K.Saminathan.M.Pharm(Ph.D) , M.B.A (Ph.D)

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In many microorganisms, dihydrofolic acid is synthesized from p-aminobenzoic acid (PABA), pteridine, and glutamate .

All the sulfonamides currently in clinical use are synthetic analogs of PABA. Because of their structural similarity to PABA, the sulfonamides compete with this substrate for the bacterial enzyme, dihydropteroate synthetase.

They thus inhibit the synthesis of bacterial dihydrofolic acid and, thereby, the formation of its essential cofactor forms. The sulfa drugs, including cotrimoxazole, are bacteriostatic.

12. MECHANISM OF SULFONAMIDES AND TRIMETHOPRIM


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13. SYNERGISM OF TRIMETHOPRIM AND SULFAMETHOXAZOLE

INHIBITION OF GROWTH OF ESCHERICHIA COLIDr.K.Saminathan.M.Pharm(Ph.D) , M.B.A (Ph.D)

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14.SOME ADVERSE REACTIONS OF SULFONAMIDES


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15. THERAPEUTIC APPLICATIONS OF CO-TRIMOXAZOLE (SULFAMETHOXAZOLE PLUS TRIMETHOPRIM).


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Methenamine must decompose at an acidic pH of 5.5 or less in the urine, thus producing formaldehyde, which is toxic to most bacteria.

The reaction is slow, requiring 3 hours to reach 90 percent decomposition. Methenamine should not be used in patients with indwelling catheters. Bacteria do not develop resistance to formaldehyde.

16. MECHANISM OF METHENAMINE


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STEPS INVOLVED IN DNA REPLICATION IN PROKARYOTES

Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D



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4.QUINOLONES AND FOLIC ACID ANTAGONISTS

Health & Medicine

generation of quinolones

common quinolones

advantages of quinolones

phd antibiotic quinolones

introduction of nalidixic

folic acid drug classification

generation levofloxacin

generation moxifloxacin