ANTIBIOTICS II.pptx .

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1. PHARMACOLOGY Ms CAROLINE

2. NUCLEIC ACID SYTHESIS INHIBITORS Drugs that interfere with nucleic acid synthesis can be classified into two. Direct inhitors - they act on topoisomerase enzymes Quinolones and Rifampin Indirect inhitors - they inhibit folic acid synthesis. Sulphonamides and trimethoprin

3. QUINOLONES The first quinolone was nalidixic acid, that was being used as an antiseptic. Fluorinated quinolones were later developed that had broader action against (pseudomonas species) Fluoroquinolones were originally developed because of their excellent activity against gram-negative aerobic bacteria; they had limited activity against gram-positive organisms Norfloxacin Ciprofloxacin Ofloxacin Levofloxacin Acrofloxacin Pefloxacin

4. Pharmacodynamics Quinolones block bacterial DNA synthesis. They interfere with separation of replicated chromosomal DNA into the respective daughter cells during cell division. They act by inhibiting the enzyme that maintains the Helical twist/structure of the DNA. They inhibit two enzymes Topoisomerase ii enzyme (DNA gyrase) in gram - ve bacteria and Topoisomerase iv enzyme in gram + ve bacteria. They are bactericidal in nature

5. Pharmacokinetics Quinolones are absorbed in the gut though aluminum and magnesium antacid interfere with the absorption . Distribution wide distribution such that they cross the placenta and are distributed in breast milk. Metabolism they under go hepatic metabolism with a variable half life Norfloxacin and ciprofloxacin half life of 2-3 hours, 5 hour ofloxacin, perfloxacin10 hour. Excretion Elimination via renal and biliary.

6. Bone marrow suppression.

7. Drug interactions These antibiotics are enzyme (cytochrome p-450) inhibitors. Interact with other drugs by inhibiting their metabolism e.g. theophylline, warfarin, and caffeine. NSAIDS and quinolones causes an increase in the risk of convulsion. NSAIDS tends to potentiate the CNS effects of fluoroquinolones. Contraindications History of epilepsy or seizures. Myasthenia gravis. Pregnancy and breast feeding. Decreases chondrogenesis in children- formation of cartilage.

8. CIPROFLOXACIN It has a half life is 3hours Abroad spectrum antibiotic that is mostly effective against gram negative bacteria and anaerobic bacilli. It is indicated for chlamydia and some mycobacteria Ciprofloxacin and ofloxacin are effective for gonococcal infection, and ofloxacin is effective for chlamydial urethritis or cervicitis Indication UTI and genital urinary tract infections. Dosage Oral 250-600mg bd, max dose of 1.2g IV infusion (30-60) 200-400mg twice daily.

9. Rifampin (rifampicin) Rifampin binds strongly to the bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis. Rifampin is used in the treatment of mycobacterial infections. Rifampin causes a harmless orange color to urine, sweat, and tears. Occasional adverse effects include rashes, thrombocytopenia, nephritis, cholestatic jaundice and occasionally hepatitis.

10. META BOLIC INHIBITORS SULPHONAMIDES These are among the first antibacterial drugs to be discovered in 1935. Sulfonamides are structurally similar to p-aminobenzoic acid (PABA). – used in folate synthesis. As structural analogs of PABA, sulfonamides inhibit dihydropteroate synthase and folate production. Sulfonamides can be divided into three major groups: (1) oral, absorbable; (2) oral, nonabsorbable; and (3) topical.

11. Examples Sulphamethoxazole , Sulphadiazine, Sulfisoxazole , Sulphadimidine , Sulfasazine , Sulfametopyrazine , Sulphaloxate

12. A. Oral Absorbable Agents Sulfisoxazole and sulfamethoxazole are short- to medium-acting agents used almost exclusively to treat urinary tract infections. Sulfadiazine in combination with pyrimethamine is first-line therapy for treatment of acute toxoplasmosis. B. Oral Nonabsorbable Agents Sulfasalazine ( salicylazosulfapyridine ) is widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease C. Topical Agents Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred for prevention of infection of burn wounds

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15. Pharmacokinetics They have good absorption except a few of them sulphadiazine and which are poorly absorbed in the gut. Widely distributed in body tissues and fluid including crossing the BBB. They are metabolized in the liver withhalf life of 10 hours. Majority are excreted in urine hence dose should be reduced in renal impairment.

16. Cotrimoxazole( sulphonamides 400mg/trimethoprim 80mg) septrin . This has replaced use of sulphonamide due to resistance. Combination of a sulfonamide with an inhibitor of dihydrofolate reductase (trimethoprim or pyrimethamine) provides synergistic activity because of sequential inhibition of folate synthesis. Trimethoprim Trimethoprim inhibits bacterial dihydrofolic acid reductase. Dihydrofolic acid reductases convert dihydrofolic acid to tetrahydrofolic acid, a stage leading to the synthesis of purines and ultimately to DNA.

17. Indications Pneumocystis carinii pneumonia Toxoplasmosis UTI sometimes chronic bronchitis Others sulphonamides are used for topical application for prophylaxis of burns, leg ulcers, pressure sores because of their wide anti bacteria spectrum

18. Side and adverse effects Hypersensitivity including Stevens-Johnson syndrome Do not administer TMP-SMZ to clients with allergies to: Sulfonamides (sulfa), Thiazide diuretics [hydrochlorothiazide (HCTZ)] , Sulfonylurea-type oral hypoglycemics [tolbutamide (Orinase)], Loop diuretics [furosemide (Lasix)] . Stop TMP-SMZ at the first indication of hypersensitivity, such as rash. Crystalluria - Maintain adequate oral fluid intake. - Instruct client to drink 2 to 3 L/day.

19. Kernicterus (jaundice, increased bilirubin levels) - Avoid administering TMP-SMZ to women who are pregnant near term, breastfeeding mothers, and infants younger than 2 months. - Monitor the client’s liver function. Photosensitivity - Avoid prolonged exposure to sunlight, use sunscreen, and wear appropriate protective clothing.

20. OTHERS

21. AZOLES This includes several classes of drugs e.g. metronidazole and tinidazole which have both anti bacteria and anti protozoal activity. others are fluconazole, itraconazole econazole, ketoconazole , and miconazole which are anti fungal drugs .( to be covered under anti fungal drugs) others are mebendazole, thiabendazole, which are anti helminths (to be covered under ant-helminths)

22. Metronidazole It is very effective against anaerobic bacterial and protozoa. Pharmacodynamics/MOA metronidazole binds to the bacterial DNA and prevents nucleic acid formation. This interferes with bacterial replication hence its bacteriostatic. Pharmacokinetics ; It is well absorbed after oral and rectal administration Distribution is wide. Metabolism is in the liver. It is excreted in urine partly unchanged and partly as metabolite. Half life is 8 hours.

23. Indications Used for treatment of sepsis caused by orgasms like bacteroides and anaerobic cocci. Intra-abdominal infections Septicemia, wounds, pelvic infection Osteomyelitis. Pelvic infections Infections of the brain and lungs.

24. Used in prevention of post operative infection especially after bowel, antibiotic related colitis. Other indications include giardiasis, acute ulcers, gingivitis, and dental infections. and anaerobic vaginosis Treatment of protozoal infections ( intestinal amoebiasis, giardiasis, trichomoniasis ) and obligate anaerobic bacteria ( Bacteroides fragilis, antibiotic-induced Clostridium difficile, Gardnerella vaginalis )

25. Dosage and route of administration Established anaerobe are usually treated for 7 days. The dose per oral is then 8oomgs initially for 3 days then 400mg or 500mg 8 hourly, or just 400mg 8 hourly for 7 days. By rectum 1gm every 8 hours for 3 days then1gm 12 hourly. By infusion 500mg 8 hourly. In children 7.5mg/kg every 8 hours by any route. for surgical prophylaxis Per oral 400mg 8 hourly started 24 hours before surgery then continued postoperatively by IV infusion until oral administration can be resumed for 2days

26. SIDE EFFECTS Gastrointestinal discomfort (nausea, vomiting, dry mouth, and metallic taste) Advise clients to observe for symptoms and to notify the provider. Darkening of urine Advise clients that this is a harmless effect of metronidazole. CNS symptoms (numbness of extremities, ataxia, and seizures) Advise clients to notify the provider if symptoms occur. Stop metronidazole.

27. Contraindications/Precautions Use cautiously in clients with renal dysfunction to prevent accumulation of toxic levels with prolonged use. Avoid use during the first trimester of pregnancy and use with caution during the rest of pregnancy because metronidazole can pass through the placenta. Interactions Medication/Food Interactions Nursing Interventions/Client Education Alcohol causes a disulfiram-like reaction/ Advise clients to avoid alcohol consumption. Metronidazole inhibits inactivation of warfarin. Monitor prothrombin time and INR, and adjust warfarin dosage accordingly