Cephalosporins pharmacology presentation

Pharmacology

1. Cephalosporins class/sub-classes , examples with available formulations, pharmacokinetics (choose a common drug in the class/sub-class), mechanism of action, mode of action, side effects, contraindications, drug interactions

2. Cephalosporins are semi synthetic beta lactam antibiotics closely related both structurally and functionally to penicillins . They have an advantage over the penicillins in that they are less susceptible to inactivation by beta lactamase enzyme and have a broader spectrum of activity. Hence are often used when penicillin treatment has proved ineffective.

3. mechanism of action of cephalosporins Initially derived from the fungus Cephalosporium sp., cephalosporins are a large group of bactericidal antimicrobials that work via their beta-lactam rings . The beta-lactam rings bind to the penicillin-binding protein and inhibit its normal activity Mode of action of cephalosporins Cephalosporins are bactericidal in action and inhibit the synthesis of the bacterial cell wall.

4. Classification of cephalosporins . Cephalosporins are classified into generations basing on bacterial susceptibility patterns and resistance to beta lactamases, as follows:-

5. First generation Cephalosporins Second generation cephalosporins Third generation cephalosporins Fourth generation cephalosporins

6. First generation Cephalosporins This group includes:- Cephalexin CefadroxiI Cephradine Cefazolin

7. First generation cephalosporins are mainly active against gram positive bacteria and have limited activity against gram negative bacteria like H. influenzae .

8. Second generation cephalosporins This group includes:- Cefuroxime , Cefaclor . Second generation cephalosporins have similar coverage against gram positive organisms as the first generation but with enhanced gram negative coverage. However, they are less active against gram + ve bacteria than the first generation and have no activity against enterococci or P. aeruginosa .

9. Third generation cephalosporins This class includes:- Ceftriaxone Cefotaxime Ceftazidime Cefixime ' Cefpodoxime Cefdinir Third generation cephalosporins are less active than the first and second generation drugs agaim'tgram + ve bacteria, but are more active against gram - YJvbacteria . including those resistant to the first and second generation. They are less active against S. aureus than the first generation drug. -

10. Fourth generation cephalosporins I • These drugs include; Cefepime . Fourth generation drugs, like the third generation, have an extended spectrum of activity against gram - ve bacteria compared to the 15t and 2nd generation. Cefepime is active against gram positive and gram negative infections including Pseudomonas aeruginosa .

11. CEPHALEXIN 1 st generation. Availa ble preparations: Capsules 2S0mg, SOOmg Powder for oral suspension 12Smg/ 5ml, 250mg/5ml. Pharmacokinetics Cephalexin is absorbed rapidly from the GIT after oral administration, distributed widely into most body tissues including the gall bladder, sputum , bone, synovial fluid. It is not metabolized. excreted in unchanged in urine.

12. mechanism of action of cephalexin Cephalexin inhibits bacterial cell wall synthesis, leading breakdown and eventualy cell death . Well absorbed from the upper gastrointestinal tract with nearly 100% oral bioavailability. Cephalexin is not absorbed in the stomach but is absorbed in the upper intestine. Mode of action Cefalexin It works by killing the bacteria that causes the infection . Cefalexin can treat a wide range of bacteria so it works well for a variety of infections, such as chest, skin or urinary tract infections (UTIs).

13. Indications Otitis media Impetigo Cellulitis Osteomyelitis Urinary tract infections Dental infections Bronchitis Prevention of bacterial endocarditis Pneumonia Erysipelas Pyomyositis Septic arthritis, Pharyngitis ,Tonsillitis. Contraindications known allergy to cephalosporins

14. Side effects Nausea, Vomiting , Abdominal pain, Dyspepsia , Loss of appetite Headache , Urticaria, Rash , Angioedema , Pruritus , Vaginal candidiasis Fatigue

15. Drug interactions Probenecid decreases renal excretion of cephalexin, increasing its blood levels . Oral contraceptives effectiveness may be reduced by cephalexin Aminoglycosides and loop diuretics may increase the nephrotoxicity caused by cephalexin.

16. CEFUROXIME 2 nd class Available preparations : Tablets 250mg, 500mg. Powder for oral suspension 125mg / 5ml Powder for Injection 750mg, 1.5g

17. Mechanism of action Cefuroxime Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis . Cefuroxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases , of Gram-negative and Gram-positive bacteria. Mode of action Cefuroxime , like the penicillins , is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits the third and last stage of bacterial cell wall synthesis .

18. Pharmacoldnetics Cefuroxime axetil is absorbed from the GIT and its absorption is enhanced by food . It penetrates well into most fluid spaces and tissues It is not metabolized and is excreted primarily in urine . Indications ; Acute and chronic bronchitis Acute otitis media , Sinusitis , Tonsillitis, Pharyngitis ,Impetigo, pyoderma , Pneumonia, Gonorrhoea , Bacterial Meningitis Surgical prophylaxis, Pelvic inflammatory disease

19. Contraindications known allergy to cephalosporins Drug interactions Efficacy of oral contraceptives may be reduced. Nephrotoxic drugs such as gentamycin, vancomycin may increase the potential for nephrotoxicity. Probenecid inhibits the tubular secretion of cefuroxime resulting into prolonged high serum concentrations A disulfiram -like reaction may occur when alcohol is given concurrently with cefuroxime

20. Side effects Skin rash, Headache Urticaria , Fever Nausea and vomiting Anorexia Diarrhoea Abdominal pain Vaginal candidiasis

21. Key issues to note Cefuroxime axetil is well absorbed after a light meal, therefore it should be administered with food Shake suspension well before use. The tablet should not be broken before swallowing Reconstituted injectable solution is stable for, 24 hours at room temperature and 48hours when refrigerated Reconstituted oral suspension may be stored at room temperature or refrigerator and discarded after 10 days

22. CEFTRIAXONE 3 rd generation Available preparations: Powder for Injection 1M / IV SOOmg , I g, 2g Pharmacokinetics Ceftriaxone is widely distributed into body tissues and fluids after parenteral administration. It penetrates well into the CSF, especially when the meninges are inflamed and it's excreted unchanged in urine.

23. Mechanism of action ceftriaxione Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall . Mode of action . The beta-lactam moiety of ceftriaxone binds to carboxypeptidases , endopeptidases , and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division.

24. Indications Indications ; Pneumonia Gonorrhoea Meningitis Otitis media, Chancroid , Urinary tract infection ,Surgical prophylaxis , Syphilis ,Typhoid, fever Osteomyelitis and septic arthritis, Pelvic inflammatory disease, Skin and soft tissue infections. Contraindications Neonates with jaundice, Acidosis ,Known hypersensitivity to cephalosporins .

25. Drug intractions Ceftriaxone may reduce the effectiveness of oral contraceptives Concomitant use with aminoglycosides produces synergistic antimicrobial activity against Pseudomonas aeruginosa and some strains of Enterobacteriaceae

26. CEFEPIME Available preparations : Powder for injection Ig , 2g Pharmacokinetics ., Cefepime is rapidly and almost completely absorbed following Intramuscular injection. It is widely distributed in body tissues and fluid and is excreted unchanged in urine . Indications Urinary tract infection Skin and skin structure infection. Nosocomial pneumonia Surgical prophylaxis Intra abdominal infections Febrile neutropenia

27. Mechanism of action of Cefepime IT inhibits bacterial cell wall synthesis by covalently binding enzymes responsible for the final step in transpeptidation during peptidoglycan wall synthesis . Mode of action. Binds to cell wall causing defects in the cell wall leading to autolysis and subsequent death of the organism.

28. Contraindications History of anaphylactic reaction to penicillins Known hypersensitivity to cephalosporins Side effects Skin Rashes , Thrombophlebitis ,Fever Vaginal candidiasis, Anaphylaxis Headache Vomiting Diarrhea ,Pseudomembranous colitis Abdominal pain , Pain at injection site.

29. Drug interactions Aminoglycosides and frusemide may increase the risk of nephrotoxicity and ototoxicity with cefepime , Probenecid decreases renal excretion of cefepime Key points to note Store the drug at room temperature and protect from light Cefepime is incompatible with metronidazole, aminoglycoside and aminophylline