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Case 1

Case 1. Tunyapon Sasithorn Pharmacology Clinical case. Problem 1.

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Case 1

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  1. Case 1 • Tunyapon Sasithorn Pharmacology Clinical case

  2. Problem 1 • A clinical study evaluating the efficiency of the antibiotic treatment of the meningitis was carried out. One group of patients with pneumococcal meningitis received parenteral penicillin. A second group received penicillin plus tetracycline therapy.

  3. pneumococcal Penicillin meningitis Penicillin plus patients tetracycline

  4. A. How do penicillin and tetracycline differ in their mechanism of action?

  5. PenicillinMechanism of Action • B- lactam antibiotics work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall. • The B- lactam moiety of penicillin binds to the enzyme (transpeptidase) that links the peptidoglycan molecules in bacteria, and this weakens the cell wall of the bacterium when it multiplies • This causes cell cytolysis or death when the bacterium tries to divide. • The build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases which further digest the bacteria's existing peptidoglycan.

  6. TetracyclineMechanism of Action • Tetracyclines inhibit bacterial protein synthesis by blocking the attachment of the transfer RNA-amino acid to the ribosome. • They are inhibitors of the codon-anticodon interaction.

  7. Penicillin Bactericidal Tetracycline Bacteriostatic Mechanism of Action

  8. 2. • Which group had a lower mortality rate?

  9. Mortality was significantly higher in the penicillin– tetracycline group compared to the single drug penicillin group: Mortality rate Penicillin – tetracyclinegroup • 79% ∞one of seven patients survived Penicillin group • 30% ∞ nine of 20 patients survived

  10. 3. • If there was a difference, what would account for the observation?

  11. Penicillin group experienced a bactericidal effect which is very important in treating patients with pneumococcal meningitis. Penicillin – tetracycline – a combination of a cell wall agent, the bactericidal activity of which depends on cell growth (penicillin), with a reversible protein synthesis inhibitor that interferes with cell growth (tetracycline), is a classical example of antibiotic antagonism, resulting in the lower mortality rate of penicillin – tetracycline group.

  12. Antagonist reaction of Penicillin and tetracycline renders these drugs in combination ineffective. • The mutual antagonist reaction produces an overall bacteriostatic activity which proves ineffective in treating patients with pneumococcal meningitis.

  13. 4. • Any other drug combination that you can recommend? On what basis?

  14. Other drug recommendationsdue to: • Meningitis with penicillin resistant pneumococcus • Other synergistic reaction

  15. Drugs of first choice Children Ceftriaxone Cefotaxime +/- Vancomycin Adults Ceftriaxone Cefotaxime Others Rifampin B lactam antibiotic Ex: Penicillin, Ampicillin, Piperacillin and Cefuroxime + Gentamicin Alternative drugs Children Chloramphenicol Systematic corticosteroids Adults Vancomycin + Ceftriaxone Vancomycin + Cefotaxime Drug combinations

  16. Thank Yousir, mam.Come again!:P

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