A STUDY On the drugs used For the treatment Of pneumonia

1. A STUDY On the drugs used For the treatment Of pneumonia • Prepared and presented by :- • Khyati kansagra • Bijjavia • Sauravkini

2. What is Pneumonia? • Pneumonia is an inflammatory condition of the lung—affecting primarily the microscopic air sacs known as alveoli. • It is usually caused by infection with viruses or bacteria. • We will be focusing only on BACTERIAL PNEUMONIA

3. What are the symptoms of Pneumonia? • Coughing • Sharp chest pain • Fever accompanied by shaking chills • Difficulty breathing • Increased respiratory rate • Blue-tinged skin • Decreased thirst • Convulsions • Persistent vomiting • Extremes of temperature • Decreased level of consciousness

4. Symptoms Symptom Frequency Cough 79–91% Fatigue 90% Fever 71–75% Shortness of breath 67–75% Sputum 60–65% Chest pain 39–49%

5. Drugs used for the treatment: • Penicillin V • Penicillin G • Amoxicillin • Augmentin

6. Penicillin • It is a group of antibiotics derived from Penicillium fungi. • All penicillins are β-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. • First noticed by Ernest Duchesne, in 1896. • Re-discovered by bacteriologist Alexander Fleming.

7. Penicillin G • ‘G’ stands for Gold standard. • Also known as Benzylpenicillin. • Formula: C16H18N2O4S • Mol. Mass: 334.4 g/mol • IUPAC Name: (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-[(phenylacetyl)amino]-4-thia-1-azabicyclo[3.92.0]heptane-2-carboxylic acid

8. Synthesis of Pencillin G • The first step is the condensation of three amino acids—L-α-aminoadipic acid, L-cysteine, L-valine into a tripeptide. • Before condensing into the tripeptide, the amino acid L-valine must undergo epimerization to become D-valine. • The condensed tripeptide is named δ-(L-α-aminoadipyl)-L-cysteine-D-valine (ACV). • The condensation reaction and epimerization are both catalyzed by the enzyme δ-(L-α-aminoadipyl)-L-cysteine-D-valinesynthetase (ACVS), a nonribosomal peptide synthetase or NRPS.

9. The second step in the biosynthesis of penicillin G is the oxidative conversion of linear ACV into the bicyclic intermediate isopenicillin N by isopenicillin N synthase (IPNS), which is encoded by the gene pcbC. • IsopenicillinN is a very weak intermediate, because it does not show strong antibiotic activity. • The final step is a transamidation by isopenicillin N N-acyltransferase, in which the α-aminoadipyl side-chain of isopenicillin N is removed and exchanged for a phenylacetyl side-chain. • This reaction is encoded by the gene penDE, which is unique in the process of obtaining penicillins.

10. Penicillin V • Also known as phenoxymethylpenicillin. • Formula: C16H18N2O5S • Mol. Mass: 350.39 g/mol • IUPAC Name: 3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

11. Synthesis of Penicillin V

13. Amoxicillin • Formula: C16H19N3O5S • Mol. Mass: 365.4 g/mol • IUPAC Name: 2S,5R,6R)-6-{[(2R)-2-amino-2-(4-hydroxyphenyl)-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

14. Synthesis of Amoxicillin • Silylation is the introduction of a substituted silyl group (R3Si) to a molecule. • That is provided by the present invention, in the process for the production of amoxicillin trihydrate which comprises the consecutive steps of: Silylating6-aminopenicillanic acid, preferably with chlorotrimethylsilane (Highlyflmmable) (TMCS) in an anhydrous solvent, preferably methylene chloride, in the presence of a strong base, preferably a tertiary aliphatic amine and especiallytriethylamine.

15. Acylatingthe silylated 6-aminopenicillanic acid formed in the previous step withD-( - )-2-para-hydroxyphenylglycine chloride hydrochloride in the presence of aweak base, preferably dimethylaniline. Hydrolyzingand neutralizing the product of said acylation to produceamoxicillintrihydrate.

16. Augmentin

17. Synthesis of Augmentin

19. Mode of action of β- Lactam antibiotics • β-Lactam antibiotics are bacteriocidal, and act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. • The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by DD-transpeptidases which are penicillin-binding proteins (PBPs). • PBPs vary in their affinity for binding penicillin or other β-lactam antibiotics. The amount of PBPs varies among bacterial species.

20. The β-lactam nucleus of the molecule irreversibly binds to (acylates) the Ser403 residue of the PBP active site. This irreversible inhibition of the PBPs prevents the final crosslinking (transpeptidation) of the nascent peptidoglycan layer, disrupting cell wall synthesis. • β-Lactam antibiotics block the division of bacteria. In contrast, they have no effect on the plastids of the highly developed vascular plants. • Under normal circumstances, peptidoglycan precursors signal a reorganisation of the bacterial cell wall and, as a consequence, trigger the activation of autolytic cell wall hydrolases.

21. Inhibition of cross-linkage by β-lactams causes a build-up of peptidoglycan precursors, which triggers the digestion of existing peptidoglycan by autolytic hydrolases without the production of new peptidoglycan. As a result, the bactericidal action of β-lactam antibiotics is further enhanced. Penicillin and most other β-lactam antibiotics act by inhibiting penicillin-binding proteins, which normally catalyze cross-linking of bacterial cell walls. In the absence of β-lactam antibiotics, the bacterial cell wall plays an important role in bacterial reproduction.

22. CREDITS:KHYATI KANSAGRABIJ JAVIASAURAV KINI