1. 1) PENICILLIN G (benzyl penicillin)
1.1. Pharmacokinetics
1.2. Adverse effects
1.3. Uses
2. Mechanism of action
2.1. Drug impermeable
3. In Gram -ve, Porin channels •lost •altered
4. Penicillin binding protein (PBP) | PnG + PBP = inhibition of transpeptidation | Production of Cell Wall Deficient forms (CWD) | Swelling and bursting (hyperosmotic pressure) | Bactericidal effect
5. Cocci 1) Highly sensitive - Pneumococci 2) Resistant - Staphylococcus aureus
6. Antibacterial spectrum
7. 1) Acid labile 2) CSF penetration - low 3) I. M. site - Sod. PnG absorption is rapid and complete 4) t1/2 : Healthy adults- 30 mins Neonates- longer 5) Rapid excretion •Glomerular filtration (10%) •Tubular secretion= Slow, blocked by Probenecid
8. 1) Streptococcal infections 2) Pneumococcal infections 3) Meningococcal infections 4) Gonorrhea 5) Syphilis, tetanus, gas gangrene, trench mouth (ulceration) 6) Diphtheria 7) Actinomycosis 8) Prophylactic use: Agranulocytosis, rheumatic fever, bactericidal endocarditis
8.1. Bacilli (gram +ve) 1) Highly sensitive - B. anthrasis, Clostridia, Cornybacterium diphtheria 2) Resistant - Bacteroides fragilis
9. Mechanism of resistance
9.1. Drug destroying
9.1.1. Production of penicillinase Gram +ve = more Gram -ve = comparatively less
9.2. Drug tolerant
9.2.1. PBP and transpeptidase enzyme | Low affinity towards PnG
10. 1) Local irritancy and direct toxicity • Pain (i.m) , nausea •Thrombophlebitis •Toxicity to brain : mental confusion, muscular twitching, convulsion 2) Hypersensitivity (major problem) •Frequent : rash, itching, urticaria, fever •Less common : wheezing, serum sickness, angioneurotic edema •More common : parenteral administration •Most allergic : Procaine penicillin
11. Naturally occurring
12. -It is similar to ampicillin except, •Oral absorption is better, food does not interefere •Incidence of diarrhea decreased.
13. 3. Sulbactam Semi synthetic 2-3 times less potent than clavulanic acid Progressive inhibitor Combination - Ampicillin
13.1. Uses : Skin and soft tissue infections Urinary, biliary and respiratory tract infections Gonorrhea
13.2. Adverse effects : Thrombophlebitis, rash, diarrhea
14. Antibacterial spectrum: Active against - S. aureus, E. coli, H. influenzae
15. Adverse effects : GI tolerance is poor Rashes, hepatic injury rare
16. Examples: 1) METHICILLIN- -It is not acid resistant. -Resistant - Staphylococcus aureus -Altered PBP's , do not bind to penicillins. -A/E: Haematuria, Albuminuria
17. B-Lactamase Inhibitors Eg. 1. Clavulanic acid 2. Coamoxiclav 3. Sulbactam 4. Tazobactam
17.1. 1. Clavulanic Acid
17.2. MOA : •Progessive inhibitor - Binding with B- lactamase is reversible than covalent. •Suicidal inhibitor - After binding to enzyme gets inactivated. •Inhibits B-Lactamase by permeating the cell wall.
17.3. 8 times more active against pseudomonas than carbenicillin. Uses- Immunocomprised and neutropenic patients.
17.3.1. P'kinetics: -BA- 60% -t1/2- 1 hr - elimination by glomerular filtration.
17.4. 2. Coamoxiclav Amoxicillin + Clavulanic acid
17.5. 4. Tazobactam Combination - Piperacillin
17.5.1. P'kinetics : Oral absorption inconsistent Given parenterally
17.5.2. Uses : Severe infections - peritonitis, pelvic / urinary / respiratory infections
18. Semi synthetic 1) Procaine penicillin 2) Benzathine penicillin
18.1. A) Acid-resistant alternative to PnG Eg. Phenoxymethyl penicillin (PnV)
18.1.1. •Side chain in structure will protect B- lactam ring. •Penicillinase producing Bacteria- very effective •Non penicillinase producing Bacteria- less effective
18.2. B) Penicillinase Resistant Eg. Methicillin & Cloxacillin
18.2.1. 2) CLOXACILLIN- -It is acid resistant -Resistant : less active against PnG sensitive organism -More active than methicillin
18.3. C) Extended Spectrum Eg.1) Aminopenicillin 2) Carboxypenicillin 3) Ureidopenicillin
18.3.1. 1. Ampicillin •Antibacterial spectrum : -Less active against gram +ve -More active against Streptococcus viridans.
18.3.1.1. P'kinetics: Incomplete oral absorption. t1/2: 1hr
18.3.1.2. Uses: •Cholesystitis ( painful inflammation of gallbladder's wall) •Typhoid fever: rarely used •Bacillary Dysentary
18.3.1.3. A/E: Diarrhea , Rashes
18.3.1.3.1. •Acid stable & better oral absorption. •More active against Gram -ve bacteria. •Antibacterial Spectrum- similar to PnG
18.3.1.4. 2.Amoxicillin
18.3.2. 1) AMINOPENICILLINS Eg. Ampicillin Amoxicillin
18.3.2.1. Uses: Bronchitis UTI Gonorrhea
18.3.3. 2) CARBOXYPENICILLINS Eg. Carbenicillin
18.3.3.1. P'kinetics - -Neither penicillinase nor acid resistant
18.3.3.2. Adverse effects : •C/I patients with renal & cardiac problem. •High doses- bleeding by interfering with platelet function
18.3.3.3. Uses : -UTI -Burns
18.4. 3) UREIDOPENICILLIN Eg. Piperacillin
18.4.1. Antibaterial Spectrum: • Susceptible : Proteus • Less susceptible :E.coli • Resistant :Gram +ve cocci