Antimicrobials 6- Penicillins

1. Antimicrobials6- Penicillins Pharmacology -2 DSX 455 Dr/ AbdulazizSaeedan Pharmacy College

2. What is Penicillin? • It is an antibiotic, discovered by Sir Alexander Fleming. • It is obtained from penicillium notatum (mold fungi). • The parent substance of this group is benzylpenicillin (Penicillin G).

3. Penicillins - Classification 1- Natural penicillin: Benzyl penicillin (Penicillin G). 2- Semisynthetic penicillins: (New penicillins). a) Penicillinasestable penicillins: Oxacillin, Cloxacillin, Flucloxacillin. b) Broad-spectrum penicillins: Ampicillin, Amoxacillin. c) Penicillinsactive against pseudomonas: Carbinicillin, Ticaracillin.

4. Natural Penicillin • Ex: Benzyl penicillin (Penicillin G): • Benzyl penicillin is the natural penicillin, obtained from penicilliumnotatum. • It is relatively unstable because it is easily destructed by moisture, temperature and enzymes as Penicillinase (ß-lactamase) which produced by Staph aureus.

5. Chemical structure: • The basic structure of penicillins is 6-aminopenicillanic acid that consists of : 1- Thiazolidinering 2- ß-lactam ring which attached to side chain (R). • Thiazolidinering is stable, while ß-lactam ring is unstable and is responsible for unstability of the compound as it is easily destructed by ß-lactamase enzyme. • Spectrum: It is a narrow spectrum antibiotic, it act on Gram +ve bacteria.

6. Absorption-Administration • After oral administration, most of the dose is destroyed by gastric acidity ► Phenoxymethylpenicillin OR Penicillin V can resist the acidity, therfore, it can be given orally • Sodium salts of penicillin are rapidly absorbed after I/M injection. • It is rapidly excreted so it act for a short period (6 h). Methods of delaying absorption of penicillin: 1- By suspending penicillin with oil. 2- By combination of penicillin with procaine in the form of procaine penicillin. ► This form is absorbed slowly so act for 24 hr. 3- By combination of penicillin with metal (aluminium monostearate). ► This combination act for several days.

7. Distribution: • Penicillin can’t cross the blood-brain barrier but in case of inflammation, it pass in low level. • It can’t cross the placental barrier except when given in large dose. • Excretion: • It is excreted mainly in urine, by active tubular secretion (80%). • Duration of penicillin is prolonged by administration of probencid which block the tubular cells, so delay the excretion of penicillin.

8. Action & MOA • Action: • Penicillin G is a bactericidal against penicillin-susceptible microorganisms during the stage of active multiplication. • It is not active against the penicillinase-producing bacteria, which include many strains of staphylococci. • MOA: • It acts by inhibiting biosynthesis of cell-wall throughinhibiting the formation of peptidoglycan which is thecross-linkers in the bacterial cell wall. • This achieved through binding to the D-alanyl-D alanine carboxypeptidase enzyme. As a consequence, the enzyme cannot catalyze formation of these cross-links

9. uses Penicillin V is the drug of choice for the treatment of streptococcal pharyngitis. It is also useful for anaerobic coverage in patients with oral cavity infections. Side effects:- Common (≥ 1% of people) diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of people) fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis