Antimicrobials 6- Penicillins Pharmacology -1 DSX 215 Dr/ Abdulaziz Saeedan Pharmacy College

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).

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

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

 Chemical structure: The basic structure of penicillins is 6-aminopenicillanic acid that consists of : 1- Thiazolidine ring 2- ß-lactam ring which attached to side chain (R). Thiazolidine ring 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.

Absorption- Administration After oral administration, most of the dose is destroyed by gastric acidity ► Phenoxymethyl penicillin 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.

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.

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 through inhibiting the formation of peptidoglycan which is the cross-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

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