penicillins

· derived from moulds of Penicillium

structure

· all share aminopenicillic ring

· b-lactam ring with attached thiazolidine ring

· drugs vary wrt. attached radicals

mode of action

· bacteriocidal

· inhibit bacterial cell wall synthesis

· inhibit membane-bound transpeptidase

· leads to weakening of cell wall and death

· bacterial resistance to penicillin occurs among organisms that produce beta-lactamase (penicillinase)

· splits beta-lactam ring of penicillin nucleus

· beta-lactamase producing organisms are

· Staph aureus

· some E coli

· Proteus mirabilus

· Pseudomonas aeruginosa

· some penicillins resistant to penicillinase

classification

Penicillinase-sensitive

Penicillin G

· benzylpenicillin

· acid-labile

· only suitable for parenteral administration

Penicillin V

· phenoxymethylpenicillin (PVK)

· similar to penicillin G but relatively acid-resistant

· suitable for oral administration

Penicillinase-resistant

Flucloxacillin

· oral and parenteral

Broad spectrum

Amoxycillin

· effective against gram-negative organisms

· oral and parenteral

kinetics

· most relatively poorly orally absorbed (5-30%)

· benzylpenicillin not absorbed

· phenoxymethylpenicillin is acid stable so somewhat absorbed

· flucloxacillin is fairly well absorbed

· exception is amoxycillin which is well absorbed

· food decreases absorption

· should be given before food

· some forms produced to delay absorption

· given IM

· give prolonged therapeutic levels

· 24 hrs for procaine penicillin

· 10 days for benzathine penicillin

· penetrates most tissues well

· penetrates CNS very well

· excreted in urine

· 90% by tubular excretion

· can be blocked by probenocid

· half-life is 30-60 min

uses

Penicillinase-sensitive

· Gram positive cocci

· Strep pyogenes

· Strep pneumoniae

· Gram negative cocci

· Neisseria meningiditis

· Gram positive bacilli

· Clostridium

· others

· Treponema pallidum

Penicillinase-resistant

· Gram positive cocci

· Staph aureus

Broad spectrum

· all of penicillin-sensitive group PLUS

· Gram negative bacilli

· Haemophilus

· Salmonella

dosage

· benzylpenicillin

· 1-2 million units (600-1200 mg) q6h IV

· phenoxypenicillin

· 500 mg qid PO

· flucloxacillin

· 1 g q6h IV

· 500 mg qid PO

adverse affects

Hypersensitivity

· occurs in 1-5%

· all penicillins are cross-sensitising and cross-reacting

· antigens are degradation products of penicillin

Anaphylactic shock

· serious side-effect

· rare (0.05%)

· fatal in 10%

Skin rashes

· common

· range

· mild urticarial eruption

· Stevens-Johnson syndrome

· usually occurs at 3-10 d

· ampicillin causes specific maculopapular rash

· in 20% of patients

· in 90% of those with infectious mononucleosis

· occurs later

Cephalosporins

· 10% of patients allergic to penicillin will develop skin rash

· anaphylaxis more likely if anaphylactic reaction to penicillin

Other

· diarrhoea

· superinfection of oropharynx

Interactions

· some drugs inhibit renal tubular secretion of penicillin

· probenocid

· indomethacin

· can use probenocid to enhance effect of penicillins

· 500 mg qid

clavulinic acid

· clavulinic acid inhibits bacterial penicillinase

· combined with amoxycillin

· used for organisms

· usually sensitive to amoxycillin

· that produce penicillinase

· not useful against organisms whose resistance not mediated by penicillinase, eg.

· flucloxacillin-resistant Staph aureus

· penicillin-resistant gonococcus or pneumococcus