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Transcript of Lactam antibiotics
Dr. Deepak Kr. Gupta
Introduction Penicillin, cephalosporins, monobactams,
carbapenems, and -lactamase inhibitors
Four-membered lactam ring.
Thiazolidine ring (A) is attached to a -lactam ring (B) that carries a secondary amino group (RNH)(B) that carries a secondary amino group (RNH)
Penicillin was discovered by chance in 1928.
Flemings (1929) found that a diffusablethat a diffusablesubstance was elaborated by Penicillium mould which destroy staphylococcus on culture plate
Chemistry Thiazolidine ring (A) is
attached to a -lactamring (B) that carries a secondary amino group (RNH).
Substituents (R) decide Substituents (R) decide the types of penicillin.
Structural integrity of the 6-aminopenicillanic acid nucleus (rings A plus B) is essential for the biologic activity of these compounds
Natural Penicillin G
Semisynthetic Acid Resistant: Penicillin V
penicillinase-resistant: methicillin, cloxacillinpenicillinase-resistant: methicillin, cloxacillin
Aminopenicillin: Ampicillin, Amoxicillin, Bacampicillin,
Antipseudomonal Penicillin Carboxypenicillin: Cerbenicillin, ticarcillin
Ureidopenicillins: Piperacillin, Mezlocillin
-lactumase inhibitors: Clavulanic acid, Sulbactam, Tazobactam
Mechanism of Action
Inhibit bacterial growth by interfering with the transpeptidation reaction of bacterial cellwall synthesis.
Cell wall is composed of a complex, Cell wall is composed of a complex,
cross-linked polymer of polysaccharides
alternating amino sugars, N-acetylglucosamine (NAG) and N -acetylmuramic acid (NAM)
terminates in D-alanyl-D-alanine
Mechanism of Action Penicillin binding protein (PBP, an enzyme)
removes the terminal alanine in the process of forming a cross-link with a nearby peptide
-Lactam Antibiotics - structural analogs of the natural D-Ala-D-Ala substrate
Covalently bind to the active site of PBPs Covalently bind to the active site of PBPs
Narrow spectrum antibiotic
Primarily to gram positive cocci, bacilli and few gram negative.and few gram negative.
Obtained from fermentations of the mold Penicilliumchrysogenum
Destroyed by gastric juice
Food interferes with its absorption hence given 2 hr after food
Doesnt readily cross BBB, but Doesnt readily cross BBB, but inflammed menninges therapeutic concentration is acieved
Probencid blocks the renal tubular secretion of penicillin prolongs its duration of action.
T1/2 = 30 minwww.facebook.com/trigemclasses
Clinical Use drug of choice for infections caused
by Streptococci Meningococci, some Enterococci, Penicillin-susceptible Pneumococci, non--lactamase-producing non--lactamase-producing
Staphylococci, Treponema pallidum Certain other spirochetes, Clostridium species, Actinomyces Certain other gram-positive rods, non--lactamase-producing gram-
negative anaerobic organisms.www.facebook.com/trigemclasses
Clinical Use 4 and 24 million units per day
administered intravenously in four to six divided doses
Depending on the organism, the site, and the severity of infection dose is decided
High-dose penicillin G - continuous High-dose penicillin G - continuous intravenous infusion severe infection
Benzathine penicillin and procaine penicillin G for intramuscular injection yield low but prolonged drug levels
Orodental infection since its active against variety of aerobic and anaerobic MCO
Sod.Penicillin G inj-0.5-5 MU i.m./i.v. 6-12 Hourly
BENZYL PENicillin G BENZYL PENicillin G 0.5-1MU I
Repository Penicillin G inj- these are insoluble salts of PnG which must be given by deep i.m (Never i.v.) slowly at the site of inj.
Procaine Penicillin G inj- 0.5-1 MU( i.m) 12-24 hourly as aqueous suspension. ( PROCAINE PENICILLIN-G 0.5 MU dry powder in vial)
Hypersensitivity most common cause of drug allergy. h/o of penicclin allergy should be taken or scratch test or
intradermal test performed.
Local pain at the site of injection, thrombophlebitison IV injection
CNS : large dose of Png produces confusion, muscle twitching, convulsion and coma
Suprainfection : rare narrow spectrum of activity
Jarish-Herxheimer reaction syphillis sudden destruction of spirochetes and release lytic products severe fevere, myalgia, shivering, exacerbation of syphilitic lesion and vascular collapse
Disadvantage of Natural Penicillin
They are not effective orally
Narrow spectrum of activity
Susceptible to b-lactamase
It can cause hypersensitivity It can cause hypersensitivity
Very high doses of penicillin G can cause seizures in kidney failure.
Used for the treatment of bacteremia and oral
Higher minimum bactericidal concentration. Higher minimum bactericidal concentration.
250-500 mg. Given 6 hourly.
Penicillinase-resistant penicillins Antistaphylococcal penicillins These penicillins are resistant to staphylococcal -
lactamases. They are active against staphylococci and streptococci
but not against enterococci, anaerobic bacteria, and gram-negative cocci and rods.gram-negative cocci and rods.
These congeners have side chains that protect the beta lactam ring from attack by staphylococcal penicillinase
Indicated in infections caused by penicillinase producing staphylococci (drugs of choice, except in MRSA) Methicillin, Cloxacillin Oxacillin, Nafcillin, Dicloxacillin
Not used clinically, except to identify resistant strains
MRSA is susceptible to Vancomycin/linezolid and rarely
It is highly penicillinase resistant but not acid resistant-
must be injected.
Adverse reaction- haematuria, albuminuria, reversible
Highly Penicillinase and Acid resistant
More active than methicillin
Less active against PnG sensitive organisms: should not be used as its
Incompletely but dependably absorbed (oral route) Incompletely but dependably absorbed (oral route)
>90% protein bound, eliminated primarily by kidney, also partly by liver
Plasma half life is about 1hr
Given in staphylococcus infection resistant to benzyl penicillin
Active against a variety of gram-negative bacilli as well.
These drugs retain the antibacterial spectrum of penicillin and have improved activity against gram-negative organisms.
Like penicillin, however, they are relatively
Extended spectrum penicillins
Like penicillin, however, they are relatively susceptible to hydrolysis by -lactamases.
Ex: Ampicillin, Bacampicillin, Pivampicclin, Talampcillin, Amoxicillin
Active against all organisms sensitive to PnG; in addition, many gram-negative bacilli
Acid resistant Acid resistant
Oral absorption is incomplete but adequate
Primary excretion is kidney, partly enterohepatic
Plasma half life is 1hr
UTI, RTI, Meningitis, Gonorrhoea, typhoid fever, bacillary dysentery,
Cholisystitis, Subacute bacterial endocarditis and Septicemias
Adverse effects:Adverse effects:
Diarrhoea(it is incompletely absorbed the unabsorbed drug
irritates the lower intestine as well as causes marked alteration of
Hydrocortisone inactivates ampicillin if mixed
in the I.V solutionin the I.V solution
Oral contraceptive failure of oral
Probenecid retards renal excretion
Adult- 250- 500 mg every 6 hr
Child- 50-100 mg/kg given in equally divided
doses every 6 hr
Maximum- 2-4 g/ day
Penicillin conger. Special feature- its activity against peudomonas
aeriginosa and indole positive Proteus. It has Gram-negative coverage which
includes Pseudomonas aeruginosa but includes Pseudomonas aeruginosa but limited Gram-positive coverage
Less active against- salmonella, E.coli, Enterobacter.
Klebisella and gram positive cocci are remain unaffect