A thiazolidine ring which is attached to β-lactam ring
6- aminopenicillanic acid nucleus is essential for activity
If the β-lactam ring is enzymatically cleaved by bacterial β-
lactamases, the resulting product, penicilloic acid lacks
Penicillin G (Benzyl penicillin)
Penicillin V has a spectrum similar to that of penicillin G, but it is
not used for treatment of bacteremia because of its poor
absorption, narrow spectrum and need for dosing four times.
Anti staphylococcal penicillins
The semi synthetic penicillins Methicillin, nafcillin, oxacillin, and
dicloxacillin are penicillinase resistant penicillins.
Because of its toxicity (interstitial nephritis), methicillin is not used
clinically except to identify resistant strains of S. aureus. Methicillin
resistant Staphylococcus aureus (MRSA) is currently a source of
serious community and nosocomial (hospital-acquired) infections
and is resistant to all commercially available β-lactam antibiotics,
including antistaphylococcal penicillins. This organism is usually
susceptible to Vancomycin.
The penicillinase-resistant penicillins have no activity versus
However, for infections caused by methicillin susceptible strains
of staphylococci these are considered the drugs of choice.
Extended spectrum penicillins
Ampicillin and Amoxicillin have an antibacterial spectrum
similar to that of penicillin G but are more effective against
gram-negative bacilli. Therefore, they are referred to as
Resistance to these antibiotics is now a major clinical problem
because of inactivation by plasmid mediated penicillinases.
Formulation with a β-lactamase inhibitor, such as clavulanic acid
or sulbactam, protects amoxicillin or ampicillin, respectively,
from enzymatic hydrolysis and extends their antimicrobial
Synergistic effect with aminoglycosides
Anti pseudomonal penicillins
Carbenicillin, ticarcillin, and piperacillin are called
antipseudomonal penicillins because of their activity
against P. aeruginosa
These drugs have activity against several gram-negative
rods, including Pseudomonas, Enterobacter, and in some
cases Klebsiella species.
susceptible to penicillinases and are often used in
combination with penicillinase inhibitors (eg, tazobactam
and clavulanic acid) to enhance their activity.
Synergism with aminoglycosides
Mechanism of action
The transpeptidation reaction in Staphylococcus aureus that is
inhibited by β-lactam antibiotics. The cell wall of gram-positive
bacteria is made up of long peptidoglycan polymer chains
consisting of the alternating N-acetylglucosamine (G) and N-
acetylmuramic acid (M) with pentapeptide side chains linked
(in S. aureus) by pentaglycine bridges. The exact composition of
the side chains varies among species. The diagram illustrates
small segments of two such polymer chains and their amino
acid side chains. These linear polymers must be cross-linked by
transpeptidation of the side chains at the points indicated by
the asterisk to achieve the strength necessary for cell viability.
0 UDP-acetylmuramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala sequence is
also called as “Park nucelotide”, formerly called as “Park
Penicillin binding proteins (PBPs) catalyze the
transpeptidase reaction that removes the terminal alanine to
form a cross link with a nearby peptide.
This gives cell wall its structural rigidity
β- lactam antibiotics are structural analogs of the D-ala-D-
This substrate is bound by PBP at active site
When a β- lactam is attached PBP, transpeptidation reaction
is blocked which leads to inhibition of peptidoglycan
synthesis and the cell dies
Exact mechanism of bacterial cell death is unknown but
involvement of autolysins activation and destabilization of
bacterial membrane against high internal osmotic pressure
1. Inactivation of antibiotic with β-lactamase
2. Modification of target PBPs
3. Impaired penetration of drug to target PBPs
4. Presence of efflux pump
β-lactamase production is the most common mechanism of
Some β-lactamase hydrolyze penicillins but not
cephalosporins e.g. those produced by E. coli, S. aureus.
Whereas, those produced by P. aeruginosa and enterobacter
Carbapenems are highly resistant to hydrolysis by
penicillinases and cephalosporinases but are hydrolyzed by
Absorption differs for different penicillins, depending
upon their acid stability and protein binding.
Methicillin is acid labile
Gastrointestinal absorption of nafcillin is erratic
Both are not suitable for oral administration.
Amoxicillin, ampicillin and dicloxacillin are acid stable
and relatively well absorbed
Absorption of most oral penicillins are impaired by food
(except amoxicillin), therefore, should be administered
1-2 hrs before meal.
Absorption through IV route is preferred due to local
irritation and pain produced by IM injection of large
Penicillins are usually excreted by kidney through urine
and small amounts are excreted by other routes
Those penicillins which are excreted through kidney, dose
must be adjusted according to renal function e.g. normal
half life of Penicillin G is usually 30 min and in renal failure
it may increase upto 10 hours.
Nafcillin is primarily cleared by biliary excretion
Oxacillin, dicloxacillin and cloxacillin are cleared by both
kidney and biliary excretion.
No dose adjustments are required for these drugs in renal
Penicillins are remarkably non toxic
1- Hypersensitivity reactions
Due to penicilloic acid (metabolite of penicillin)
From skin rash to anaphylactic shock (includes fever,
nephritis, pruritis, urticaria, joint swelling etc.)
Methicillin cause interstitial nephritis while nafcillin
Incidence of allergic reaction in small children is negligible
Due to over growth of G+ organisms or by direct irritation
Nausea, vomiting, diarrhea
Pseudomembranous colitis (Inflammation of colon)
MOA: Penicillin causes normal flora to alter. When an
antibiotic kills competing bacteria in the intestine, the
remaining bacteria will have less competition for space
and nutrition. The net effect is to permit more extensive
growth than normal of certain bacteria. E.g. C. difficile.
Vaginal candidiasis can also occur.
Penicillin G causes seizures if given intra-thecal in
patients especially with renal failure patients. They also
can cause confusion and psychosis (neurotoxicity).
MOA: Most widely accepted theory involves binding to
GABA receptors which are involved in inhibitory
Benzodiazepines and Barbiturates are used as treatment
Cessation of seizure activity has been reported 12-72 hrs
after therapy is discontinued. The epilepticogenic
activity may be due to β-lactam ring
Treatment / Anti-dot
Allergy is treated by Anti-histamine
Desensitization can be accomplished with gradually
increasing doses of penicillin
Anaphylactic shock is treated by Adrenaline and
MOA: Vasodilation (Fall in BP) and bronchoconstriction are
important symptoms of anaphylactic shock, whereas,
adrenaline causes vasoconstriction and bronchodilation.
Corticosteroids have anti-inflammatory effects
Penicillins and carbapenems are both neurotoxic. Dose
adjustment in renal failure is key strategy to avoid
Contraindications / drug
Captopril (capotein) – Increase potassium level.
Spironolactone (Aldactone) – K+ sparing diuretics
K+ suppliments (KCl).
Especially with those penicillins which are available in
Hyperkalemia can generate arrhythmia in cardiac patients.
Sodium salts should be avoided in hypertensive patients.
Ticarcillin and carbencillin have antiplatelet aggregation
Be careful when administering Streptokinase, warfarin,
heparin, clopidogrel etc to patients who are already taking
Penicillins inhibit the excretion of methotrexate (anti-
cancer) due to which toxic effects of methotrexate occur,
such as, bone marrow depression.
Probencid is a uricosuric agent. It increases the
concentration of penicillin and inhibit its excretion.
Penicillins decrease the effectiveness of estrogens in
Dose of penicillins should be increased in
Should not be taken with acidic juices and should be
administered with full glass of water.
Hypertensive (having low salt diet)
Impaired renal function
Tendency to bleed
Parece que tiene un bloqueador de anuncios ejecutándose. Poniendo SlideShare en la lista blanca de su bloqueador de anuncios, está apoyando a nuestra comunidad de creadores de contenidos.
¿Odia los anuncios?
Hemos actualizado nuestra política de privacidad.
Hemos actualizado su política de privacidad para cumplir con las cambiantes normativas de privacidad internacionales y para ofrecerle información sobre las limitadas formas en las que utilizamos sus datos.
Puede leer los detalles a continuación. Al aceptar, usted acepta la política de privacidad actualizada.