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PENICILLINS

One of the most important groups of
antibiotics.

They are still widely used .

Drugs of choice for a large number of
infectious diseases.
O
C
R
S
N
C
C
O
B-Beta-Lactam ring
B
C
N
A
CH3
C CH3
C
COOH
A-Thiazolidine ring
CH2
R=
Penicillin G
CLASSIFICATION OF THE
PENICILLINS
Natural penicillins (Pen G and V)
 Penicillinase-resistant penicillins
 Aminopenicillins
 Carboxypenicillins
 Ureidopenicillins
 Combinations with -lactamase
inhibitors

PENICILLIN G AND V

Antimicrobial activity-NONPENICILLINASE producing strains of
most cocci, gram positive bacilli and
spirochetes.
DISTRIBUTION

Widely distributed throughout body
spaces.
INFLAMED MENINGES
NORMAL MENINGES
Pen G
injected
HOURS
METABOLISM AND
EXCRETION

Only a small amount is metabolized.

Pen G is eliminated rapidly and
primarily by active renal tubular
secretion with a short half-life.
REPOSITORY PREPARATIONS

Penicillin G procaine and Penicillin G
benzathine (IM).
Blood Level
Pen G (IM)
Pen V (Oral)
Pen G (Oral)
Procaine Pen G
Benzathine Pen G
2
4
6
12
Time (hrs)
18
24
THERAPEUTIC USES

Penicillin G is the first choice for most
infections due to bacteria sensitive to
penicillin.
Acute
pneumococcal
pneumonia
THERAPEUTIC USES

Syphilis (Benzathine Pen G)
Bacteroides fragilis
PROPHYLACTIC USES

Streptococcal infections.

Recurrences of rheumatic fever.

Syphilis.
PENICILLIN V

Continued treatment of infections
initially treated with parenteral Pen G.

Prophylaxis of streptococcal infections
(e.g.rheumatic fever).
SEMISYNTHETIC PENICILLINS
PENICILLINASE RESISTANT
PENICILLINS-PROPERTIES

Resistant to hydrolysis by staphylococcal
penicillinase.

Less active vs other penicillin-sensitive
organisms.
THERAPEUTIC USES

Drugs of choice for infections caused by
penicillinase-producing Staph. aureus.
METHICILLIN
OCH3
RESISTANT TO
PENICILLINASE
OCH3
ORAL ABSORPTION IS
POOR
NARROW SPECTRUM
METHICILLIN-RESISTANT STAPH.
(MRSA) INFECTIONS

Most commonly identified antibiotic-resistant
pathogen in US hospitals.

MRSA has spread beyond health care facilities
emerging in the community, where it is rapidly
becoming a dominant pathogen.

Resistant to several antibiotics including
penicillins and cephalosporins.
TREATMENT OF HA-MRSA

Vancomycin is the treatment of choice.
CA-MRSA

Patients with serious CA-MRSA infections
should be hospitalized and treated with IV
vancomycin, linezolid or daptomycin.

For less serious CA-MRSA skin or soft tissue
infections, oral TMP/SMX, minocycline,
doxycycline, clindamycin or linezolid could be
tried.
ISOXAZOLYL PENICILLINS

Acid stable and adequately absorbed
after oral administration.

Orally for infections of moderate severity
and for prolonged outpatient treatment
of chronic infections (e.g. osteomyelitis).

Parenterally for serious staph infections.
NAFCILLIN
GI ABSORPTION
IS VARIABLE
OC2H5
AMINOPENICILLINS

Increased activity against many gram organisms.

Metabolized by -lactamases from both gram +
and – bacteria.

Not substitutes for penicillin G or V.

Includes AMOXICILLIN, AMPICILLIN
and congeners.
AMINOPENICILLINS
HO
H
O
C
C
N
H
AMOXICILLIN
Good oral absorption
AMOXICILLIN-THERAPEUTIC
USES

Sinusitis and other upper respiratory
infections.

Bacterial endocarditis prophylaxis-DOC
for prophylaxis in patients at risk while
undergoing dental, oral or upper
respiratory tract procedures.
ANTIPSEUDOMONAL
PENICILLINS



Extended antibacterial range compared
to amoxicillin.
Hydrolyzed by penicillinases.
Carboxypenicillins and ureidopenicillins.
TICARCILLIN (Ticar)

Must be given parenterally.

Gram negative infections caused by
Pseudomonas and Proteus.

For most serious systemic pseudomonal
infections use an antipseudomonal
penicillin plus an aminoglycoside.
UREIDOPENICILLINSMEZLOCILLIN AND
PIPERACILLIN

Given parenterally.
THERAPEUTIC USES

Serious gram negative infections,
especially pseudomonas.
COMBINATIONS WITH BETA
LACTAMASE INHIBITORS

Penicillin plus a beta lactamase inhibitor.
BETA-LACTAMASE
INHIBITOR COMBINATIONS

Inhibitor has only weak intrinsic activity.

Combination has a broader spectrum
than penicillin alone.
THERAPEUTIC USES

Useful in infections caused by lactamase producing bacteria, certain
anaerobic infections and other infections
usually not sensitive to penicillin.
SUMMARY OF THE USES OF THE DIFFERENT PENICILLINS
Penicillin G
Penicillin V
Streptococci,
syphilis, anaerobic
infections,
Prophylactic use
Similar to
penicillin G but
for oral use
Isoxazolyl
penicillins
Staph infections
Aminopenicillins
Gram- infections
SUMMARY OF THE USES OF THE DIFFERENT
PENICILLINS
Carboxypenicillins Pseudomonal
infections
Ureidopenicillins
Pseudomonal
infections
Penicillins +beta
lactamase
inhibitors
Extended
spectrum
ADVERSE REACTIONS TO THE
PENICILLINS
HYPERSENSITIVITY
REACTIONS

Cross allergenicity among all the
penicillins.

Result from a previous treatment.
HYPERSENSITIVITY
REACTIONS

Occur with almost any dosage form of
penicillin. Oral penicillins have a lower
risk than parenterals.

Usually clear with elimination of the
penicillin.
HYPERSENSITIVITY
REACTIONS

Skin rashes.

Fever.
Bronchospasm.
Vasculitis, serum sickness, exfoliative
dermatitis, contact sensitivity, local swelling
and redness,oral lesions, eosinophilia.


 ANGIOEDEMA AND
ANAPHYLAXIS.
ANAPHYLAXIS

Most important immediate danger.

Incidence is low (0.04 -0.2%).

Sudden, severe hypotension and rapid
death.
ANAPHYLAXIS
 Careful
observation of the
patient is important.
ANAPHYLAXIS-TREATMENT

Epinephrine (IV or IM)

IV steroids

Supportive measures
MGMT. OF THE PATIENT
POTENTIALLY ALLERGIC

Evaluation and history.
DESENSITIZATION.
DIRECT PENICILLIN TOXICITY

Pain and inflammation at the site of IM
injection.

Phlebitis when given IV.

GI Irritation when given orally.
DIRECT TOXICITY

Neurological effects - CNS and PNS.

Renal/electrolyte toxicity -cation
intoxication, interstitial nephritis and
renal failure.

Hematological toxicity- bone marrow
depression and impairment of platelet
aggregation.
SUPERINFECTIONS
PENICILLINS
SAFEST
OF ALL
ANTIBIOTICS IN
PREGNANCY
MECHANISM OF ACTION

They inhibit the formation of the
bacterial cell wall.
Dividing Bacteria
Division
Plus penicillin
Emerging Spheroplast
Growth
Growth site
Spheroplast
Penicillin Binding Proteins
Transpeptidases
Penicillin
Carboxypeptidases
Endopeptidases
AUTOLYSINS
MECHANISM OF ACTION

All beta-lactam antibiotics act by the
same mechanism.
RESISTANCE

Structural differences in the penicillin
binding proteins.

Inability to penetrate to its site of action.
Headache,
Dizziness
GI Upset
E. Coli
(coliforms)
Pen G and Pen V
H. influenzae
AND: Spirochetes
Bacteroides spp
P. aeruginosa
Clostridium spp
S. aureus
Enterococcus spp
Streptococcus spp
Gram-positive
Anaerobic
Penicillins:
Gram-negative
Neissseria spp
Penicillins:
Penicillinase-resistant
Gram-negative
Neissseria spp
H. influenzae
Bacteroides spp
P. aeruginosa
Clostridium spp
S. aureus
Enterococcus spp
Streptococcus spp
Gram-positive
Anaerobic
E. Coli
(coliforms)
S
O
C N
R
C
C
CH3
C CH3
C
O
N
C
COOH
Penicillinase
R
O
C
S
N
O C
OH
C
CH3
C CH3
N
C
Penicilloic Acid
COOH
R
S
O
C N
C
C
CH3
C CH3
C
O
N
C
COOH
Amidase
R
O
CH
S
2HN
C
C
CH3
C CH3
C
O
N
C
6-Aminopenicillanic Acid
COOH
Glycopeptide
Polymer
Glycopeptide
Polymer
Mur NAc
Mur NAc
Transpeptidase
Glycopeptide
Polymer
D-Alanine