Natural penicillin

Pen G and Pen V

Natural penicillin are

which are highly active against gram (+) cocci

Unit or IU

Natural penicillin

When the unit/expression is

(natural source)

metric

Natural penicillin

When the unit/expression is

(synthetic)

1 mg of PEN Procaine - 1,009 U

Natural Penicillin

(used in syphilis)

Potassium penicillin G

contains about 1.7 meq of K+ per million units of penicillin (2.8 meq/g).

Procaine salts and benzathine

provide repository forms for intramuscular injection.

Dry crystalline form

stable for long periods (eg, for years at 4 °C) - contained in a vial

Degradation

may be due to water, alkaline or acid solutions and enzymes

penicilloic acid → penilloic acid

In basic media

penicillamine (chelating agent), penilloic acid and penilloaldehyde

In acid media

6.0 and 6.8

Degradation reactions can be retarded clinically by buffering solution of penicillins between pH

Streptococcus pyogenes (Group A

strep), Streptococcus agalactiae (Group B

strep), viridans streptococci, Enterococci.

Gram-positive aerobic cocci:

Gram-positive aerobic cocci: Streptococcus pyogenes (Group A strep), Streptococcus agalactiae (Group B strep), viridans streptococci, Enterococci.

Useful for skin and soft tissue infections caused by Streptocccus pyogenes,

Gram-positive aerobic cocci: Streptococcus pyogenes (Group A strep), Streptococcus agalactiae (Group B strep), viridans streptococci, Enterococci

Oral or dental infections which frequently involve anaerobic streptococci,

Neisseria meningitidis, Pasteurella multocida.

Gram-negative aerobes

Gram-negative aerobes: Neisseria meningitidis, Pasteurella multocida.

Use for meningitis

Anaerobes: Clostridium species, Fusobacterium species, Actinomyces israelii.

Other: Treponema pallidum, Listeria monocytogenes.

Used for Syphilis

Spectrum act.

Clostridium species, Fusobacterium species, Actinomyces israelii.

Anaerobes:

Procaine

penicillin G

uncomplicated pneumonia caused by penicillin-susceptible Streptococcus pneumoniae

Procaine

penicillin G

Also used in gonorrhea

Benzathine

penicillin G

1.2 mU IM once every 3-4 weeks

- Effective in the tx of beta-hemolytic streptococcal pharyngiti

Penicillin V K

Indicated only for minor infections

because of relatively low bioavailab

Penicillin V K

need for dosing 4x a day

narrow antibacterial spectrum

Can be oral route

A. Hypersensitivity reactions manifested by:

a. Rashes

b. eosinophilia

c. ever

d. interstitial nephritis

e. Jarisch-Herxheimer Phenomenon

i. Develop after antibiotic used in patients with syphilis

ii. Symptoms: mild fever, chills, malaise, headache, muscle aches

iii. Occur with most spirochetes because of the release of a pyrogen

B. Central nervous stimulation including myoclonic twitching and seizures.

PENICILLIN G (BENZYLPENICILLIN)

GENERAL SIDE EFFECTS/PRECAUTIONS:

ANTISTAPHYLOCOCCAL PENICILLIN / PENICILLINASE RESISTANT PENICILLINS

These are less potent against bacteria that do not produce beta lactamase, but are effective against those that do.

1. Methicillin

2. Nafcilli

3. Oxacillin

4. Cloxacillin

5. Dicloxacillin

lsoxazoyl derivatives: Oxacillin, Cloxacillin, Dicloxacillin

ANTISTAPHYLOCOCCAL PENICILLIN /

PENICILLINASE RESISTANT PENICILLINS

Examples

Oxacillin, Cloxacillin, Dicloxacillin

lsoxazoyl derivatives:

ANTISTAPHYLOCOCCAL PENICILLIN / PENICILLINASE RESISTANT PENICILLINS

Use: Infection by B-lactamase producing staphylococci

Isoxazolyl penicillins (Oxacillin, Cloxacillin, Dicloxacillin)

are eliminated by both kidney and biliary excretion.

- no dosage adjustment is required in renal failure

Methicillin, Oxacillin, Nafcillin

ANTISTAPHYLOCOCCAL PENICILLIN /

PENICILLINASE RESISTANT PENICILLINS

Intravenous

Cloxacillin, Dicloxacillin, Flucloxacillin

ANTISTAPHYLOCOCCAL PENICILLIN /

PENICILLINASE RESISTANT PENICILLINS

Oral

Methicillin

may cause nephrotoxicity and interstitial nephritis

Oxacillin

may be hepatotoxic. (consider the liver function: ALT and AST)

AMINOPENICILLIN

● Broad spectrum with extended spectrum of activity

● Antimicrobial activity includes such gram (-) microorganisms such as He. influenzae, E. coli and P. mirabilis. (haemophilus, proteus)

● Contains amino group in their structure

1. Ampicillin

2. Amoxicillin

3. Cyclacillin

4. Bacampicillin

5. Hetacillin

AMINOPENICILLIN

Examples

Cyclacillin, Bacampicillin, and Hetacillin

are prodrugs of ampicillin

Ampicillin and amoxicillin

most commonly associated with drug-induced rash and diarrhea.

Ampicillin

is equivalent in activity to Pen G, widely used for out-patients for uncomplicated

Amoxicillin

more acidic → better oral absorption

→ enhanced blood levels, less GI disturbance.

Antimicrobial activity and spectrum similar to ampicillin. less frequent dosing (Q8 vs Q6 hours for ampicillin).

ANTIPSEUDOMONAL PENICILLINS

Activity is extended against Pseudomonas, Enterobacter and Proteus sp., klebsiela sp. and other gram (-) microorganisms.

Carbenicillin

2. Ticarcillin

3. Mezlocillin

4. Piperacillin

ANTIPSEUDOMONAL PENICILLINS

Examples

(carbenicillin, ticarcillin)

Carboxypenicillins ex.

Ureidopenicillin (Mezlocillin, piperacillin, azlocillin)

are effective or additional activity against Klebsiella pneumoniae

Pseudomonas (blue-green pus) and Klebsiella

are capable of causing hospital-acquired pneumonia

BETA LACTAMASE INHIBITORS

Used to produced synergistic activity against resistant strains

BETA LACTAMASE INHIBITORS

Inhibits the enzymes that inactivates or hydrolyzes the lactam ring resulting to inactivation

Augmentin®

Amoxicillin + Clavulanic acid

Piptaz®

Piperacillin +Tazobactam

Unasyn®

Ampicillin + Sulbactam

Class I Inhibitors

Prolongs inactivation of enzymes

- Protects penicillin from beta lactamase degredation

Class I Inhibitors

Used with extended-spectrum spectrum and β-lactamase-sensitive penicillins

Sulbactam, clavulanic acid and tazobactam

Class I Inhibitors

Clavulanic Acid

a. naturally occurring, from S. clavuligerus

b. Has weak antibacterial activity

Clavulanic Acid

c. Combined with Amoxicillin for skin, respiratory, ear and UTI

d. Combined with Ticarcillin for septicemia, lower RTI and UTI

Sulbactam + Ampicillin

Sultamicillin (Unasyn)

Sulbactam

Non-synergistic with Carbenicillin

Sulbactam

Has weak antibacterial activity but potentiates activity of ampicillin and carbenicillin against β-lactamase producing staphylococcus and enterobacteriaceae

Tazobactam

More potent than sulbactam, slightly broader in spectrum than

clavulanic acid, weak antibacterial activity

Tazobactam

With piperacillin for appendicitis, postpartum endometriosis and pelvic inflammatory infections

Carbapenem, Monobactams

Class II Inhibitors

Ex.

Carbapenem, Monobactams

possess potent antibacterial activity in addition to its ability to cause transient inhibition of some β-lactamases

(Imipenem, Meropenem, Ertapenem)

CARBAPENEMS

Ex.

Imipenem

penetrates bacterial porins well, and is stable to and inhibitory for many beta lactamases

Imipenem

It is not orally active

Broad spectrum

Imipenem

First discovered Carbapenem

Used for UTI

Imipenem

With cilastatin sodium, an inhibitor of renal dehydropeptidase 1, which attacks and inactivates it.

Imipenem

The discovery of Meropenem and Ertapenem is resistant to

dehydropeptidase 1; cilastatin is no longer needed

Sulfacezin, Aztreonam

MONOBACTAMS example

Sulfacezin, Aztreonam

A product of fermentation of unusual microorganisms

Sulfacezin, Aztreonam

It is a totally synthetic parenteral antibiotic which is active almost entirely against gram negative bacteria.

Sulfacezin, Aztreonam

Also effective in gram (-) Its mechanism is similar to the penicillins

Sulfacezin, Aztreonam

The spectrum is similar to aminoglycoside (gram(-) aerobic bacteria))

Aztreonam

Imp.monobactams

1. Natural Penicillins

2. Penicillinase-Resistant Penicillins or

Antistaphylococcal Penicillins

(staphylococcus can produce beta

lactamases that destroy penicillin)

3. Aminopenicillins

4. Antipseudomonal Penicilli

CLASSIFICATION OF PENICILLINS: