The whole study about (Penicillin)

 

Penicillin

The first antibiotic discovered

That changed the world

·   Penicillin G is one of the natural penicillin’s.

·    It discover at 1929 and did not use until 1941.

· Penicillin may be used once sensitivities are established. Satisfactory for pneumococci, streptococci, and susceptible staphylococci. Use higher than standard doses in Group B Strep (GBS) infections. Use Benzathine Pen G or Procaine Pen G for gonococci or asymptomatic congenital syphilis.

 

What to learn?

·    Clinical Uses

·    Classifications

·    Mechanism of action

·    Dosing &Dosing can’t

·    Pharmacokinetics &Pharmacokinetics can’t

·    Drug interactions

·    Contraindications

·    Clinical Applications

·    Key side effects

·    Toxicity

·    TL; DR

Clinical Uses

·    To treat infection caused by gram-

 positive cocci, gram-positive rods and

gram-negative cocci.

·    The spectrum of activity depends on

 the generation of penicillin used.

·    Some bacterial may develop resistance:

·    Beta: lactamase: can be countered

 by adding clavulanic acid.

·    MRSA: need to use other class of

 drugs, such as vancomycin. 

 

Classifications

·    Penicillin G – effective against Gram-positive cocci/rods and Gram-negative cocci

·    Anti staphylococcal penicillin’s –

Effective against Staphylococcus aureus

·    Nafcillin, Oxacillin, Cloxacillin, Dicloxacillin

·    2^nd generation board spectrum – effective Against Gram-negative bacilli

Ampicillin, Amoxicillin

·    3^rd generation board spectrum – more resistance to the beta-lactamases

·    Carbenicillin, Ticarcillin

·    4^th generation board spectrum – activity Against strains of Klebsiella

·    Piperacillin

·    Beta-lactamase inhibitor – not exactly Penicillin, but used to increase spectrum

·    Clavulanic acid, Sulbactam 

Mechanism of action

1.         Bind to the penicillin-binding proteins     (PBPs)

2.         Inhibit the final transpeptidation step of     peptidoglycan synthesis.

3.         Bacteria cannot synthesize cell wall

4.         Bacteria eventually lyse due to ongoing       activity of cell wall autolytic enzymes  

Dosing &Dosing can’t

Dosing:-

·    Doses for oral therapy are 375 mg to 1 g divided 3 to 4 times daily; intravenous doses are 300,000 units to 1.2 million units/day divided every 3 to 4 h;

·    continuous intravenous infusions of 10 to 20 million units have been given over 20 h/day for several weeks.

 

Dosing can't:-

·    patients with severe renal dysfunction require intravenous dose adjustments; pediatric oral doses are 25 to 50 mg/kg/day divided every 6 to 8 h;

·    pediatric parenteral doses are 300,000 units to 1.2 million units/day given

·    every 3 to 4 h, to a maximum of 50,000 units/kg/dose or 5 million units/dose and 30 million units/day.

Pharmacokinetics

·     Intravenous doses produce peak serum levels within 1 h.

·     Intramuscular doses of the benzathine form produce peak serum levels at 24 h.

·    less than 30% of an oral dose is absorbed from the gastrointestinal tract

 

Pharmacokinetics can't

·    protein binding is 65%

·    elimination half-life is 20 to 50 min and the half-life is reduced by 50% following hemodialysis

·    approximately 30% is hepatically metabolized to penicilloic acid

·    79% to 85% is excreted in the

·    urine as unchanged drug.

Drug interactions

·    Penicillin’s can decrease the effectiveness of oral contraceptives.

·    Tetracyclines, erythromycins, lincomycin’s

·    all decrease the antimicrobial effectiveness of penicillin.

·    Aspirin, probenecid, and butazolidin may potentiate penicillin's effects.

·    Penicillin may potentiate coumadin and tandearil effects.

Contraindications

·    Patients with known allergies to penicillin, which is approximately 3% of the population.

·    In patients with renal impairment, dosages should be decreased since excretion of drug is by the renal system.

          Toxicity

·    Allergy (rash, urticaria, anaphylaxis, fever), change in bowel flora, Candida superinfection, diarrhoea, haemolytic anemia, haematuria, interstitial nephritis. Cutaneous allergic rash is rare in neonates.

·    Seizures may occur with IV bolus injection, particularly with the higher doses used in meningitis; therefore, the drug should be administered IV over 15-30 minutes.

TL; DR

• Penicillin is an antibiotic used for treating Gram-negative & Gram-negative infection.

• There are several generation of penicillin, in which the newer generation cover a broader spectrum.

• It works by binding to PBP to inhibit bacterial call wall synthesis.

• One key concern is the allergic reaction to beta-lactam, thus patient history should be carefully taken.