Penicillins

PREPARATIONS OF PENICILLINS

Antibacterial spectrum

• Gram-positive cocci, e.g. streptococci, pneumococci and & staphylococci.

• Gram-negative cocci: gonococci & meningococci.

• Gram-positive bacilli: anthrax bacillus, C. diphtheria & clostridia.

• Gram-negative bacilli: shigella, salmonella, etc.

• *Spirochetes: treponema pallidum.

• _Actinomyces

MOA: Cidal & Beta-lactams

Mechanism of Action (Inhibit cell wall by 2 main mechanisms):

1. Bind with penicillin binding sites, then blocks the activity of Transpeptidase enzyme which takes part in cell wall strength.

2. Autolytic enzyme activation

Pharmacokinetics

• Cross placenta; none teratogenic drug
• Do not cross BBB (only in the case of Inflammation; meningitis). 

Excretion: Elimination of most penicillin occurs rapidly and is mainly renal, 90% being through the organic acid (tubular) secretory system of the kidney and by glomerular filtration. Propenecid inhibits the secretion of penicillins by competition and thus can increase blood levels.

Penicillins are excreted into breast milk and saliva.

All secreted by kidney (Tubular system) which is Inhibited by Propenecid. & Naficillen secreted by Biliary route

Therapeutic Uses

A. Treatment of infection: Penicillins may be used in the treatment of:

1. Streptococcal infections, e.g. wound sepsis, puerperal fever acute throat infections, subacute bacterial endocarditis,.. etc.

2. Staphylococcal infections of skin, mucous membrane and bone.

3. Pneumococcal infections e.g. pneumonia and empyema.

4. Syphilis  and gonorrhoea. Penicillin G remains the drug of choice for syphilis.

5. Meningococcal infections.

6. Typhoid and paratyphoid fevers: ampicillin & amoxycillin. on H-Pylori treatment

7. Pseudomonas infection.

8. Other uses:

   • Actinomycosis, Anthrax and H. influenza infections.
   • Diphtheria, tetanus and gas gangrene (Penicillin may be used together with the specific antitoxins).
   • Peptic ulcer

B-Prophylaxis: Penicillins may be used prophylactically in the following conditions:

•  1-To prevent recurrence of Rheumatic Fever.

• 2-To prevent gonorrhoeal ophthalmia in neonates:

• 3-To prevent subacute bacterial endocarditis due to bacteraemia resulting from operative procedures such as dental extraction, tonsillectomy…etc. in patients with congenital or acquired valvular disease or immunocompromised patient. ((one dosage, 6 pieces for safe definite treatment))

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Adverse Effects

penicillins are among the most widely used and least toxic antibiotics available.

A-Hypersensitivity (10% of patients):RR

hypersensitivity reactions are common with prolonged course, history of other allergic disease and with procaine penicillin. Allergy generally occurs to all forms of penicillins at once.

•  Allergic reactions occur in 0.7% – 8% of treatments
• urticaria, pruritus, angioedema
• 10% of allergic reactions are life-threatening
• and 10% of these are fatal

Prevention: Never give penicillin if there is history of penicillin allergy. - Test for hypersensitivity Treatment: ECAA;Epinephrine = antihistamine (e.g.chlorpheniramine)corticosteroids andaminophylline.*

Types: 1-Early (Type I reaction-anaphylactic):   Immediate - within 20 minutes

• apprehension, pruritis_, numbness__,_ choking,, edema, severe fall in blood pressure occurs, with bronchoconstriction, angioedema (including larynx) and sometimes death due to loss of fluid from the intravascular compartment. , loss of consciousness, death

• Anaphylactic shock usually occurs suddenly, in less than an hour after the drug has been given orally, but within minutes if it has been given IV.

2-Accelerated - 1-72 hrs after administration: mainly hives 

3-Delayed (Type III reaction, serum sickness): it occurs after 2-12 days in the form of fever, malaise, arthralgia, skin rash and angioedema.

B-Neurotoxicity

Convulsions, coma, and death has followed intrathecal injections of penicillin. It occurs after high doses and in renal failure.

C-Glossitis, stomatitis and superinfection:

Superinfection by Candida albicans, notably with ampicillin. Diarrhea is frequently observed in patients receiving ampicillin and on occasion with amoxicillin.

D-Cation toxicity:

Large doses of the sodium or potassium salt of penicillin-G in patients with renal insufficiency can result in excessive blood levels of these cations.

E-Procaine penicillin:

It produces mental changes, convulsion, pulmonary infarction (due to accidental IV administration).

F-Herxheimer reaction

in late Syphilis:** CC ex.process

G-Masking of infection (syphilis and gonorrhea):

If theres combined infection, where clinical picture appear later due to small dosage of penicillin.

H-Other Adverse effects:

Both carbenicillin and ticarcillin may interfere with platelet aggregation and; occasionally, cause bleeding problems.

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InteractionsY

• 1-Penicillins with bacteriostatic drugs (e.g. tetracycline, chloroamphenicol, erythromycin): since penicillin act by inhibiting cell wall synthesis, but drugs which decreases protein synthesis, interfere with the action of penicillin.

• 2-All antipseudomonal penicillins impair the antibacterial action of gentamicin when the 2 drugs are mixed together in vitro. This inactivation is  likely to occur in  patients  with severe renal impairment.

• 3-e.g. combined use of penicillin and an aminoglycoside antibiotic (such as gentamicin) on the enterococcus. In this example, inhibition of cell wall synthesis by penicillin permits better penetration of the cell wall by the aminoglycoside and more effective inhibition of protein synthesis than either drug alone.