Penicillin and Its Adverse Reactions

Penicillin

• Penicillin V is absorbed better than Penicillin G and is less affected by food.
• Penicillin V is less affected by disturbances in the gastrointestinal tract.
• Penicillin V is used to treat respiratory tract infections, urinary tract infections, dental infections, and β-hemolytic Streptococcal pharyngitis.
• Benzathine Ampicillin is used to treat Staph.Pseudomonas infections, shigellosis, and syphilis.
• Penicillin is used for prophylaxis against infective endocarditis.

Adverse Reactions of Penicillin

• Hypersensitivity: Most common drug implicated in drug allergies, can cause rash, itching, urticaria, fever, and anaphylaxis.
• More common with parenteral administration, Highest with procaine penicillin
• Skin sensitivity test (A scratch test or intradermal test) should be done before parenteral administration.
• Thrombophlebitis of injected vein.
• Diarrhea with ampicillin.
• Seizures: especially in renal impairment.

Drug Interactions of Penicillin

• Synergism: Penicillin + Aminoglycosides; both drugs shouldn’t be mixed in the same syringe. Penicillin facilitates the entry of aminoglycosides by inhibiting the cell wall synthesis.
• Antagonism: Penicillin + Tetracyclines: Bacteriostatic (Tetracyclines) with bactericidal effect of penicillin.
• Potentiation: Penicillin + Probenecid: Probenecid competes with penicillin on the excretory pathway leading to increased plasma concentration of penicillins.
• Penicillins decrease the effect of oral contraceptive pills.

Vancomycin

• Poorly absorbed orally.
• Administered intravenously as an infusion over 1 hour.
• Used to treat MRSA infections (e.g., osteomyelitis, pneumonia, endocarditis).
• Used orally to treat Pseudomembranous colitis, although metronidazole is preferred due to less resistance.
• Adverse effects: Infusion-related reactions, Red-man syndrome.

Fosfomycin

• Used to treat urinary tract infection and cystitis in women.
• Safe during pregnancy.

Teicoplanin

• Used to treat serious staphylococcal and streptococcal infections.
• Has no gram-negative activity.
• Long duration of action.
• Indicated for MRSA infection, multi-resistant gram-positive infections (e.g., Enterococcus faecium), and serious gram-positive infections in patients allergic to other antimicrobials.

Beta-Lactamase Inhibitors

• Beta-Lactamase enzymes are produced by bacteria that inactivate beta-lactam antibiotics.
• Beta-lactamase inhibitors include clavulanic acid, sulbactam, and tazobactam.
• Examples:
  • Amoxicillin + Clavulanic Acid
  • Ampicillin + Sulbactam
  • Piperacillin + Tazobactam
• Hepatotoxicity has been reported with the use of amoxicillin + clavulanic acid but not with amoxicillin alone.

Cephalosporins

• Cephalosporins are grouped into generations based on their development and clinical uses.
• Later generations have greater gram-negative activity and are more resistant to β-lactamase.
• First Generation: Cephradine, Cephalexin, Cefazolin
  • Uses: Respiratory tract infections, urinary tract infections, surgical prophylaxis (Cefazolin).
• Second Generation: Cefaclor, Cefamandole, Cefuroxime.
  • Uses: Respiratory tract infections, urinary tract infections, Meningitis (Cefazolin).
• Third Generation:
  • Parenteral: Cefotaxime, Ceftazidime, Ceftriaxone, Cefoperazone.
  • Oral: Cefixime, Cefdinir.
  • Ceftriaxone passes the blood-brain barrier and undergoes biliary excretion, making it safe for renal excretion.
• Fourth Generation: Cefepime.
  • Wider spectrum of activity, including Pseudomonas aeruginosa.

Pharmacokinetics of Cephalosporins

• Cefotaxime, ceftazidime, and ceftriaxone pass the blood-brain barrier.