Ceftriazone and Cefpirome: Properties and Uses

Ceftriazone Disodium Properties and Uses

• Ceftriazone disodium exists as white crystals, soluble in water, and exhibits broad-spectrum activity against both gram-positive and gram-negative bacteria.

Cefpirome Properties and Uses

• Cefpirome is used to treat susceptible infections, including urinary and respiratory tract infections, skin infections, septicaemia, and infections in immuno-compromised patients.
• The intravenous dose for adults as sulphate is 1–2 g every 12 h over 3–5 min or infused over 20–30 min.

Ceftaroline Fosamil Properties and Uses

• Ceftaroline fosamil is a relatively recent approved cephalosporin from the fifth-generation.
• Ceftaroline is an oxyimino compound based on the structure of cefozopran (a fourth-generation representative).
• Ceftaroline fosamil is a prodrug that turns in vivo into ceftaroline (the active metabolite).
• The oxime group in the C7 acyl moiety and a 1,3-thiazole ring attached to the central nucleus (C3 position) facilitate the increased activity against MRSA.

SAR of Cephalosporins

• 7-Acylamino substitution:
  • The addition of amino group and a hydrogen to α and α1 position produces a basic compound, which is protonated under acidic conditions of the stomach.
  • The ammonium ion improves the stability of β-lactam of cephalosporins and makes them active orally.
  • Activity against positive bacteria is increased, and gram-negative is decreased by acylation of the amino group.
  • When the new acyl groups are derived from carboxylic acids, it shows good spectrum of antibacterial action for gram-positive bacteria.

Antibodies

• Antibodies are sometimes used as a quick and potent immunosuppressive therapy to prevent acute rejection reactions.
• Types of antibodies:
  • Polyclonal antibodies:
    • Antilymphocyte globulins (ALG)
    • Antithymocyte globulins (ATG)
  • Monoclonal antibodies:
    • Rho (D) immunoglobulin
    • Basiliximab
    • Daclizumab

Antibodies Preparation

• 1. By immunization of either horses or rabbits with human lymphoid cells producing mixtures of polyclonal antibodies directed against a number of lymphocyte antigens (variable, less specific).
• 2. Hybridoma technology:
  • Produce antigen-specific, monoclonal antibody (homogenous, specific)
  • Produced by fusing mouse antibody-producing cells with immortal, malignant plasma cells
  • Hybrid cells are selected, cloned, and the selectivity of the clone can be determined
  • Recombinant DNA technology can be used to replace part of the mouse gene sequence with human genetic material (less antigenicity - longer half-life)
  • Antibodies from mouse contain Muro in their names
  • Humanized antibodies contain ZU (humanized) or XI (chimeric) in their names

Antilymphocyte Globulins (ALG) & Antithymocyte Globulins (ATG)

• Polyclonal antibodies obtained from plasma or serum of horses hyper-immunized with human lymphocytes
• Bind to the surface of circulating T lymphocytes, which are phagocytosed in the liver and spleen, giving lymphopenia and impaired T-cell responses & cellular immunity
• Kinetics:
  • Given i.m. or slowly infused intravenously
  • Half-life extends from 3-9 days
  • Uses:
    • Combined with cyclosporine for bone marrow transplantation
    • To treat acute allograft rejection

Interferons

• Families:
  • Type I IFNs (IFN-α, β):
    • Induced by viral infections
    • Leukocyte produces IFN-α
    • Fibroblasts & endothelial cells produce IFN-β
  • Type II IFN (IFN-γ):
    • Produced by Activated T lymphocytes
• Interferon types and uses:
  • IFN-α:
    • Hepatitis B & C infections
    • Treatment of cancer (malignant melanoma)
  • IFN-β:
    • Multiple sclerosis
  • IFN-γ:
    • Treatment of chronic granulomatous diseases

Diuretics

• Diuretics are drugs that increase the rate of urine flow and also increase excretion of Na+ and an accompanying anion (negatively charged ion) like Cl–
• Diuretics reduce extracellular fluid volume (decrease in oedema) by decreasing total body NaCl content
• Compensatory mechanisms:
  • Activation of the renin-angiotensin-aldosterone pathway
  • The sympathetic nervous system
• Diuretics inhibit the reabsorption of Na+ ions, thereby reducing the quantity of water in body fluids

Carbonic Anhydrase Inhibitors

• Derived from sulphonamide antibacterials
• Sulfonamide group (—SO2NH2) is essential for its activity
• Inhibit carbonic anhydrase enzyme in the membrane and cytoplasm of the epithelial cells
• Primary site of action is proximal tubules
• Interfere with the reabsorption of HCO3–

Nephron Parts and Characters

• Proximal Tubule:
  • Leaky - Freely permeable to water, solutes
  • Active absorption of:
    • Sodium Chloride
    • Sodium Bicarbonate
    • Glucose
    • Amino Acids
    • Organic Solutes
  • Followed by passive absorption of water
• Loop of Henle:
  • Descending limb: Permeable to water
  • Thick ascending limb: Impermeable to water but permeable to sodium by Na+K+2Cl- Co transport
  • About 25% of filtered sodium is absorbed here
• Macula Densa and Juxtaglomerular Apparatus:
  • Contact between ascending limb with afferent arterioles - by specialized columnar epithelial cells Macula Densa
  • Macula Densa sense NaCl conc. in filtrate
  • Give signal to J.G. Cells present in afferent arterioles
  • J.G. Cells of afferent arterioles secrete Renin
• RAAS in response to low BP, or Low Na:
  • Renin-Angiotensinogen - Angiotensin I
  • ACE-Angiotensin II
  • Sympathetic, Aldosterone
  • Vasoconstriction, Sodium and water retention
• Early Distal Tubule:
  • Active transport of sodium by NaCl symport
  • Calcium excretion is regulated (Parathomone and Calcitriol, increase absorption of calcium)
• Collecting Tubule and Collecting Duct:
  • Aldosterone: On membrane receptor and cause sodium absorption by Na+/H+/K+ Exchange
  • ADH: Collecting tubular epithelium permeable to water (Water enters through aquaporin-2)

Nephron Parts and Their Functions

• SEGMENT FUNCTION
  • Glomerulus Formation of glomerular filtrate
  • Proximal convoluted tubule Reabsorption of 65% of filtered Na+/K+/Ca2+, and Mg2+; 85% of NaHCO3, and nearly 100% of glucose and amino acids.

Learn about the properties and uses of Ceftriazone disodium and Cefpirome, including their solubility, antibacterial activity, and dosage instructions.