midterm 2

• Preservatives


  Used to prevent microbial contamination
• Ideal characteristics of preservatives

  • Effective at low concentrations against all possible microorganisms, nontoxic, compatible with other constituents used in the preparation, stable for the shelf-life of the preparation
• Parabens


  1. hydroxybenzoic acid, useful as preservative for liquid dosage forms, have antifungal properties, preservative effect tends to increase with molecular weight
• Methylparaben


  More effective against molds
• Propylparaben


  More effective against yeasts, more oil-soluble so preferred for oils and fats
• Chlorobutanol


  Alcohol-based, stops growth, employed as a bacteriostatic agent in pharmaceuticals for injection, ophthalmic use, and intranasal administration
• Benzyl alcohol


  Commonly used as preservative in vials of injectable drugs in concentrations of 1% to 4% in water or saline solution, has local anesthetic action
• Phenylethyl alcohol


  Occurs naturally in rose oil and pine-needle oil, used primarily in perfumery
• Benzoic acid


  Used externally as an antiseptic for lotions, ointments and mouthwashes, more effective as a preservative in foods and pharmaceutical products at low pH
• Sodium benzoate


  Used as preservative in acidic liquid preparations in which benzoic acid is released
• Sodium propionate


  Effective antifungal that is used as preservative
• Sorbic acid


  An effective antifungal preservative, used to preserve syrups, elixirs, ointments, and lotions containing components such as sugars that support mold growth
• Potassium sorbate


  Used the same way as sorbic acid
• Phenylmercuric nitrate


  Used to preserve injectable drugs but bacteriostatic efficacy is reduced in the presence of serum
• Phenylmercuric acetate


  Used as preservative
• Antitubercular agents


  • Kill specific bacteria, synthetic drugs, target Mycobacterium tuberculosis, acid fast bacteria, rod shaped, aerobic, do not form spores, facultative intracellular, obligate aerobe, causes Koch's disease, grow on Lowenstein-Jensen medium
• Isoniazid (INH or H)


  Isonicotinic acid hydrazide, NydrazidⓇ, inhibits the synthesis of mycolic acid, an important component of the cell wall of mycobacteria, principal adverse effect is peripheral neuritis due to competition with pyridoxal phosphate for the enzyme apotryptophanase, antidote is pyridoxine, used with acid alcohol (3% HCl, 95% ROH, 2% water)
• Co-administration of pyridoxine prevents peripheral neuritis caused by isoniazid
• Ethionamide


  Trecator SC®, structural analogue of isoniazid, used in the treatment of isoniazid-resistant tuberculosis, side effects include GI irritation, hepatotoxicity, peripheral neuropathies, optic neuritis
• Pyrazinamide (PZA or Z)


  Pyrazinecarboxamide, mechanism of action unknown, used in combination with other agents because resistance develops rapidly, side effect is hepatotoxicity (increased ALT/AST), must be enzymatically hydrolyzed to pyrazinoic acid (active form)
• Ethambutol (EMB or E)


  Myambutol, side effect is optic neuritis and loss of ability to discriminate between red and green (color blindness), mechanism of action is inhibition of incorporation of mycolic acids in the cell walls of the bacteria
• Para-Aminosalicylic Acid (PASA/PAS)


  Mechanism of action is competitive inhibition of p-aminobenzoic acid (PABA) in folate biosynthesis, side effect is severe gastric irritation, used as second-line treatment for TB
• Clofazimine


  Lamprene, mechanism of action unknown, basic red-dye used in the treatment of leprosy, including dapsone-resistant forms, side effect is colored-maroon urine
• Rifamycins


  Obtained from Streptomyces mediterranei, includes Rifampin and Rifabutin, the most active agent against TB, enzyme inducer, toxic effects are relatively infrequent, when taken with INH or ethambutol, incidence of hepatotoxicity is significantly higher
• Rifampin


  Rifadin, Rimactane, Rifampicin, first line treatment for TB, side effects include reddish color of body secretions and hepatotoxicity
• First line treatment for TB

  1. Rifampin

  2. Isoniazid

  3. Pyrazinamide

  4. Ethambutol

  5. Streptomycin
• PTB treatment is 2 months of RIPE with or without Streptomycin, followed by 4 months maintenance phase of Rifampin and Isoniazid
• Cycloserine


  Seromycin, isolated from different species of Streptomyces, mechanism of action is prevention of synthesis of cross-linking peptide in the formation of bacterial cell walls
• Capreomycin


  Isolated from Streptomyces capreolus
• Streptomycin


  The only aminoglycoside used for tuberculosis, the first antibiotic effective in the treatment of TB (discovered in 1944 by Waksman)