Pyrogens are fever-producing substances produced by microorganisms like bacteria, yeasts, and molds. They are lipid substances associated with a carrier molecule like a polysaccharide or peptide. Pyrogens can be classified as either exogenous or endogenous. Endogenous pyrogens are low-molecular weight proteins produced by leukocytes in response to exogenous pyrogens that induce fever by acting on the hypothalamus. Exogenous pyrogens come from external sources like bacterial endotoxins, viruses, or incompatible blood products. Sources of pyrogens include water used in drug purification and crystallization, packaging components, and equipment used in product preparation.

1. Pathogenesis
• PYROGENS
• ▸ Pyrogens arefeverproducingsubstances,which aremetabolicproducts of
microorganisms.
• Chemically,theyarelipidsubstancesassociatedwithacarrier molecule,whichis usuallya
polysaccharide. The carrier may alsobe a peptide. These carriers increase thesolubility ofthe
lipid.
• ▸ Pyrogens areproducedbymanymicroorganismsincluding bacteria, yeasts and moulds.
Mostpotentpyrogensaretheendotoxinsproducedfromthecell walls oftheGram-negative
bacteria.

2. Classification of pyrogens
• Classification of Pyrogens
• ▸ Exogenous Pyrogen (Exotoxins)
• > Endogenous Pyrogen (Endotoxin)

3. Classification of pyrogens
• 1.Endogenous pyrogen
• low-molecular-weightprotein is produced by phagocytic leukocytes in response to
stimulation by exogenous pyrogensand released into the circulation.
• It induces fever by acting on the preoptic area of the hypothalamusto raise the set-point
of the hypothalamicthermostat..

4. Classification of pyrogens
• 2.Exogenous pyrogen
• fever-producing agents of external origin,
• e.g.,bacterialendotoxinsandothermicrobialproducts,antigen-antibodycomplexes,
virusesand syntheticpolynucleotides, incompatiblebloodandbloodproducts,and
androgen breakdown products such as etiocholanolone.

5. Source of pyrogens
• Source of pyrogen
• water used at the end stages of the purification.
• ⚫ crystallization of the drug or excipients: water used during
• processing.
• ⚫ packaging components; chemicals, raw materials or equipment used in the preparation of the product.
• • The presence of endotoxins on devices may be attributed to water in the manufacturing process.
• Washingofcomponentssuch asfilter media(filters). Washing/rinsingoftubingorother plasticdevices
prior to their sterilization.