Pyrogen and Particulate Matter Flashcards
When are compounded sterile preparations (CSPs) most hazardous to patients?
Contaminated CSPs are potentially most hazardous to patients when administered into body cavities, central nervous and vascular systems, eyes, and joints, and when used as
baths for live organs and tissues.
What are parenteral preparations? How are they administrated?
Sterile preparations intended for administration by injection, infusion or implantation into the human or animal body
What does the word pyrogen mean and what happens when a pyrogenic reaction occurs?
Pyro = pyrexia
Gen = agent
Substance/chemical that increases body temperature (induced fever). It is NOT an ORGANISM.
What are the 4 properties that pyrogens share?
- Water soluble
- Macromolecules
- Thermostable (meaning that it needs a high temperature to be inactivated)
- Non-volatile in steam (when steam is produced, it will be free of pyrogen) –> property exploited in the preparation of both forms of Water for Injections B.P.)
What is the main pyrogen produced by microbes? What properties does this pyrogen have for it to be the most common cause of toxic reactions?
Bacterial endotoxin (gram-negative)
> These endotoxins are lipopolysaccharides (LPS). LPS forms part of the cell wall in gram-negative bacteria
- Lipo = Hydrophobic properties which make it stick to the wall of a container
- Polysaccharide = Water soluble
What does the absence of bacterial endotoxins in a product mean?
Absence of pyrogenic components
What are the differences between exotoxins and endotoxins? Explain how they leave their structues.
- Exotoxins: Produce inside mostly gram-positive bacteria. Release following lysis into surrounding medium
- Endotoxins: Part of the outer portion of the cell wall (LPS) of gram-negative bacteria. Released when bacteria die and the cell wall breaks apart.
What response does the pyrogen (pyrogenic response) induce in a human/animal?
(clue: 4 steps)
- Macrophage ingests gram-negative bacterium
- Bacterium is broken down, releasing endotoxins that induce the macrophage to produce interleukin-1 (IL-1)
- IL-1 is released by the macrophage into the bloodstream, it then travels to the hypothalamus of the brain
- IL-1 induces the hypothalamus to produce prostaglandins which reset the body’s temperature to a higher temperature. PRODUCES FEVER
Give 4 examples of sources of pyrogens and explain how they may cause pyrogenic activity.
- Aqueous system that is allowed to stand
- Distilled water contaminated with airborne bacteria/ entrainment by a poor distillation procedure
- Apparatus and containers
- Medicaments such as glucose, sodium citrate, and sodium chloride
Why must any type of container be fitted with baffles (covers)?
To prevent the entrainment of droplets from the boiling water into the distillate
Provide THREE methods for the prevention of pyrogens. Explain why they work
Safeguards against the contamination of the distillate by airborne bacteria must be exercised
- Distilled water must be covered during its collection, and must be used as soon as possible after distillation to prevent multiplication of bacteria
Solutions should be filtered, packed, sealed and sterilized as rapidly as possible
- Will reduce the possibility of bacterial multiplication and as a result, lessen the chances for the development of pyrogens
Choice of parenteral medications and preparation of apparatus (compounding and packaging) –> properly designed and operated still, fitted with baffles
- Prevent entrainment of droplets from boiling water into the distillate
Provide two methods for the removal of pyrogens
It is better to prevent the formation of pyrogens than to attempt their removal.
- Dry heat at 230ºC or higher for a period of time. (thermostable apparatus and medicaments)
- Adsorption on activated asbestos or charcoal (may adsorb active ingredients) or by ultrafiltration. (Thermolabile medicaments –> destroyed by heat)
Which products are tested for pyrogens?
- Injectable drugs and medical devices which will have contact with blood or spinal fluid
- Includes raw materials, water and in process monitoring
How is testing for pyrogens done?
Clue: 3 methods
- Rabbit pyrogen test
- Monocyte-activation test (MAT) –> a replacement for the rabbit pyrogen test
- LAL test
What is the process for the rabbit pyrogen test?
- Substance being tested is injected in rabbits ear
- Measure the rabbit rectal temperature, the temperature depends on how many rabbits are being tested (see attached image)
Main test: volume, route and time (initial temperature, max temperature response; summed response)
