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N, P Reaction
Nuclear reaction in which a neutron enters the nucleus and a proton is emitted.
Contrast Agents
(CA) Contrast agents are used to change the imaging characteristics, resulting in additional information about anatomy, morphology or physiology of the human body. Radiocontrast agents (also called photon-based imaging agents) are used to improve the visibility of internal body structures in x-ray and CT procedures. Contrast agents are also used to increase the contrast between different tissues in MRI (magnetic resonance imaging) and ultrasound imaging. The ideal imaging agent provides enhanced contrast with little biological interaction.
First investigations with radiopaque materials are done shortly after the discovery of x-rays. These positive contrast agents attenuate x-rays more than body soft tissues due to their high atomic weight. Iodine and barium have been identified as suitable materials with high radiodensity and are used until today in x-ray and CT contrast agents. Iodine-based contrast agents are water-soluble and the solutions are used nearly anywhere in the body. Iodinated contrast materials are most administered intravenous, but can also be introduced intraarterial, intrathecal, oral, rectal, intravesical, or installed in body cavities. Barium sulfate is only used for opacification of the gastrointestinal tract. Negative contrast agents attenuate x-rays less than body soft tissues, for example gas.

Iodinated contrast media are differentiated in;

Intravascular iodinated contrast agents are required for a large number of x-ray and CT studies to enhance vessels and organs dependent on the blood supply. Injectable contrast agents are diluted in the bloodstream and rapidly distributed throughout the extracellular fluid. The main route of excretion is through the kidneys, related to the poor binding of the agent to serum albumin. The liver (gall bladder) and small intestine provide alternate routes of elimination particularly in patients with severe renal impairment. The use of special biliary contrast agents is suitable for gallbladder CT and cholecystograms because they are concentrated by the liver to be detectable in the hepatic bile.
The introduction of fast multi-detector row CT technology, has led to the development of optimized contrast injection techniques. The amount of contrast enhancement depends on the contrast agent characteristics, such as iodine concentration, osmolality, viscosity, and the injection protocol, such as iodine flux and iodine dose. Adverse reactions are rare and have decreased with the introduction of nonionic contrast agents.
See also Contrast Enhanced Computed Tomography, Abdomen CT, Contrast Media Injector, Single-Head CT Power Injector, Multi-Head Contrast Media Injector, Syringeless CT Power Injector, CT Power Injector.
Adverse Reaction
Adverse reactions on contrast agents are rare, but like all other pharmaceuticals, contrast media are not completely without side effects.
Adverse effects to contrast media include allergic symptoms, anaphylactoid reactions, chemotoxic reactions, idiosyncratic reactions, contrast-induced nephropathy, iodide-induced hyperthyroidism and local tissue damage. An adverse reaction can be related to dose, the toxicity, and the physio-chemical properties of the contrast agent, for example osmolality, viscosity, and hydrophilicity.
Side effects such as a metallic taste in the mouth, generalized warmth or flushing, nausea and vomiting, increase with rapid flow and large volume of the injected agent. Although venous tolerance is usually good, there have been reports of sensation like burning, stinging or numbness and of venospasm.

Characterization of adverse reactions include:
Allergic drug reactions never occurs on the first exposure, but it can occur even with small amounts.
Chemotoxic reactions result from the properties and characteristics of the used drug, the dose, speed of injection, etc. Hemodynamic disturbances and injuries to organs or vessels perfused by the contrast agent are included.
Idiosyncratic reactions can occur on first exposure to the contrast medium. And unlike a side effect, the reaction occurs only in susceptible individuals, probably due to a genetic or metabolic abnormality.
Accelerator
An accelerator uses electrostatic or electromagnetic fields to increase the kinetic energy of charged particles (see alpha particle, beta particle) in order to produce ionization or a nuclear reaction in a target.
Accelerators (see cyclotron, linear accelerator) are used for the production of radionuclides (see Fluorine-18, Molybdenum, Technetium-99m) or directly for radiation therapy. Accelerator-produced radioactive material (ARM) is any radioactive substance that is produced by a particle accelerator. The accelerators used for radiation therapy generate gamma rays (also called Bremsstrahlung) with continuous energy by collision of high energy electrons on materials with high density (also referred as 'high z' - chemical elements with a high atomic number (Z)).
Electron accelerators with energies above 10 MeV can also produce neutrons induced by photons in the accelerator head material (mainly caused by photo nuclear reaction).
Drug Development and Approval Process (USA)
Different stages of the drug development and approval process in the USA, lead from preclinical trials (testing in animals), first application in humans through limited and broad clinical tests, to postmarketing studies.

Years Test Population Purpose Success Rate
Preclinical Testing 3.5 Laboratory and animal studies Assess safety and biological activity 5,000 compounds evaluated
File IND at FDA
Phase I 1 20 to 80 healthy volunteers Determine safety and dosage 5 enter trials
Phase II 2 100 to 300 patient volunteers Evaluate effectiveness, look for side effects
Phase III 3 1000 to 3000 patient volunteers Verify effectiveness, monitor adverse reactions from long-term use
File NDA at FDA
FDA 2.5 Review process / Approval 1 approved
12 Total
Phase IV Additional Post marketing testing required by FDA

By Dale E. Wierenga, Ph.D. and C. Robert Eaton
Office of Research and Development
Pharmaceutical Manufacturers Association

'In reviewing this report, it is important to keep in mind the realities of the drug discovery and development process. The U.S. system of new drug approvals is perhaps the most rigorous in the world. On average, it costs a company $359 million to get one new medicine from the laboratory to the pharmacist's shelf, according to a February 1993 report by the Congressional Office of Technology Assessment.'

See also Phase 1 2 3 4 Drug Trials, Clinical Trial, Food and Drug Administration, and European Medicines Agency.
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