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Pharmacology


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Pharmacology is the study of drugs in living systems. It encompasses the understanding of all medication effects, whether diagnostic, therapeutic, or adverse. Drugs have led to the control or cure of many medical disorders. However, drugs have also been responsible for many unwanted illnesses and deaths over the years. All students of pharmacology must remember that medications can be very helpful but can also cause serious harm to patients. No one should prescribe or administer medication without knowledge and comprehension of pharmacologic data. As a medical professional, you should learn all that you can about the potential poisons that will be placed into your patient. This book is designed to teach important principles surrounding the pharmacologic agents used frequently in the radiologic sciences


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Every medication has a generic name. A brand name is given to the drug by the particular manufacturer. Each manufacturer uses a different brand name for its version of the generic drug. In essence, the brand name is used as a marketing tool. The original generic drug is developed by one company. The developing company then acquires a patent for exclusive rights to manufacture and sell the generic drug as its brand drug for a specified number of years. After the patent expires, other companies may produce the same generic drug under different brand names.


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There are more than 1000 chemicals in a cup of coffee. Of these, only 26 have been tested, and half caused cancer in rats.


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LEGEND DRUGS

Medications that require a prescription are called legend drugs. These all have a written legend (or caption) on the package stating, “CAUTION: Federal Law prohibits dispensing without a prescription.” Radiopaque contrast agents and other medications administered in the radiology department fall into the category of legend drugs. The imaging technologist must therefore know what constitutes a legal prescription before dispensing or administering drugs or diagnostic agents ordered.


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THE LEGAL PRESCRIPTION

A valid prescription or order for a drug includes at least the following seven components:

1.Patient name, room number or address, and identification numbers

2.Drug name (generic or brand)

3.Dosage (in proper units of measure for particular drug)

4.Dosage form (e.g., tablet, injection, solution)

5.Route of administration (e.g., oral, parenteral, rectal)

6.Date order is written

7.Prescriber's signature


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INTRODUCTION

For a drug to produce pharmacologic effects in the body, it must first reach the site of action. The process required for a drug to reach the site of action is best described using biopharmaceutic and pharmacokinetic principles.

BIOPHARMACEUTICS

Biopharmaceutics is the area of pharmacology that focuses on the method for achieving effective drug administration. Drugs are placed into vehicles by the manufacturing process. A drug vehicle is a substance into which a drug is compounded for initial delivery into the body. A dosage form—solid, liquid, gas, or any combination of these—is the combination of both the drug and the vehicle used to deliver the drug. A dosage form must be capable of releasing its contents so that the drug can be delivered to the site of action.


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The bathroom medicine cabinet is one of the worst places to keep medicines. The heat and moisture of the bathroom are just the conditions required to alter the chemistry of medications, making them weaker, possibly ineffective, and in some cases, toxic. A cool, dry area away from sunlight and children is optimal.


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Solid dosage forms used for oral administration include:

  • Tablets

  • Capsules

  • Troches

  • Suppositories


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A tablet generally consists of an active ingredient (drug), various fillers and disintegrators, dyes, flavoring agents, and an outside coating. Fillers help the powdered mass to maintain form when compressed in the manufacturing process. Disintegrators aid in chemical disintegration when subjected to fluids or temperature changes. The disintegration process is required for the solid to become a solution before absorption across a biologic membrane. If something is not done to make it dissolve, the solid will come out in the same lump as initially used. Dyes and flavoring agents help make the dosage form palatable. The coating may help with palatability and aid in the drug-releasing process.


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Various types of tablets are produced to aid in the delivery of medication, as follows:

  • Compressedtablets are compacted with no special coating; they are subject to chemical degradation from the environment.

  • Sugar-coated tablets have a thin layer of sugar coating designed to mask bad taste and to protect the active ingredients from chemical oxidation.

  • Film-coatedtablets have a thin coating of material other than sugar. This type of coating serves the same function as a sugar coating but is less expensive to manufacture.

  • Enteric-coated tablets are designed to pass through the gastric area and release the active ingredients into the small intestine. This technology is used to prevent the strongly acidic contents of the stomach from chemically destroying the activity of a drug. Enteric coating is also used to prevent gastric upset by a drug known to cause significant local irritation in the stomach.

  • Multiple-compressedtablets and controlled-release tablets are both designed to mask taste, protect contents against chemical oxidation, and allow for periodic release of contents in a controlled manner throughout the gastrointestinal (GI) transit. Many drugs used for maintenance therapy, such as cardiovascular, pulmonary, antiepileptic, and antirheumatic medications, are formulated this way to allow for once-daily or twice-daily dosing to improve patient compliance.


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•Effervescent tablets contain sodium bicarbonate and an organic acid such as citrate or tartrate. These tablets liberate carbon dioxide and disintegrate into an effervescent solution in the presence of water.

•Buccal or sublingual tablets, such as nitroglycerin, are designed to disintegrate in the buccal or sublingual space and become absorbed through the buccal or sublingual vasculature


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Capsules generally consist of either a hard or a soft gelatin shell that encloses the active ingredient. A hard gelatin capsule is a two-piece shell made from calcium alginate, methylcellulose, and gelatin. A soft gelatin capsule is a one-piece shell made from similar material. Capsules are designed to mask taste, allow for ease of swallowing, and contribute to a controlled-release mechanism. The capsule must dissolve so that the active ingredient may be released.

Troches are generally in the form of or pastilles. These are solids that contain medicine in a hard sugar or glycerinated gelatin base designed to dissolve slowly in the mouth. Topical oral antifungals and anesthetics are most often placed in this dosage form so that continued contact will be made between the medication and the oral mucosa.

Compressed suppositories or inserts are solid dosage forms generally designed for vaginal or rectal delivery. On contact with the mucosa and in the presence of body temperature, these dosage forms melt away to release the medicinal agent.


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Liquid dosage forms :

  • Solutions

  • Emulsions

  • Suspensions


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Parenteral dosage forms are given by injection under or through one or more layers of skin or mucous membrane. This route includes following administrations

  • Subcutaneous

  • Intradermal

  • Intrathecal

  • Intramuscular

  • Intravenous

  • Intraarterial


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Intrathecal Injection


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Intravenous injection


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There are several complications that can occur from intravenous administration:

  • Thrombosis formation can results from many factors: extremes in solution pH, particulate material, irritant properties of the drug, needle or catheter trauma, and selection of too small a vein for the volume of solution injected

  • Phlebitis, or inflammation of the vein, can be caused by the same factors that cause thrombosis.

  • Air emboli occur when air is introduced into the vein. The human body is not harmed by small amounts of air, but a good practice is to purge all air bubbles from the formulation and administration sets before use.

  • Particulate material is generally small pieces of glass that chip from the formulation vial or rubber that comes from the rubber closure on injection vials. Although great care is taken to elimination the presence of particulate material, a final filter in the administration line just before entering the venous system is a typical precaution.


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Gas dosage forms are typically used for oxygen therapy, anesthesia, and aerosol inhalers. Oxygen is in gaseous form at room temperature and requires no dispersing agent. Most anesthetics are also gaseous at room temperature. The inhalers usually contain a liquified medication dispersed in a gas propellant, such as a fluorinated hydrocarbon; on inhaler actuation, the fluorinated hydrocarbon gas disperses the liquified medication to the bronchial system.

Abraham Lincoln's mother died when the family dairy cow ate poisonous mushrooms and Mrs. Lincoln drank the milk.


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Disintegration and Dissolution

Medication is absorbed in either liquid or gaseous solution. Therefore, any solid or semisolid drug must first enter into one of these solution forms before becoming absorbed across a cellular membrane. A medication in solid form will generally require more time to enter the body than the same medication in liquid form. Disintegration and dissolution are generally considered to constitute the beginning of the pharmacokinetic process.


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Immediately on medication administration, a drug begins to undergo the pharmacokinetic process. Pharmacokinetics consists of the process of how a drug is absorbed, distributed, metabolized, and eliminated throughout the body. These parameters determine the onset, duration, and extent of drug action.


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Absorption

Prior to systemic action, a drug must either undergo the absorption process or be administered by direct intravenous injection, thus bypassing the need for absorption. Numerous anatomic sites, including GI tract, lungs, mucous membranes, eyes, skin, muscle, and subcutaneous tissues, can be used for systemic drug absorption.


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For absorption to occur, the physiochemical properties of the drug and the vehicle must be compatible with the site for administration. Rate and extent of drug absorption depend on dissolution properties of the dosage form (previously discussed), surface area at the site, blood flow to the site, concentration of drug at the site, acid-base properties surrounding the absorbing surface, lipophilicity (attraction to fat) of the drug, and compatibility with other chemicals or drugs.

Surface area.


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A large surface area allows for better absorption than does a smaller area. Pulmonary alveoli and GI rugae give rise to some of the largest surface areas for absorption in the human body. One could compare this concept to the distance between two points. As the eagle flies, it may be 5 miles from point A to point B. If you are driving in the mountains from point A to point B, however, you may zigzag back and forth on many curves and actually drive 25 miles. Similarly, with lungs and intestines, all the “ins” and “outs” add surface area.

Some analgesic formulas, such as Alka-Seltzer and Bromo-Seltzer, are liquid (disintegrated) when they enter the body. This does shorten the time between administration and onset of action (pain relief).


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Blood flow.

A large amount of blood supplies these sites. Blood must be flowing to the absorbing surface during the absorptive process to allow entry into the systemic circulation. Altered blood flow, such as occurs in cardiovascular shock, may change the drug absorption profile. Consequently, a patient who is in shock generally requires medication delivered through the intravenous route.


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Distribution

Once a drug is absorbed into the bloodstream, it is immediately distributed throughout the body by the circulation of the blood. Distribution is defined as the transport of a drug in body fluids from the bloodstream to various tissues of the body and ultimately to its site of action.

Several factors affect distribution, as follows:

1.Cardiac output: amount of blood pumped by the heart per minute.

2.Regional blood flow: amount of blood supplied to a specific organ or tissue.

3.Drug reservoirs: drug accumulations that are bound to specific sites, such as plasma, fat tissue, and bone tissue


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Excretion

Drug molecules, whether they are intact or metabolized, eventually must be removed from the body. This elimination is primarily accomplished by the kidneys. They filter the blood and remove unbound, water-soluble compounds. This is one reason why drug testing is often done on urine.

The intestines may also eliminate drug compounds. After metabolism by the liver, a metabolite may be secreted into the bile, passed into the duodenum, and eliminated in the feces.

The third mechanism of excretion is the respiratory system. Gases or volatile liquids that are administered through the respiratory system usually are eliminated by the same route.

Breast milk, sweat, and saliva also contain certain drug compounds but are not the body's predominant mechanisms for elimination


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CARDIAC MEDICATIONS

Antiarrhythmic (or antidysrhythmic) medications are those drugs that affect the electrical conduction system of the myocardium. The actions of these medications differ among the individual drugs.

The ultimate goal for this class of medications is to suppress excess electrical conduction within the cardiac system and thus decrease arrhythmia (dysrhythmia) production

Antihypertensive medications assist in lowering the blood pressure to safe, long-term goals. These drugs also affect heart failure in a positive way by decreasing the pressure against which the heart must pump. This allows the failing heart to pump more efficiently without “tiring out.” Many studies are now confirming the positive long-term effects that some antihypertensives have on the duration of life.

The first known heart medicine was discovered in an English garden. In 1799, physician John Ferriar noted the effect of dried leaves of the common foxglove plant, Digitalis purpurea, on heart action. Still used in heart medications, digitalis slows the pulse and increases the force of heart contractions and the amount of blood pumped per heartbeat.


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Diuretics are frequently referred to a “water pills.” These medications are designed to eliminate excess fluid and sodium from the bloodstream, thus decreasing the overall pressure within the vessels. Overuse or improper use can lead to dehydration and kidney failure. Some of the more common diuretics include: furosemide.


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Pharmacodynamic effects can be therapeutic, diagnostic, or adverse. Diagnostic effects of intravascular radiopaque contrast media (ROCM) are a function of the iodine contained within them. Adverse effects elicited by ROCM depend at least partially on their serum or tissue iodine concentration and osmolality and immune system–stimulating abilities.


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Serum iodine concentration must be within the range of 280 to 370 mg/ml for a normal x-ray film to reflect the vascular lumen. To achieve this high iodine concentration, the ROCM must contain a large proportion of iodine (see Chapter 6 for iodine concentrations) and must be injected intravascularly at a rate equal to or greater than blood flow. If the contrast medium is injected slowly, the cardiovascular system will significantly dilute the iodine concentration before imaging. Rapid intravascular injection thus helps to limit the early dilutional effects on the iodine by the cardiovascular system. High concentrations of iodine pharmacodynamically prevent the penetration of photons so that a shadow is projected onto the radiographic film.

For computed tomography (CT) or digital subtraction angiography (DSA), the serum iodine concentration needs only to be between 2 and 8 mg/ml. Thus, either a less concentrated iodine contrast medium or a slower intravascular infusion will produce adequate pharmacodynamic action for these imaging procedures.


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ANTICOAGULANT, ANTIPLATELET, AND THROMBOLYTIC MEDICATIONS

Patients receiving any of the anticoagulant, antiplatelet, or thrombolytic medications are at risk for bleeding. In some cases, such as with the thrombolytics, severe bleeding can to lead to hemorrhagic stroke. Therefore, the imaging technologist should know about the signs and symptoms of an evolving stroke so that it can be reported quickly if patients are taking one of these medications


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Anticoagulant medication is frequently used in patients who have either a history of blood clot formation or the potential to develop blood clots. Warfarin is an oral medication used to prevent the absorption of vitamin K from the intestinal tract, thus preventing the formation of the blood-clotting factors responsible for the propagation of a blood clot. Heparinis an examples of medication that affect the activity of thrombin in various ways to inhibit clot formation.

Antiplatelet medication is generally used in patients who have experienced an acute ischemic event to either their heart or their brain in the past. Since platelets are one of the initial instigators of blood clot formation, cardiologists and neurologists will prescribe antiplatelet drugs to prevent that portion of the coagulation cascade. Aspirin is one of the most common oral medications for inhibiting platelet effects.

Thrombolytic medication is used to actively break up a newly formed clot, such as found in patients with acute myocardial infarction, acute stroke secondary to blood clot, or lower leg ischemia. Alteplase, retaplase, streptokinase, tenecteplase, and urokinase are the most frequently used medications in this class. If a patient has recently been given an agent in this class, the patient is at very high risk for bleeding internally and externally. Use caution with all intravenous (IV) sites. Do not start an IV line in these patients without physician orders and close supervision.


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ANALGESIC MEDICATIONS

Analgesic medications are prescribed more frequently than any other medication on the market. The drugs are used to treat both acute and chronic pain syndromes, such as arthritis, headache, muscle sprains, cancer pain, surgical and traumatic pain, nerve pain, and in some cases, anxiety.

Narcotic medications stimulate central nervous system receptors known as opioid receptors and cause a decrease in the perception of pain. These are very potent analgesics and are associated with the potential for physical and psychological addiction. The narcotic class of analgesic is generally highly controlled by the local and federal enforcement agencies to prevent misappropriation into the community. The narcotics are also dangerous in that respiratory depression can rapidly occur to the point of respiratory arrest if the dose is too great. The technologist should keep this concept in mind if patients are being treated with narcotic medications. If respiratory arrest occurs, naloxone is the drug of choice (given intravenously, intramuscularly, or endotracheally) to reverse immediately the respiratory depressant effects of narcotic agents. Examples of common narcotic medications include morphine


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Aspirin went on sale as the first pharmaceutical drug in 1899, after Felix Hoffman, a German chemist at the drug company Bayer, successfully modified salicylic acid, a compound found in willow bark, to produce aspirin.

Acetaminophen is probably the most common analgesic in use today. It is contained in almost all pain medication combinations and is in a subclass by itself. It is not fully known just how acetaminophen elicits its effects, but some believe that it acts by inhibiting prostaglandins in the central nervous system that are responsible for pain production. Acetaminophen is a low-potency pain reliever and must not exceed 4000 mg per day because it is associated with severe liver damage at high doses. Long-term use of high doses can also cause renal and cardiac damage.


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ANTIHISTAMINE MEDICATIONS

Antihistamines are medications used to block histamine from producing adverse effects such as itching, inflammation, respiratory distress, and overall allergic reactions. Common antihistamines include hydroxyzine (Vistaril, Atarax) and diphenhydramine (Benadryl).


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ENDOCRINE MEDICATIONS

Diabetes and hypothyroidism are two common endocrine problems for which patients frequently receive drug treatment.

Antidiabetic medication is required for patients who have difficulty maintaining proper balance between blood sugar and tissue sugar. Some patients are termed insulin dependent (diabetes mellitus type 1) because they have little or no circulating endogenous insulin. Diabetic patients who have sufficient circulating endogenous insulin but poor receptor sensitivity to the insulin are termed non–insulin dependent (diabetes mellitus type 2).

Technologists need to always be aware of patients receiving metformin because this drug should be held before and for at least 48 hours after receiving a radiopaque contrast agent. If metformin is not held, the patient is put at increased risk for severe metabolic acidosis secondary to metformin metabolite accumulation, in the event renal dysfunction is caused by the radiopaque contrast agent.


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ANTIINFECTIVE AGENTS

Antibiotics are therapeutic agents used to kill or suppress pathologic microorganisms responsible for causing infectious diseases. Antifungals are agents used to kill mycotic (fungal) organisms, and antivirals are used to suppress and limit the spread or shedding of viruses that invade the human body. Generally, these three medication subclasses act at the cellular level to destroy, inhibit, or suppress the cell wall, enzymatic activity, or ribosomal or deoxyribonucleic acid (DNA) function of an invading microorganism.


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CHEMOTHERAPY AGENTS

Chemotherapy drugs are extremely toxic compounds designed to kill off rapidly growing (e.g., cancerous) cells of the human body by altering or destroying the various stages in cellular division. These agents are toxic to all cells that are in a growth stage, not only cancerous cells. Special precautions should be taken with all chemotherapy patients so that no medication touches the unexposed skin of a health care worker. Coming into physical contact with these medications can put the health care worker at risk of serious side effects, including the stimulation of a cancerous condition. Even coming into contact with bodily fluids into which the chemotherapy is secreted, such as urine, can pose a potential threat to the clinician. Universal precautions and special gloves and gowns should be worn when dealing with chemotherapy.

The rosy periwinkle plant, found in Madagascar, is used to cure leukemia


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RADIOPAQUE CONTRAST MEDIA

Radiopaque contrast media (ROCM) are high-density pharmacologic agents used to visualize low-contrast tissues in the body, such as the vasculature, kidneys, gastrointestinal (GI) tract, and biliary tree.

The most frequently prescribed ROCM are iodine and barium. The atomic number of iodine is 53, and the atomic number of barium is 56. Each has a much higher atomic number and mass density than the low-contrast tissues listed above. When an iodinated compound fills a blood vessel or when barium fills a portion of the GI tract, these internal organs become visible on a radiograph. Low-kilovoltage techniques (below 80 kilovoltage peak [kVp]) are usually selected to produce high-contrast radiographs of the blood vessels or genitourinary tract. Higher-kilovoltage operation (above 90 kVp) is used in GI examinations not only to reveal the presence of the organ, but also to penetrate the contrast media to see the walls and inner structures.


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ADVERSE PHARMACODYNAMICS

Serious adverse effects from ROCM do occur. An estimated one of every 20,000 to 40,000 patients receiving ROCM dies as a result of these effects. Although the odds of death appear low, they become very real if it happens to you or your patient. Thus, it is paramount that the technologist understand adverse effects so that proper actions can be instituted as rapidly as possible.


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ROCM are available in parenteral and enteral, ionic and nonionic, and high-osmolality and low-osmolality forms.

Iodine molecules contained within ROCM are effective photon absorbers in the human body. The iodine molecules essentially do not allow as many photons to pass through for projection onto the radiographic film. Thus, iodine molecules are responsible for the silhouette images projected. Radiopacity elicited by ROCM is a direct function of the percentage of iodine (except in the case of barium sulfate) in the molecule and the concentration of media present. In the case of barium sulfate, barium acts as iodine.


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INTRAVASCULAR RADIOPAQUE CONTRAST MEDIA

Intravascular (i.e., intravenous or intraarterial) ROCM are used to add density to vascular structures. Increased density of the media alters the attenuation of x-rays passing through the area, thus enhancing the anatomic image on the radiographic film.

Categories

Three broad categories of intravascular ROCM exist: high-osmolality ionic, low-osmolality nonionic, and low-osmolality ionic ROCM. Generally, ionic ROCM exist in salt forms consisting of sodium and meglumine whereas nonionic ROCM are supplied as nonsalt forms.

High-osmolality ionic ROCM,contain three iodine atoms per molecule and dissociate into two osmotically active particles when injected into the bloodstream. These particles consist of one radiopaque anion (negatively charged particle) and one cation (positively charged particle) for every three iodine atoms in solution.

The newer low-osmolality nonionic ROCM, contain three iodine atoms per molecule and do not dissociate in solution


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The newer low-osmolality ionic ROCM, consist of six iodine atoms per molecule and dissociate into two osmotically active particles. These are also considered to be ratio-3.0 media because there are six iodine atoms and two dissociated particles per molecule for a ratio of 6:2, which equals 3:1


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Excretion

Intravascular ROCM are excreted primarily via the kidneys; they are concentrated in the kidneys and subsequently opacify the entire renal system. Generally, renal parenchyma is opacified first, followed by the tubular structures, renal calyces, and pelvis, and ending with the ureter and bladder. In normal renal function, up to 100% of an intravascular dose is excreted in 24 hours. A very small percentage may be excreted into the intestines through the hepatic-biliary system. Several days may be required for complete excretion in patients with renal impairment. Consequently, these patients have much lower to no opacification in the kidneys because up to 50% of the ROCM may be eliminated via the hepatic-biliary system, thus opacifying the biliary and GI tracts.


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ENTERAL RADIOPAQUE CONTRAST MEDIA

Enteral ROCM are used to diagnose and evaluate disorders of the GI system. These agents may also be used to help define the cardiac shadow. Enteral ROCM can be broken down into the categories of aqueous solutions, suspensions, and tablets.


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Solutions

Diatrizoate meglumine and diatrizoate sodium solutions are used for oral or rectal administration to aid in the diagnosis of GI tract disorders. Generally, these solutions are used when barium sulfate suspension is potentially harmful, such as in GI perforation. The high osmolality of these agents causes significant osmotic action within the GI tract. This leads to significant dilution of the iodine as well as a profuse diarrhea, systemic hypovolemia, dehydration, and electrolyte imbalance. Iodine dilution leads to less definitive diagnostic studies; this, along with the adverse effect profile of iodine, is why barium sulfate is often the preferred diagnostic GI agent. The diatrizoate compounds are preferred over barium sulfate for CT because of less artifact production.

Radiodensity (radiopacity) occurs immediately in the esophagus and stomach after oral administration but may take 15 to 90 minutes for the duodenum. Immediate radiodensity occurs in the rectum and colon following rectal administration.

Gastrointestinal ROCM are not absorbed through the GI wall and are thus distributed solely into the GI lumen. These agents are excreted by the GI tract into the feces.


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Suspensions

Barium sulfate is an ROCM suspension used for oral or rectal administration to aid in the diagnosis of GI tract disorders. Barium is radiodense in the same manner as iodine. Radiodensity occurs immediately in the esophagus and stomach after oral administration but may take 15 to 90 minutes for the duodenum. Immediate radiodensity occurs in the rectum and colon following rectal administration.

Barium sulfate is generally the preferred GI ROCM because it provides a more thorough visualization of structures, especially the mucosa, without extensive local adverse effects. Barium sulfate may produce significant artifact in CT evaluation of the GI tract and thus is not the preferred agent for this radiologic examination.

Barium sulfate is not absorbed through the GI wall and thus is distributed solely into the GI lumen. It is excreted by the GI tract into the feces.


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Tablets

Iocetamic acid (Cholebrine) is an oral ROCM used for opacifying the gallbladder. Absorption varies from person to person, but the gallbladder can generally be visualized approximately 10 to 15 hours after oral administration

Most of the iocetamic acid is excreted into the urine 48 hours after administration. Some is excreted via the biliary system into the feces.


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