Mark Corson

By T. Fedor. Montana State University College of Technology, Great Falls. 2018.

The deleterious effects of food on drug absorption have prompted the use of dietary strategies in order to improve oral bioavailability buy cozaar 50 mg low price. For example cheap cozaar 25 mg on line, the drug L-dopa purchase cozaar 50 mg mastercard, used in the treatment of Parkinson’s disease, is absorbed via a stereospecific, saturable active transport mechanism shared by large neutral amino acids such as phenylalanine and tyrosine. The breakdown products of dietary proteins can compete with L-dopa for this active transport mechanism, thereby reducing its oral bioavailability. Taking L-dopa at least 30 min before eating and controlling dietary protein has been shown to improve L-dopa treatment in Parkinson’s disease. A further example is the avoidance of milk 2 h prior to taking preparations containing tetracyclines, as these drugs chelate calcium ions in milk, forming a poorly absorbable complex. Interestingly, the presence of food may favor drug absorption in other situations. The positive effect of food on the absorption of this drug was also observed with Eudragit S100 nanoparticles. The administration of a 150 mg diclofenac hydrogel-based capsule dose within 30 min following a standardized breakfast was shown to minimally affect the bioavailability of dicolfenac relative to administration under fasted conditions. The insoluble fraction forms 141 a semi-impermeant layer, which, in conjunction with bicarbonates (secreted by gastric cells at the surface and in gastric pits), protects underlying cells from damage by gastric acid. Studies have shown that gastrointestinal mucus presents a physical barrier to the diffusion of small molecules such as urea, benzoic acid, antipyrine, l-phenylalanine and warfarin as well as to large protein molecules. Similarly, the passive absorption of testosterone was shown to be doubled upon ridding the intestinal epithelial cells of the overlying mucus layer. However, the situation regarding the effect of mucus on oral bioavailability is a complex one; for example, it has been shown that drug binding to the mucosal surface is essential to the absorption of barbituric acid derivatives from the rat small intestine. Gender Gastric acid secretion is greater in men than in women, whereas gastric emptying time is slower in women. Enzyme expression is also different between men and women; for example, sex-related cytochrome P-450 isozymes and glucuronidation enzymes are more abundant in men. However, in general, gender differences are small and insufficient to warrant a modification in dosage regiments. Pregnancy results in reduced gastric acid secretion, increased intestinal motility, increased plasma volume, decreased plasma drug binding and also an additional pharmacokinetic compartment. These altered pharmacokinetic factors may require modifications in the dosage regimen for certain drugs. Race Racial differences in oral drug bioavailability are known to exist and may be due to environmental, dietary or genetic differences. These differences are becoming increasingly important in therapeutics, due to both the increasingly international nature of drug development and use, and also the multi-racial nature of the population of many countries. The hydroxylation defect for debrisoquine also applies to the oxidative metabolim of codeine, metoprolol, and perphenazine. The clinical conse-qunces of polymorphic oxidation have not been examined in great detail. Obviously, the small percentage of the population who are poor metabolizers may be at considerable risk of adverse effects from the usual doses of many drugs. Age Few pharmacokinetic studies are carried out beyond the range of 28–40 years and, consequently, there are few data on oral bioavailability for extremes of age. Gastric fluid is less acidic in newborns than in adults, which can affect the absorption of ionizable and acid-labile drugs. Decreased enzymatic activity, including hepatic first-pass metabolism, is associated with the elderly, which may result in an increased oral bioavailabiliy for drugs subject to the first- pass effect. The effect of the shunt is to increase the presistence of the drug in the body and, provided the concentrations of the drug at its sites of action are sufficiently high, to prolong its duration of action. It is important to remember that although a drug molecule may be predominantly absorbed via one particular route/mechanism, it is also likely that suboptimal transport will occur via alternative routes and mechanisms. Diffusion is driven by a concentration gradient and is inversely related to molecular weight. The junctional complexes begin immediately below the luminal surface and are made up of three components (Section 1. Thus only small hydrophilic molecules, such as, for example, mannitol, are capable of squeezing through the junctional complexes to be absorbed via the paracellular route. The rate of absorption is governed by Fick’s Law and is determined by the physicochemical properties of the drug as well as the concentration gradient across the cells (Section 1. Carrier-mediated transport Amino acid transporters, oligopeptide transporters, glucose transporters, lactic acid transporters, monocarboxylic acid transporters, phosphate transporters, bile acid transporters and other transporters present on the apical membrane of the epithelial cells serve as carriers to facilitate nutrient absorption by the intestine. Drug moieties possessing similar structures to nutrients that are absorbed by such carriers may also be absorbed in this manner. Endocytic processes Considerable evidence has accumulated indicating that macromolecules and microparticulates can be taken up by the intestinal enterocytes, generally via pinocytosis. For example, studies have shown that receptor-mediated endocytosis via enterocytes is a major pathway for the intemalization of certain antisense oligonucleotides. In contrast, endocytic uptake of macromolecules and microparticles is carried out extensively by the M cells of the 144 Peyer’s patches. Transcellular shuttling through the M cells to the underlying Peyer’s patch may involve an adsorptive and/or receptor-mediated process, with membrane-bound vacuoles or vacuoles already present in the apical cytoplasm of the cells (see below, Section 6. Therefore, they are ionized to a certain extent, determined by their pKa and the pH of the biological fluid in which they are dissolved; the extent of ionization can be quantified by the Henderson-Hasselbalch Equation (see Section 1. According to the pH-partition hypothesis, the nonionized form of a drug, with a more favorable oil/water partition coefficient (Ko/w) than the ionized form, is preferentially absorbed. For example, the absorption of salicylic acid, a weakly acidic drug, is approximately twice as high at pH 4 than at pH 7. By contrast, quinine, a weakly basic drug, is absorbed approximately four times higher at pH 7 than at pH 4 (Table 6. The numbers refer to 1, atenolol; 2, practolol; 3, pindolol; 4, metoprolol; 5, oxprenolol; and 6, alprenolol.

Feed the Fire Feeding the Fire is another technique that you can use when your mind is being self-critical buy 50 mg cozaar with mastercard, blaming and angry proven 50 mg cozaar. Poor Mika had forgotten her friend’s birthday and her mind was saying order cozaar 25 mg with visa, “You’re so thoughtless, stupid and horrible. She could intentionally worsen the content of her inner-commentary to make it more and more outlandish and ridiculous under the circumstances. There is a part inside of Mika that knows that these increasingly ridiculous thoughts are untrue. By intentionally worsening the content of your self-criticism, you will quickly see that it’s untrue and often unfounded. The idea is to exaggerate your critical thoughts so that you can see them as false and even silly, not to spiral down into greater depths of self-criticism and depression. As you become more confident in your ability to stand back and observe your thoughts from a place of stability and strength, then you may find this technique to be of value. Reframe The Situation Another valuable tool in your fight against stress is the technique of Reframing. Reframing is the process by which you look at a situation from another point of view (i. This technique goes well with the practice of mindfulness and it should be used whenever possible. In times of stress, you really do need all the help you can get, so use everything you’ve got in order to get through. Once you have seen how a story is created from the initial perception or sensation, the next step is to address the validity of your mind’s assessment. Take a moment, when you become aware of a stream of thought and a storyline, to think about whether the story that you’re telling yourself is true, helpful, or wise? However, this assumption, 142 • Mindfulness Medication that whatever you think is automatically true, is not valid or even helpful. As we’ve discussed before, your thoughts reflect your conditioned belief system and that is specific to you personally. Unfortunately, the reactive stories that your mind comes up with are often extreme and unbalanced and usually predict some sort of catastrophe. Catastrophizing is what people do when they make mountains out of molehills, predict the worst possible outcome of any situation and generally believe it all to be a foregone conclusion, i. Later, you will be able to go through the reframing process in your mind and may only need to resort to writing things down with particularly persistent thoughts. Think about a distressing situation and listen to the statements that you are telling yourself about it. Make three vertical columns on a sheet of paper and in the first column write down these statements as best you can. Just the exercise of bringing these thoughts into the light of day will help you to reframe the situation. When you can pause and examine what you are really saying to yourself, what follows may be a sense that these statements, comments and criticisms are most likely unfair and untrue. Going back to Mika and the time that she forgot her friend’s birthday as an example, when Mika’s friend mentioned that she had just celebrated her birthday, Mika went into hyper, self-critical mode: Other Techniques for Stress Management • 143 How could you have forgotten her birthday? In response to her thoughts and their emotionally draining storyline, Mika felt tremendously sad, guilty and frightened. After her conversation with her friend, Mika decided to use the technique of reframing to reduce her sense of stress in the situation. In the first column she entered the thoughts that she was having about the situation. These questions and statements really captured the essence of what was happening in the moment for her. Next Mika looked at each thought that she’d written down and asked herself, “Is this true? The worst-case scenarios seldom come to pass and when they do, they are often not as bad as you thought they would be. Are you really a thoughtless, inconsiderate and terrible person or did you just forget something? Another way to look at this is to ask yourself, “What would you say to a friend who was in a similar situation? She wrote this down in column three and began to feel her stress ease as she reframed the episode. Even if you are not in a position to write your thoughts down you can still begin the reframing process in your mind and continue with the writing exercise later. In this instance, Mika had bought a necklace and her mind started to say, “How could you have bought that necklace? Mika recognized that she was starting to get quite upset and in that moment she asked herself, “Is this true? I have bought other expensive things before, for myself and my family, without any problems. You too can practice reframing, both in a stressful moment as well as afterward when you have time to reflect and write things down. Reframing is a continuous process of examining whether your story about a situation is true or not and then trying to look at the situation from another perspective.

Daily loss of protein in urine normally does not interpretation of turbidimetric tests difficult discount 25 mg cozaar with amex. Which of the following is least likely to cause a occur in the absence of renal disease buy 50 mg cozaar fast delivery. Penicillin or sulfa antibiotics taking megadoses of ascorbic acid (vitamin C) may D order 25mg cozaar otc. Ascorbic acid show negative interference with tests for glucose, Body fluids/Apply knowledge to identify sources of blood, bilirubin, and nitrite. Ascorbate does not cause error/Urinary protein/2 either a false-negative or positive reaction for protein. Testing may detect early renal involvement in sensitivity (detection limit below 15 mg/dL), and is diabetes mellitus recommended for persons who are at risk for B. Microalbuminuria refers to a specific subfraction chronic renal disease, especially persons with of albumin found only in persons with diabetic diabetes mellitus. In diabetes, an early sign of renal nephropathy involvement is an increased rate of albumin excretion C. A positive test result indicates the presence of in the range of 20–200 μg/mL or in excess of orthostatic albuminuria 30 mg albumin per gram creatinine. Testing should be part of the routine urinalysis range are significant in the at-risk population even though the dry reagent strip test for protein may be Body fluids/Correlate clinical and laboratory negative. Consequently, dry reagent strip tests for data/Urinary protein/2 microalbuminuria are too sensitive for use in routine urinalysis, but are useful in screening persons with diabetes and hypertension for increased urinary albumin excretion. Dry reagent strip tests for microalbuminuria that Answers to Questions 35–39 compare albumin to creatinine determine the creatinine concentration based upon which 35. Formation of a Cu+2-creatinine complex tetramethylbenzidine, and diisopropyl benzene B. Reaction of creatinine with alkaline sodium oxidation of a benzidine derivative by an alcoholic picrate peroxide, forming a blue color on the test pad. Change in pH as creatinine is converted to intensity is proportional to creatinine concentration. Positive interference Body fluids/Apply principles of special laboratory occurs from hemoglobin and some drugs (e. Which of the following conditions is least likely concentration is determined by the protein error to be detected by dry reagent strip tests for of indicator effect using a dye with increased proteinuria? Renal tubular proteinuria orthostatic albuminuria and renal diseases, with Body fluids/Apply principles of basic laboratory the exception of tubular proteinuria. Renal tubular procedures/Urine protein/2 proteinuria results from failure of damaged tubules to 37. D The renal threshold is the concentration of a substance characteristics/Urine glucose/1 (e. In which of the following conditions is glycosuria require a carrier to transport them from the tubular most likely? C In addition to diabetes mellitus, glycosuria may occur Body fluids/Correlate clinical and laboratory data/ in other endocrine diseases, pregnancy, in response Urine glucose/2 to drugs that affect glucose tolerance or renal threshold, and several other conditions, especially 39. In addition to ascorbate, the glucose oxidase those involving the liver or central nervous system reaction may be inhibited by which substance? Hyperpituitarism causes Body fluids/Apply knowledge to identify sources of hyperglycemia mediated by increased release of error/Urine glucose/1 growth hormone. A positive glucose oxidase test and a negative test Answers to Questions 40–44 for reducing sugars indicates: A. False-positive reagent strip test a positive reaction is always considered significant C. Galactosuria should not be used to confirm a positive glucose oxidase test because it is not as specific or as Body fluids/Evaluate laboratory data to determine sensitive. Reducing sugar tests are used to screen possible inconsistent results/Urine glucose/2 infants for inborn errors of carbohydrate metabolism 41. A negative glucose oxidase test and a positive test such as galactosuria but are not used to screen for for reducing sugars in urine indicates: glycosuria. Te presence of a nonglucose reducing sugar including several sugars and antibiotics, may react, such as galactose making the test inappropriate as a screening test for D. A positive test for reducing sugars seen with Body fluids/Evaluate laboratory data to determine a negative glucose oxidase test may occur in lactose, possible inconsistent results/Urine glucose/2 galactose, and fructosuria and other disorders of 42. Excessive use of vitamin C low estimate of serum or urine ketones in diabetic Body fluids/Apply knowledge to identify sources of ketoacidosis. Ketonuria has many causes other than error/Urinary ketones/2 diabetic ketoacidosis such as pregnancy, fever, protein calorie malnutrition, and dietary carbohydrate 43. A Urinary ketones are detected using alkaline sodium Body fluids/Apply principles of basic laboratory nitroprusside (nitroferricyanide). Nondiabetic ketonuria can occur in all of the and some antibiotics with the classical tube test. Lactate acidosis carbohydrate restriction, alkalosis, lactate acidosis, and von Gierke disease (glycogen stores cannot Body fluids/Correlate clinical and laboratory data/ be utilized). Ketonuria also occurs in pregnancy, Urinary ketones/2 associated with increased vomiting and cyclic fever. Which of the following statements regarding the Answers to Questions 45–49 classical nitroprusside reaction for ketones is true? It may be falsely positive in phenylketonuria (phenylketonuria) will cause a false-positive D.

After Jeremy reflects on the list of Prosecutor Investigative Questions purchase 25mg cozaar fast delivery, his therapist advises him to take another look at his Thoughts on Trial Worksheet and try to add more evidence and logic to his case (see Worksheet 6-5) purchase cozaar 50mg with visa. Worksheet 6-5 Jeremy’s Revised Thought on Trial Worksheet Accused thought: I couldn’t stand to see the look of repulsion on her face generic 25 mg cozaar free shipping. Actually, there are a few people I know who haven’t been shocked or repulsed by my scars. I’ve seen the look of shock on people’s My family seems to have gotten faces before. If they can, it’s certainly possible that others could do the same — especially if they cared about me. I can remember my mother crying when Just because my mother cried she saw how badly I was burned. Chapter 6: Indicting and Rehabilitating Thoughts 81 Defending the Thought Prosecuting the Thought After one surgery, a physical therapist The physical therapist was right in made a comment that my burns were that I do have to live with this. But permanently deforming and I’d just have that doesn’t mean I can’t have a to learn to live with them. Sometimes when I go for a checkup, I My burns are noticeable; it doesn’t hear people talking about me. If someone really likes and cares about me, she ought to be able to look past my scars. At this point, Jeremy carefully reviews the case presented in his Revised Thought on Trial Worksheet. He and his therapist agree to work on a replacement thought for his most malicious thought (see the sec- tion “After the Verdict: Replacing and Rehabilitating Your Thoughts” later in this chapter). After he creates the first replacement though, he continues putting his other malicious thoughts on trial and replacing them, one at a time. Putting your thoughts on trial You guessed it; it’s your turn to visit Thought Court. Don’t be concerned if you struggle in your initial attempts; this important exercise takes practice. Pay attention to your body’s signals and write them down whenever you feel some- thing unpleasant. Refer to the Daily Unpleasant Emotions Checklist in Chapter 4 for help finding the right feeling words. Rate your feeling on a scale of intensity from 1 (almost undetectable) to 100 (maximal). Ask yourself what was going on when you started noticing your emotions and your body’s signals. The corresponding event can be something happening in your world, but an event can also be in the form of a thought or image that runs through your mind. Be concrete and specific; don’t write something overly general such as “I hate my work. Refer to The Thought Query Quiz in Chapter 4 if you experience any difficulty figuring out your thoughts about the event. Review your thoughts and write down the thought or thoughts that evoke the great- est amount of emotion — your most malicious thoughts. Worksheet 6-6 My Thought Tracker Feelings & Sensations Corresponding Events Thoughts/Interpretations (Rated 1–100) Chapter 6: Indicting and Rehabilitating Thoughts 83 My most malicious thoughts: 1. In time, you’re likely to start changing the way you think and, therefore, the way you feel. Take a malicious thought and consider the Prosecutor’s Investigative Questions in Worksheet 6-3. After you put one thought on trial using the instructions that follow, proceed to put other malicious thoughts through the same process. In Worksheet 6-8, designate one of your most malicious thoughts as the accused thought and write it down. In the left-hand column, write all the reasons, evidence, and logic that support the truth of your accused thought. In the right-hand column, write refutations of all the reasons, evidence, and logic presented by the defense. After all, you need to use the Thought Court method numerous times to feel the full benefit. After you complete the Thought Court process, decide for yourself whether or not your thought is guilty of causing you unneeded emotional distress such as anxiety, depression, or other difficult feelings. Even if you conclude that your thought has some grain of truth, you’re likely to discover that it’s highly suspect of causing you more harm than good. In Thought Court, you don’t judge your thought guilty only on the basis of “beyond a reason- able doubt. Reviewing more Thought Court cases To help you understand Thought Court better, this section contains a few more examples. Because the Thought Tracker also appears in Chapters 4 and 5, we start with the accused thought here, which comes from the most malicious thoughts at the end of a Thought Tracker (see “Putting your thoughts on trial”). Connor: Doomed to unhappiness Over the years, Connor, a 58-year-old high school teacher, became an avid outdoorsman, spending his summer vacations camping, fishing, and hiking. Although his arthritis has been getting progressively worse, Connor has tried to ignore the pain. His doctor refers him to an orthopedic specialist who tells Connor he needs a hip replacement.

Immunofluorescence testing for antinuclear systemic autoimmune diseases and in many normal antibodies persons at a titer below 10 buy generic cozaar 25 mg line. A Antibodies to thyroid peroxidase may be detected Immunology/Apply knowledge of fundamental in both Graves’ disease (hyperthyroidism) and biological characteristics/Autoimmune/Testing/1 Hashimoto’s thyroiditis (hypothyroidism) discount cozaar 25 mg line. Antibodies to thyroid peroxidase can be detected can be measured to distinguish between the two by using agglutination assays order cozaar 50 mg amex. Granulomatous thyroid disease tests for the detection of antibodies to islet cells and D. Addison’s disease insulin may help to initiate early treatment before complete destruction of β cells. B While antibodies to tissue transglutaminase and gliadin are often found in celiac disease, their 16. What is the main use of laboratory tests to detect combined sensitivity is less than 100%. To regulate levels of injected insulin not diagnostic of celiac disease, but provide a B. To rule out the presence of other autoimmune who meet the clinical diagnostic criteria for celiac diseases disease. IgM level Immunology/Select routine laboratory procedures/ Autoimmune/Celiac disease/Testing/2 102 Chapter 3 | Immunology 18. Which of the following is a description of a type I Answers to Questions 1–4 hypersensitivity reaction? A Type I immediate hypersensitivity (anaphylactic) of mast cells, causing release of preformed mediators responses are characterized by IgE molecules binding and resulting in symptoms of an allergic reaction to mast cells via the Fc receptor. Anti-Fya from a pregnant woman crosses the surface IgE caused by binding of allergens causes placenta and attaches to the Fya antigen-positive the mast cell to degranulate, releasing histamine red cells of the fetus, destroying the red cells and other chemical mediators of allergy. Exposure to poison ivy causes sensitized T cells than in vitro tests that measure either total or to release lymphokines that cause a localized antigen-specific IgE. Allergen-specific IgE assays are available than other methods based upon solid-phase enzyme immunoassay. It has greater sensitivity than in vitro measurements The allergen is covalently bound to a cellulose solid C. It is more likely to be positive for IgE-specific phase and reacts with specific IgE in the serum. The unbound antibody further allergen sensitivity conjugate is washed away and fluorogenic substrate Immunology/Apply principles of basic laboratory (4-methylumbelliferyl-β-D-galactose) is added. A patient who is blood group O is accidentally transfused with group A blood and develops a reaction during the transfusion. IgG Immunology/Apply principles of basic laboratory procedures/Hypersensitivity/Testing/1 103 104 Chapter 3 | Immunology 5. Which test would measure the coating of red cells Answers to Questions 5–10 by antibody as occurs in hemolytic transfusion reactions? For procedures/Hemolytic reaction/1 example, renal biopsies from patients with Goodpasture’s syndrome exhibit a smooth pattern 6. A Insufficient washing can cause incomplete removal procedures/Hemolytic reactions/1 of excess or unbound immunoglobulins and other proteins, which may neutralize the antiglobulin 7. Use of heavy chain–specific polyclonal of antigen–antibody complexes that deposit in the anti-human Ig tissues, causing local inflammation and necrosis C. Use of excessive centrifugal force induced by complement activation, phagocytosis, D. Some patients make monoclonal or polyclonal antibodies Immunology/Apply knowledge to identify sources of with rheumatoid factor activity that bind to serum error/Hemolytic reactions/3 immunoglobulins, forming aggregates that 8. These circulating immune circulating immune complexes in the serum of complexes are detected by allowing a blood some patients with systemic autoimmune diseases sample to clot at 37°C, transferring the serum to a such as rheumatoid arthritis? Indirect antiglobulin test in patients displaying anergy and other signs of Immunology/Apply knowledge of fundamental immunodeficiency. The C1q assay and the Raji cell biological characteristics/Hypersensitivity/1 assays detect circulating immune complexes that 9. Immune complexes that have fixed complement will bind to Raji cells and can be Immunology/Apply principles of special laboratory identified using radiolabeled or enzyme labeled procedures/Hypersensitivity/Testing/1 anti-immunoglobulin. The skin reaction is characterized by biological characteristics/Hypersensitivity/1 a lesion containing a mononuclear cell infiltrate. A patient receives a transfusion of packed red Answers to Questions 11–12 cells and fresh frozen plasma and develops an anaphylactic, nonhemolytic reaction. A The fact that this is a nonhemolytic reaction receiving a transfusion 20 years earlier. She had suggests that a non–red cell antigen may be no reaction to the previous transfusion, but she involved. Which of the approximately 1 in 700 individuals and is often following transfused substances most likely elicited asymptomatic. An antigen belonging to the Duffy system explain the “poor feeling” the patient had after the initial transfusion. A subsequent transfusion Immunology/Apply knowledge of fundamental biological may lead to an Arthus reaction if IgG anti-IgA is characteristics/Immune deficiency/Hypersensitivity/3 present or an anaphylactic reaction if IgE anti-IgA 12. Immunology/Apply knowledge of fundamental biological characteristics/Immune deficiency/ Hypersensitivity/2 3. Which of the following symptoms in a young child Answers to Questions 1–4 may indicate an immunodeficiency syndrome? Recurrent bacterial, fungal, and viral infections recurrent bacterial, fungal, and viral infections D.