By B. Tizgar. Webb Institute. 2019.

The choice of drug depends on the effectiveness of host defense mechanisms in controlling the infection order indomethacin 50mg online. The drug selected for use may be either a bactericidal agent (causing the death of the microorganism) or bacteriostatic agent (temporarily inhibiting the growth of the microorganism) order 75 mg indomethacin visa. Drug choice is related to the mechanism of drug action in one of the following general categories: a buy indomethacin 50mg otc. Host determinants include history of drug reactions; site of infection; renal cheap 25mg indomethacin free shipping, hepatic, and immune status; age; pregnancy and lactation; metabolic abnormalities; pharmacokinetic factors; preexisting organ dysfunction; and genetic factors. Bacterial determinants include intrinsic resistance, escape from antibiotic effect, and acquired resistance, which can occur as a result of the following: 1. Spontaneous, random chromosomal mutations, which occur at a frequency of 10–12 to 10–5. These mutations are commonly due to a change in either a structural protein receptor for an antibiotic or a protein involved in drug transport. Conjugation is the passage of genes from bacteria to bacteria via direct contact through a sex pilus or bridge. Conjugation occurs primarily in gram-negative bacilli, and it is the prin- cipal mechanism of acquired resistance among enterobacteria. Structure and mechanism of action (1) Penicillins are analogues of alanine dipeptide (Fig. Modifications of the R-group side- chain (attached to the b-lactam ring) alter the pharmacologic properties and resistance to b-lactamase. Gram-positive bacteria with thick external cell walls are particularly susceptible. The genes for b-lactamases can be transmitted during conjugation or as small plasmids (minus conjugation genes) via transduction. Common organisms capable of producing penicillinase include Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Neisseria gonorrhoeae, and Bacillus, Proteus, and Bacteroides species. Selected drugs and their therapeutic uses (Table 11-1) (1) Penicillin G and penicillin V are mainly used to treat infections with the following organisms (resistant strains of bacteria are being isolated more frequently): (a) Gram-positive cocci (aerobic): Pneumococci, streptococci (except S. This group represents the most common pathogens for which first-generation penicillins are used today. Pro- benicid, a uricosuric agent that blocks renal secretion of penicillin, is used rarely for this purpose. Chapter 11 Drugs Used in Treatment of Infectious Diseases 255 (3) Penicillinase-resistant penicillins (oxacillin, dicloxacillin, and nafcillin) are used pre- dominantly for penicillinase-producing staphylococcal infections. Ampicillin is useful for infections caused by Haemophilus influenzae, Streptococcus pneumonia, Streptococcus pyrogenes, Neisseria meningitides, Pro- teus mirabilis, and Enterococcus faecalis. Amox- icillin is commonly used for endocarditis prophylaxis before major procedures. Piperacillin/tazobactam is effective against most gram-negative organisms, including Pseudomonas spp. Adverse effects (1) Penicillins cause hypersensitivity reactions in nearly 10% of patients. All types of reac- tions, from a simple rash to anaphylaxis, can be observed within 2 minutes or up to 3 days following administration. Endocarditis prophylaxis (1) Endocarditis prophylaxis is indicated for patients with prosthetic heart valves; those who have previously been diagnosed with endocarditis; patients born with cyanotic heart disease; and patients with surgically constructed systemic pulmonary shunts. Patients with intermediate risk for endocarditis are those who were born with other con- genital cardiac abnormalities; those with acquired valvular dysfunction; and patients with hypertrophic cardiomyopathy. Structure and mechanism of action (1) Cephalosporins consist of a 7-aminocephalosporanic acid nucleus and a b-lactam ring linked to a dihydrothiazine ring (see Fig. Third-generation cephalosporins are sensitive to another class of b-lactamase, the cephalosporinases (genes are generally located on chromosomes as opposed to plasmids). They are used in treatment of streptococcal infections as well as infections Chapter 11 Drugs Used in Treatment of Infectious Diseases 257 caused by E. Ceftriaxone is used for sexually trans- mitted infections caused by gonorrhea, as well as in empiric therapy for commu- nity-acquired meningitis. Adverse effects and drug interactions (1) Cephalosporins most commonly cause hypersensitivity reactions (2%–5%); 5%–10% of penicillin-sensitive persons are also hypersensitive to cephalosporins. Aztreonam (Azactam) (1) Aztreonam is a naturally occurring monobactam lacking the thiazolidine ring that is highly resistant to b-lactamases. Vancomycin (Vancocin, Vancoled) (1) Vancomycin is a tricyclic glycopeptide that binds to the terminal end of growing pepti- doglycan to prevent further elongation and cross-linking; this results in decreased cell membrane activity and increased cell lysis. Rapid infusion may cause anaphylactoid reactions and ‘‘red neck’’ syndrome (flushing caused by release of histamine). Bacitracin (1) Bacitracin inhibits dephosphorylation and reuse of the phospholipid required for accep- tance of N-acetylmuramic acid pentapeptide, the building block of the peptidoglycan complex. Cycloserine (Seromycin) (1) Cycloserine is an amino acid analogue that inhibits alanine racemase and the incorpo- ration of alanine into the peptidoglycan pentapeptide.

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You don’t need to be downing protein-rich sports drinks order 75 mg indomethacin visa, or eating tons of meat and eggs daily or immediately after exercising order indomethacin 25mg amex. If you choose to have animal foods discount indomethacin 25 mg visa, which are not necessary for muscles or for good health buy generic indomethacin 25 mg on line, then eat lean meat, poultry (grass-fed, free-ranged, hormone- and antibiotic-free), and fish in the context of your three daily meals surrounded by lots of unrefined plant foods. You meat-eating and dairy-supplementing gym rats have been duped into thinking you have to consume lots of protein and animal foods to be strong and athletic. He was telling me about his weight issues and medical problems with diabetes, hypertension, and kidney issues. He was a classic “dairy-aholic” and was stunned when I told him to elimi- nate the dairy, cut back on the meat, and eat more vegetables, and that he’d still be fine in the gym. I also told him he’d drop some weight and probably improve his diabetes and kidney function. He was fearful of not being strong and muscular if he cut back on those foods (meat and dairy, to which he was addicted). Americans have been brainwashed by the propaganda that you have to consume meat, poultry, fish, and dairy products to be healthy and strong. He or she doesn’t have hours and hours to train in the gym, is not an elite athlete train- ing for some type of competition, and is not a movie star trying to tweak a particular area of his or her body. That said, building lean body mass is not only healthy for our metabolism (blood sugar control and immune function), but also helps us function in our daily lives, especially as we get older. It is fast; there are no weights to put away; it is safe; you don’t need a partner or coach; it works different muscle groups in their full range of motion; it works the body symmetrically; it is easy for anyone to use after maybe one or two sessions of instruction; and it has some cardiovascular benefit (not a lot) if you keep moving. I included fifteen minutes because that is what it takes me: fifteen minutes at a consistent pace to do six different upper-body exer- cises and six lower-body exercises. Just do circuit training in the above-mentioned fashion for two months (along with a whole-food, plant-strong diet). If you want to speed up the process, do the circuit training every other day for a month. If you want to spend twenty-five to thirty minutes doing circuit training, do just ten to twelve different upper-body exer- cises and ten to twelve different lower-body exercises. The key is moving steadily between stations; alternate arm and leg exercises so you don’t fatigue a group of muscles. Do as many different ex- ercises as the machines allow before repeating an exercise so you work as many different muscle groups and go through as many different ranges of motion as possible. Keep the number of sets of exercises even between the upper and lower body to help keep some balance between the strength and bulk in our lower bodies compared to our upper bodies. When you can do fifteen or more repetitions easily, try increasing the weight, number of plates, or resistance on the machines. My goal is to give you fast, efficient, and safe ways to get to a very high state of health with minimal expense and time in your busy, modern lifestyle. If you lose weight at the same time, you will become doubly excited about seeing the fat go away and the curves come out of nowhere! I recommend warming up with your aerobic exercises prior to your circuit training to allow the muscles to be warm and have some blood flow going through them before challenging them. Then do anywhere from ten to thirty minutes of stretching after your circuit training. After doing this routine several months, you may adapt your warm-up and stretching any way you feel comfort- able. Circuit training with machines is just fast and efficient and can get you results quickly. As I mentioned, for fast results I would do the circuit train- ing every other day for a month or two. For older individuals, the muscle recovery may not be as quick, and every other day may create some extra soreness. If you’re too sore, don’t push yourself as hard and still go every other day, or put two days in between your circuit training regularly or periodically, depending on your soreness. It is true that some species of gorillas, especially lowland gorillas, eat a fair amount of ants and termites (maybe up to 3 percent of - 170 - the triad exercise program their diet) and get protein and certain trace minerals from these insects, but the bulk of their protein comes from massive quan- tities of leafy plant foods, stems, bark, and fruit when available. Mountain gorillas tend to have a more limited diet and eat fewer termites, ants and fruit, and more leafy foliage and other vegeta- tion. David Jenkins and colleagues after studying the diets of western lowland gorillas: “…The macronutrient profile of this diet would be as follows: 2. We suggest that humans also evolved consuming similar high foliage, high fiber diets, which were low in fat and dietary cholesterol. If you want to get “Gorilla Buff” fast, it isn’t all in the strength training you do. Building muscle under a layer of fat is still building mus- cle, but it isn’t getting the shape or the look you want. If you are overweight, you want to eat whole foods, although you might stay away from or reduce consumption of even whole-grain breads for a while since they are more calorie dense (see Chapter 13, Reduc- ing Caloric Density) than eating the basic cooked grains until you lean out.

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By transforming Biff’s deviation into standard deviation units buy generic indomethacin 25mg on line, we have computed his z-score buy indomethacin 25mg with mastercard. A z-score is the distance a raw score is from the mean when measured in standard deviations buy indomethacin 75 mg without a prescription. A z-score always has two components: (1) either a positive or negative sign which indicates whether the raw score is above or below the mean buy discount indomethacin 75 mg line, and (2) the absolute value of the z-score which indicates how far the score lies from the mean when measured in standard deviations. By knowing where a score is relative to the mean, we know the score’s rela- tive standing within the distribution. Of course, a raw score that equals the mean produces a z-score of 0, because it is zero distance from itself. For example, an attractiveness score of 60 will produce an X and X that are the same number, so their difference is 0. Understanding z-Scores 113 We can also compute a z-score for a score in a population, if we know the population mean ( ) and the true standard deviation of the population 1σX2. For example, say that in the popula- tion of attractiveness scores, 5 60 and σX 5 10. Notice that the size of a z-score will depend on both the size of the raw score’s deviation and the size of the standard deviation. Biff’s deviation of 130 was impressive because the standard deviation was only 10. If the standard deviation had been 30, then Biff would have had z 5 190 2 602>30 511. Now he is not so impressive because his deviation equals the “average” deviation, indicating that his raw score is among the more common scores. Computing a Raw Score When z Is Known Sometimes we know a z-score and want to find the corresponding raw score. The above logic is also used to transform a z-score into its corresponding raw score in the population. Using the symbols for the population gives The formula for transforming a z-score in a population into a raw score is X 5 1z21σX2 1 Here, we multiply the z-score times the population standard deviation and then add. After transforming a raw score or z-score, always check whether your answer makes sense. At the very least, raw scores smaller than the mean must produce negative z-scores, and raw scores larger than the mean must produce positive z-scores. When working with z-score, always pay close attention to the positive or negative sign! Further, as you’ll see, we seldom obtain z-scores greater than 13 or less than 23. Although they are possible, be very skeptical if you compute such a z-score, and double-check your work. The way to see this is to first envision any sample or popula- tion as a z-distribution. A z-distribution is the distribution produced by transforming all raw scores in the data into z-scores. For example, say that our attractiveness scores produce the z-distribution shown in Figure 6. The X axis is also labeled using the original raw scores to show that by creating a z-distribution, we only change the way that we identify each score. Saying that Biff has a z of 13 is merely another way to say that he has a raw score of 90. He is still at the same point on the distribution, so Biff’s z of 13 has the same frequency, relative frequency, and percentile as his raw score of 90. By envisioning such a z-distribution, you can see how z-scores form a standard way to communicate relative standing. A “1” indicates that the z-score (and raw score) is above and graphed to the right of the mean. Larger positive z-scores (and their corresponding raw scores) occur less frequently. Conversely, a “2” indicates that the z-score (and raw score) is below and graphed to the left of the mean. Larger negative z-scores (and their corresponding raw scores) occur less frequently. Do not be misled by negative z-scores: A raw score that is farther below the mean is a smaller raw score, but it produces a negative z-score whose absolute value is larger. Thus, for example, a z-score of 22 corresponds to a lower raw score than a z-score of 21. For some variables, the goal is to have as low a raw score as possible (for example, errors on a test). Only when the underlying raw score distribution is normal will its z-distribution be normal. Whether the standard deviation in the raw scores is 10 or 100, it is still one standard deviation, which transforms into an amount in z-scores of 1. Now you can see why z-scores are so useful: All normal z-distributions are similar, so a particular z-score will convey the same information in every distribution.

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Design of appropriate delivery devices has taken a num ber of directions including double balloon catheters and perforated balloons allow ing high pressure injection through radial pores cheap indomethacin 50 mg amex. Various approaches have been used to lim it experim ental restenosis by inducing cell death (e generic indomethacin 25mg overnight delivery. There is a vast am ount of experim ental data indomethacin 25mg discount, w ith early results from gene therapy trials for angiogenesis purchase indomethacin 50 mg on-line, but clinical trials for restenosis are aw aited. Brachytherapy O ver the last few years there has been considerable interest in intravascular brachytherapy (radiation therapy). A variety of catheter based delivery system s and radioactive stents are available using either beta (e. A num ber of studies have show n im pressive results on reducing restenosis rates and m any m ore are underw ay but enthusiasm for the technique should be tem pered because there are concerns about long term safety. M any of the sensitising agents that have been studied have been products of porphyrin m etabolism such as 5-am inolaevulinic acid. M uch of the w ork in this field to date has been in the treatm ent of cancer but there is an accum ulation of sm all and large anim al data show ing a reduction in neointim al hyperplasia after balloon injury. Favourable vessel w all rem odelling has also been observed in a pig m odel of balloon coronary and iliac angioplasty. Reduction in the response to coronary and iliac artery injury w ith photodynam ic therapy using 5-am ino- laevulinic acid. Pathophysiology and pharm a- cological approaches for prevention of coronary artery restenosis follow ing coronary artery balloon angioplasty and related procedures. Effectiveness of an antioxidant in preventing restenosis after percutaneous translum inal coronary angio- plasty: the Probucol Angioplasty Restenosis Trial. Anthony Gershlick Thrombolysis Natural throm bolysis occurs via the action of plasm in on fibrin throm bi. Plasm in is a non-specific protease and dissolves coagulation factors as w ell as fibrin clots. The resultant con- form ational change exposes the active site on plasm inogen to induce the form ation of plasm in. Som e, but not all, of these theoretical advantages translate into definite clinical benefit. The Fibrinolytic Therapy Trialists Collaborative Group1 sum m arised results from throm bolytic trials encom passing m ore than 100,000 patients. The overall relative risk reduction in 35 day m ortality w ith treatm ent w as 18% (p < 0. How ever, in real life w here the population is older than in the trials the true m ortality is about 18–20%. Adm inistration of a throm bolytic saves about 30 lives in a 1000 in those presenting w ithin 6 hours of sym ptom onset but only 20 lives in a 1000 w hen patients receive treatm ent betw een 6 and 12 hours after sym ptom onset. Prehospital throm bolysis has been show n to reduce cardiac m ortality com pared to in-hospital throm bolysis by 17% (p = 0. Indications for fibrinolytic therapy in suspected acute m yocardial infarction: collaborative overview of early m ortality and m ajor m orbidity from all random ised trials of m ore than 1000 patients. Aspirin absorption rates and platelet inhibition tim es w ith 325m g buffered aspirin tablets (chew ed or sw allow ed w hole) and w ith buffered aspirin solution. Pre-hospital throm bolytic therapy in patients w ith suspected acute m yocardial infarction. A factorial random ised trial of alteplase versus streptokinase and heparin versus no heparin am ong 12,490 patients w ith acute m yocardial infarction. The concept of equivalence and its application to the assessm ent of throm bolytic effects. W hich patients should receive prim ary or “hot” angioplasty for these conditions? How ever, data suggest that the success of prim ary intervention is dependent on the frequency w ith w hich the procedure is perform ed. A com parison of im m ediate angioplasty w ith throm bolytic therapy for acute m yocardial infarction. A clinical trial com paring prim ary coronary angioplasty w ith tissue plasm inogen activator for acute m yocordial infarction. Com parison of prim ary coronary angioplasty and intravenous throm bolytic therapy for acute m yocardial infarction: a quantitative review. Lim itations of throm bolytic therapy for acute m yocardial infarction com plicated by congestive heart failure and cardiogenic shock. The volum e of prim ary angio- plasty procedures and survival after acute m yocardial infarction. Kenneth W Mahaffey Haem orrhagic com plications (particularly intracranial) are the m ost im portant risks associated w ith throm bolysis. In cases w here the nature of the stroke (haem orrhagic or otherw ise) is unknow n, then the risk of not adm inistering a throm bolytic agent should be considered. The m ajority of strokes are occlusive in origin, and thus lack of certain know ledge should probably not represent a contraindication to throm bolysis in those patients (such as those w ith extensive territories of m yocardial infarction w ho present early) w ho have m ost to gain. Currently, therefore, diabetic retinopathy is only considered a contraindication to throm bolysis if there is clear evidence of recent retinal haem orrhage.