Solian

By Y. Campa. University of Texas Health Center at Tyler. 2019.

It seems very likely that the Hippocratic authors regarded writing as an instrument for the organisation of knowledge concerning a great variety of phenomena generic 50mg solian free shipping, that is cheap solian 100mg mastercard, not only in order to prevent knowledge from being forgotten – a desire they shared with, for example Herodotus – but also to keep knowledge available for 56 On Regimen in Acute Diseases 3 (2. And it seems entirely reasonable that medicine (rather than, say, mathematics or astronomy) should play this part: for, on the one hand, the empirical data reflected in case histories such as the Epidemics must soon have reached such unmanageable proportions and such a high degree of detail that it could not possibly be remembered; so there was a need for storage of information based on the belief that such information might remain useful. On the other hand, since medicine was incessantly confronted with new cases in which existing knowledge had to be applied or against which it had to be checked and, if necessary, modified, it had to be accessible in a conveniently retrievable form. If all this is plausible, the emergence of the Hippocratic writings and especially the variety of forms they display can be seen as a result of the need for organisation of knowledge and research – a need arising also from the fact that their authors must have formed a community of scholars rather than being single scientists working independently. This might also suggest an alternative explanation of why all the Hippocratic writings are anonymous (cf. In the course of the fourth century the collection and organisation of knowledge was further implemented and applied to a much broader area by Aristotle and his pupils (or colleagues), and a similar process of data preservation, common intellectual property and exchange of information evidently took place in the Lyceum. More could be said from a contextual point of view about these and other features of medical and philosophical ‘discourse’. For example, there is the formation of a scientific terminology and its relation to ordinary language, with stylistic and syntactic anomalies such as the use of ‘shorthand’ (brachylogy), ‘aphoristic’ style and formulaic language, or structural characteristics such as ring composition, paragraph division, use of introductory and concluding formulae and other structuring de- vices. Particularly interesting is the presence or absence of the author in 60 See Ostwald and Lynch (1992). Furthermore, of great interest are the use of rhetorical questions, formulae for fictional objections, modes of argument used by the Hippocratic writers, Diocles and Aristotle, the use of metaphors and analogies, and patterns of thought, such as antithesis, binary or quaternary schemata, the various forms of overstatement, or the ways in which ancient scientific writers, just like orators, tried to convey a certain ¯ethos (in the ancient rhetorical sense of ‘personality’) to their audiences, for example by presenting themselves in a certain way or assuming a certain pose with re- gard to their audience and their subject matter. Alternatively, the author may present himself as a venerable authority, as a schoolmas- ter ready to praise good suggestions and to castigate foolish answers, as a dispassionate self-deprecating seeker of the truth, or a committed human being who brings the whole of his life experience to bear on the subject he is dealing with, and so on. As many readers of this volume will be aware from their own experience with communication to academic audiences, these are different styles of discourse, with different stylistic registers, types of ar- gument, appeals to the audience, commonplaces, and suchlike; what they were like in the ancient world deserves to be described, and the attempt should be made to detect patterns, and perhaps systematicity, in them. Ancient scientists, like orators, had an interest in captatio benevolentiae and were aware of the importance of strategies such as a ‘rhetoric of modesty’, a ‘rhetoric of confidence’. In this respect the dialogues of Plato provide good examples of these attitudes, and they may serve as starting-points for similar analysis of scientific writing which is not in the form of a dialogue. The works of Galen present a particularly promising area of study, for one can hardly imagine a more self-conscious, rhetorical, argumentative, polemicising and manipulating ancient scientific writer than the doctor 61 In chapter 1 we shall see an interesting example of a significant alternation of singular and plural by the author of On the Sacred Disease, where the author cleverly tries to make his audience feel involved in a course of religious action which he defends and indeed opposes to the magical one advocated by his opponents. And, as I have shown elsewhere, the works of Caelius Aurelianus present a further example of medical literature full of rhetorical and argumentative fireworks. At the same time, it will have become clear that these formal aspects of Greek and Latin medical writing are of great significance when it comes to the use of these texts as sources for what used to be seen as the primary jobs of the medical historian, namely the reconstruction of the nosological reality of the past and of the human response to this reality. I have dealt with this area more elaborately in a separate collaborative vol- ume on medical doxography and historiography. Many ancient medical writers, philosophers and scientists (as well as historians) regarded themselves as part of a long tradition, and they explicitly discussed the value of this tradition, and their own contribution to it, in a prominent part of their own written work, often in the preface. Yet, more recently, scholarship has drawn attention to the large variety of ways in which ancient scientific and philosophical discourse received and reused traditional material and to the many different purposes and strategies the description of this material served. Ancient writers on science and philosophy received and constructed particular versions of the 63 See van der Eijk (1999c). The modalities of these processes have turned out to be very complicated indeed, and it has become clear that the subject of ‘tradition’ in ancient thought comprises much more than just one authoritative thinker exercising ‘influence’ on another. Our understanding of ‘doxography’ and other genres of ancient ‘intel- lectual historiography’ has been significantly enhanced over the last two decades, and it has contributed to a greater appreciation of the various dimensions – textual, subtextual and intertextual – of much Greek and Roman philosophical and medical discourse. In particular, it has shed further light on the possible reasons behind the ways in which ideas are presented in texts and the modes in which ancient authors contextualise themselves, aspects which are of great relevance to the interpretation and evaluation of these ideas. He has been credited with attempting a ‘natural’ or ‘rational’ explanation of a disease which was generally believed to be of divine origin and to be curable only by means of apotropaeic ritual and other magical instruments. The identity, claims and practices of the magicians have also been studied by Lanata (1967); Temkin (1971) 10–15;Dolger (¨ 1922) 359–77; Moulinier (1952) 134–7; Nilsson (1955) 798–800. Miller (1953) 1–15; Nestle (1938) 1–16;Norenberg (¨ 1968); Thivel (1975); Vlastos (1945) 581. Consequently the influence, or the manifestations, of the divine are regarded as natural processes and no longer as supernatural interventions of gods within natural or human situations. On this view, the writer of On the Sacred Disease may be seen as the exponent of a ‘rationalistic’ or ‘naturalistic’ religiosity, or in any case as an adherent of a more advanced way of thinking about the divine, which can be observed in some of the Presocratic philosophers as well (e. On the other hand, it has been recognised by several interpreters6 that the author’s criticism of the magicians, which occupies the entire first chapter of the treatise (and which is echoed several times later on),7 reflects an authentic religious conviction. This applies particularly to his repeated accusations of impiety (asebeia) and even atheism (atheos) in sections 1. In these passages the author shows himself both a defender of religion and a critic of magic: he expresses definite opinions on what he believes to be the different domains of human action and divine action (1. The religious belief which apparently underlies these passages is far more traditional and less ‘advanced’ than the naturalistic theology which is reflected in the statements on the divine character of the disease, since it appears that the author of On the Sacred Disease believes in a supreme divine power which cleanses men of their moral transgressions and which is accessible to cultic worship in sacred buildings by means of prayer and sacrifice. The problem I intend to deal with in this chapter is how these two different sets of religious ideas are related to each other. None of these scholars, however, have satisfactorily solved the problem of this apparently ‘double-faced’ religiosity (see below).

The abuse potential of benzodiazepines is low compared with that of other classes of seda- tive–hypnotic drugs except when there is already a history of substance abuse buy discount solian 50 mg. Withdrawal occurs sooner and is more severe after abrupt discontinuation of shorter-acting benzodiazepines; the effects associated with withdrawal can be minimized by tapering the dose reduction or substituting longer- acting benzodiazepines such as diazepam discount solian 100 mg mastercard. Zolpidem, zaleplon, and eszoplicone are widely used for short-term treatment of insomnia; Zolpidem has some minimal anxiolytic activity as well. Dosage of these drugs should be reduced in the elderly and in patients with hepatic impairment. These drugs have only weak muscle-relaxing or anticonvulsant activity, with reduced potential compared to the benzodiazepines for tolerance, abuse, physical dependence, or rebound insomnia. Eszopiclone is reported to also produce dry mouth, some sedation, and an unpleasant taste. A week or more of administration may be required to achieve the therapeutic effects of buspirone. Ramelteon is rapidly absorbed and metabolized to an active longer-acting metabolite. Barbiturates are classified according to the rate of onset and duration of the therapeutic action. Metabolism (oxidation and conjugation in the liver) and excretion are more important determinants for less lipid-soluble barbiturates. Alkalinization of the urine enhances excretion and shortens its dura- tion of action. With long-term use, these drugs, particularly phenobarbital, may induce the synthesis of hepatic microsomal enzymes and increase their own metabolism or the metabolism of numerous other drugs. Barbiturates increase porphyrin synthesis by the induction of hepatic d-aminolevulinic acid synthase, and they can precipitate acute intermittent porphyria. The use of these drugs as sedative–hypnotic agents is almost obsolete, supplanted by ben- zodiazepines and other nonbenzodiazepine sedative–hypnotic agents. Barbiturates produce dose-related respiratory depression with cerebral hypoxia, possibly leading to coma or death; this effect results from abuse or suicide attempt. Treatment includes ventilation, gastric lavage, hemodialysis, osmotic diuretics, and (for phenobarbital) alkalinization of urine. Phenobarbital and pentobarbital are occasionally used to treat the physical dependence associated with long-term use of sedative–hypnotic drugs. Conventional antipsychotic drugs are often subclassified according to their oral milligram potency (high potency or low potency). Other conventional heterocyclic antipsychotic drugs such as loxapine and molindone, with intermediate potency, have no clear advantage over other conventional drugs. The therapeutic action of the conventional antipsychotic drugs is correlated best with antago- nist activity at postjunctional dopamine D2-receptors, where dopamine normally inhibits adenylyl cyclase activity. Most of these drugs show little correlation between plasma levels and therapeutic action. Most antipsychotic drugs are highly lipophilic and have long half-lives (10–20 h). Thioridazine is metabolized to mesoridazine, which accounts for most of the parent compound’s effects. Esterification of fluphenazine and haloperidol (fluphenazine decanoate, haloperidol dec- anoate) results in long-acting depot forms (2- to 3-week duration of action) that can be used to 106 Pharmacology manage compliance issues. Plasma esterases convert the parent compound to the active drug when the ester diffuses into the bloodstream. However, their antipsychotic effects, including decreased symptoms of thought disorders, paranoid features, delusions, hostility, hallucinations (the positive symptoms of schizophrenia) and, to a lesser degree, decreased withdrawal, apathy, and blunted affect (the negative symptoms of schizophre- nia), typically take longer to occur (a week or more). Atypical antipsychotic drugs, particu- larly clozapine, have a seemingly greater effect on negative symptoms than the conventional agents. Tourette syndrome (haloperidol or pimozide [Orap]), to suppress severe tics and vocalization e. Severe nausea or vomiting associated with a variety of diseases, radiation treatment, and cancer chemotherapy, as well as postoperative nausea and vomiting. Conventional antipsy- chotic agents, with the exception of thioridazine, have strong antiemetic activity due to dopamine D2-receptor blockade in the chemoreceptor trigger zone of the medulla. The most commonly used are the phenothiazine prochlorperazine, which is marketed only as an antiemetic, and promethazine, which has no antipsychotic activity. Selection of a specific antipsychotic agent for therapeu- tic use is often based on its associated adverse effects rather than therapeutic efficacy. They are less likely to occur with low-potency conventional antipsychotic drugs such as thioridazine, which have lower affinity for dopamine D2-receptors than high-potency drugs. With the exception of risperidone, they are also unlikely to occur with atypical antipsychotic drugs such as clozapine and olanzapine. Extrapyramidal effects are also less likely to occur with those conventional agents that also have sub- stantial antagonist activity at cholinoceptors in the basal ganglia. Chapter 5 Drugs Acting on the Central Nervous System 107 table 5-3 Potency and Selected Adverse Effects of Representative Conventional Antipsychotic Drugs Extrapyramidal Autonomic Drugs Oral Dose (mg) Effectsa Effects Sedation Conventional drugs Aliphatic phenothiazines Chlorpromazine 100 ++ +++ +++ Triflupromazine 50 ++ +++ +++ Piperidine phenothiazines Thioridazineb,c 100 + +++ +++ Mesoridazinec 50 + +++ +++ Piperazine phenothiazines Trifluoperazine 10 +++ ++ ++ Fluphenazined 5 +++ ++ ++ Butyrophenones Haloperidol 2 +++ + + Other related drugs Molindonec 20–200 +++ ++ ++ Loxapine 20–250 +++ ++ ++ aExcluding tardive dyskinesia.

Since vancomycin is cleared by the kidneys order solian 100mg with visa, renal functional status needs to be considered when prescribing such a drug purchase solian 50 mg free shipping, because it may accumulate and produce undesirable toxic side effects. Switching from the vancomycin to an oral preparation will reduce its bioavaila- bility. There is no indication that the patient is in the state of increased volume of distribution (such as edema), and water restriction will not have a noticeable effect on apparent volume of 23 24 Pharmacology distribution. Changes to the current regimen are necessary because of the patient’s acute renal failure, and this has to be done regardless of the urgency of the situation. The fact that the patient is being ventilated may indicate that she needs extra hydration because of increased insensible losses, but this has nothing to do with her vancomycin dose directly. First-pass metabolism simply means passage through the portal circulation before reaching the systemic circulation. A hepatic function panel is generally not used to deduce a patient’s sus- ceptibility to the drug. Bioavailability of drugs is decreased, not increased by the fraction removed after the first pass through the liver. Drugs are usually less rapidly metabolized when hepatic enzymes are elevated (which indicates hepatic dysfunction). Alterations of urinary pH affect renal distal tubular reabsorption of drugs by changing the degree of ionization. Glomerular filtration depends mainly on the size of the drug as well as protein binding. Drug metabolism is not affected at the levels of the kidney, where most elimination takes place. Alkalinization of urine is unlikely to affect undesirable side effects of the drug. Dosing schedules of drugs are adjusted according to their half-lives to achieve steady-state plasma concentration. Attempting to avoid the toxicity of the drug because of its low therapeutic index represents an unlikely scenario, since to reduce toxicity of a drug with a low therapeutic index, one would reduce the dosing schedule, not increase it. Some fluctuation in plasma concentration occurs even at steady state; it is the aver- age concentration over time that is the goal of steady state. The rationale for the loading dose is to give a patient a sufficient dose of a med- ication to achieve the desired effect quickly, which is necessary in some situation (such as pre- vention of further seizures). When drug is administered at maintenance rate, steady state is achieved after about five half-lives. The loading dose depends on the volume of distribution, whereas the maintenance dose depends on the clearance of the drug. To calculate the volume of distribution, use the formula in which the dose of the drug is divided by the plasma concentration. For the plasma concentration of drug to decrease by 50%, half the drug present in the body initially must be eliminated. The amount of drug in the body initially is the volume of distribution 3 the plasma concentration (50 liters 3 4 mg/liter ¼ 200 mg). When the plasma concentration falls to 2 mg/liter, the body will contain 100 mg of drug (50 L 3 2 mg/L ¼ 100 mg). Since the body eliminates the drug at a rate of 2 mg/hour, it will require 50 hours for 100 mg of the drug to be eliminated. Thus, the average plasma concentration will remain the same, but decreasing both the dose and the dose interval will decrease the peak to trough variation of plasma concentration. The initial rate of distribution of a drug to a tissue depends primarily on the rate of blood flow to that tissue. At longer times, however, a drug may undergo redistribution Chapter 1 General Principles of Drug Action 25 among various tissues, e. The induction of the cytochrome P-450 following chronic administration will increase the conversion of the inactive pro-drug to the active form. Maintenance dose rate ¼ (clearance) 3 (desired plasma concentration), and the whole body clearance is the sum of all the individual organ clearances. In most patients the hepatic metabolism, renal filtration, and biliary excretion account for 25%, 50%, and 25% of the whole body clearance, respectively. Since the creatinine clearance in this patient indicates that the renal filtration is only half normal, the renal clearance of the drug will be decreased by 12. This means that the whole body clearance will be 75% of that of normal (25% hepatic, 25% renal, and 25% biliary). If the oral dosing rate is constant but bioavailability increases, the fraction of the administered dose that reaches the general circulation unaltered increases. Thus, a decrease in clearance will increase the plasma drug concentration, whereas an increase in any of the other three parameters will decrease the steady state plasma concentration. Inspection of the plasma concentration values indicates that the half-life of drug does not become constant until 1–9 hours after administration. The drug concentration decreases by 12 (from 50 to 25 mcg/L) between 1 and 5 hours (a 4-hour interval) and again decreases by 12 (from 25 to 12. The rapid decrease in plasma concentration between 0 and 1 hour, followed by a slower decrease thereafter (and the constant half-life there- after) indicates that this drug obeys a two-compartment model with an initial distribution phase followed by an elimination phase.

Performance Parameters of Gamma Cameras Effects of High Counting Rates As discussed in Chapter 8 order 50mg solian otc, the scintillation cameras suffer count losses at high counting rates due to pulse pileup order 50mg solian amex. Pulse pileup results from the detec- tion by the camera of two events simultaneously as one event with ampli- tude different from that of either original event. If one or both of the events are photopeaks, then the amplitude of the new event will be outside the pulse-height window setting and so the event will be rejected resulting in a loss of counts. If, however, two Compton scattered photons are processed together to produce an event equivalent to the photopeak in amplitude, then the event will be counted within the window setting. But the X, Y posi- tion of the event will be misplaced on the image somewhere between the locations of the two events. Both count rate loss and image distortion at high count rates must be taken into consider- ation in evaluating the performance of different cameras. Several techniques are employed to improve the high count rate performance of a gamma camera. In modern cameras, buffers (or deran- domizers) are used in which pulses are processed one at a time, and over- lapping events are kept on “hold” until the processing of the preceding event is completed. Other cameras use pulse pileup rejection circuits to minimize the count loss and image dis- tortion and thus to improve images, although they tend to increase the dead time of the camera. Recent developments include high-speed electronics that reduce the number of misplaced events and improve the image quality significantly. Contrast Contrast of an image is the relative variations in count densities between adjacent areas in the image of an object. Contrast (C) gives a measure of detectability of an abnormality relative to normal tissue and is expressed as A − C = (10. Lesions on the image are seen as either “hot” or “cold” spots indicating increased or decreased uptakes of radioactivity in the corresponding areas in the object. Several factors affect the contrast of the image, namely, count density, scattered radiation, pulse pileup, size of the lesion, and patient motion, and each contributes to the contrast to a varying degree. Quality Control Tests for Gamma Cameras 133 Statistical variations of the count rates give rise to noise that increases with decreasing information density or count density (counts/cm2) and is given by (1/ N ) × 100, where N is the count density. For a given imaging setting, a minimum number of counts need to be collected for rea- sonable image contrast. Even with adequate spatial resolution from the imaging device, lack of sufficient counts may give rise to poor contrast due to increased noise, so much so that lesions may be missed. This count density depends on the amount of activity administered and the uptake in the organ of interest. Contrast is improved with increasing administered activity and also with the differential uptake between the normal and abnormal tissues. However, due consideration should be given to the radiation dose to the patient from a large amount of administered activity. Sometimes, high count density is achieved by counting for a longer period of time in the case of low administered activity. It should be emphasized that spatial resolution is not affected by the increased count density from increased administered activity or longer counting. Background in the image increases with scattered radiations and thus degrades the image contrast. As discussed above, at high count rates, pulse pileup can degrade the image contrast. Image contrast to distinguish a lesion depends on its size relative to system resolution and its surrounding background. Unless a minimum size of a lesion larger than system resolution develops, contrast may not be suf- ficient to appreciate the lesion, even at higher count density. The lesion size factor depends on the background activity surrounding it and on whether it is a “cold” or “hot” lesion. A relatively small-size “hot” lesion can be well contrasted against a lower background, whereas a small “cold” lesion may be missed against surrounding tissues of increased activities. This primar- ily results from the overlapping of normal and abnormal areas by the move- ment of the organ. It is somewhat alleviated by restraining the patients or by having them in a comfortable position. Quality Control Tests for Gamma Cameras To ensure high quality of images produced by imaging devices, several quality control tests must be performed routinely on gamma cameras. The frequency of tests is daily, weekly, and, for some tests, monthly or even quarterly. Performance Parameters of Gamma Cameras (peaking), uniformity, and spatial resolution of the camera. These tests can be carried out with the collimator attached to the camera (extrinsic) or without the collimator (intrinsic), and should be performed for each radionuclide used in a specific clinical study. In the intrinsic method, the source of a particular radionuclide contain- ing approximately 100 to 200mCi (3. Because the collimator is removed, the integrity of the collimator cannot be assessed by this method.