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Esmolol Esmolol is a β -selective blocker that is rapidly metabolized via hydrolysis by red blood cell esterases generic mycelex-g 100mg otc antifungal quiz questions. The infusion is typically started at 50–150 mcg/kg/min trusted 100 mg mycelex-g antifungal extra thick, and the dose increased every 5 minutes cheap mycelex-g 100 mg on-line antifungal kitten shampoo, up to 300 mcg/kg/min order mycelex-g 100 mg fast delivery antifungal used in cell culture, as needed to achieve the desired therapeutic effect. Esmolol is used for management of intraoperative and postoperative hypertension, and sometimes for hypertensive emergencies, particularly when hypertension is associated with tachycardia or when there is concern about toxicity such as aggravation of severe heart failure, in which case a drug with a short duration of action that can be discontinued quickly is advantageous. These agents produce less reflex tachycardia when lowering blood pressure than do nonselective α antagonists such as phentolamine. Alpha -receptor selectivity allows norepinephrine to exert unopposed negative feedback1 (mediated by presynaptic α receptors) on its own release (see2 Chapter 6); in contrast, phentolamine blocks both presynaptic and postsynaptic α receptors, with the result that reflex activation of sympathetic neurons by phentolamine’s effects produces greater release of transmitter onto β receptors and correspondingly greater cardioacceleration. The drugs are more effective when used in combination with other agents, such as a β blocker and a diuretic, than when used alone. Owing to their beneficial effects in men with prostatic hyperplasia and bladder obstruction symptoms, these drugs are used primarily in men with concurrent hypertension and benign prostatic hyperplasia. Terazosin is also extensively metabolized but undergoes very little first-pass metabolism and has a half-life of 12 hours. Although long-term treatment with these α blockers causes relatively little postural hypotension, a precipitous drop in standing blood pressure develops in some patients shortly after the first dose is absorbed. Although the mechanism of this first-dose phenomenon is not clear, it occurs more commonly in patients who are salt- and volume- depleted. Aside from the first-dose phenomenon, the reported toxicities of the α blockers are relatively infrequent and mild. Some patients develop a positive test for antinuclear factor in serum while on prazosin therapy, but this has not been associated with rheumatic symptoms. The α blockers do not1 adversely and may even beneficially affect plasma lipid profiles, but this action has not been shown to confer any benefit on clinical outcomes. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system (Figure 11–4), as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. Vasodilators work best in combination with other antihypertensive drugs that oppose the compensatory cardiovascular responses. It has been available for many years, although it was initially thought not to be particularly effective because tachyphylaxis to its antihypertensive effects developed rapidly. The benefits of combination therapy are now recognized, and hydralazine may be used more effectively, particularly in severe hypertension. The combination of hydralazine with nitrates is effective in heart failure and should be considered in patients with both hypertension and heart failure, especially in African-American patients. Pharmacokinetics & Dosage Hydralazine is well absorbed and rapidly metabolized by the liver during the first pass, so that bioavailability is low (averaging 25%) and variable among individuals. It is metabolized in part by acetylation at a rate that appears to be bimodally distributed in the population (see Chapter 4). As a consequence, rapid acetylators have greater first-pass metabolism, lower blood levels, and less antihypertensive benefit from a given dose than do slow acetylators. The higher dosage was selected as the dose at which there is a small possibility of developing the lupus erythematosus-like syndrome described in the next section. Toxicity The most common adverse effects of hydralazine are headache, nausea, anorexia, palpitations, sweating, and flushing. In patients with ischemic heart disease, reflex tachycardia and sympathetic stimulation may provoke angina or ischemic arrhythmias. With dosages of 400 mg/d or more, there is a 10–20% incidence—chiefly in persons who slowly acetylate the drug—of a syndrome characterized by arthralgia, myalgia, skin rashes, and fever that resembles lupus erythematosus. The effect results from the opening of potassium channels in smooth muscle membranes by minoxidil sulfate, the active metabolite. Increased potassium permeability stabilizes the membrane at its resting potential and makes contraction less likely. Because of its greater potential antihypertensive effect, minoxidil should replace hydralazine when maximal doses of the latter are not effective or in patients with renal failure and severe hypertension, who do not respond well to hydralazine. Even more than with hydralazine, the use of minoxidil is associated with reflex sympathetic stimulation and sodium and fluid retention. Toxicity Tachycardia, palpitations, angina, and edema are observed when doses of co-administered β blockers and diuretics are inadequate. Headache, sweating, and hypertrichosis (the latter particularly bothersome in women) are relatively common. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. In the absence of heart failure, blood pressure decreases, owing to decreased vascular resistance, whereas cardiac output does not change or decreases slightly. In patients with heart failure and low cardiac output, output often increases owing to afterload reduction. Cyanide in turn is metabolized by the mitochondrial enzyme rhodanese, in the presence of a sulfur donor, to the less toxic thiocyanate. Nitroprusside rapidly lowers blood pressure, and its effects disappear within 1–10 minutes after discontinuation. Sodium nitroprusside in aqueous solution is sensitive to light and must therefore be made up fresh before each administration and covered with opaque foil. Because of its efficacy and rapid onset of effect, nitroprusside should be administered by infusion pump and arterial blood pressure continuously monitored via intra-arterial recording. Toxicity Other than excessive blood pressure lowering, the most serious toxicity is related to accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension, and death have resulted. In a few cases, toxicity after relatively low doses of nitroprusside suggested a defect in cyanide metabolism. Both have been advocated for prophylaxis or treatment of cyanide poisoning during nitroprusside infusion. Thiocyanate may accumulate over the course of prolonged administration, usually several days or more, particularly in patients with renal insufficiency who do not excrete thiocyanate at a normal rate. Thiocyanate toxicity is manifested as weakness, disorientation, psychosis, muscle spasms, and convulsions, and the diagnosis is confirmed by finding serum concentrations greater than 10 mg/dL. Rarely, delayed hypothyroidism occurs, owing to thiocyanate inhibition of iodide uptake by the thyroid. Injection of diazoxide results in a rapid fall in systemic vascular resistance and mean arterial blood pressure. Studies of its mechanism suggest that it prevents vascular smooth muscle contraction by opening potassium channels and stabilizing the membrane potential at the resting level.
Importantly mycelex-g 100mg free shipping fungal disease definition, these are the only two dental anesthetics that are formulated as 4% solutions; the others are all marketed at lower concentrations (eg generic 100mg mycelex-g mastercard antifungal roof shingles, the maximum concentration of lidocaine used for dental anesthesia is 2%) order mycelex-g 100 mg mastercard fungus symptoms, and it is well established that anesthetic neurotoxicity is generic mycelex-g 100mg otc anti fungal tea, to some extent, concentration-dependent. Thus, it is quite possible that enhanced risk derives from the formulation rather than from an intrinsic property of the anesthetic. However, despite over a century of use for this purpose, its popularity has recently diminished owing to increasing concerns regarding its potential to induce methemoglobinemia. Elevated levels can be due to inborn errors, or can occur with exposure to an oxidizing agent, and such is the case with significant exposure to benzocaine (or nitrites, see Chapter 12). Because methemoglobin does not transport oxygen, elevated levels pose serious risk, with severity obviously paralleling blood levels. It is often the agent of choice for epidural infusions used for postoperative pain control and for labor analgesia. However, spinal bupivacaine is not well suited for outpatient or ambulatory surgery, because its relatively long duration of action can delay recovery, resulting in a longer stay prior to discharge to home. Chloroprocaine gained widespread use as an epidural agent in obstetrical anesthesia where its rapid hydrolysis served to minimize risk of systemic toxicity or fetal exposure. The unfortunate reports of neurologic injury associated with apparent intrathecal misplacement of large doses intended for the epidural space led to its near abandonment. Although never exonerated with respect to the early neurologic injuries associated with epidural anesthesia, it is now appreciated that high doses of any local anesthetic are capable of inducing neurotoxic injury. Nonetheless, documented use as a spinal anesthetic is relatively limited, and additional experience will be required to firmly establish safety. In addition to chloroprocaine’s emerging use for spinal anesthesia, it still finds some current use as an epidural anesthetic, particularly in circumstances where there is an indwelling catheter and the need for quick attainment of surgical anesthesia, such as caesarian section for a laboring parturient with a compromised fetus. Even here, use has diminished in favor of other anesthetics combined with vasoconstrictors because of concerns about systemic toxicity, as well as the inconvenience of dispensing and handling this controlled substance. It has a tendency to produce an inverse differential block (ie, compared with other anesthetics such as bupivacaine, it produces excessive motor relative to sensory block), which is rarely a favorable attribute. It is also less potent, and tends to have a longer duration of action, though the magnitude of these effects is too small to have any substantial clinical significance. Interestingly, recent work with lipid resuscitation suggests a potential advantage of levobupivacaine over ropivacaine, as the former is more effectively sequestered into a so-called lipid sink, implying greater ability to reverse toxic effects should they occur. However, it differs from lidocaine with respect to vasoactivity, as it has a tendency toward vasoconstriction rather than vasodilation. This characteristic likely accounts for its slightly longer duration of action, which has made it a popular choice for major peripheral blocks. Lidocaine has retained its dominance over mepivacaine for epidural anesthesia, where the routine placement of a catheter negates the importance of a longer duration. More importantly, mepivacaine is slowly metabolized by the fetus, making it a poor choice for epidural anesthesia in the parturient. Unfortunately, this is somewhat offset by its propensity to induce methemoglobinemia, which results from accumulation of one its metabolites, ortho-toluidine, an oxidizing agent. It is gaining increasing use for spinal anesthesia in Europe, where it has been marketed specifically for this purpose. Although there is some evidence to suggest that ropivacaine might produce a more favorable differential block than bupivacaine, the lack of equivalent clinical potency adds complexity to such comparisons. It is commonly used in pediatrics to anesthetize the skin prior to venipuncture for intravenous catheter placement. More recently, efforts have focused on drug delivery systems that can slowly release anesthetic, thereby providing extended duration without the drawbacks of a catheter. Preliminary work encapsulating local anesthetic into microspheres, liposomes, and other microparticles has established proof of concept, although significant developmental problems, as well as questions regarding potential tissue toxicity, remain to be resolved. Less Toxic Agents; More Selective Agents It has been clearly demonstrated that anesthetic neurotoxicity does not result from blockade of the voltage-gated sodium channel. Thus, effect and tissue toxicity are not mediated by a common mechanism, establishing the possibility of developing compounds with considerably better therapeutic indexes. As previously discussed, the identification and subclassification of families of neuronal sodium channels has spurred research aimed at development of more selective sodium channel blockers. The variable neuronal distribution of these isoforms and the unique role that some play in pain signaling suggests that selective blockade of these channels is feasible, and may greatly improve the therapeutic index of sodium channel modulators. American Society of Regional Anesthesia and Pain Medicine: Checklist for treatment of local anesthetic systemic toxicity. Auroy Y et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Cave G, Harvey M: Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Di Gregorio G et al: Clinical presentation of local anesthetic systemic toxicity: A review of published cases, 1979 to 2009. Drasner K et al: Persistent sacral sensory deficit induced by intrathecal local anesthetic infusion in the rat. Groban L: Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Sakura S et al: Local anesthetic neurotoxicity does not result from blockade of voltage-gated sodium channels. Schneider M et al: Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. It has an adequately long duration of action and a relatively unblemished record with respect to neurotoxic injury and transient neurologic symptoms, which are the complications of most concern with spinal anesthetic technique. Although bupivacaine has greater potential for cardiotoxicity, this is not a concern when the drug is used for spinal anesthesia because of the extremely low doses required for intrathecal administration. If an epidural technique were chosen for the surgical procedure, the potential for systemic toxicity would need to be considered, making lidocaine or mepivacaine (generally with epinephrine) preferable to bupivacaine (or even ropivacaine or levobupivacaine) because of their better therapeutic indexes with respect to cardiotoxicity. However, this does not apply to epidural administration for postoperative pain control, which involves administration of more dilute anesthetic at a slower rate. Her past medical history is significant only for asthma, for which she has been intubated once in the past. There are multiple lacerations on her face and extremities and a large open fracture of her right femur. An orthopedic surgeon has scheduled immediate operative repair of the femur fracture, and the plastic surgeon wants to suture the facial lacerations at the same time. Would you choose the same agent if she had experienced a 30% total body burn in a fire at the time of the accident? These compounds are used primarily as adjuncts during general anesthesia to optimize surgical conditions and to facilitate endotracheal intubation in order to ensure adequate ventilation. Drugs in the spasmolytic group have traditionally been called “centrally acting” muscle relaxants and are used primarily to treat chronic back pain and painful fibromyalgic conditions. Dantrolene, a spasmolytic agent that has no significant central effects and is used primarily to treat a rare anesthetic-related complication, malignant hyperthermia, is also discussed in this chapter.
From an anatomic point of view discount mycelex-g 100mg visa fungus gnats sink drains, Within the field of comparative craniology mycelex-g 100 mg low cost fungus under fingernails, a both ontogenetically and phylogenetically buy 100 mg mycelex-g fungus video, the accu- search for a horizontal plane for the skull was per- racy of these midline structures located at the mid- formed by Daubenton (Daubenton and Daele 1764) generic mycelex-g 100 mg otc fungus gnats lawn, 12 Chapter 2 by Cuvier (1835) and later by Lucae (1872), along B The Need for a Consensus with many others. In his communication to the French Academy of Science in 1764, Daubenton de- Given the presence of several reference lines, an at- scribed the importance of the plane of the foramen tempt to find a consensus became obvious and nec- magnum as the horizontal plane tangent at the mid- essary. Following a meeting in Göttingen, German dle of its posterior border to the condylar processes anthropologists adopted the line advocated by Von of the skull. He pointed out that this plane is differ- Baer, which corresponds to the superior border of ently oriented in humans as compared with animals, the zygomatic arch, and named it the horizontal line passing through the inferior aspect of the orbits in of Göttingen (1860). This line modifies to some ex- man and considered by him as horizontal and per- tent the line of Lucae (1872) who defined as the pendicular to the vertical axis of the body and neck horizontal, the line passing through the axis of the when an erect position is assumed. Dauben- the head, observed that the horizontal plane corre- ton was convinced that horizontality is closely relat- sponds to the alveolar-condylar plane, defined as the ed to the orientation and position of the foramen reference plane passing through the inferior aspect magnum located in a central position at the base of of the occipital condyles and joining the middle of the skull, stating “plus le grand trou occipital est éloi- the alveolar ridge. Broca considered and defended gné du fond de l’occiput plus le plan de cette ouver- this plane as the horizontal plane of the cranium ture approche de la direction horizontale” (Dauben- (1873). His contribution to ly, the glabella-lambda plane, which was roughly craniology and anatomy differs from previous con- parallel to the latter. From 1862 to 1877, Broca evalu- tributions in this field, which lacked precision in the ated this plane with respect to many others, such as choice of anatomic landmarks. Camper’s horizontal plane was slightly modi- attached to Merckel’s “orbito-auditory” plane (1882), fied by Cuvier (1795)for use in his works on compar- also named “auriculo-suborbital” plane by Ihering ative anatomy. At the same time, Blumenbach de- (1872), and modified by Virchow and Hoelder to be- fined the norma verticalis of the cranium when lying come the “supra-auricular-infra-orbital” plane. From his research on brain proportions, Combe pro- posed a frontoparietal line, which was to be defined later by one of his pupils, Morton (1839), in the Unit- ed States, as the line joining the frontal to the parietal ossification centers of the skull. The “bi-orbital” plane of Broca (1877) 1234 Cephalic Reference Lines Suitable for Neuroimaging 13 gress (1877) and adopted in Frankfurt as the “infra- D The Choice of a Nomenclature orbital-meatal” plane, widely known as the Frank- furt-Virchow plane, which received the general ac- The development and diversification of increasing- ceptance of most of the anthropologists of the time. In a study meeting of the World Federation Planes of Neurology, held in Milan in 1961 and oriented toward problems of projections and nomenclature, A great number of cranial and cephalic reference the commission of nomenclature retained as basal planes and lines have been described, which are of reference lines two so-called horizontal baselines of variable importance based on an anatomic, phyloge- radiological importance: (1) the anthropological netic or anthropologic point of view. The craniofacial references reported in his exhaustive review of the literature are grouped as follows: craniofacial planes based on external landmarks, including superior horizontal planes (Table 2. A total of six cephalic reference lines and planes are Some of these are of great interest as they are used currently used in neuroimaging fields, which are in anthropology as well as in radiology and are wide- suitable for diagnostic, functional or interventional ly applied. These are: the bicom- plane, the nasion-opisthion, the nasion-basion, and missural plane (Talairach et al. Olivier (1978) pointed out, in view of com- commissural plane (Schaltenbrand and Bailey parative studies on craniofacial planes, that the na- 1959), the cephalic reference plane of Delmas and sion-opisthion and the Frankfurt-Virchow planes Pertuiset (1959), the neuro-ocular plane (Cabanis et are remarkably constant. Superior horizontal cranial reference lines (modified from Saban 1980) Literature reference Reference line Description Hamy 1873 Glabella-lambda line Roughly parallel to the alveolar-condylar plane of Broca Krogmann 1931 Horizontal line Parallel to Frankfurt plane, proceeding from the nasion Lucae 1872 Axis of the zygomatic arches Merkel 1882 Horizontal orbital-auditory line Center of the external auditory meatus; inferior rim of the orbit Morton 1839; Combe 1839 Horizontal plane Plane passing through the four prominent points of the frontal and parietal bones Perez 1922 Vestibian axis Virchow-Hoelder 1875 Supra-auricular-suborbital plane Superior border of the external auditory meatus; (Topinard 1882) Horizontal line of Munich (1877) inferior border of the orbit Von Baer 1860 Horizontal line of Göttingen Superior border of the zygomatic arch 1234 14 Chapter 2 Table 2. Inferior horizontal cranial reference lines (modified from Saban 1980) Literature reference Reference line Description Barclay 1803 Inferior facial plane Tangent to inferior border of the mandible Blumenbach 1795 Cranium in norma verticalis Lying on its base over a horizontal plane Broca 1862 Plane of mastication Inferior border of the teeth of the maxilla Broca 1862 Horizontal plane of the head Alveolar point at the inferior border of the alveolar Alveolar-condylar plane ridge – inferior aspect of both occipital condyles Cardinal plane of the cranium (1873) Broca 1862 Plane of horizontal vision, or The natural attitude of the head is that which permits visual plane (1873) or the eyes to reach the horizon without muscular bi-orbital plane (1877) contraction Daubenton and Daele 1764 Plane of the foramen magnum Center of the posterior edge of the occiput – condylar facet Camper 1791 Horizontal plane Spina nasalis anterior – center of the external auditory meati Doornik 1808 Horizontal line Incisors – most prominent point of the occiput His 1860, 1876 Horizontal line Spina nasalis anterior – opisthion (plane perpendicular to midsagittal) Lucae 1872 Horizontal line Spina nasalis anterior – basion Martin 1928 Line of the alveolar ridge or Alveolar border between median incisors and the horizontal alveolar line molars (study of the mandible) Martin 1928 Line of the base of the skull Nasion-basion (perpendicular to midsagittal plane) Spix 1815 Alveolar-condylar plane Tangent to the inferior aspect of the occipital condyles – median-most declivitous point of the superior alveolar ridge Table 2. Vertical reference lines of the skull (modified from Saban 1980) Literature reference Reference line Description Busk 1861 Vertical plane Auriculo-bregmatic line Bell 1806 Vertical axis of the cranium Cranium maintained in equilibrium over a stick held through the center of the foramen magnum Clavelin 1932 Vertical plane of the mandible Glenion – posterior border of the mandible Klaatsch 1909 Vertical line Bregma – basion Maly 1924 Vertical plane of the orbital Superior border – inferior border of the orbital aperture aperture Table 2. Cranial reference lines based on endocranial landmarks (modified from Saban 1980) Literature reference Reference line Description Barclay 1803 Palatine plane Passing through the palatine vault Beauvieux 1934 Plane of the ampullas Passing through the three ampullas of the semicircular canals Bjork 1947 Horizontal plane Nasion – center of the sella turcica Girard 1911 Plane of the horizontal semicircular canal Huxley 1863 Basi-cranial axis or basi-occipital Middle of the anterior border of the foramen magnum line – anterior extremity of the sphenoid Villemin and Beauvieux 1937 Nasion-opisthion line Walther 1802 Horizontal line Crista galli-inioning) Table 2. The opinion that the reference and the related target structure ought to pertain to the same ontoge- netic system is still accepted. Thus, it totally differs from the chiasmatico-commissural line on anatomic, ontogenetic and phylogenetic grounds, the latter being situated more caudally at the level of the diencephalon-mesencephalic junction. The bicommissural line also maintains to some extent reliable relationships to telencephalic struc- tures and helps in the localization of individual gyri on the brain cortex as demonstrated by numerous works carried out by Salamon and Talairach. Moreover, in their neu- roimaging and anatomic study of 30 brains oriented according to the bicommissural line, these authors reported difficulties in the identification of three major regions: the temporal parieto-occipital, the pars triangularis of the inferior frontal gyrus, and the paracentral lobule, due to important individual variations. In the view of the authors this is even more accurate for central sul- cus identification than the vertical planes defined using the bicommissural system of Talairach (Szikla and Talairach 1965; Talairach et al. The rolandic line is generated by joining the two intersection points between the callosal planes and the tangential hemi- spheric extending from the posterior superior to the anterior inferior points, parallel to the direction of the central sulcus (Fig. According to the au- thors, the central sulcus can be identified on any sag- ittal cut using the rolandic line, which may also be displayed on the lateral angiograms. The inferior tangential line is traced from the lateral sagittal im- age at a distance of 30 mm from the midsagittal cut. The major anatomic correlations observed by the authors show that the rolandic line seems to follow the direction of the central sulcus, beginning at the sulcal fundus or at the depth of its midextension in nearly 90% of cases. This work, presented as a three-dimensional atlas, provides important topometric data for 21 anatomic structures studied by the authors which are: the an- terior, centromedian, dorsomedian, ventral anterior, ventral posterior, lateral and medial pulvinar tha- lamic nuclei, the lateral and medial geniculate bod- ies, the mamillary body, the red nucleus, the subtha- lamic nucleus, the substantia nigra, the zona incerta, the amygdala, the pallidum, the caudate nucleus, the putamen, the superior and inferior colliculi, and the dentate nucleus of the cerebellum. Interesting data concerning variations in volume and position of such deep brain structures with respect to the ceph- alic index are shown. The first group com- prises the mamillary body, the lateral and medial geniculate bodies, and the superior and inferior col- Fig. The second group, represented by the Cephalic Reference Lines Suitable for Neuroimaging 23 nucleus subthalamicus, the putamen, the amygdala, tion. This includes the thalamic anterior and ventral and the dentate nucleus, showed symmetrical varia- anterior nuclei, the medial geniculate body, and the tions in volume. These two groups behave differently from presented an asymmetric increase in volume, in- the more laterally located structures, such as the len- cluding the dorsomedian, centromedian, ventral tiform and the caudate nuclei, which seem to vary in posterior and the medial pulvinar thalamic nuclei, relation to the cortex. Considering variations in position, the authors emphasized the close relation observed based on the cephalic index (Fig. On the other hand, these variations differ also with respect to the position of the anatomic structure as compared to the midsagittal plane. The medially located struc- tures, including the red nucleus, substantia nigra, subthalamic nucleus, mamillary body, dentate nucle- Fig. Topometric variations observed in cephalic indices us, and the dorsomedian, centromedian and medial comprised between 78 and 89. The anatomic correlation obtained by Cabanis brought a definite confirmation to the clinical rele- vance of this cephalic orientation, which is most suit- able for the exploration of the visual pathways (Fig. Bony landmarks, defined by tation for investigations in the axial and coronal Cephalic Reference Lines Suitable for Neuroimaging 25 A B Fig. The anatomic cuts in this work are de- visual pathway maintains a roughly horizontal ori- tailed views based on these references. Similarly, the hori- cludes the main anatomic correlations observed, zontal cuts reproduced in the atlas of Delmas and 26 Chapter 2 A B Fig. The topometric results derived duction of the amount of radiation to the lens during from the work of Delmas may, therefore, be used in slice acquisition. It is interesting to note also that the angle of the visu- Moreover, exhaustive work on the relation of the or- al pathways with respect to the base of the skull bital axis plane to several craniofacial reference lines changes with age due to the well-known occipital has been reported, including the important contri- descent (Delattre and Fenart 1960). However, once bution from the comparative anatomy laboratory of maturation is complete, the angle between the visual Dr. A third per- On the other hand, the relationship of this plane pendicular plane is drawn midway between the two with the basal ganglia seems more tentative, as they and is called the midcommissural plane. The The corpus callosum is the major telencephalic horizontal plane through this line can also be used in commissure influencing the shape of the adjacent the comparative anatomy of vertebrates if needed. It has the choice of this pivotal line, situated as it is at the been used for the preoperative identification of the midbrain-diencephalic junction corresponding to central sulcus (Lehman et al.
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Upon return to work mycelex-g 100mg generic fungus on toenails, use of proper respiratory protection and adherence to protective work practices are essential discount 100mg mycelex-g antifungal treatment for grass. The emergency physician performs endotracheal intubation and administers a drug intravenously order mycelex-g 100mg without prescription fungus gnats natural removal, followed by another substance via a nasogastric tube order mycelex-g 100mg fungus za mdomoni. The patient is admitted to the intensive care unit for continued supportive care and recovers the next morning. Childhood deaths due to accidental ingestion of a drug or toxic household product have been markedly reduced in the last 40 years as a result of safety packaging and effective poisoning prevention education. Even with a serious exposure, poisoning is rarely fatal if the victim receives prompt medical attention and good supportive care. Careful management of respiratory failure, hypotension, seizures, and thermoregulatory disturbances has resulted in improved survival of patients who reach the hospital alive. This chapter reviews the basic principles of poisoning, initial management, and specialized treatment of poisoning, including methods of increasing the elimination of drugs and toxins. The term toxicodynamics is used to denote the injurious effects of these substances on body functions. Although many similarities exist between the pharmacokinetics and toxicokinetics of most substances, there are also important differences. A large V implies that the drug is not readily accessible to measures aimed at purifying the blood, such as hemodialysis. Examples of drugs with large volumes of distribution (> 5 L/kg) include antidepressants, antipsychotics, antimalarials, opioids, propranolol, and verapamil. Drugs with a relatively small V (< 1 L/kg) include salicylate, ethanol, phenobarbital, lithium, valproic acid, and phenytoin (see Table 3–1). Clearance Clearance is a measure of the volume of plasma that is cleared of drug per unit time (see Chapter 3). The total clearance for most drugs is the sum of clearances via excretion by the kidneys and metabolism by the liver. In planning a detoxification strategy, it is important to know the contribution of each organ to total clearance. For example, if a drug is 95% cleared by liver metabolism and only 5% cleared by renal excretion, even a dramatic increase in urinary concentration of the drug will have little effect on overall elimination. Overdosage of a drug can alter the usual pharmacokinetic processes, and this must be considered when applying kinetics to poisoned patients. For example, dissolution of tablets or gastric emptying time may be slowed so that absorption and peak toxic effects are delayed. Drugs may injure the epithelial barrier of the gastrointestinal tract and thereby increase absorption. If the capacity of the liver to metabolize a drug is exceeded, the first-pass effect will be reduced and more drug will be delivered to the circulation. With a dramatic increase in the concentration of drug in the blood, protein-binding capacity may be exceeded, resulting in an increased fraction of free drug and greater toxic effect. At normal dosage, most drugs are eliminated at a rate proportional to the plasma concentration (first-order kinetics). If the plasma concentration is very high and normal metabolism is saturated, the rate of elimination may become fixed (zero-order kinetics). When considering quantal dose-response data, both the therapeutic index and the overlap of therapeutic and toxic response curves must be considered. For instance, two drugs may have the same therapeutic index but unequal safe dosing ranges if the slopes of their dose-response curves are not the same. For some drugs, eg, sedative-hypnotics, the major toxic effect is a direct extension of the therapeutic action, as shown by their graded dose-response curve (see Figure 22–1). In the case of a drug with a linear dose-response curve (drug A), lethal effects may occur at 10 times the normal therapeutic dose. In contrast, a drug with a curve that reaches a plateau (drug B) may not be lethal at 100 times the normal dose. For example, intoxication with drugs that have atropine-like effects (eg, tricyclic antidepressants) reduces sweating, making it more difficult to dissipate heat. In tricyclic antidepressant intoxication, there may also be increased muscular activity or seizures; the body’s production of heat is thus enhanced, and lethal hyperpyrexia may result. Overdoses of drugs that depress the cardiovascular system, eg, β blockers or calcium channel blockers, can profoundly alter not only cardiac function but all functions that are dependent on blood flow. These include renal and hepatic elimination of the toxin and that of any other drugs that may be given. An understanding of common mechanisms of death due to poisoning can help prepare the care-giver to treat patients effectively. Thus, they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdoses of narcotics and sedative-hypnotic drugs (eg, barbiturates and alcohol). Hypotension may be due to depression of cardiac contractility; hypovolemia resulting from vomiting, diarrhea, or fluid sequestration; peripheral vascular collapse due to blockade of α-adrenoceptor-mediated vascular tone; or cardiac arrhythmias. Hypothermia or hyperthermia due to exposure as well as the temperature-dysregulating effects of many drugs can also produce hypotension. Lethal arrhythmias such as ventricular tachycardia and fibrillation can occur with overdoses of many cardioactive drugs such as ephedrine, amphetamines, cocaine, digitalis, and theophylline; and drugs not usually considered cardioactive, such as tricyclic antidepressants, antihistamines, and some opioid analogs. Cellular hypoxia may occur in spite of adequate ventilation and oxygen administration when poisoning is due to cyanide, hydrogen sulfide, carbon monoxide, and other poisons that interfere with transport or utilization of oxygen. Such patients may not be cyanotic, but cellular hypoxia is evident by the development of tachycardia, hypotension, severe lactic acidosis, and signs of ischemia on the electrocardiogram. Hyperthermia may result from sustained muscular hyperactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic acidosis, and hyperkalemia. Paraquat attacks lung tissue, resulting in pulmonary fibrosis, beginning several days after ingestion. Massive hepatic necrosis due to poisoning by acetaminophen or certain mushrooms results in hepatic encephalopathy and death 48–72 hours or longer after ingestion. Finally, some patients may die before hospitalization because the behavioral effects of the ingested drug may result in traumatic injury. Intoxication with alcohol and other sedative-hypnotic drugs is a common contributing factor to motor vehicle accidents. First, the airway should be cleared of vomitus or any other obstruction and an oral airway or endotracheal tube inserted if needed. For many patients, simple positioning in the lateral, leftside-down position is sufficient to move the flaccid tongue out of the airway. Breathing should be assessed by observation and pulse oximetry and, if in doubt, by measuring arterial blood gases.
