Loading

Digoxin

By N. Sibur-Narad. Dallas Theological Seminary.

A 74-year-old man with complaints of memory loss who has 55% st enosis in t he left int ernal carot id art ery B cheap digoxin line arteria gastrica sinistra. A 8 3 -year - old wo m an wit h d iz z in ess an d u n st ead y gait wit h 1 0 0 % occlusion of the left carotid artery C cheapest generic digoxin uk blood pressure chart home use. A 70-year-old man with transient loss of vision in the left eye that recovered after 20 minutes buy 0.25mg digoxin arteria umbilical percentil 95, and he has 75% left carotid stenosis E. The margin of benefit in an asymptomatic patient is smaller t han the margin for a symptomat ic pat ient. Continued optimal medical management may be the best recommendation for this patient. H e h as 90% left car ot id ar t er y st en osis wit h complet e occlu - sion of t he cont ralat eral carot id art ery. Because of t he cont ralat eral carot id occlusion, a temporary shunt during the operation may be the best choice given. The patient described in “A” is asymptomatic with 55% stenosis of the left carotid artery. The patient in “B” has complete occlusion of the left carotid and cannot benefit from revascularization. Findings from the cardiopulmonary exam- in a t io n s a re wit h in n o rm a l lim it s. Most likely diagnosis: W i lm s t u m o r ( n e p h r o b la s t o m a ) i n vo lvi n g the le ft k i d n e y. Best treatment: The best treatment will ultimately depend on the staging and local extent of t he disease. O perat ive t reat ment s include nephrectomies and nephron-sparing operat ions such as part ial nephrectomies. In general, treatments are multimodality and include surgical resection, chemotherapy, and/ or radiat ion therapy. Some minor t reat ment cont roversies exist because of different recommendations by the different international pediatric oncol- ogy groups. Become familiar with common presentation, differential diagnosis, and the initial evaluat ion of an abdominal mass in a newborn or pediat ric pat ient. Co n s i d e r a t i o n s Nephroblastomas (also known as Wilms tumor) are renal embryonal neoplasms that occur with peak incidence in young children between the ages of 1 to 5 years and peak age 3 to 4 years of age. Ten percent of t he pat ient s’ t umors are incident ally ident ified aft er t rauma, 25% of t he pat ient s have microscopic h ematuria, and 25% of the patient s have gross hematuria. H ypertension is a finding that occurs in some patients, as the result of excess renin production by the tumors. Optimal treatment of most patients with Wilms tumors consist of surgical resec- tion, radiation therapy, and chemotherapy. T h e except ion t o the mu lt imodalit y treatment approach is a patient < 2 years of age with stage I disease with favor- able h ist ology; for this t ype of pat ient, surgical resect ion wit h close surveillance may be sufficient treatment. Treatment for patients with Wilms tumor follows a prot ocol at most inst itut ions, wit h t reat ment s out lined by t he various clinical trials (see Tables 55– 1 and 55– 2 for staging and stratification). Modern multi- modality treatment outcomes are excellent for patients with Wilms tumors: St age I: 88% to 95% 5-year disease-free survival and 99% overall survival. W it h modern t reat ment and long-term survival for pat ient s wit h W ilms t umors, secon d malign an cies are begin n ing t o be rec- ognized in some of the survivors. In the analysis of international cohorts of over 13,000 patients treated for W ilms tumor, the risk of a second solid tumor occur- rence was 6. Pat ient s also had increased risk of leukemia development wit hin 5 years of diagnosis and treatment for Wilms tumors. When identified in the abdomen, these lesions can grow to large sizes before they produce obstructive symptoms. The determinations for surgery or ch emot herapy as t he init ial t reat ment are somet imes dict at ed by t he locat ion and local ext ent of the t umors, and available surgical expert ise. When a kidney containing Wilms tumor is removed and con- tains nephroblastomatosis, the risk of Wilms tumor development in the contralat- eral kidney is 20%. O t her syndromes associat ed wit h nephroblast omat osis include Beckwit h -Weid eman n an d D r ash syn d r omes. The etiology of an abdominal mass in a pediatric patient depends to a large ext ent on t he age of t he pat ient at present at ion. Knowledge of t he pat ient ’s age and relevant det ails from a focused history and physical examinat ion can allow the examiner to formulate a list of differential diagnoses. W ith this list generated, imaging studies and select ive laborat ory evaluat ions can be obt ained for definit ive diagnosis of the abdominal masses. Table 55– 4 lists the likely diagnosis for abdom- inal masses in neonat es (< 1 mont h of age), and Table 55– 5 list s the likely diagnosis for abdomin al masses in older in fant s and ch ildren. D uring the history and physical examinat ion, it is import ant t o find out from t he pat ient and t he family h ow long the mass has been present or noticed. It is also helpful to illicit other associated symptoms including ch an ges in eat in g h abit s, ch an ges in bowel or blad d er fu n ct ion s, sign s of fat igu e, night sweats, abnormal bleeding or bruising, or any other changes in behavior or activities. An important consideration for neonates is the maternal prenatal history, especially data from prenatal ultrasound and information regarding the presence or absence of polyhydramnios. Ra d i o g r a p h i c Ev a l u a t i o n s a n d P r e o p e r a t i v e P l a n n i n g Plain abdominal radiography can be helpful during the initial evaluation of an abdominal mass, because t his imaging modalit y can help ident ify solid masses occupying the abdomen and identify intestinal obstructive patterns. Calcifica- tions distributed along the intestines within the abdomen of neonates may indi- cat e mecon iu m ileu s; wh er eas, calcificat ion s wit h in a mass in the abd om en may help suggest neuroblastomas in older infants. When findings from plain radiography are not helpful, abdominal ult rasound can be t he next imaging modalit y of choice. Ult rasonog- raphy can generally help identify the organs of origin of abdominal masses. It is important to recognize that the sensitivity and specificity of ultrasonography is always highly operator dependent. It is import ant to bear in mind that in an infant or child wit h a neu- roblastoma, urinary studies for catecholamines should be obt ained to identify and address potent ial excess cat echolamine st at e relat ed t o t he tumor. In a pat ient wit h an abdominal mass that is suspected to be hepatoblastoma, the serum alpha-fet al- protein level should be assessed prior to tumor resection. Patients with stage I disease and favorable histology should be treated wit h surgery and chemot herapy 55. N euroblastoma is the third most common extracranial solid tumor in ch ild r en B. W ilm s t u m o r s o ccu r fr eq u en t ly in asso ciat io n wit h t r iso m y 2 1 gen et ic defect C. Plain film of the abdomen can be specific for the diagnosis of neuroblas- tomas of the abdomen D. Plain film of the abdomen is not indicated for the evaluation of newborn intest inal obst ruct ion E. N euroblastoma has been found to be associated with conditions such as Hirschsprung’s disease 55. M an ifest at io n s are n o n sp ecific an d can in clu d e sen so r y, m o t o r, an d gait dysfunctions C.

Hyperprolactinemia purchase 0.25 mg digoxin overnight delivery blood pressure medication hold parameters, diarrhea buy genuine digoxin online arteriografia, and dietary modifcations are not suffcient to alleviate constipa­ hematologic toxicity have also been reported buy digoxin 0.25mg fast delivery blood pressure medication that starts with t. Bulk­ pramide is contraindicated in persons with seizure disorders, forming laxatives can be used on a long­term basis without mechanical obstruction of the gastrointestinal tract, gastro­ noticeable side effects. Chapter 28 y Drugs for Gastrointestinal Tract Disorders 301 Antispasmodic Agents patients with drug overdose or poisoning. Lower doses of Muscarinic Receptor Antagonists magnesium oxide can be used to prevent constipation in Historically, atropine was used to treat peptic ulcer disease, some patients, such as those receiving opioid analgesics. Hence, these agents should be that inhibits histamine release from gastric paracrine cells limited to short­term use. Atropine, hyoscyamine, dicyclomine, and scopolamine It is converted to low­molecular­weight acids by colonic are used as antispasmodic agents to temporarily relieve bacteria that osmotically attract water and thereby stimulate intestinal cramping and pain and other symptoms of intes­ peristalsis. For this reason, lactulose is formulations with barbiturates for this indication such as used for the treatment of hepatic encephalopathy associ­ Donnatal, containing atropine, hyoscyamine, phenobarbi­ ated with elevated blood ammonia levels. Laxatives Stimulant (Secretory) Laxatives Bulk-Forming Laxatives The stimulant laxatives include a large group of natural and Bulk­forming laxatives are indigestible hydrophilic sub­ synthetic compounds that act directly on the intestinal stances, such as psyllium hydrophilic mucilloid and calcium mucosa to alter fuid secretion and stimulate peristalsis. Bisacodyl is available in oral and rectal mechanical distention of the intestinal wall and stimulate suppository formulations that are used in evacuating the peristalsis. Bulk­forming laxatives are available in several bowel before surgery or examination. The stimulant laxa­ preparations, including fber tablets and packets of psyllium tives can cause a number of adverse effects, including granules. They must be taken with a full glass of water to abdominal cramping and signifcant electrolyte and fuid ensure adequate hydration of the preparation and avoid depletion. Bulk­forming laxatives are the safest limited to the short-term treatment of constipation and and most physiologic type of laxative, and they rarely cause bowel evacuation. For this reason, they are the preferred drugs for the management of chronic constipation. Because of Other Agents their ability to absorb water and irritant substances such as Lubiprostone and Tegaserod bile salts, these drugs are also used in the treatment of diar­ Lubiprostone is a new type of drug that is approved for rhea (see later). Stool soften­ Lubiprostone activates the chloride ClC-2 channel in ers are primarily benefcial when fecal materials are hard or the apical (luminal) membrane of the intestinal epithelium dry and when their passage is irritating and painful (e. They testinal lumen, thereby increasing intestinal motility and are also useful when patients must avoid straining during relieving constipation. These substances attract and retain water being signifcantly relieved 2 or more weeks of the month in the intestinal lumen and increase intraluminal pressure, in 2 out of 3 months. They can be taken orally, and of patients, which is reduced by taking it with food, and some can be administered as an enema. Loperamide is available without a prescription and can effectively control mild diarrhea. The frequency of elimination and consistency of stools vary from person to person. Diarrhea is a condition characterized Locally Acting Drugs by an increase in the number and liquidity of a person’s Psyllium hydrophilic mucilloid and calcium polycarbophil stools. It can be acute or chronic, it can range in severity control diarrhea by acting locally within the intestinal tract from mild to life­threatening, and it has many causes and to adsorb water and irritant substances such as bile acids. Secretory diarrhea can be These substances are suitable for the treatment of mild caused by microbial toxins, laxatives, vasoactive intestinal diarrhea. Bismuth subsalicylate suspension, however, must active secretion of electrolytes and water into the intestinal be given frequently and repeatedly for maximal effcacy lumen. Some mediators of diarrhea also inhibit ion absorp­ (30 mL every 30 minutes for up to eight doses per day). This preparation causes few side effects, but excessively Severe diarrhea caused by bacterial infections and other large doses can expose the patient to bismuth or salicylate conditions can lead to signifcant loss of fuids and electro­ toxicity. If fever or systemic symptoms are present, patients with diarrhea should be Alosetron examined for microbial or parasitic infections. This condition requires a plain primarily of diarrhea, whereas constipation predomi­ more thorough diagnostic workup to determine the underly­ nates in others. Activation of these receptors causes neuronal that contain the correct proportions of glucose and electro­ depolarization and releases acetylcholine, which increases lytes for fuid and electrolyte replacement are available. As bowel movements decrease, a employed in women whose symptoms have lasted 6 months bland diet can be started. In these of Lactobacillus preparations can help restore the normal patients, alosetron increases colonic transit time and reduces bowel fora and reduce diarrhea in these patients. Alosetron may infrequently cause adverse gastrointestinal Opioid Drugs effects, including ischemic colitis, that rarely require blood The opioids are the most effcacious antidiarrheal drugs. Opioids act by inducing a sustained condition does not respond to conventional antidiarrheal segmental contraction of intestinal smooth muscle, which and antispasmodic medications. All of the more potent opioid ence of irritating and potentially harmful substances in receptor agonists are effective antidiarrheal compounds. Emetic stimuli travel from the gastrointestinal tract via the solitary tract nucleus to arrive at the vomiting center in the medulla. Vomiting is initiated by a nucleus of cells located in the The neural pathways involved in emesis and the sites of medulla that is called the vomiting or emesis center. The vestibular apparatus activates the vomiting center with nausea, which is an intensely unpleasant feeling of the via fbers that project to the cerebellum and release 304 Section V y Pharmacology of the Respiratory and Other Systems acetylcholine or histamine. Noxious substances in the gut the prevention and treatment of postoperative emesis, can activate vagal afferent pathways to the solitary tract whereas ondansetron and granisetron are used to prevent nucleus, which projects to the vomiting center, as well as nausea and vomiting caused by radiation therapy. Because Most antiemetic drugs act by blocking dopamine, sero- of its longer duration of action, a single dose of palonosetron tonin, muscarinic, or histamine receptors. Some drugs may prevent nausea and vomiting for up to 7 days after appear to inhibit several pathways that lead to vomiting chemotherapy. Muscarinic receptor antagonists can block the and delayed chemotherapy­induced nausea and vomiting. Dexamethasone, a glucocorticoid (see Chapter nausea and vomiting in persons receiving emetogenic 33), is an effective antiemetic whose mechanism is not chemotherapy. It was found to signifcantly who underwent laparoscopic cholecystectomy, for example, reduce the number of episodes of emesis in patients treated ondansetron was found to be more effective than metoclo­ with cisplatin, which is one of the most highly emetogenic pramide or a placebo in controlling emesis. The half­lives of afferent impulses from the gut by antagonizing receptors in granisetron, ondansetron, and dolasetron are 4, 6, and 7 the solitary tract nucleus. Ondansetron and dolasetron are both approved for stered parenterally or as a rectal suppository in patients who Chapter 28 y Drugs for Gastrointestinal Tract Disorders 305 are unable to take oral medication. For moderately as effective as other drugs in treating chemotherapy- emetogenic chemotherapy, a serotonin antagonist and induced emesis. For minimally emetogenic chemotherapy, a low dose of dexamethasone is Neurokinin-1 Receptor Antagonists recommended. Aprepitant Substance P is a peptide of the tachykinin family that acts as a neurotransmitter in the gut and brain.

Because of its ability to promote cellular uptake of potassium and thereby lower plasma potassium levels buy 0.25 mg digoxin free shipping blood pressure medication make you cold, insulin infusion is employed to treat hyperkalemia discount digoxin 0.25mg with visa blood pressure high in morning. The cardinal feature of both conditions is hyperglycemic crisis and associated loss of fluid and electrolytes buy cheap digoxin 0.25 mg on-line hypertension glaucoma. Both conditions can be life-threatening, and hence immediate treatment should be implemented. This syndrome is characterized by hyperglycemia, production of ketoacids, hemoconcentration, acidosis, and coma. These symptoms typically evolve quickly, over a period of several hours to a couple of days. Before insulin became available, practically all patients with type 1 diabetes died from ketoacidosis. Altered glucose metabolism causes hyperglycemia, water loss, and hemoconcentration. Note that, in its final stages, the syndrome consists of hemoconcentration and shock in addition to ketoacidosis. The alterations in fat and glucose metabolism that lead to ketoacidosis are described in detail later. Treatment is directed at correcting hyperglycemia and acidosis, replacing lost water and sodium, and normalizing potassium balance. Although it might seem reasonable to drive glucose levels down quickly with lots of insulin, doing so is unsafe and should be avoided. When plasma glucose has fallen to 200 mg/dL, the infusion rate should be reduced to 0. Thereafter the insulin dosage should be adjusted as needed to maintain plasma glucose levels between 150 and 200 mg/dL until acidosis has resolved. Switching to subQ insulin is common and acceptable after the patient recovers from the acute episode. Also, when insulin is administered subQ, insulin levels cannot be lowered quickly in response to inadvertent excessive dosing, and hence avoiding hypoglycemia may be difficult. Studies have failed to demonstrate any benefit of giving bicarbonate to patients with severe acidosis (blood pH 6. Nonetheless, some authorities recommend empiric therapy with bicarbonate if blood pH is below 6. Because bicarbonate promotes hypokalemia, potassium should be infused along with the bicarbonate, as noted earlier, unless hyperkalemia (serum potassium above 5. Adults usually require between 8 and 10 L of fluid during the first 12 hours of treatment. In older-adult patients and patients with heart disease, central venous pressure should be monitored. Because hypokalemia predisposes the patient to dysrhythmias, electrocardiographic monitoring is essential. Treatment of potassium loss is tricky because plasma potassium levels may be normal even though intracellular potassium is very low. When insulin is administered, causing cellular uptake of potassium to increase, severe hypokalemia can develop as plasma potassium rushes into potassium-depleted cells. Because of this relationship between insulin administration and plasma potassium levels, the following guidelines apply: (1) if plasma potassium is normal, no potassium should be administered until plasma potassium declines in response to insulin; (2) if plasma potassium is low, potassium should be given immediately (and then readministered if potassium levels fall after insulin administration). Normalization of Glucose Levels Treatment of ketoacidosis with insulin may convert hyperglycemia into hypoglycemia. Because cellular uptake of glucose is impaired by insulin deficiency, ketoacidosis is likely to be associated with a reduction in intracellular glucose—despite elevations in plasma glucose content. Under these conditions, giving insulin will cause plasma glucose to rush into the glucose-depleted cells, thereby causing plasma levels of glucose to drop precipitously. If insulin therapy induces hypoglycemia, plasma glucose can be restored by giving glucagon or glucose. As noted, the central characteristic in both disorders is severe hyperglycemia brought on by insulin deficiency. The result is dehydration and loss of blood volume, which greatly increases the blood concentrations of electrolytes and nonelectrolytes (particularly glucose)—hence the term hyperosmolar. For high-dose therapy, furosemide can be administered by continuous infusion at a rate of 4 mg/min or slower. Mannitol, an Osmotic Diuretic Osmotic diuretics differ from other diuretics with regard to mechanism and uses. At this time, mannitol is the only osmotic diuretic available in the United States. Mannitol [Osmitrol] is a simple six-carbon sugar that embodies the following four properties of an ideal osmotic diuretic: • Is freely filtered at the glomerulus • Undergoes minimal tubular reabsorption • Undergoes minimal metabolism • Is pharmacologically inert (i. As a result, most of the filtered drug remains in the nephron, creating an osmotic force that inhibits passive reabsorption of water. The degree of diuresis produced is directly related to the concentration of mannitol in the filtrate: the more mannitol present, the greater the diuresis. Mannitol has no significant effect on the excretion of potassium and other electrolytes. When the volume of filtrate is this low, transport mechanisms of the nephron are able to reabsorb virtually all of the sodium and chloride present, causing complete reabsorption of water as well. Because filtered mannitol is not reabsorbed—even when filtrate volume is small—filtered mannitol will remain in the nephron, drawing water with it. Thiazides and loop diuretics are not as effective for this application because, under conditions of low filtrate production, there is such an excess of reabsorptive capacity (relative to the amount of filtrate) that these drugs are unable to produce sufficient blockade of reabsorption to promote diuresis. There is no risk for increasing cerebral edema because mannitol cannot exit the capillary beds of the brain. The hyperosmotic plasma creates an osmotic force that draws ocular fluid into the blood. Adverse Effects Edema Mannitol can leave the vascular system at all capillary beds except those of the brain. The infusion rate should be set to elicit a urine flow of at least 30 to 50 mL/hr. If urine flow declines to a very low rate or ceases entirely, the infusion should be stopped. Because digoxin can be given orally, it is the only inotropic agent suited for long-term therapy. Sympathomimetic Drugs: Dopamine and Dobutamine The basic pharmacology of dopamine and dobutamine is presented in Chapter 13. Dopamine Dopamine is a catecholamine that can activate (1) beta -adrenergic receptors in1 the heart, (2) dopamine receptors in the kidney, and (3) at high doses, alpha -1 adrenergic receptors in blood vessels. Activation of beta receptors increases1 myocardial contractility, thereby improving cardiac performance. Activation of dopamine receptors dilates renal blood vessels, thereby increasing renal blood flow and urine output.

The other major structure of the larynx is the conus elasticus order digoxin on line heart attack or heartburn, another broad ligament inferior to the quadrangular membrane order digoxin 0.25mg free shipping blood pressure which arm. The free superior border also attaches to the arytenoid car- tilage and forms the vocal ligament (true vocal fold) order digoxin 0.25mg amex arrhythmia ablation. When the rima glottidis is narrow, the expelled air will vibrate the vocal folds and produce a sound. The intrinsic musculature of the larynx is devoted mostly to fine-motor con- trol of the vocal folds to modulate pitch and intonation during speech. Perhaps the most important muscles are the posterior cricoarytenoids, which are the only muscles used to abduct the vocal folds and are necessary to widen the rima glot- tidis for breathing. All of the other muscles function to adduct the rima glottidis or modulate the tension of the vocal chords. The transverse and oblique arytenoid muscles bring the two arytenoid cartilages together, which indirectly act to close the posterior portion of the rima glottidis. The cricothyroids lengthen and tighten the vocal fold, whereas the thy- roarytenoid relaxes it. The vocalis muscle runs under the vocal fold and produces local modulations in tightness (e. Several structures protect the trachea from food or liquid traveling to the esoph- agus. The first of these is the epiglottis, which deflects food laterally around the quadrangular membrane to the piriform recess and into the esophagus. The epi- glottis itself does not apply sufficient force to completely close off the laryngeal inlet. During swallowing, the suprahyoid muscles contract and, through the thyro- hyoid membrane, lift the larynx up against the epiglottis. The infrahyoid muscles attached to the external face of the thyroid cartilage help to return the larynx to its resting position. The only exception is the crico- thyroid, which is innervated by the external branch of the superior laryngeal nerve, also a branch of the vagus. Thus, damage to the superior laryngeal nerve will affect voice quality, particularly the ability to reach high tones. More significantly, damage to the recurrent laryngeal nerve will impair the ability to abduct the vocal folds, possibly leading to respiratory distress if the injury is bilateral. Unilateral damage to the recurrent laryngeal nerve will result in inability to tightly adduct the two vocal folds, resulting in hoarseness. In addition, the protective function of the rima glottidis may be lost, and food or liquid that does not go down the esophagus may flow into the trachea and cause a choking response. In the supraglottic region (above the vocal fold), the mucosa is innervated by the internal branch of the superior laryngeal nerve. In the infraglottic region (below the fold), the mucosa is innervated by the recurrent laryngeal nerve. Thus, damage to the superior and recurrent laryngeal nerves may also have deficits in reflex behaviors that depend on sensory input from the larynx. Which of the following nerves is responsible for carrying the sensa- tion for this pain? The posterior cricoarytenoid muscles are the only muscles that abduct the vocal folds and are necessary to widen the rima glottidis for breathing. Injury to the recurrent laryngeal nerve is common during thyroid surgery and may lead to the inability to tightly adduct the two vocal folds, resulting in hoarseness. In addition, the protective function of the rima glottidis may be lost, and food or liquid that does not go down the esophagus may flow into the trachea and cause a choking response. The laryngeal mucosa above the vocal cords is innervated by the superior laryngeal nerve, whereas mucosa below the vocal cords is innervated by the recurrent laryngeal nerve. On examination, he has a blood pressure of 150/90 mmHg and a normal body temperature. If the deficits were to resolve before 24 h, it would be called a transient ischemic attack. If the deficits were to continue beyond 24 h, it would be called a cerebrovas- cular accident, or stroke. Differentiating between the two is important because fibrinolytic therapy (medication that dissolves blood clots) would be contraindicated with hemorrhagic strokes. In this patient, the bruits identified on the carotid arteries are likely due to increased rate and tur- bulence of blood flow through the stenotic vessels. Immediate management of this patient would include administration of an antiplatelet medication such as aspirin and/or clopidogrel. After stabilization of the patient, carotid endarterectomy surgery may be indicated. Be able to review the somatotopic organization of sensory and motor regions in the brain 2. Be able to list the branches of the common carotid artery and the vascular sup- ply to the brain and identify the sites most susceptible to formation of athero- sclerotic plaques 3. The cerebrum is involved in the major functions of sensory perception, motor control, and the associational processing that integrates the two. The surface or cortex of the cerebrum is folded into a number of ridges (gyri) separated by valleys (sulci) of different depths. The brain is divided into lobes named for the overlying cranial bones: frontal, temporal, parietal, and occipital. The precentral gyrus controls voluntary motion, whereas the postcentral gyrus is the site of somatosensory perception. The sensory and motor areas are arranged according to a somatotopic organi- zation. The lower extremity is represented medially along the gyrus; the upper extremity, more laterally; and the head and neck, most laterally. The tracts going to and from the sensory and motor areas cross in the lower brain and spinal cord to control the opposite side of the body. Another important region is the motor speech area (Broca area), which is a small gyrus in the anterior parietal cortex of the left brain, called the operculum, just superior to the temporal lobe. These basic organizational features are important because they help physicians identify the region of the brain damaged by a stroke or hemorrhage. Thus, numbness or paralysis of the right upper extremity indicates damage on the left side of the brain, which will frequently involve the motor speech area. The blood supply to the brain is from the common carotid and the vertebral arteries (Figure 37-1). The vertebral artery ascends through the transverse foramina of the cervical vertebrae without giving off any major branches. The common carotid bifurcates at about the level of the hyoid bone (vertebrae C3 and C4).

In the report buy 0.25mg digoxin mastercard heart attack is recognized by, they discussed 11 cases of hepatotoxicity from the United States and Europe in which the victims required a liver transplant owing to severe liver failure order digoxin 0.25 mg with visa blood pressure chart pictures. Because of concerns over hepatotoxicity purchase discount digoxin hypertension with stage v renal disease, kava sales have been restricted in Germany, Canada, Switzerland, France, and Australia—but not yet in the United States. High-dose ephedra has been associated with stroke, myocardial infarction, and death. To date, more than 17,000 adverse events have been reported, and at least 155 users have died. The ban was challenged by an ephedra producer and, in 2005, was partially reversed: a federal court upheld the ban for ephedra products that contain more than 10 mg/dose, but reversed the ban for products that contain 10 mg or less, arguing that there are insufficient data to prove that low doses pose a “significant or unreasonable risk. Each day, 190 million doses of antibiotics are given in hospitals, making these drugs one of our most widely used groups of medicines. Modern antimicrobial agents had their debut in the 1930s and 1940s and have greatly reduced morbidity and mortality from infection. As newer drugs are introduced, our ability to fight infections increases even more. There remain organisms that respond poorly to available drugs; there are effective drugs whose use is limited by toxicity; and there is, because of evolving microbial resistance, the constant threat that currently effective antibiotics will be rendered useless. The first is microbial susceptibility to drugs, with special emphasis on resistance. Topics addressed include criteria for drug selection, host factors that modify drug use, use of antimicrobial combinations, and use of antimicrobial agents for prophylaxis. Before going further, we need to consider two terms: antibiotic and antimicrobial drug. In common practice, the terms antibiotic and antimicrobial drug are used interchangeably, as they are in this book. Strictly speaking, an antibiotic is a chemical that is produced by one microbe and has the ability to harm other microbes. Under this definition, only those compounds that are actually made by microorganisms qualify as antibiotics. Drugs such as the sulfonamides, which are produced in the laboratory, would not be considered antibiotics under the strict definition. In contrast, an antimicrobial drug is defined as any agent, natural or synthetic, that has the ability to kill or suppress microorganisms. Under this definition, no distinction is made between compounds produced by microbes and those made by chemists. From the perspective of therapeutics, there is no benefit to distinguishing between drugs made by microorganisms and drugs made by chemists. Hence, the current practice is to use the terms antibiotic and antimicrobial drug interchangeably. Selective Toxicity Selective toxicity is defined as the ability of a drug to injure a target cell or target organism without injuring other cells or organisms that are in intimate contact with the target. As applied to antimicrobial drugs, selective toxicity indicates the ability of an antibiotic to kill or suppress microbial pathogens without causing injury to the host. Achieving Selective Toxicity How can a drug be highly toxic to microbes but harmless to the host? The answer lies with differences in the cellular chemistry of mammals and microbes. There are biochemical processes critical to microbial well-being that do not take place in mammalian cells. Hence, drugs that selectively interfere with these unique microbial processes can cause serious injury to microorganisms while leaving mammalian cells intact. Disruption of the Bacterial Cell Wall Unlike mammalian cells, bacteria are encased in a rigid cell wall. The protoplasm within this wall has a high concentration of solutes, making osmotic pressure within the bacterium high. If it were not for the cell wall, bacteria would absorb water, swell, and then burst. Because mammalian cells have no cell wall, drugs directed at this structure do not affect us. Inhibition of an Enzyme Unique to Bacteria The sulfonamides represent antibiotics that are selectively toxic because they inhibit an enzyme critical to bacterial survival but not to our survival. Specifically, sulfonamides inhibit an enzyme needed to make folic acid, a compound required by all cells, both mammalian and bacterial. Because we can use folic acid from dietary sources, sulfonamides are safe for human consumption. Because mammalian cells do not make their own folic acid, sulfonamide toxicity is limited to microbes. Disruption of Bacterial Protein Synthesis In bacteria, as in mammalian cells, protein synthesis is done by ribosomes. However, bacterial and mammalian ribosomes are not identical, and hence we can make drugs that disrupt function of one but not the other. As a result, we can impair protein synthesis in bacteria while leaving mammalian protein synthesis untouched. Classification of Antimicrobial Drugs Various schemes are employed to classify antimicrobial drugs. Classification by Susceptible Organism Antibiotics differ widely in their antimicrobial activity. Some agents, called narrow-spectrum antibiotics, are active against only a few species of microorganisms. In contrast, broad-spectrum antibiotics are active against a wide variety of microbes. As discussed later, narrow-spectrum drugs are generally preferred to broad-spectrum drugs. The table shows three major groups: antibacterial drugs, antifungal drugs, and antiviral drugs. In addition, the table subdivides the antibacterial drugs into narrow-spectrum and broad-spectrum agents and indicates the principal classes of bacteria against which they are active. We do not know why inhibition of protein synthesis by these agents results in cell death. However, in contrast to the aminoglycosides, these agents only slow microbial growth—they do not kill bacteria at clinically achievable concentrations. Members of this group include rifampin, metronidazole, and the fluoroquinolones (e. The result is either a decrease in the synthesis of essential cell constituents or synthesis of nonfunctional analogs of normal metabolites. When considering the antibacterial drugs, it is useful to distinguish between agents that are bactericidal and agents that are bacteriostatic.