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External genitalia examination reveals a 2-cm nontender mass in the right testicle that shows no light penetration with transillumination purchase 1 mg coumadin otc arrhythmia specialist. He jogs several miles each day and denies lifting heavy objects purchase cheap coumadin blood pressure goes up after eating, scrotal trauma buy 5mg coumadin visa 000 heart attack, and urinary problems purchase coumadin 1mg without prescription pulse pressure transducer. A history of trivial scrotal trauma is not uncommon, which often brings the scrotal mass to the patient’s attention. Testicular carcinoma should be ruled out before other condi- tions are considered, such as varicocele, spermatocele, hydrocele, epididymitis, or testicular torsion. Regular scrotal examination is advocated but rarely performed, and personal embarrassment often delays medical consultation. All of these structures lie within the boundaries of the urogenital triangle of the perineum. The relations of the perineal fascia and spaces (pouches) of the male perineum are similar to those described for the female perineum (see Case 27). However, in the male perineum, the fatty layer of the superficial fascia is virtually absent on the penis and is replaced by smooth (dartos) muscles in the scrotum. The membranous layer of the superficial fascia is continu- ous in the penis and scrotum as the dartos fascia (Figures 28-1 and 28-2). The penis is developmentally homologous to the clitoris in the female and has many anatomical similarities. Skin Colles’ fascia Buck’s fascia Tunica albuginea Corpus cavernosum Corpus spongiosum Urethra figure 28-2. Paired corpora cavernosa attach to the posterior portion of the ischiopubic rami (the crura of the penis) and converge anteriorly at the pubic symphysis. The single corpus spongiosum begins as an expanded region called the bulb of the penis, which is attached to the inferior surface of the perineal membrane, and into which the urethra passes. The corpus spongiosum with the urethra within it courses anteriorly to meet and fuse with the paired corpora cavernosa and form the body of the penis. The distal por- tion of the corpus spongiosum is expanded as the glans, which caps the distal ends of the paired corpora cavernosa. The three fused erectile bodies are surrounded by a deep (Buck) fascia, thin loose connective tissue, and thin, somewhat pigmented skin. The glans is covered by a redundant fold of skin called the prepuce (foreskin) and is removed if a child is circumcised. The posterior crural portion of the corpora cavernosa are covered with ischiocavernosus muscles, and the corpus spongiosum is covered by the paired bulbospongiosus muscles. Superficial transverse perineal muscles are also present at the posterior margin of the perineal membrane and attach to the perineal body. The scrotum is a sac of pigmented skin and the dartos fascial layer, which con- tains smooth muscle fibers that produce the characteristic wrinkling of the skin. The scrotum is posteroinferior to the penis and is divided into two compartments by an internal septum. Each testis is ovoid with a thick fibrous capsule, the tunica albu- ginea, from which incomplete connective tissue septa divide the interior into lob- ules. The lobules contain testosterone-producing interstitial cells (of Leydig) and coiled seminiferous tubules where spermatozoa (sperm) are produced. The seminiferous tubules converge toward the posteriorly located mediastinum to form tubules (straight tubules, rete testes, and efferent tubules), which convey sperm to the epididymis.

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Levodopa is transported across the gut wall and the blood- brain barrier and is converted to dopamine in striatal neurons purchase coumadin with mastercard blood pressure medication used in pregnancy. Carbidopa inhibits the peripheral decarboxylation of levodopa and thereby increases the amount of levodopa that enters the brain generic coumadin 1mg amex arteria tapada. Carbidopa does not cross the blood-brain barrier and does not inhibit dopamine synthesis in the brain purchase coumadin online now blood pressure 5332. Tolcapone and entacapone inhibit the methylation of levodopa in both peripheral tissues and the brain 2mg coumadin free shipping blood pressure chart morning. Tolcapone and entacapone increase levodopa bioavailability and increase brain uptake of levodopa. By this action, selegiline increases dopamine levels in the striatum, and it may reduce the formation of free radicals that are derived from H2O2. Bromocriptine and other dopamine-receptor agonists activate dopamine receptors in the striatum. Levodopa, also called L-dopa or enhance the peripheral decarboxylation of levodopa and dihydroxyphenylalanine, is the biosynthetic precursor of should not be coadministered with levodopa. Levodopa is absorbed from the proximal duodenum by Mechanisms and Pharmacologic Effects. In the brain, the same process that absorbs large neutral amino acids (see levodopa is taken up by dopaminergic neurons in the stria- Fig. Levodopa transport into the circulation, and amino acids can also thereby increases the amount of dopamine released by reduce the transport of levodopa into the brain. Levodopa can counteract all of the effectiveness of levodopa, and a protein-restricted diet may signs of parkinsonism, although the degree and duration of improve the response to levodopa in some patients. As the disease pro- Levodopa is metabolized by two pathways in peripheral gresses and more dopaminergic neurons are lost, the conver- tissues. It is converted to dopamine by aromatic L-amino sion of levodopa to dopamine declines. Over time, patients with levodopa to increase the amount of levodopa that enters begin to experience two types of fuctuation in the effective- brain tissue. The frst Carbidopa substantially reduces the gastrointestinal and type, a wearing off effect, occurs toward the end of a dosage cardiovascular side effects of levodopa and enables about a interval. The second type, the on-off phenomenon, is char- 75% reduction in the dosage of levodopa. When levodopa is used alone, nausea and sustained-release formulations that contain different and vomiting occur in about 80% of patients, orthostatic ratios of the two drugs. The sustained-release formulations hypotension is reported in 25%, and cardiac dysrhythmias are designed to reduce the “wearing off ” effect described occur in 10%. Amantadine appears to work by increasing a long-term basis eventually develop involuntary move- the release of dopamine from nigrostriatal neurons, but it ments, or dyskinesias, as a result of excessive dopamine may also inhibit the reuptake of dopamine by these neurons. Dyskinesias most often occur Amantadine is generally better tolerated than levodopa or when levodopa concentrations are highest, in which case dopamine agonists, but it is also less effective. Its adverse effects include appear as if they are chewing on large pieces of food while sedation, restlessness, vivid dreams, nausea, dry mouth, protruding their lips. It can also cause livedo reticularis, writhing and finging movements of the arms and legs. Although dyskinesias and psy- chotic effects could be managed by reducing the levodopa Selegiline dosage, the therapeutic effcacy of the drug would be reduced Pharmacokinetics.

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The half­lives of afferent impulses from the gut by antagonizing receptors in granisetron buy generic coumadin 1 mg on-line heart attack 30s, ondansetron discount coumadin 5 mg amex heart attack 4sh, and dolasetron are 4 buy discount coumadin on-line blood pressure 5040, 6 buy coumadin 2 mg on-line blood pressure medication most common, 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. Cimetidine inhibits cytochrome P450 isozymes and may increase the plasma concentrations of many other Other Antiemetics drugs, potentially causing adverse effects. Dronabinol is usually administered several hours peptic ulcers, and they are the drugs of choice for use before chemotherapy and is then administered every 4 to 6 in patients with gastrin-secreting tumors (gastrinomas) hours during a 12­hour period after chemotherapy. It • Sucralfate is a cytoprotective drug that binds to the is less effective than serotonin antagonists and has about ulcer crater and forms a barrier to acid and pepsin. Misoprostol is a prostaglandin E1 analogue that Dronabinol is also approved as an appetite stimulant for increases the production of mucus and bicarbonate anorexic patients with acquired immunodefciency syn­ while reducing the secretion of gastric acid. Two of these agents, dimenhydrinate and meclizine, are Crohn’s disease) are primarily treated with gluco- used in the management of motion sickness. Another of corticoids, aminosalicylates (sulfasalazine and mesala- these agents, promethazine, is an H1 antihistamine that also mine), and infiximab (an antibody to tumor necrosis has signifcant antimuscarinic activity and is used to prevent factor-α). In addition to being • Laxatives are drugs used to facilitate defecation and used by persons traveling in cars, planes, or boats for extended evacuate the bowels. Scopolamine tives (psyllium), surfactant laxatives (docusate sodium), is available as a skin patch that slowly releases the drug over osmotic laxatives (magnesium oxide and sodium phos- 72 hours. Bulk-forming laxatives are preferred for the treatment Guidelines for Chemotherapy-Induced Emesis of chronic constipation. Osmotic and stimulant laxa- The Multinational Association for Supportive Care in tives are used to clear the bowels of patients preparing Cancer guidelines for antiemetic therapy recommend a sero­ for intestinal surgery or diagnostic examination and tonin antagonist plus dexamethasone and aprepitant for patients being treated for a drug overdose or preventing acute emesis caused by highly emetogenic drugs poisoning. Which and others) are the most effcacious antiemetics for combination of drugs is recommended for this purpose the management of cancer chemotherapy-induced in current guidelines? Aprepitant, a neurokinin 1 (A) palonosetron, dexamethasone, and aprepitant receptor antagonist, also prevents chemotherapy- (B) dexamethasone only induced emesis. Metoclopramide and other D2 recep- (C) dexamethasone and aprepitant tor antagonists (e. Motion sickness can be prevented by meclizine and dimenhy- drinate (H1 receptor antagonists), or by scopolamine, Answers And explAnAtions a muscarinic receptor antagonist. The woman is most likely taking scopolamine, a muscarinic receptor antagonist that review Questions may cause dry mouth. A woman is using a skin patch medication to prevent heartburn, or headache (A, B, and C). It is not associated with pulmonary (B) heartburn fbrosis, ischemic heart disease, gastric ulcer, or muscle (C) headache rigidity and tremor (A, C, D, and E). The answer is D: a proton pump inhibitor plus sequen­ (E) dry mouth tial administration of amoxicillin followed by clarithro­ 2. Short­course sequential therapy episodes of abdominal pain, fatulence, and diarrhea that offers a high rate of H. Combinations of an acid inhibitor or cytoprotective agent (A) pulmonary fbrosis with amoxicillin and clarithromycin (A, C, and E) are not (B) ischemic colitis as effective as other regimens because of the high rate of (C) ischemic heart disease resistance to clarithromycin.

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Therefore vaccination is most beneficial when done before vaccinated patients become sexually active order coumadin once a day heart attack 2013 film, which is the case for most girls in this age group order coumadin without prescription hypertension drug. Shortly after Gardasil was approved discount coumadin 5mg with amex blood pressure variation, bills to make vaccination mandatory were introduced in 24 states buy cheap coumadin 2mg on line toprol xl arrhythmia. However, as of November 2015, only Kentucky, Rhode Island, Virginia, and the District of Columbia required the vaccine for school attendance. Furthermore, parents in Virginia who object can easily have their daughters opt out. Parents who are considering withholding vaccination would do well to ask this question: does protecting my daughter against developing cervical cancer later in life outweigh my concerns about vaccination? Unlike Gardasil, Cervarix is not indicated to prevent vaginal or vulvar cancer in females, or anal cancer or genital warts in females or males. Efficacy The efficacy of Cervarix was evaluated in a trial that enrolled about 18,000 girls and women aged 15 through 25 years. Half received Cervarix, and half received a control vaccine (Havrix, a vaccine against hepatitis A). Like Gardasil, Cervarix does not confer 100% protection against cervical cancer and is not active against cancer that began before the vaccine was given. Accordingly, vaccinated women should still undergo routine Pap screens to permit early detection and treatment of precancerous lesions. Duration of Protection Protection with Cervarix may last longer than with Gardasil because Cervarix is made with a unique adjuvant, a combination of aluminum hydroxide and monophosphoryl lipid A (derived from the bacterial cell wall). This adjuvant induces a stronger immune response than does the adjuvant in Gardasil (aluminum hydroxyphosphate sulfate). Like Gardasil, Cervarix has been associated with fainting, primarily in teenage girls. In addition, vaccination is recommended for all girls and women 13 to 26 years old who were not vaccinated when they were younger. Like Gardasil, Cervarix is not recommended for patients who are pregnant but may be used by those who are breastfeeding. Symptoms include symmetrical weakness in the arms and legs, sensory abnormalities, and paralysis of the muscles of respiration. The compound plays an important role in allergic reactions and regulation of gastric acid secretion. Accordingly, the chapter begins with a discussion of histamine, emphasizing its contribution to allergic responses. Histamine Histamine is a locally acting compound with prominent and varied effects. In the vascular system, histamine dilates small blood vessels and increases capillary permeability. Despite this impressive spectrum of actions, clinical use of histamine is limited to diagnostic procedures. However, although its clinical utility is minimal, histamine is still of great interest owing to its involvement in two common pathologic states: allergic disorders and peptic ulcer disease. Distribution, Synthesis, Storage, and Release Distribution Histamine is present in practically all tissues.

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