By W. Akrabor. Reed College. 2019.
Donor sites for cartilage grafts Dissection and Mobilization of Septal Cartilage Nasal septum □ auricle: right □ left □ rib □ 1 purchase wellbutrin cheap online. Nasal deviation Straight: □ Deviated: □ The approach to the nasal septum is usually done endonasally through an incision at the caudal margin of the septum purchase cheap wellbutrin on-line, making Upper third: right □ left □ subperichondrial tunnels bilaterally in an anterior order wellbutrin overnight delivery, inferior cheap 300 mg wellbutrin overnight delivery, and Middle third: right □ left □ posterior fashion. If there are any inferior or posterior deflec- Lower third (nasal tip): right □ left: □ tions that must be corrected at the maxillary crest or ethmoid bone, they are usually performed. Once this intranasal portion of the operation is completed, the open rhinoplasty approach is used, and the nasal tip and dorsum are exposed. In the crooked nose, it is usually necessary to free the dorsal portion of the septal cartilage from the upper lateral cartilages bilaterally. This will give the surgeon a clear view of the nasal septum, and the middle and lower third of the nose. Additionally, once the septal cartilage is freed from all its extrinsic forces and attachments, its deviations can be eval- uated and cartilage (if available) can be harvested for grafting. If cartilage is going to be harvested from the septum, care should be taken to leave at least 1. This inverted L of cartilage should remain if should be left caudally and dorsally, leaving a strong inverted L of possible to avoid any postsurgical loss of support to the nasal cartilage as support to the underlying structures of the nose. Remaining cartilage will be used in other areas of the nose as struts, tip grafts, or morselized cartilage. Ethnic patients frequently have short nasal bones, weak upper lateral cartilages, and poor support in the caudal edge of the septum, which add an additional risk factor to the surgery. Special care should be taken not only to correct any asymme- tries or deviations but also to reinforce the “natural” support structures of the middle vault area and the lower third of the nose. In this way, a normal dorsal contour can be reconstituted without the risk of having collapses or deformities produced because structures were not reinforced in a proper fashion. The workhorse options in these two areas are the spreader grafts in the middle third of the nose and the caudal septal extension graft, which will give additional support to the pedestal and the tripod. Isolated dorsal deviations can be treated with unilateral or bilateral spreader grafts depending on the severity of the deformity. Spreader grafts are the workhorse when treating and/or reinforcing the middle-third structures of the nose. Grafts are carved ideally from septal cartilage and usually extend from the nasal bone cephalically down to the anterior septal angle caudally. When septal cartilage is not available, conchal cartilage can also be used with good results. The dimensions vary, but depending on the patient’s needs, they can measure from 2 to 4mm in thickness and height and 10 to 25mm in length. Grafts should be carved thicker ceph- alically where you want them to restore the trapezoid shape of the upper middle third of the nose and thinner caudally in the internal nasal valve area. If the middle nasal vault area is asym- metric, a thicker graft or a double spreader can be placed in the area where the depression is bigger. Sutures should be placed cephalically near the bony cartilagi- nous junction, caudally at the level of the anterior septal angle and in between. The upper lateral cartilages are then fixed to this complex at the same height of the grafts and the Fig. The reconstituted mid- is freed from the upper lateral cartilage and the concavity can be dle third of the nose should be smooth and any irregularities of clearly visualized. Dorsal deviations postoperative frontal pictures of patient whose deviation was in this area can be corrected by extending the spreader grafts corrected with hump removal, bilateral spreader grafts, and medial all the way down to the anterior septal angle. Note excessive widening in this area, grafts should be beveled smooth dorsal profile, with correction of big hump and deformity. In cases where the posterior septal angle is shifted oﬀ the midline from the nasal spine, the septum is freed from its liga- performed so that the septum can be fixed again in the midline. Sutures must fix graft inferiorly to the nasal spine, superiorly, and in the middle, making sure graft is securely fixed and will not move. Where the feet of the medial crura are fixed will define the height of the nasal tip. The height of the nasal tip is set depending on how much tip rota- graft should be placed overlapping the caudal edge of the sep- tion, projection, or counterrotation the patient needs. Sutures should be placed at the anterior septal angle, the Alignment of Bony Pyramid posterior septal angle, and the distance between these two in such a way that it becomes a stable pedestal for the structures Once the cartilaginous portion of the nose has been addressed, of the nasal tip. It is important to make sure that the overlap- the septum stabilized in the midline, and grafts placed for ping segment of the graft does not produce obstruction of the structural support, osteotomies are performed. If this is the case, the edge of the graft should be care- mobilization of nasal bones can be achieved using medial and fully beveled before placement. In the cases where Medial osteotomies are usually done before lateral osteoto- the existing septal cartilage was deviated to one side, the graft mies are performed. A 3-mm osteotome should be placed at the can be placed on the contralateral side to compensate for this junction of the upper lateral cartilages with the nasal bones just deviation. Crushed or morselized cartilage is frequently used over the bony dorsum, upper lateral cartilages, supratip, and nasal tip area to compensate for any depression or irregularity. If there is no cartilage available, temporalis fascia can also be used with good results. Cartilage should be morselized in such a way that it has the texture of a carpet to avoid excessive resorption. Skin care is a priority in these only the periosteum around the incision so the osteotome can patients and should include a home regimen with dermatologic fit comfortably. The periosteum is left intact over the lateral skin treatment products that control acne flareups, skin pH, nasal walls. The osteotomy is done high along the pyriform and presence of blackheads and pimples in this area. If medial sage over fracture lines should be taught to the patient and osteotomies were done previously, these are connected to the should be encouraged several times a day to help with healing lateral osteotomy, mobilizing all the nasal bony pyramid process over the dorsum. Straight noses are hard to achieve in these patients, and they Percutaneous osteotomies are done occasionally with a should be aware of this when they decide they want surgery. In the author’s hands, this type of osteotomy A good physician-patient relationship is indispensable, and is reserved for patients who need a controlled fracture at the patients have to understand that the healing process will take level of the ascending maxilla and nasal bones or to complete time. It is important to patients to have a more pleasing profile, the back fracture of a lateral osteotomy at the level of the nicer and straighter, although they might still have imperfec- medial canthus. Correction should be planned keeping in mind the ethnic characteristics of each patient and whenever possible respect- ing and maintaining distinctive facial features. Surgical techni- ques should be focused on strengthening support structures of the nose. The surgical approach in the crooked nose has a func- tional and a cosmetic purpose and both have to be dealt with accordingly. Surgery should be performed using a stepwise approach where all compromised areas of the nose are dealt with accordingly to obtain long-term results that can be more durable and satisfying to the patient. The most important area for the airway is the described to achieve this goal, ranging from suture techniques nasal vestibule and the valve region. However, a deviated behavior of cartilage after correction, however, is not always or thickened perpendicular plate sometimes combined with a predictable because of the “memory eﬀect. This may induce an overcor- view, correction of the caudal (cartilaginous) part of the nasal rection and may result in nasal obstruction on the contralateral septum is crucial. This is why a distinction between septoplasty side of the former septal deflection. An overcorrection may pri- (Cottle) and submucosal septal resection (Killian) has to be marily appear in patients younger than 30 and is attributed to made, in spite of the fact that both terms are very often used still growing cartilage. Very often this deformity is sion in the mucosa, leaving a frame of septal cartilage at the thought to be a problem of the cartilaginous septum alone. Only the central and However, in most cases, it is the sign of a deviation of the nasal posterior parts of the cartilaginous and bony septum are bones from the midline. However, not only do the terms for septal correction have to be defined, but also what is in general called a “complication. A mistake, however, is the result of inadequate planning or execution of the operation, sometimes also because of the postoperative treatment. If it happens, the surgeon must ask whether it is a complication or a mistake and very often will find something in between.
A meta-analysis of postmarketing studies revealed no significant increase in cardiovascular events between subjects taking omalizumab and a placebo buy discount wellbutrin on-line. There was a small increase in rare malignancy occurrence in subjects taking omalizumab; however wellbutrin 300 mg without prescription, a clear relationship to the drug has not been established purchase wellbutrin mastercard. Life-threatening anaphylaxis—characterized by urticaria and edema of the throat and/or tongue—has occurred rarely (in less than 0 purchase wellbutrin in india. Anaphylaxis is most likely with the first dose but can also occur after receiving repeated doses with no apparent sensitivity. To minimize injury from anaphylaxis, patients should be observed for 2 hours after the first three doses and for 30 minutes after all subsequent doses. Preparations, Dosage, and Administration Omalizumab [Xolair] is available as a powder (202. Dissolving the powder, which can take 20 minutes or longer, yields a final solution of 150 mg/1. Administration is by subQ injection, which may take 5 to 10 seconds because the solution is somewhat viscous. The reconstituted solution should be used within 4 hours (if stored at room temperature) or within 8 hours (if stored cold). The size of each dose and the dosing interval are determined by body weight and total serum IgE, measured at baseline. This is why most patients who require a bronchodilator also use an inhaled glucocorticoid for long-term suppression of inflammation. Monotherapy with a bronchodilator is appropriate only when asthma is very mild and attacks are infrequent. Virtually all patients with asthma use these first-line drugs as a component of an asthma management regimen. Safety and efficacy of anticholinergics has not been established for children younger than 11 years. It is important to consider variable drug clearance across age ranges when dosing. Pregnant women must have adequate respiratory exchange to ensure adequate oxygenation of the developing fetus. Breastfeeding Breastfeeding is not contraindicated with beta agonists or anticholinergics; however, manufacturers2 women of both drugs recommend caution. Labeling for methylxanthines warns against breastfeeding only if the mother may have toxic levels. Systemic anticholinergics are included in Beers Criteria for Potentially Inappropriate Use in Older Adults; they should not be substituted for inhaled anticholinergics. Mechanism of Action The beta agonists are sympathomimetic drugs that activate beta -adrenergic2 2 receptors. By activating beta receptors in smooth muscle of the lung, these2 drugs promote bronchodilation and thus relieve bronchospasm. In addition, beta2 agonists have a limited role in suppressing histamine release in the lung and increasing ciliary motility. Classification by Route and Time Course Beta agonists may be administered orally or by inhalation, and their effects may2 be brief or prolonged. With the short-acting inhaled preparations, effects begin almost immediately, peak in 30 to 60 minutes, and persist for 3 to 5 hours. However, because these drugs are used on a fixed schedule for long-term control, the difference in onset is not very important. Use in Asthma and Chronic Obstructive Pulmonary Disease Beta agonists are employed for quick relief and long-term control. Like the long-acting inhaled beta agonists, the oral agents are2 not first-line therapy. Systemic effects—tachycardia, angina, and tremor—can occur, but are usually minimal. Oral Preparations P a t i e n t E d u c a t i o n Beta Adrenergic Agonists2 Instruct patients on the proper use of this inhalers. For patients who have difficulty with hand-breath coordination, using a spacer with a one-way valve may improve results. Instruct patients to report chest pain associated with changes in heart rate or rhythm. If dosage is excessive, stimulation1 of cardiac beta receptors can cause 1 angina pectoris and tachydysrhythmias. Patients should be instructed to report chest pain or changes in heart rate or rhythm. Oral beta agonists often cause 2 tremor by activating beta receptors in skeletal2 muscle. Preparations, Dosage, and Administration Nine selective beta agonists are available (2 Table 60. Inhaled Preparations for Quick Relief To provide quick relief, beta agonists must be administered by inhalation. During this interval, some bronchodilation develops, facilitating penetration of the second inhalation. Some patients who have become unresponsive to a beta agonist delivered with an inhaler may2 respond to the same drug when it is given with a nebulizer. The nebulizer delivers the dose slowly (over several minutes); as the bronchi gradually dilate, the drug gains deeper and deeper access to the lungs. Rather, they should always be combined with an inhaled glucocorticoid, preferably in the same inhaler device. Although salmeterol is usually inhaled twice daily (every 12 hours), with continuous use, more frequent dosing may be needed because benefits seem to persist for a shorter time as the duration of treatment increases. Oral Preparations for Long-Term Control Two oral beta agonists—albuterol and terbutaline—are approved for long-term2 control of asthma. Theophylline Theophylline [Theo-24, Theochron, Elixophyllin, Theolair, Uniphyl ] is the principal methylxanthine employed in asthma. Theophylline has a narrow therapeutic range, so dosage must be carefully controlled. The drug is usually administered by mouth but may also be administered intravenously. Mechanism of Action Theophylline produces bronchodilation by relaxing smooth muscle of the bronchi. Although the mechanism of bronchodilation has not been firmly established, the most probable is blockade of receptors for adenosine. Use in Asthma and Chronic Obstructive Pulmonary Disease Oral theophylline is used for maintenance therapy of chronic stable asthma. Although less effective than beta agonists, theophylline has a longer duration of2 action (when administered in a sustained-release formulation). With regular use, theophylline can decrease the frequency and severity of asthma attacks. Because its effects are prolonged, theophylline may be most appropriate for patients who experience nocturnal attacks. Evidence-based guidelines recommend its use only if beta2 agonists and anticholinergics are not available or if the patient cannot afford long-term therapy with other drugs. However, the drug is no more effective than beta agonists and glucocorticoids and is clearly2 more dangerous. Oral theophylline is available in sustained-release formulations and as an elixir. Absorption from sustained-release preparations is slow, but the resulting plasma levels are stable, being free of the wide fluctuations associated with the immediate-release products. Rates of metabolism are affected by multiple factors—age, disease, drugs—and show wide individual variation. As a result, the plasma half-life of theophylline varies considerably among patients. For example, although the average half-life in nonsmoking adults is about 8 hours, the half-life can be as short as 2 hours in some adults and as long as 15 hours in others. Smoking either tobacco or marijuana accelerates metabolism and decreases the half-life. Safe and effective therapy requires periodic measurement of theophylline blood levels.
Unfortunately purchase wellbutrin master card, although this combination is effective and inexpensive buy wellbutrin 300 mg low cost, it has drawbacks quality wellbutrin 300mg. Specifically order wellbutrin with a visa, the neomycin component is ototoxic and causes local swelling and erythema in about 15% of patients. Unlike many otic preparations, quinolones and quinolone/glucocorticoid combinations are safe for patients who have perforated tympanic membranes. The glucocorticoid has the added benefit of decreasing pain by reducing swelling caused by inflammation. Principal drawbacks of these preparations are expense and the potential to promote resistance to quinolone antibiotics. Applying ear drops correctly can improve outcomes and reduce drug-related discomfort. Instillation of cold solutions can cause dizziness; therefore, ear drops should be warmed before administration. The wick should be replaced at least every 48 hours to allow cleaning and to determine whether further wicking is still needed. For adults, ciprofloxacin [Cipro] is a good choice; however, because oral quinolones can cause tendon rupture in younger patients, it should not be given to patients younger than 18 years. Spread of infection to the skull base can affect cranial nerves, and spread to the dura mater can cause meningitis and possibly lateral sinus thrombosis. The two most common pathogens are Aspergillus, which causes 80% to 90% of otomycoses, and Candida. As a rule, otomycosis can be managed with thorough cleansing and application of acidifying drops (e. If these measures are inadequate, the patient can apply a solution that contains an antifungal drug (e. Complications include development of language problems secondary to hearing deficits and development of drug-resistant bacteria (primarily as a result of not taking medication as directed or stopping them prematurely). Identifying High-Risk Patients • Assess for penicillin allergy before prescribing amoxicillin or amoxicillin/clavulanate. For patients who have experienced a mild reaction to penicillins, guidelines recommend a cephalosporin such as cefdinir, cefuroxime, or cefpodoxime. For a severe reaction such as anaphylaxis, azithromycin or clarithromycin is recommended. Instead, prescribe a quinolone or quinolone/glucocorticoid combination because these are safe for patients who have perforated tympanic membranes. Before leaving the clinic, they should be instructed to return if they do not have improvement or if their condition worsens. For this reason, tympanometry and pneumatic otoscopy will not reflect a normal response to pressure changes for several weeks or even months. Many of these protocols allow for the replacement of electrolytes by the registered nurse. Three groups of agents are considered for replacement: (1) drugs used to correct disorders of fluid volume and osmolality, (2) drugs used to correct disturbances of hydrogen ion concentration (acid-base status), and (3) drugs used to correct electrolyte imbalances. Disorders of Fluid Volume and Osmolality Good health requires that both the volume and osmolality of extracellular and intracellular fluids remain within a normal range. If a substantial alteration in either the volume or osmolality of these fluids develops, significant harm can result. Maintenance of fluid volume and osmolality is primarily the job of the kidneys, and, even under adverse conditions, renal mechanisms usually succeed in keeping the volume and composition of body fluids within acceptable limits. However, circumstances can arise in which the regulatory capacity of the kidneys is exceeded. Abnormal states of hydration can be divided into two major categories: volume contraction and volume expansion. Volume contraction is defined as a decrease in total body water; conversely, volume expansion is defined as an increase in total body water. States of volume contraction and volume expansion have three subclassifications based on alterations in extracellular osmolality. For volume contraction, the subcategories are isotonic contraction, hypertonic contraction, and hypotonic contraction. In the clinical setting, changes in osmolality are described in terms of the sodium content of plasma. Sodium is used as the reference for classification because this ion is the principal extracellular solute. In most cases, the total osmolality of plasma is about 2 times the osmolality of sodium. Volume Contraction Isotonic Contraction Definition and Causes Isotonic contraction is defined as volume contraction in which sodium and water are lost in isotonic proportions. Hence, although there is a decrease in the total volume of extracellular fluid, there is no change in osmolality. Causes of isotonic contraction include vomiting, diarrhea, kidney disease, and misuse of diuretics. Hypertonic Contraction Definition and Causes Hypertonic contraction is defined as volume contraction in which loss of water exceeds loss of sodium. Hence there is a reduction in extracellular fluid volume coupled with an increase in osmolality. Because of extracellular hypertonicity, water is drawn out of cells, thereby producing intracellular dehydration and partial compensation for lost extracellular volume. Causes of hypertonic contraction include excessive sweating, osmotic diuresis, and feeding excessively concentrated foods to infants. Treatment Volume replacement in hypertonic contraction should be accomplished with hypotonic fluids (e. About 50% of the estimated loss should be replaced during the first 24 hours of treatment. Hypotonic Contraction Definition and Causes Hypotonic contraction is defined as volume contraction in which loss of sodium exceeds loss of water. Because intracellular osmolality now exceeds extracellular osmolality, extracellular volume becomes diminished further by movement of water into cells. The principal cause of hypotonic contraction is excessive loss of sodium through the kidneys. This may occur because of diuretic therapy, chronic renal insufficiency, or lack of aldosterone (the adrenocortical hormone that promotes renal retention of sodium). Treatment If hyponatremia is mild, and if renal function is adequate, hypotonic contraction can be corrected by infusing isotonic sodium chloride solution for injection. Administration should continue until plasma sodium concentration has been raised to about 130 mEq/L. Patients should be monitored for signs of fluid overload (distention of neck veins, peripheral or pulmonary edema). Volume Expansion Volume expansion is defined as an increase in the total volume of body fluid. As with volume contraction, volume expansion may be isotonic, hypertonic, or hypotonic. The principal drugs employed to correct volume expansion are diuretics and the agents used for heart failure. Acid-Base Disturbances Maintenance of acid-base balance is a complex process, the full discussion of which is beyond the scope of this text. The most important are (1) the bicarbonate–carbonic acid buffer system, (2) the respiratory system, and (3) the kidneys. Conversely, by increasing bicarbonate excretion, the kidneys can lower pH, and thereby compensate for alkalosis. There are four principal types of acid-base imbalance: (1) respiratory alkalosis, (2) respiratory acidosis, (3) metabolic alkalosis, and (4) metabolic acidosis. Respiratory Alkalosis Causes Respiratory alkalosis is produced by hyperventilation. Mild hyperventilation may result from a number of causes, including hypoxia, pulmonary disease, and drugs (especially aspirin and other salicylates). Treatment Management of respiratory alkalosis is dictated by the severity of pH elevation. Although this technique has been used for many years, there remains a lack of evidence regarding its efficacy in respiratory alkalosis. Primary causes of impaired ventilation are (1) depression of the medullary respiratory center and (2) pathologic changes in the lungs (e. Over time, the kidneys compensate for respiratory acidosis by excreting less bicarbonate.
Her symptoms and laboratory values are indicative has also had more trouble than usual with constipation and of mild hypothyroidism purchase wellbutrin master card. On physical examina- centration is the primary test used to evaluate replacement tion generic 300 mg wellbutrin amex, her temperature is 97 cheap wellbutrin 300mg. Suppressive therapy thereby reduces Pharmacokinetic Properties goiter size and thyroid gland volume wellbutrin 300 mg sale. Relative potency 1 4 Oral bioavailability 80% (variable) 95% Adverse Effects Elimination half-life 7 days 1 day Thyroid hormone preparations rarely cause adverse reac- Daily doses 1 1-3 tions if dosage is appropriate and is carefully monitored during the initial treatment of hypothyroidism and perio- dically thereafter. Excessive doses produce symptoms of pharmacologic and pharmacokinetic properties of levothy- hyperthyroidism. Interactions Levothyroxine Aluminum hydroxide, calcium supplements, cholestyramine, Pharmacokinetics ferrous sulfate, and sucralfate are among the drugs that The oral bioavailability of levothyroxine is about 80%. These ferent brands and generic formulations of levothyroxine vary drugs should be administered 2 hours before or after levo- in hormone content and bioavailability, and formulations thyroxine is administered. For this roxine be taken at the same mealtime each day in order to reason, the dosage of levothyroxine usually does not need to achieve consistent blood levels. Because the half-life of levo- be adjusted in persons who are taking steroid hormones. Liothyronine Because about 35% of T4 is converted to T3 in peripheral As shown in Table 32-1, liothyronine (T3) is more potent tissues, levothyroxine administration produces physiologic than levothyroxine (T4) and has a higher oral bioavailabil- levels of both T4 and T3. It is seldom used in the treatment of hypothyroidism, however, because it has several disadvantages. Liothyronine Indications has a much shorter half-life than levothyroxine, and mul- Levothyroxine is the drug of choice for thyroid hormone tiple daily doses may be needed to obtain a smooth response replacement in patients with hypothyroidism, because it is during hormone replacement therapy. Liothyronine does chemically stable, is nonallergenic, and can be given orally not increase plasma T4 levels, so it is diffcult to monitor once a day. Liothyronine also causes pool of T4 that is converted to T3 at a steady and consistent more adverse cardiac effects and is more expensive than rate. The dose is then increased ism include thioamide drugs, β-adrenoceptor antagonists, at monthly intervals until a full replacement dose is achieved. A gradual increase in the dose prevents excessive stress on The thioamide drugs inhibit the synthesis of thyroid hor- the cardiovascular and other organ systems and thereby mones, whereas suffcient doses of iodide salts inhibit the causes fewer adverse reactions. The β-blockers are used to control higher doses per kilogram of body weight than do adults. Levothyroxine is also the drug of choice for suppressive Drug Properties therapy in patients with thyroid nodules, diffuse goiters, or Mechanisms. The thioamide drugs are well azole is not bound to plasma proteins, and it readily crosses absorbed from the gut after oral administration. The thioamide drugs are appears to be the drug of choice just before and during the extensively metabolized before undergoing renal excretion. The effects of thioamide drugs are delayed Thyroid hormones and the sympathetic nervous system act because it takes about 4 to 8 weeks of therapy before the synergistically on cardiovascular function. This explains why glandular hormone stores are depleted and circulating increased levels of thyroid hormones cause tachycardia, hormone levels start to return to the normal range. They act immediately the objective is long-term remission of Graves disease, and are particularly useful during severe acute thyrotoxicosis patients usually remain on the drug for 12 to 24 months. They are also used to control symptoms of About 45% of patients will eventually achieve a permanent hyperthyroidism in patients awaiting either surgery or a remission. Persons with persistent thyroid-stimulating antibodies Iodide Salts have a higher incidence of relapse than do persons without Iodide salts are contained in potassium iodide tablets and persistent antibodies. Pruritic maculopapular rash, arthralgia, and Lugol solution (elemental iodine and potassium iodide). Less frequently, a lupus erythematosus–like patients with acute thyrotoxicosis, to prepare patients for syndrome, hepatitis, or gastrointestinal distress is reported. Iodide salts can also be used to with a white blood cell count of less than 4000/µL. Potassium iodide preparations acterized by a granulocyte count of less than 250/µL. Severe are available without prescription for this purpose (Thyro- agranulocytosis usually develops during the frst 3 months Safe, ThyroShield). Patients and fatal liver failure, but a recent analysis of adverse drug with hyperthyroidism usually obtain symptomatic improve- reactions by the U. The isotope is rapidly • β-Adrenoceptor antagonists are used to control the absorbed from the gut and concentrated by the thyroid cardiovascular symptoms of hyperthyroidism in pati- gland. In the gland, it emits β-particles that destroy thyroid ents who are suffering from acute thyrotoxicosis, are tissue. Potassium iodide solutions are used β-blockers alone are not adequate to control these symp- to control symptoms of acute thyrotoxicosis, to reduce toms. A man is given a drug to reduce thyroid gland size and vascularity before surgical thyroidectomy. A woman with weight loss, nervousness, heat intolerance, pling of iodotyrosines to form T3 and T4. Which serious adverse effect has • The thyroid hormones, which activate cytoplasmic been associated with this medication? In the (A) gastrointestinal bleeding nucleus, they activate gene transcription and thereby (B) thromboembolism increase the metabolic rate and accelerate a wide (C) agranulocytosis range of cellular activities required for normal growth (D) hepatic failure and development and for the maintenance of normal (E) esophageal ulcer metabolism. After total thyroidectomy, a woman is placed on a drug • Levothyroxine (synthetic T4) is the drug of choice for whose oral bioavailability is about 80%. It has a (C) the most potent thyroid hormone available shorter half-life, however, and may need to be given (D) has a half-life of about 1 day several times a day. After exposure to radioactive fallout containing 131I, thyroperoxidase-catalyzed steps in the synthesis of which agent could be administered to prevent destruction thyroid hormone. The onset of action of these drugs (A) liothyronine is delayed because of the time required to deplete (B) methimazole glandular stores of thyroid hormone. After absorption, about 35% of levo- Potassium iodide reduces the release of thyroid hormone thyroxine is eventually converted to triiodothyronine. Its absorption is reduced by iron and aluminum sodium/iodide symporter, or reduce synthesis of thyroid salts. Thioamide drugs are would compete with radioactive iodide for uptake by the associated with leukopenia and, rarely, agranulocytosis, thyroid gland. Suffcient doses of potassium iodide can and patients should be carefully monitored for these prevent destruction of the thyroid gland after exposure 131 conditions. Also shown is the site of action of drugs that inhibit adre- Adrenal Steroid Drugs nocorticoid synthesis. Cortisol exerts several effects that increase the body’s resis- Corticosteroid Synthesis Inhibitors tance to stress. This is why exogenously • Metyrapone (Metopirone) administered glucocorticoids can suppress the hypothalamic- Corticosteroid Receptor Antagonists pituitary-adrenal axis and inhibit endogenous cortisol pro- • Mifepristone (Mifeprex) duction, leading toadrenal insuffciencywhen the exogenous • Spironolactone (Aldactone) glucocorticoid is withdrawn. These actions lead to the various metabolic and The adrenal glands are situated on top of the kidneys (as antiinfammatory effects of glucocorticoids, which are obvious from their name) and are essential for life. In the renal tubules, activation of the adrenal glands are composed of two major parts: the adrenal mineralocorticoid receptor stimulates the synthesis of cortex and the adrenal medulla, also called chromaffn tissue sodium channels and sodium-potassium adenosine tri- owing to its brightly staining characteristics. This chapter describes the drugs that The glucocorticoid receptor has a high affnity for cor- serve as replacements or alter the effects of steroid hormones tisol but a much lower affnity for aldosterone, whereas the produced by the adrenal cortex. Glu- classifed as mineralocorticoids, glucocorticoids, and cocorticoids also activate enzymes involved in protein adrenal androgens. The mineralocorticoids are primarily catabolism, thereby increasing the supply of amino acids produced in the outer layer (zona glomerulosa), whereas the needed for gluconeogenesis. Glucocorticoids stimulate glucocorticoids and adrenal androgens are produced in the lipolysis and inhibit the uptake of glucose by adipose tissue. A, Major pathways for mineralocorticoid, glucocorticoid, and androgen biosynthesis are shown. Aminoglutethimide blocks the synthesis of all adrenal steroids by inhibiting the conversion of cholesterol to pregnenolone. The most common defect causing congenital adrenal hyperplasia is P45021 defciency. B, The structure of dexamethasone is shown in the inset in the lower right corner. In the synthetic steroids, glucocorticoid potency is enhanced by the introduction of a double bond at the 1,2 position or the introduction of a hydroxyl or methyl group at the 16 position. Both glucocorticoid and mineralocorticoid activities are increased by a fuorine substitution at the 9 position.