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By V. Nasib. Cleveland Chiropractic College.

Pa t ie n t Eva lu a t io n The diagnosis of biliary atresia is based on timing of jaundice presentation and imaging findings t hat rule out ot her mechanical causes order prochlorperazine 5 mg online. Identifying a cause for hyperbilirubinemia is important and the process should be performed in an expeditious manner so that if a portoenteros- tomy is to be performed buy generic prochlorperazine online, it can be done prior to the onset of irreversible injuries to the liver discount generic prochlorperazine uk. Bi l i a r y At r e s i a S c r e e n i n g In some countries, there are widely implemented biliary atresia screening systems, wh ich at t empt t o ident ify the disease at the early st ages. In Taiwan, the screen- ing prot ocol involves giving mot hers color-coded cards t o help t hem ident ify pale stools. T his screening program has been reported to shorten the t ime to portoen- terostomy to a median infant age of < 50 days. Pre o p e ra t ive Pre p a ra t io n o f Pa t ie n t s wit h Bilia ry At re sia Prior to surgical treatment, the patients need to be evaluated for coagulation abnormalit ies, anemia, and hypoprot einemia. Parent s of pat ient s with biliary at resia should be made aware of t he long-t erm prognosis of the disease and underst and t he role of portoenenterostomy. The operat ion involves excision of the ent ire ext rahepat ic biliary t ree and explorat ion of t he port a hepat is at t he liver hilum t o expose t he duct ules wit h in t he liver. A Roux-limb (defunct ionalized limb) of jejunum is t h en anast omosed t o the cut sur face of the liver. This pr ocedure is opt imal for pat ient s wit h preser ved liver fu n ct ion s an d n o cir r h osis; t h er efor e, the t im in g of d iagn osis an d r efer r al for su r gi- cal t r eat ment is cr it ical for t h ese pat ient s. Some gr oups believe that best out com es are achieved wit h t he operat ions being performed before 8 weeks of age. Unfortu- nately, there is no clear evidence available to indicate the optimal time when biliary decompression procedures should be accomplished. In some centers, the approach is t o forego port oent erost omy and proceed direct ly t o liver t ransplant at ion if the patient is older than 100 days of age. Po st o p e ra t ive Ca re a n d Ou t co m e s Important postsurgical care for these patients includes prevention, detection, and t reat ment of cholangit is, as infect ions cause addit ional liver damage. Impor- tant nutritional goals in postoperatively include the preventing malnutrition and addressing t he malabsorpt ion caused by liver dysfunct ion. It is important to treat the steator- rhea and malabsorption of fat soluble vit amins that are common in these pat ient s. Some groups believe that corticosteroid treatment is important based on their anti- inflammat ory and immunomodulat ory propert ies; however, post operat ive st eroids benefits are not substantiated by strong clinical evidence. Postoperative success following portoenterostomy is defined by a normal serum bilirubin concentration at 6 months following the operation. Following Kasai por- toenterostomy, 70% of the patients will develop progressive biliary obstruction. A review of operative outcomes suggests that > 80% of the patients will go on to sur vive more t han 10 years following a successful operat ion. For many individu- als wit h biliary at resia, liver t ransplant at ion is t he t reat ment t hat ult imat ely gives them the opportunity for prolonged survival. The timing of liver transplantation is largely based on the success of the in it ial Kasai port oent erost omy. Current ly, 90% of the transplant patients receive liver transplantation as a secondary treatment following Kasai por t oent erost omies, an d on ly a ver y small percent age of pat ient s undergo liver transplantation as their primary treatments. Liver transplantations for this popu lat ion can be eit h er a liver-relat ed par t ial liver t ran splant at ion or orthotopic graft placement. The overall 10-year graft and patient survival are 73% and 86%, respect ively for liver t ransplant at ion performed in children wit h biliary at resia. W hich of the following st atement s is t rue regard- ing t he portoenterost omy procedure? A successful operation provides the opportunity for 95% of the patients to live a normal life span B. T h e o p er at io n is asso ciat ed wit h b et t er o u t co m es wh en it is d elayed t o let the infant grow larger C. It is difficult to differentiate patients with biliary atresia from those with ch oled och al cyst s pr ior t o su r gical explor at ion s D. Portoenterostomy rarely improves the hyperbilirubinemia in the major- it y of pat ient s E. Liver transplantation may be the better initial surgical option for infants older than 120 days 56. W hich of the following diagnostic st udies will help different iat e choledochal cyst from biliary at resia as t he con- dition causing his jaundice? P at h olo gic h yp er b ilir u b in em ia in n ewb or n s is d efin ed as level > 1 7 m g/ d L C. The negative effects of hyperbilirubinemia in the newborn occur only in the neurons D. Phototherapy is the mainstay of treatment, and it helps to convert biliru- bin to its water-soluble isomers E. W hich of the following diagnostic studies will provide a definitive diagnosis of biliary at resia? Portoenterostomy when done early before the onset of irreversible liver damage works best for the patients. In most cases, if the infant is older than 100 days, the long-term success of the procedure is limited and the patient may benefit from liver transplantation as the primary treatment. The ultrasound should demonstrate dilatation of the intrahepatic and/ or extrahepatic biliary tree in patients with choledochal cysts, whereas, bile ducts will be nonvisualizable in cases of biliary atresia. The other choices provided will not be able to help differentiate these two diagonoses. All of t he st atement s are t rue except for t he st atement “neonat al jaundice is most common in post -t erm newborns. The infant described has a classic presentation of postportoenterostomy ch olan git is. O ccasionally, it is done for pro- cedu r e that fails pr imar ily im mediat ely p ost op er at ively. St an dar d t r eat ment for this pat ient in cludes suppor t ive care, blood cu lt ures, ant ibiot ics, an d st e- roids (for the choleretic and anti-inflammatory effects). Liver transplantation may be best initial treatment in this 150-day-old infant wit h biliary at resia, as observat ions suggest t hat out comes are best wh en port oent erost omies are performed prior t o 8 weeks (56 days). He reports waking up from sleep at least three to fo u r t im e s e a ch n ig h t t o u rin a t e. He d e n ie s u re t h ra l d isch a rg e o r h ist o r y o f se xu a lly transmitted diseases. Th e p a t i e n t r e p o r t s t h a the h a s h a d t w o b o u t s o f u r i n a r y t r a c t i n fe c t i o n s d u r i n g the past year, and these infections have been treated with outpatient antibiotics. His vit a l sig n s a re n o rm a l, a n d h is ca rd io p u lm o n a r y a n d a b d o m in a l e xa m in a t io n is u n re m a rka b le. Best initial therapy: Init ial t reat ment includes life st yle modificat ion and phar- macologic treatment with either an α -1-blocker or a 5-α reduct ase inh ibit or if the patient is bothered significantly by his symptoms. H ow often do you have the sensation of not completely emptying you bladder aft er you finished urinat ing?

She states that her menses began at age 12 years discount 5mg prochlorperazine free shipping, and they occur at regu- la r 28-d a y in t e rva ls order prochlorperazine mastercard. She denies sexually transmitted diseases cheap prochlorperazine american express, and a hysterosalpingogram shows patent tubes and a normal uterine cavit y. Co n s i d e r a t i o n s This 31-year-old woman has secondary infertility, meaning she has had a preg- nancy in the past. In approaching infertility, there are five basic factors to examine: (1) ovulatory, (2) uterine, (3) tubal, (4) male factor, and (5) peritoneal factor (endo- metriosis). H er history is consistent with regular ovulation; this is further sup- ported by the biphasic basal body temperature chart. The uterine and tubal factors are normal based on the normal hysterosalpingogram (a radiologic study in which dye is placed into the uterine cavity via a transcervical catheter). If the pat ient h ad prior cr yot h erapy t o the cervix, the examiner might be directed to consider cervical factor (rare); simi- larly, if the pat ient complained of the t h ree D s of endomet riosis (dysmenorrh ea, dyspareunia, and dyschezia), then the clinician would be pointed toward the peri- toneal factor. Since there are no hints favoring one factor over another, the clinician must pick the most common condition, which is endometriosis. Fecundabi l i t y, defined as the probability of achieving a pregnancy within one menstrual cycle, has been estimated at 20%to 25%for a normal couple. On the basis of this estimate, approximately 90% of couples should conceive after 12 months. The physician’s initial encounter with the couple is very important and sets the tone for further evaluation and treatment. It is extremely important that after the initial evaluation, a realistic plan be established and followed (Table 56– 1). O vu la t o r y d i s o r d e r s a cco u n t fo r a p p r o x- imat ely 30% t o 40% of all cases of female infert ilit y. A hist ory of regularit y or irregularit y of t he menses is fairly predict ive of the regularit y of ovulat ion. The basal body temperature chart is the easiest and least expensive method of detecting ovulation (Figure 56– 1). The temperature should be determined orally, preferably with a basal body thermometer, before the patient arises out of bed, eats, or drinks. The rise of temperature accounts for the biphasic pattern indicative of ovulation. It should be performed between days 6 and10 of the u raphy can also be performed to image the endometrial cavity. A h ist or y of ch lam yd ial or gon o co ccal cer vicit is or salp in git is m ay 2. The hysterosalpingogram is the initial test for intrauterine e p t r 5 10 15 20 25 30 rate but not perfect. A normal test shows a thin line of dye through the tubes m = menses Da y of cycle menting ovulation. H yst eroscopy likewise provides direct visualizat ion of the ut erine cavit y can be d et ect ed wit h self-adm in ist er ed u r in e t est kit s. Other tests include ing a decrease in follicular size and presence of fluid in t he cul-de-sac, suggest - ing ovulat ion. For women older t han age 30, assessment of ovarian reserve level t est ing may be h elpful (see Case 30). The semen analysis is a very basic and noninvasive test and should be one of the init ial examinat ions. O ne abnormal test is not sufficient to establish the diagnosis of a male fact or abnormalit y, and the t est sh ould be repeat ed aft er 2 t o 3 mont h s (t h e pro- cess of transforming spermatogonia into mature sperm cells requires 74 days). En d omet r iosis, a com mon con dit ion associ- ated with infert ilit y, should be suspected in any infert ile woman. Fecundit y, defined as t he probabilit y of a woman ach ieving a livebirth in a given mont h, ranges from 0. The suspicion should increase if she complains of dysmenorrhea and dyspareunia, but often is pres- ent even in asympt omat ic women. Alt hough not complet ely underst ood, endomet riosis may cause infert ilit y by inh ibit ing ovulat ion, inducing adh e- sions, and, perhaps, interfering wit h fert ilizat ion. Laparoscopy is t he gold st andard for t he diagnosis of endomet riosis, and can allow for surgical abla- tion/ excision of the lesions. Lesions can be of various appearances, from clear to red to the classic“powder burn”color. Current evidence indicates that medical therapy is not as beneficial for endomet riosis-associated infertility. Surgical treatment in the form of laparoscopy or laparotomy is the efficacious choice with the former providing shorter hospi- talization, shorter recovery, potentially less adhesions, and less discomfort to the patient. Restoration of the anatomy with excision of endometrial nodules, removal of endometriomas, and adhesiolysis is the mainstay in the treatment of advanced st ages of endomet riosis associat ed wit h infert ilit y. H owever, despit e surgical exci- sion, concept ion rat es seem t o be less in women wit h ext ensive disease. Regardless, it seems int uit ive that a st ruct ural normalizat ion of severely dist ort ed pelvic anat - omy can improve conception outcomes, quality of life for the patient, and facilitate egg retrieval in cases of in vitro fertilization. Surgical options remain controversial in early st ages of endomet riosis wit hout anat omical dist ort ion. T here is an absence of qualified evidence to indicate that fertility is enhanced with preoperative or post- operative medical therapy. The theoretical benefits do not seem to outweigh the increased cost s and rat es of morbidit y. Medical t herapy alone or in combinat ion wit h surgery may only serve t o delay fert ilit y. As s i s t e d Re p r o d u c t i v e The c h n o l o g i e s Assisted reproduct ive technologies now account for 1% to 2% of pregnancies in the United States. The indications include severe tubal factor, male factor, endome- triosis, or unexplained or other infertility not responsive to medical therapy. Careful monitoring of t he pat ient with serial ult rasounds and est ra- diol levels is important to avoid the dangerous ovarian hyperstimulation syndrome. In general, the “quality”of the oocyte is the single most important factor dictating successful pregnancy. D on or eggs can be u sed if the pat ient ’s oocyt es are of ques- tionable quality. Preimplant at ion gen et ic d iagn osis can be p er for m ed by r em ovin g 1 or 2 cells at the 6 t o 8 cell blas- tocyst stage, to test for single gene disorders or translocations. Cryopreservation is often used for those fertilized oocytes that are not implanted, and can be thawed and used at a later t ime. Note: Cervical factor is considered an infrequent etiology and may be suspected wit h t hick viscid cervical mucus before ovulat ion.

Steps in Renal Drug Excretion Urinary excretion is the net result of three processes: (1) glomerular filtration prochlorperazine 5 mg amex, (2) passive tubular reabsorption buy prochlorperazine online now, and (3) active tubular secretion order discount prochlorperazine online. Glomerular Filtration Renal excretion begins at the glomerulus of the kidney tubule. As blood flows through the glomerular capillaries, fluids and small molecules—including drugs —are forced through the pores of the capillary wall. This process, called glomerular filtration, moves drugs from the blood into the tubular urine. Because large molecules are not filtered, drugs bound to albumin remain in the blood. At this distal site, drug concentrations in the blood are lower than drug concentrations in the tubule. This concentration gradient acts as a driving force to move drugs from the lumen of the tubule back into the blood. Because lipid-soluble drugs can readily cross the membranes that compose the tubular and vascular walls, drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood. In contrast, drugs that are not lipid soluble (ions and polar compounds) remain in the urine to be excreted. Active Tubular Secretion There are active transport systems in the kidney tubules that pump drugs from the blood to the tubular urine. These pumps have a relatively high capacity and play a significant role in excreting certain compounds. Factors That Modify Renal Drug Excretion Renal drug excretion varies from patient to patient. Three other important factors to consider are pH-dependent ionization, competition for active tubular transport, and patient age. Because ions are not lipid soluble, drugs that are ionized at the pH of tubular urine will remain in the tubule and be excreted. This principle has been employed to promote the excretion of poisons as well as medications that have been taken in toxic doses. Competition for Active Tubular Transport Competition between drugs for active tubular transport can delay renal excretion, thereby prolonging effects. The active transport systems of the renal tubules can be envisioned as motor-driven revolving doors that carry drugs from the plasma into the renal tubules. These “revolving doors” can carry only a limited number of drug molecules per unit of time. Because of competition, if we administer two drugs at the same time, and if both drugs use the same transport system, excretion of each will be delayed by the presence of the other. Until their kidneys reach full capacity (a few months after birth), infants have a limited capacity to excrete drugs. Nonrenal Routes of Drug Excretion In most cases, excretion of drugs by nonrenal routes has minimal clinical significance. However, in certain situations, nonrenal excretion can have important therapeutic and toxicologic consequences. Breast Milk Some drugs taken by breast-feeding women can undergo excretion into milk. The factors that influence the appearance of drugs in breast milk are the same factors that determine the passage of drugs across membranes. Accordingly, lipid-soluble drugs have ready access to breast milk, whereas drugs that are polar, ionized, or protein bound cannot enter in significant amounts. Other Nonrenal Routes of Excretion The bile is an important route of excretion for certain drugs. Because bile is secreted into the small intestine, drugs that do not undergo enterohepatic recirculation leave the body in the feces. Time Course of Drug Responses It is possible to regulate the time at which drug responses start, the time they are most intense, and the time they cease. Because the four pharmacokinetic processes—absorption, distribution, metabolism, and excretion—determine how much drug will be at its sites of action at any given time, these processes are the major determinants of the time course over which drug responses take place. Plasma Drug Levels In most cases, the time course of drug action bears a direct relationship to the concentration of a drug in the blood. Hence, before discussing the time course per se, we need to review several important concepts related to plasma drug levels. Clinical Significance of Plasma Drug Levels Providers frequently monitor plasma drug levels in efforts to regulate drug responses. When measurements indicate that drug levels are inappropriate, these levels can be adjusted up or down by changing dosage size, dosage timing, or both. The practice of regulating plasma drug levels to control drug responses should seem a bit odd, given that (1) drug responses are related to drug concentrations at sites of action and (2) the site of action of most drugs is not in the blood. More often than not, it is a practical impossibility to measure drug concentrations at sites of action. Experience has shown that, for most drugs, there is a direct correlation between therapeutic and toxic responses and the amount of drug present in plasma. Therefore, although we cannot usually measure drug concentrations at sites of action, we can determine plasma drug concentrations that, in turn, are highly predictive of therapeutic and toxic responses. Accordingly, the dosing objective is commonly spoken of in terms of achieving a specific plasma level of a drug. Two Plasma Drug Levels Defined Two plasma drug levels are of special importance: (1) the minimum effective concentration, and (2) the toxic concentration. When plasma levels are within the therapeutic range, there is enough drug present to produce therapeutic responses but not so much that toxicity results. The objective of drug dosing is to maintain plasma drug levels within the therapeutic range. The width of the therapeutic range is a major determinant of the ease with which a drug can be used safely. Conversely, drugs that have a wide therapeutic range can be administered safely with relative ease. The principle is the same as that of the therapeutic index discussed in Chapter 3. Because drugs with a narrow therapeutic range are more dangerous than drugs with a wide therapeutic range, patients taking drugs with a narrow therapeutic range are the most likely to require intervention for drug-related complications. The provider who is aware of this fact can focus additional attention on monitoring these patients for signs and symptoms of toxicity. Drug levels then decline as metabolism and excretion eliminate the drug from the body. The duration of effects is determined largely by the combination of metabolism and excretion. Because metabolism and excretion are the processes most responsible for causing plasma drug levels to fall, these processes are the primary determinants of how long drug effects will persist.

O n h ospit al day 3 buy prochlorperazine with a mastercard, sh e st abi- lizes from the h emodynamic st andpoint and remains on the vent ilat or cheap prochlorperazine online mastercard. O n examinat ion generic prochlorperazine 5mg with amex, she is awake wit h abdominal dist ension and some epigast ric tenderness on examination. She is expected to require mechanical ventila- tion for several more days based on the intensivist’s best estimation. Placement of feeding jejunostomy tube by laparoscopy and initiate feeding on ce the t ube is placed R-3. A 73-year-old woman with past history of diverticulitis presents to the emergency cent er wit h fever, abdominal pain, abdominal t enderness, and hypotension (blood pressure of 90/ 50). The patient reports that the pain is ver y sim ila r in p at t er n, lo cat io n, a n d ch a r act er ist ics t o h er p r evio u s b o u t s o f diverticulitis. Which of the following choices represents the best sequence of prioritized t reatments for this pat ient? Lab o r at o r y b lo o d wo r k s, I V flu id s, C T scan of ab d o m en an d p elvis, surgical consult at ion and broad-spect rum ant ibiot ics C. A 24-year-old man suffered deep partial-thickness burn wounds to the ent ire ant erior ch est and abdomen, and circumferent ial burns t o bot h arms wh en h is clot h es caught fire at a barbecue pit. Based on the P ar klan d for m u la for b u r n patient r esu scit at ion, wh at is the est imat ed volume of fluid t o be administ ered for t he init ial 8 hours? W hich of t he following operat ions is t he most appropriate for this patient with this condition? A43-year-old man with a12-cm distal,right thigh massarisingfrom the anterior thigh muscle compart ment undergoes core needle biopsy of the mass, which reveals moderately well-differentiated liposarcoma. Which of the following choices is considered the most appropriate surgical approach for this patient? Wide local excision of the tumor with a 2-cm margin including right gr oin sent in el lymph n od e biop sy D. Wide local excision of the tumor with a 2-cm margin including right gr oin lymph n od e dissect ion E. A63-year-oldmanwithhistoryofhypertensionandcoronaryarterydisease presents for the evaluation of pain in his right calf whenever he attempts to walk more than one cit y block. Because of this pain, he has been having significant problems performing daily act ivit ies, such as shopping, going to the bank, and going to visit friends. Despite your advice for him to stop smoking, he cont inues t o smoke one and a half packs of cigarett es daily. The examination of his peripheral pulses reveal normal femoral pulses bilaterally, normal left popliteal and pedal pulses, and absence of right pop- lit eal and pedal pulses. T h ere is no evidence of crit ical t issue isch emia in eit h er lower ext remit y. W hich of t he following diagnost ic st udies is the most appropriate next step for this patient? A63-year-oldwoman isbrought totheemergencydepartment after being foun d t o h ave collapsed in side h er h ome. H er family repor t s that sh e st ayed home from work because she woke up with upper abdominal pain and chills. An ultrasound of the abdomen reveals no free fluid in the abdomen, normal abdominal aorta, gallstones in the gallbladder, and dilatation of the intrahepatic bile ducts. Whichofthefollowingpatientswithmassoftheheadofthepancreasisa can did at e for su r gical r esect ion? A 43-year-old woman with a 2-cm mass in the head of the pancreas and a 2-cm lymph node along t he lesser curve of t he mid-body of the st omach. A 46-year-old woman who underwent pancreaticoduodenectomy 14 months ago presents with new 1-cm lesion in segment 2 of the liver. A 43-year-old woman with a 12-cm cystic neoplasm in the body of the head and body of the pancreas. Imaging studies demonstrate invasion of the dist al stomach, left kidney, left adrenal gland, and the aort a R-10. A 59-year-old post men opau sal woman is foun d on h er an nual mam- mogram to have a cluster of suspicious pleomorphic microcalcifications. A stereotactic image-guided core needle biopsy was performed, and the radiologist reports that 15 separate core biopsy specimens were obtained. Pathology of the core needle biopsy procedure revealed benign breast tissue wit hout evidence of malignancy. W hich of t he following factors is helpful in det ermining t hat t he lesions are benign? Two sent in el lymph n odes an d t wo en larged n on sent i- nel lymph nodes were identified and removed. T h e false n egat ive r at e of sen t in el lym p h n o d e b io p sies is 1 0 % C. Random lymph node sampling yielding more than 2 negative lymph nodes from the axilla is sufficient for axillary staging D. Sentinel lymph node biopsy has not been validated for the axillary st aging of male breast cancer E. Sentinel lymph node biopsy and axillary dissections are associated wit h ident ical rates of complicat ions R-12. Clinical observations have reported that 60% of adrenal corticocarci- nomas are > 6 cm at the time of diagnosis B. Density of the adrenal incident alomas by imaging is based on the levels of water content of the tissue C. Functional analyses of adrenal incidentalomas consist of serum mea- surement s of cort isol and cat echolamines levels E. Fine-needle aspiration is important to obtain whenever the decision is made to observe a patient’s adrenal incidentaloma R-13. Which of the followin g con dit ion s is respon sible for the development of early recurrent st enosis (wit hin 2 years) following carot id endart erect omy? Which of the following is the most accurat e st at ement regarding can cers? Female breast cancer incidence and case fatality have both increased in North America over the past 20 years B. Lu n g can cer in cid en ce h as d ecr eased in m ales an d fem ales in the U n it ed States over the past 20 years C. The worldwide incidence, prevalence, and case fatality of thyroid can cer h ave st ead ily in cr eased over the past 20 year s D. Malignant melanoma has the highest case fat alit y rate among the skin can cer s E.

Family history should include others with bleeding prob- lems cheap prochlorperazine amex, such as excessive hemorrhage after surgery and women requiring hysterec- tomy after child birth prochlorperazine 5mg without prescription. After verifying that the patient is not pregnant order 5mg prochlorperazine amex, the next most important labo- ratory evaluation is the hemoglobin and hematocrit. The degree of anemia helps categorize the severity of bleeding and helps guide management (Figure 57–1). Women with hemoglobin greater than 12 g/dL are considered to have mild bleed- ing, and may be managed with iron supplements and careful follow-up alone. Women with hemoglobin less than 7 g/dL or less than 10 g/dL with significant orthostatic blood pressure changes are considered to have severe bleeding, and may need hospitalization and blood trans- fusion. Intravenous estrogen (Premarin) and high-dose oral contraceptives are used until the bleeding stops; further bleeding despite these measures may require dilation and curettage. Although these high doses of estrogen raise theoretical con- cerns about thrombotic events, none have been reported with the short-term use required in this condition. Iron supplementation should be continued for 2 months after the anemia is resolved. Upon further questioning you learn that she has had near- syncopal episodes the last few times she has tried to stand up. She denies fever, sexual activity, previous episodes of midcycle vaginal bleeding, and abdominal or genitourinary trauma. She has abdominal pain with rebound and guarding in the upper and lower left quadrants that radiates to the back. Her hemoglobin is 5 g/dL, her white count is 12,000/mm3, and her platelet count is 210,000/mm3. She had been seen 3 months ago when you noted a mild anemia of 13 g/dL, diagnosed her with abnormal uterine bleeding, and started her on iron supplements. Her hemoglobin in your clinic is 6 g/dL, her platelet count is normal, and her urine pregnancy test remains negative. You admit her to your local hospital and order a transfusion of packed red blood cells. In addition to stabilizing her circulatory system, which of the following is the most appropriate next step in the acute manage- ment of her condition? Her urine pregnancy test is negative, and an ultrasound of her right lower quadrant is negative for appendicitis. Which of the following is the appropriate outpatient management for her likely condition? Levofloxacin, 500 mg orally once a day, and doxycycline, 100 mg orally twice a day, both for 14 days E. The classic triad of abdominal pain, vaginal bleeding, and amenorrhea only occurs in about 50% of cases of ectopic pregnancy. Because ectopic pregnancy is the leading cause of pregnancy-related death in the first trimester, a physi- cian must consider the diagnosis for any woman of childbearing age with abdominal pain. Because this patient is hemodynamically unstable, admission and surgery are indicated; however, hemodynamically stable patients with an unrup- tured ectopic pregnancy and good follow-up may be managed expectantly or treated with methotrexate. Types 6 and 11 cause about 90% of all genital warts, but carry a low risk of malig- nancy. Immunization before sexual debut is ideal, but even women who are sexually active may benefit from the vaccine; because there is no commercially avail- able screening test to determine the serotypes to which a woman has been exposed, the vaccine may still provide some protection. Boys, too, receive this vaccination beginning at the age of 11 years in the effort to prevent warts and spread of the virus. Syncope has been reported in the adolescent population with all vaccines; current recommendations suggest observing adolescents for 15 minutes after immunization. Based on her anemia, this adolescent’s abnormal uterine bleeding is clas- sified as severe and warrants hospitalization. Stabilization of her circula- tory system is the first priority, and then steps must be taken to stop the bleeding. She has tried over-the-counter benzoyl peroxide for 2 months to no avail, and has stopped eating chocolate and French fries on her mother’s advice. Isotreti- noin (oral tretinoin) is reserved for severe, resistant nodulocystic acne. Considerations Acne vulgaris has the potential to be as damaging to the psyche as it can be to the skin. Managing acne successfully involves promoting patient understanding of the basics behind its development, creating thoughtful treatment regimens tailored to each patient, and periodically reassessing acne control in an effort to prevent pos- sible emotional and physical scarring. Pubertal hormonal surges lead to an increase in sebum production by sebaceous glands. Proliferation of the bacterium Propionibacterium acnes leads to distention of follicular walls, caus- ing obstruction of sebum flow. Follicles reach a maximum capacity and rupture, releasing their inflammatory contents. Inflammatory lesions are characterized by the presence of papules, pustules, nodules, or cysts. Physical examination of the patient with acne should include a thorough observation and description of lesion type(s) and distribution across the body (face, chest, back). Examples include tinea barbae pustules composed of dermatophytes under the beard of a rancher working with livestock and requiring an antifungal (griseofulvin); erythematous and papulopus- tular rosacea with undetermined etiology on the nose and cheeks of a teenager usually responding to a topical antibacterial (metronidazole); and allergic dermatitis with inflammatory papules on the chin of a toddler often controlled with an emol- lient or an occasional low-strength topical steroid (hydrocortisone). Acne treatment goals are elimination of lesions and diminishment of scarring (Table 58–1). Improvement may not be noticed for at least a month after therapy is initiated, with flare-ups possible during treatment. Patients should be discouraged from manipulating skin lesions because doing so will increase inflammation and promote scarring. The affected skin should be gently washed using antibacterial soap and rinsed well to prevent soap buildup on the skin surface. Scrubbing agents and harsh soaps should not be used, because they may stimulate more oil produc- tion and promote acne. Evidence-based guidelines for acne treatment, based on severity and lesion type, were issued by the American Acne and Rosacea Society and endorsed by the American Academy of Pediatrics in 2013. First-line management should begin with topical benzoyl peroxide or a comedo- lytic agent such as a retinoid (Retin-A). The combination of benzoyl peroxide in the morning and a comedolytic agent at night may be effective when either alone has failed. Benzoyl peroxide must be washed off prior to application of tretinoin or the retinoid will be rendered ineffective. It is available in over-the-counter preparations with variable uniformity, stability, and efficacy. Although these over- the-counter preparations eliminate bacteria at the skin surface, they do not have a carrier vehicle that allows deep follicular penetration.

Inter- receptor agonist whose properties are outlined in Table 24-1 feron beta-1b increases the cytotoxicity of natural killer cells and discussed later generic 5mg prochlorperazine with mastercard. The decline in muscle strength may be and increases the phagocytic activity of macrophages cheap prochlorperazine 5mg with amex. In slowed by gabapentin buy cheap prochlorperazine 5 mg on line, an antiepileptic drug discussed in addition, it reduces the amount of interferon-γ secreted by Chapter 20. Riluzole is believed to protect motor neurons from predecessor, it works as an immunomodulator and is synthe- the neurotoxic effects of excitatory amino acids (e. A monoclonal tamate) and to prevent the anoxia-related death of cortical preparation called natalizumab works by blocking the neurons. Glatiramer acetate is a synthetic protein that that may occur from injury or a neurologic disease. The term mimics the structure of myelin basic protein, a component antispasmodic agent is also used; however, this term is more of the myelin covering nerve fbers. This drug blocks myelin- properly applied to spasmolytic agents that may be used in damaging T cells by acting as a myelin decoy. Spasticity is frequently treated with physical therapy, but antispastic • Parkinson disease is a chronic disease caused by drugs, such as baclofen (see Table 24-1) may be useful in degeneration of dopaminergic neurons that arise in severe cases. Amantadine increases dopamine indicated for the short-term treatment of muscle spasms release and may inhibit its neuronal reuptake. Their mechanism of These drugs are often used as adjuncts to levodopa in action is not clear but includes centrally mediated effects the treatment of patients whose response to levodopa on catecholamine reuptake, and antimuscarinic and antihis- is inadequate. Degeneration of neurons leads to excessive Dantrolene acts by blocking the release of calcium ions dopamine neurotransmission and choreoathetoid from the sarcoplasmic reticulum in muscle fbers. Dopamine-receptor antagonists can decouples the excitation-contraction at the muscle endplate provide some improvement in affected patients. It is a life-saving drug • Alzheimer disease is a progressive dementia partly in cases of malignant hyperthermia triggered by haloge- caused by loss of cholinergic neurons in the cortex and nated anesthetics (see Chapter 21), is used in neuroleptic limbic structures of the brain. Donepezil, rivastigmine, malignant syndrome seen with high-potency antipsychotics and galantamine—centrally acting, reversible cholines- (see Chapter 22), and is also indicated for the management terase inhibitors—as well as well as memantine, an of spasticity from a number of disorders (e. Botulinum toxin A, widely known by its trade name, • Multiple sclerosis is a demyelinating disease whose Botox, has recently been approved for a number of medical exacerbations may be attenuated with corticosteroid indications besides the more famous (or infamous) use as a drugs. It can be used to treat immunomodifers retards disease progression in some upper-limb spasticity in stroke patients, for cervical dystonia patients. It was also sphingosine-1-phosphate receptor modulator, appears recently approved to treat urinary incontinence resulting to reduce lymphocyte infltration and autoimmune from detrusor overactivity in patients with spinal cord injury destruction of oligodendrocytes. Botox paralyzes muscles by blocking the release • Amyotrophic lateral sclerosis is a progressive disease of acetylcholine on the presynaptic side of the muscle end- of the motor neurons. Which of the following is not a mechanism of action for lead to cardiac arrhythmias by direct action of dopamine antiparkinsonism agents? Administration of l-dopa (A) direct dopamine agonist with carbidopa will decrease the formation of dopamine (B) precursor loading in the periphery and decrease the likelihood of cardiac (C) dopamine metabolism inhibition abnormalities. Answer A, direct action on cardiac dopa- (D) cholinergic receptor blocking mine receptors, may be a possible mechanism if there (E) selective dopamine reuptake inhibition were signifcant dopamine receptors in the heart modu- 2. Cardiac arrhythmias after initial doses of levodopa (l- lating cardiac rhythm, but there are not. Which of the following decreased release of catecholamines, would decrease most likely explains this occurrence? Answer D, increased release of dopa- (A) direct action on cardiac dopamine receptors mine, is not the best answer because increased peripheral (B) decreased release of catecholamines formation is not the same as increased neuronal release. The answer is C: neurotransmitter imbalance in the basal parkinsonism because of which one of the following ganglia. Acetylcholine (muscarinic) (B) continuing degeneration of dopamine neurons antagonists rebalance this abnormality. Answer A, (C) neurotransmitter imbalance in the basal ganglia decreased levels of acetylcholine from loss of neurons, (D) increased activity of acetylcholinesterase would not be a reason to give an antagonist to correct this (E) increased release of dopamine in basal ganglia condition. Selegiline, an antidepressant also used for the treatment dopamine neurons, is a fact of the progression of the of Parkinson disease, has which one of the following disease state, but antimuscarinic agents do not retard the mechanisms of action? Answer D, it increases release of dopamine AnsweRs And explAnAtions vesicles, is the mechanism of amantadine. Answers agonist, is a mechanism used by dopamine agonists such B through E are incorrect because they are the mecha- as bromocriptine. Answer B, precursor loading, is the nisms of anticholinergics, amantadine, memantine, and mechanism of l-dopa. Answer D, cholinergic receptor blocking, is a mechanism also used for the treat- ment of parkinsonism by such agents as benztropine. The chapter ends with a Alcohols and Glycols discussion of pharmacologic agents used to treat drug • Ethanol dependence and the agents’ mechanisms of action. Nearly every society in recorded history Barbiturates and Benzodiazepines has sanctioned the use of certain drugs while banning the • Pentobarbital (Nembutal) use of others. In other countries, • Oxycodone (OxyContin) use of alcohol is discouraged, but the use of other psychoac- tive drugs, such as marijuana, is socially acceptable. Hence, Central Nervous System Stimulants what constitutes drug abuse from a social or political per- Amphetamine and Its Derivatives spective is highly dependent on cultural attitudes and legal • Amphetamine restrictions. Drug abuse is not restricted • Caffeine to the use of illegal drugs, as the cumulative health and social • Nicotine effects caused by the use of alcoholic beverages and tobacco products in the United States far outweigh the negative Other Psychoactive Drugs effects of all illicit drug use. Cannabis and Its Derivatives • Marijuana Drug Dependence • Dronabinol (Marinol) Drug dependence is a condition in which an individual feels • Nabilone (Cesamet) compelled to repeatedly administer a psychoactive drug. Psychological dependence is caused by the • Acamprosate calcium (Campral) positive reinforcement of drug use that results from the • Naltrexone (ReVia, Depade, Vivitrol) activation of neurons located in the nucleus accumbens. Both psychological and physical dependence a appear to result from neuronal adaptation to the presence Used for the treatment of methanol or ethylene glycol poisoning. This similarity with a review of general concepts and mechanisms of drug supports the hypothesis that psychological dependence 260 Chapter 25 y Drugs of Abuse 261 is mediated by a common neuronal pathway that leads to behavioral reinforcement of drug use. Psychoactive drugs that evoke behavioral reinforcement of their use appear to sensitize dopaminergic neurons that project from the ventral tegmental area to the nucleus accumbens. Much evidence indicates that dopamine mediates drug Ventral tegmental area reinforcement by binding to dopamine D1 receptors in the nucleus accumbens. The kinases, in turn, activate other proteins in the Nicotine signal transduction pathway, including transcription factors. A schematic of a rat brain (midsagittal section) is transduction molecules that amplify responses to dopamine. Dopamine released in the nucleus synaptic pathways for dopamine neurotransmission in a accumbens is the fnal common pathway for reinforcing drugs (and addic- tive behaviors). Cocaine and amphetamines cause an increased release of manner much like the molecular mechanisms of learning dopamine directly at the nerve terminals in the nucleus accumbens. The degree of short-term reinforce- Drug Addiction ment of drug use is linked to the rate of increase of dopa- Drug addiction usually refers to an extreme pattern of drug mine levels in the nucleus accumbens.

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