By C. Kurt. Brigham Young University Idaho.
Gynecologic patients: Adnexal masses evaluated by sonography are assessed for size and echogenic texture; simple (fluid filled) versus com- plex (fluid and solid components) versus solid proven 130 mg malegra dxt. The uterus can be char- act erized for presence of masses cheap malegra dxt, such as ut erine fibroids cheap malegra dxt 130 mg on-line, and t he endo- metrial stripe can be measured. The gynecologic ult rasound examinat ion usually also includes invest igat ion of t he kidneys, because hydroneph rosis may sug- gest a p elvic pr ocess ( u r et er al obst r u ct ion ). Salin e in fu sion int o the ut er- ine cavit y via a t ranscervical cat het er can enhance t he ult rasound exami- nation of intrauterine growths such as polyps. Becauseo ftherad iatio n co n cern s,this pro ced ureis usually n o tper- formed on pregn ant women un less son ograph y is n ot h elpfu l, an d it is deemed necessary. T heC T scan isusefulin wo m en with po ssibleabd o m in alan d /o rpelvic masses, and may help to delineate the lymph nodes and retroperitoneal disorders. Id en tifiesso fttissueplan esverywellan d m ayassistin d efin in gm üllerian defects such as vaginal agenesis or uterine didelphys (condition of double uterus and double cervix), and in selected circumst ances may also aid in the evaluation of uterine anomalies. M ay behelpfulin establishin gthelo catio n o fa pregn an cy such asin d if- ferent iat in g a n ormal pregn an cy from a cer vical pregn an cy. In traven o usd yeisused to assesstheco n cen tratin gabilityo fthekid n eys, the patency of the ureters, and the integrity of the bladder. Itisalso usefulin d etectin g hyd ro n ephro sis,ureteralsto n e,o rureteral obstruction. Asm allam o un to frad io paqued yeisin tro d uced thro ugh a tran scervical can nu la an d r adiogr aph s are t aken. Itisusefulfo rthed etectio n o fin trauterin eabn o rm alities(subm uco us fibr oid s or in t r au t er in e ad h esion s) an d p at en cy of the fallop ian t u bes (tubal obstruction or hydrosalpinx). Ap p ro a ch t o Clin ica l Pro b le m So lvin g There are typically four distinct steps that a clinician undertakes to solve most clin ical pr oblems syst emat ically: 1. The process includes knowing which pieces of information are meaningful and which may be thrown out. Experience and knowledge help to guide the physician to “key in” on the most important possibilities. A good clinician also knows how to ask the same question in several different ways, and use different terminology. For example, patients at times may deny having been treated for “pelvic inflammatory disease,” but will answer affirmatively to being hospitalized for “a tubal infection. The patient’s presentation is then matched up against each of these possibilities, and each is either placed high up on the list as a potential etiol- ogy, or moved lower down because of disease prevalence, the patient’s presentation, or other clues. Usually, a long list of possible diagnoses can be pared down to two to three most likely ones, based on selective laboratory or imaging tests. For example, a woman wh o complains of lower abdominal pain and has a hist ory of a prior sexu- ally t ransmitt ed disease may have salpingit is; anot her pat ient who has abdominal pain, amenorrhea, and a history of prior tubal surgery may have an ectopic preg- nancy. Furthermore, yet another woman with a 1-day history of periumbilical pain localizing t o the right lower quadrant may h ave acut e appendicit is. With some infections, such as syphilis, the staging depends on the duration and ext ent of t he infect ion, and follows along t he nat ural h ist ory of t he infect ion (ie, primary syphilis, secondary, latent period, and tertiary/ neurosyphilis). If neither the prognosis nor the treatment was influenced by the st age of the disease process, there would not be a reason to sub- cat egor ize a disease as m ild or sever e. As an example, a pr egn ant woman at 34 weeks’ gest at ion wit h m ild pr eeclamp sia is at less r isk from the d isease t h an if sh e d evel- oped severe preeclampsia (particularly if the severe preeclampsia were pulmonary edema or eclampsia). Accordingly, wit h mild preeclampsia, t he management may be expectant, letting the pregnancy continue while watching for any danger signs (severe disease). In contrast, if preeclampsia with severe features complicated this same 34-week pregnancy, t he t reat ment would be magnesium sulfate to prevent seizures (eclampsia) and, most import ant ly, delivery. In this disease, severe preeclampsia means both maternal and fet al risks are increased. As anot her example, urinary t ract infect ions may be subdivided int o lower t ract infect ions (cyst it is) t hat are t reat ed by oral ant ibiot ics on an outpatient basis, versus upper tract infections (pyelonephritis) that generally require hospitalization and intravenous antibiotics. Hence, the student should approach a new disease by learning the mechanism, clin ical pr esent at ion, st agin g, an d the t r eat ment based on st age. Some responses are clinical such as improvement (or lack of improvement) in a patient’s abdominal pain, t emperat ure, or pulmonary examinat ion. O bviously, t he st udent must work on being more skilled in eliciting the data in an unbiased and stan- dardized manner. The student must be prepared to know what to do if the measured marker does not respond according to what is expected. Is the next step to retreat, or to reconsider the diagnosis, or to repeat the metastatic work-up, or t o follow up wit h anot h er more specific t est? Ap p r o a c h t o Re a d in g The clinical problem-oriented approach to reading is different from the classic “s y s t e m a t i c ” r e s e a r c h o f a d i s e a s e. P a t i e n t s r a r e l y p r e s e n t w i t h a c l e a r d i a g n o s i s ; hence, the student must become skilled in applying the textbook information to the clinical setting. In ot her words, t he student should read with t he goal of answering specific quest ions. Likewise, t he st udent should have a plan for t he acquisit ion and use of the information; the process is similar to having a mental “flowchart” and each st ep sift ing t hrough diagnost ic possibilit ies, t h erapy, complicat ions, and risk fact ors. T h ere are several fundament al quest ions that facilit at e clinical t h in king. The method of establishing the diagnosis has been covered in the previous section. One way of attacking this problem is to develop standard “approaches”to common clin ical sit u at ion s. It is h elpfu l t o u n d er st an d the most com mon cau ses of var iou s presentations such as “the most common cause of postpartum hemorrhage is uter- ine atony. With no other information to go on, the student would note that this patient has postpartum hemorrhage (blood loss of > 500 mL with a vaginal delivery). Using the “most common cause”information, the student would make an educated guess that the patient has uterine atony. Now the most likely diagnosis is a genital tract laceration, usually involving the cer vix. Th u s, the f i r s t s t e p i n p a t i e n t a s s e s s m e n t a n d m a n a g e m e n t i s u t e r i n e massage to check if the uterus is boggy. This question is difficult because the next step has many possibilities; the answer may be to obt ain more diagnostic information, st age the illness, or introduce ther- apy. It is often a more challenging quest ion than “W hat is the most likeyly diag- nosis? Another possibility is that there is enough information for a probable diagnosis, and the next step is to st age t he disease. Hence,from clinicaldata,a judgment needs to be rendered regardinghow far along one is on the road of: Make a diagnosis → St age t he disease → Treat based on stage → Follow response Frequent ly, the st udent is t aught t o “regurgit at e” the informat ion that someone has written about a particular disease, but is not skilled at giving the next step.
In patients with · · respiratory disease causing shunt or V/Q mismatch this value can exceed 5kPa and is the most common cause of arterial hypoxaemia order 130mg malegra dxt with mastercard. Alveolar gas equation End-expired gas contains a variable mixture of gas from regions of alve- · · olar dead space generic malegra dxt 130 mg online, from alveoli with V/Q ratios > 1 order malegra dxt overnight, and from ‘ideal’ alveoli. Oxygen carriage in the blood Oxygen is carried in the blood in two forms: in combination with haemo- globin and in solution. Haemoglobin The haemoglobin molecule consists of four subunits, each containing an iron-porphyrin group attached to a globin chain. Three normal forms of globin chain exist (α, β, and γ), with adult haemoglobin A (HbA) consisting of two α and two β chains. Weak electrostatic bonds that determine the quaternary structure of haemoglobin are responsible for the features of the binding of oxygen by haemoglobin. In oxyhaemoglobin (HbO2) the electrostatic bonds are weaker and haemoglobin assumes its relaxed (R) state. This allows an oxygen molecule better access to the haem group which lies at the bottom of a crevice in the globin chain, such that the afﬁnity for oxygen increases by 500 times. One oxygen molecule binding to one globin chain alters the conformation, and therefore oxygen afﬁnity, of the other three globins, an effect referred to as co-operativity that explains the well- known shape of the haemoglobin (Hb) dissociation curve. A single amino acid substitution in the globin chain profoundly alters the function of the Hb molecule. Suppression of HbA production leads to a compensatory production of HbF, which shifts the oxyhaemoglobin dissociation curve to the left. A small proportion of the iron in Hb exists as the ferric form (Fe3+), and these molecules of methaemoglobin (metHb) are unable to carry oxygen. Carbon dioxide in solution hydrates to form carbonic acid, a reaction which is catalysed by the enzyme carbonic anhydrase, before the carbonic acid dissociates into bicarbonate and hydrogen ions. Intracellular accumulation of these ions is overcome by the following: • Buffering of H+ ions by Hb, the capacity of which increases as oxygen is dissociated from the Hb • Hamburger or chloride shift—excess bicarbonate ions are actively transported out of the cell in exchange for chloride ions to maintain electrical neutrality. This classiﬁcation is in widespread use, but most diseases that traditionally cause Type 1 respiratory failure can also result in hypercapnia. The pathophysiological concepts responsible for the failure of gas exchange are fully dealt with in b Respiratory physiology and pathophysi- ology, p 2, but for the purposes of diagnosis, the causes of hypoxia and hypercapnia can be simpliﬁed as follows. Causes of hypoxia · · • Regional mismatching of ventilation and perfusion (V/Q) in the lung. The history may be obtainable from the patient, but may have to be sought from the relatives, the notes, or other healthcare professionals. Some types of severe hypoventilatory failure can develop with minimal breathlessness (particularly some chest bellows syndromes and muscular dystrophies). In these cases, worsening respiratory function is more likely to present as increasing lethargy and stupor. Nevertheless, certain patterns of dyspnoea are helpful: • Abrupt commanding dyspnoea suggests large airway narrowing (inhaled foreign body, anaphylactic laryngeal oedema), major pulmonary embolism (associated anterior chest tightness), or tension pneumothorax (often recall initial pleuritic pain when questioned). Although always a worrying symptom for both patient and doctor, in many cases no underlying diagnosis is found. Past medical history A past history of respiratory disease is clearly relevant but non-respiratory disease may also carry signiﬁcance. Recurrent sickling results in pulmonary hypertension and a restrictive pattern of lung function. Pets The presence of pets can often give an indication to the potential underlying respiratory problem. This is partly explained by an increase in aspira- tion risk and impaired innate immunity (reduced macrophage phagocytic function and neutrophil chemotaxis). This condition is now being described as ‘alcoholic lung’ and consists of: • Reduced pulmonary glutathione levels. The mortality of pneumonia in this group is much higher than the mor- tality predicted using physiological scoring systems. Non-respiratory symptoms • Loss of appetite, poor motivation, and fatigue are associated with gradually advancing hypoventilation in neuromuscular disorders. Examination Physical examination in the intensive care setting has constraints due to limited patient accessibility (intubation, invasive lines, monitoring equip- ment etc. Nevertheless regular clinical examination should be conducted rather than relying solely on monitored physiological parameters, imaging, or laboratory results. Initial observation Skin colour • Central cyanosis due to deoxyhaemoglobin is readily detected in polycythaemia and easily missed in anaemia. Skin perfusion • Warm vasodilated extremities and bounding pulse associated with chronic hypercapnia, sepsis, or anaphylaxis. Nutritional state • Pickwickian habitus of chronic hypoventilation syndrome or obstructive sleep apnoea. Respiratory system assessment The respiratory examination is well described elsewhere, and a detailed discussion is beyond the scope of this book. May be inspiratory or expiratory depending on whether the obstruction is extrathoracic or intrathoracic, respectively. Consolidation is also caused by ﬂuid (pulmonary oedema), blood (pulmonary haemorrhage), and tumours. Review of progress Respiratory failure is a dynamic process that may alter during the course of the illness, and whilst therapy is directed where possible at restoring normal function, the underlying aetiology or the associated treatment (e. Vigilance for alter- ations in the pattern of respiratory failure and low threshold for diagnostic review is appropriate throughout but essential for patients in the critical care environment. If progress is unexpectedly slow, or deterioration takes place, consider: • Is the diagnosis correct? Consider all sources (brain, meninges, sinuses, pleura, lung, heart, biliary tree and liver, abdomen, bone, joints, vascular devices, drains, skin, urine, blood). Whenever clinical concern is raised regarding worsening of respiratory failure, a complete reappraisal should be undertaken: reassess the history, examination, and investigations, and update the current examination and investigations. Investigation of respiratory disease Pulse oximetry The amounts of red (660nm wavelength) and infra-red (940nm wave- length) light absorbed by blood varies with the proportion of oxygen- ated to deoxygenated haemoglobin. Pulse-oximetry uses this principle to measure the percentage oxygen saturation in arterial blood. It only meas- ures pulsatile ﬂow, so it is not affected by static signals (such as those from venous or capillary blood). Readings are not affected by jaundice or anaemia, but there are some reports of inaccuracy in pigmented patients. Accuracy is also affected by: • Haemodynamic instability • Carboxyhaemoglobin (registers as SaO2 90%) • Methaemoglobinaemia (registers as SaO2 85%) • Low oxygen saturations (<80%) • Pulsatile venous ﬂow (e. Capillary blood gas sampling offers an excellent but underutilized alternative to serial arte- rial puncture outside the high-dependency setting (allowing for an under- read of 0. PaO2 PaO2 alone is insufﬁcient to fully evaluate the defect in oxygenation and a number of methods have been described to analyse it further: • The PaO2/FiO2 ratio • The A-aO2 gradient. PaO2/FiO2 ratio PaO2/FiO2 attempts to quantify the severity of hypoxaemia, although gas exchange and ventilation are not analysed individually. The American European Consensus Conference set the following PaO2/FiO2 ratio diagnostic criteria in 1994: • Acute lung injury <40kPa (approx.
Side effects are nausea purchase malegra dxt 130 mg amex, diarrhoea buy malegra dxt canada, arthralgia purchase malegra dxt toronto, headache, increased hepatic serum enzyme levels and rash. There may be chronic renal failure, acute renal failure (due to obstructive uropathy) and nephrolithiasis. Presentation of a Case: • This patient has erythematous and scaly rash along the butterfy distribution and also in forehead. A: I want to take the history of: • Whether the rash is aggravated on exposure to sunlight (photosensitivity). A: It is an autoimmune chronic multi-system disease characterized by production of multiple auto-antibodies, immune complexes and widespread immune-mediated organ damage. Fixed erythema, fat or raised, over the malar eminences, sparing nasolabial folds. Chronic cutaneous lupus: Discoid rash, erythematous raised patches with adherent keratotic scales and follicular plugging 6 atrophic scarring. Erythema, pigmented hyperkeratotic oedematous papules, atrophic depressed lesions. Neurological features: Seizures, psychosis, mononeuritis multiplex, Myelitis, peripheral or cranial neuropathy; cerebritis/acute confusional state in absence of other causes. Lungs (involved up to 50% cases): • Pleurisy, pleural effusion (may be bilateral) and pneumonitis. Haematological: • Anaemia (normocytic normochromic) and Coombs positive auto-immune haemolytic anaemia. Kidney: • Glomerulonephritis (commonly proliferative, may be mesangial, focal or diffuse, membranous). A: It is characterized by scaly red patch or circular, fat, red lesions (confused with psoriasis) on the upper torso and upper limbs, highly photosensitive. Arthralgia and mouth ulceration may be present but signifcant organ involvement is rare. Rarely, deformity may occur similar to rheumatoid arthri- tis, called Jaccoud’s arthritis. Probably steroid causes hypertrophy of lipocytes, which compresses blood vessels, leading to ischaemic necro- sis of bone). General measures: • Explanation and education regarding the nature of the disease. Chloroquine or hydroxychloroquine (in skin lesion, arthritis, arthralgia, serositis without organ involvement). A: When the disease activity (both clinically and biochemically) disappears, steroid should be reduced slowly over months and can be withdrawn (may be needed to continue for 2 to 3 years. Alternately, cyclophosphamide 250 mg/m2 body surface, every 15 days for 12 doses, followed • by prednisolone as maintenance therapy. Remember the following: • Advantages of azathioprine: no gonadal toxicity and no adverse effect on pregnancy. It is due to production of acrolein, a metabolite from cyclophosphamide that is highly toxic to the mucosa of urinary bladder. In early age, death is usually due to infection (mostly opportunistic), renal or cerebral disease. In later age, accelerated atherosclerosis is common, incidence of myocardial infarction is 5 times more than in general population (so, risk factor for atherosclerosis should be controlled, such as avoid smoking, control hypertension, obesity, hyperlipidaemia etc. Clinical features are: • Common in females, third to fourth decade, rare in children and elderly. Sjögren’s syndrome, may develop later • Lung involvement occurs in 85% cases, but frequently asymptomatic. There are Progression to nephrotic syndrome, segmental and global lesions as well as active and hypertension and renal insuffciency. Pulse therapy with methylprednisolone for 3 days followed by maintenance with prednisolone is necessary. Sometimes azathioprine 2 to 3 mg/kg body weight or cyclophosphamide 100 to 150 mg daily with prednisolone may be given. Even in inactive disease, prednisolone 10 mg/day should be given (dexam- ethasone or beclomethasone should be avoided). It is associated with recurrent arterial or venous thrombosis, recurrent foetal loss, thrombocytopenia. Some patients with anti-phospholipid antibody may not get anti-phospholipid syndrome. Presence of anti-phospholipid antibody is associated with: • Thrombosis, venous or arterial, 17% of stroke,45 years of age is thought to be due to anti- phospholipid antibody. In,1% cases of anti-phospholipid syndrome, a severe type called catastrophic anti-phospholipid syndrome may occur. In such case, there may be diffuse thrombosis, thrombotic microangiopathy and multiorgan failure. It is treated with intravenous heparin, high dose steroid, intravenous immune globulin and plasmapheresis. This reduces the chance of miscarriage, but pre-eclampsia and poor foetal growth remain common. Presentation of a Case: • There are few infarctions at the tip of great and second toe of right foot, also one small infarction at the tip of small toe of left foot. Vasculitis (toes) Vasculitis (fingers) Vasculitis (skin rash) Q:What are the differential diagnoses? A: Vasculitis syndrome is a heterogeneous group of disorders characterized by infammation and necrosis of the walls of affected blood vessels, with associated damage to the skin, kidney, lung, heart, brain and gastrointestinal tract. Vasculitis may be primary in the absence of any cause or secondary to many infammatory or infective diseases. Involvement of small artery: • Immune complex mediated: Henoch–Schönlein purpura, essential cryoglobulinaemia, cutaneous leucocytoclastic vasculitis. Cutaneous small vessel (post-capillary venule): • Idiopathic cutaneous small vessel vasculitis. Constitutional symptoms: Fever, weight loss, malaise, arthralgia, arthritis, myalgia. Features due multiple system involvement of the body: • Skin: painful palpable purpura, vesiculo-bullous lesions, urticaria, cutaneous nodules, ulcers, livedo reticularis, digital gangrene. A: As follows: • Bouchard’s node is the new bone formation at the proximal interphalangeal joint. A: I want to examine other joints, especially the knee joints, ankles, cervical and lumbar spine. A: It is a degenerative disease of the synovial joint characterized by focal loss of articular hyaline cartilage with proliferation of new bone and remodelling of joint contour. Secondary: to some other diseases, usually asymmetrical, commonly involves the weight- bearing joints. A: It is a primary generalized osteoarthrosis, which is autosomal dominant and occurs mainly in middle-aged women. Investigation: • X-ray of the affected joints: shows joint space narrowing, osteophyte and marginal sclerosis. Charcot’s joint of both elbow Charcot’s joint of both knee Charcot’s joint of both feet Q:What is Charcot’s joint?
Sideline evaluation tools are available for older children malegra dxt 130mg overnight delivery, and assess for the signs and symptoms that define a concussion order 130mg malegra dxt amex. The athlete should be removed from play and is not to return to any level of activity on the same day a concussion is sustained purchase 130 mg malegra dxt with mastercard. Otherwise the child’s caregiver should be informed of the event, the definition of a concus- sion, and instructed to observe the child for 24 to 48 hours. Emergent care is to be obtained if increasing headache, vomiting, confusion, or unusual behavior develops. Cognitive exertion or physical activity can cause wors- ening of symptoms, so the best management after a concussion is physical and cog- nitive rest. A concussion is more of a functional brain injury than a structural injury so neuroimaging is usually normal. For optimal patient safety, graduated return-to-play protocols have been devel- oped and provide guidelines for a stepwise approach to advance activity while monitoring for symptoms. The protocol is not initiated until the athlete has been asymptomatic for 24 hours without the use of any medications, including acetamino- phen, ibuprofen, or aspirin. Within these protocols, a 24-hour symptom-free period is also required before advancing to the next level. It takes a minimum of 5 days to complete the protocol and no limit exists on how long the athlete may remain at a certain level. Signs and symptoms of concussions have been documented to worsen with activity so if recurrence is noted, the protocol is discontinued until the athlete is asymptomatic for a 24-hour period. Then the protocol can be resumed at the level the athlete was at before symptom onset. Failure to properly manage concussions can lead to serious long-term conse- quences ranging from second impact syndrome to chronic traumatic encephalopa- thy. All reported cases of second impact syndrome have been in athletes younger than 20 years. Returning to play too early and/or repeat concussions can be det- rimental; it is important to educate the child or adolescent and parent about the dangers of returning to activity before the concussion has resolved. Athletes who have symptoms lasting over 3 months or who sustain three concussions in a single season should be disqualified from return to the sport. Thus, the child with failure to thrive (Case 10) due to child abuse (Case 38) may have symptoms of head injury. Secondary head- ache (Case 48) is a common complaint among those who have sustained a concussion-producing injury. Acute onset of neurologic symptoms in the patient with sickle cell disease (Case 13) may be confused with concussion, especially if the stroke causes a fall with resultant head injury. The adolescent with substance abuse disorder (Case 49) often participates in high-risk activi- ties, thus has a higher rate of accidents and concussion. She initially had a headache when the injury occurred but it resolved and her energy level has returned to normal. She has now gone back to school but gets a headache about 20 minutes after she starts her first class of the morning. She does not get the headache if she takes acetaminophen before leaving for school. Her mother is concerned because school standardized testing is beginning in 48 hours and her daughter seems to be falling behind in her studies. Reassure the mother that her daughter will be fine and there is no reason to be concerned about the testing. Recommend continued treatment with acetaminophen or ibuprofen for symptom relief, and obtain a more thorough history regarding the head- ache to determine if she has migraines. Explain to the mother that the persistent headache is still secondary to the concussion and provide documentation to the school for the girl to have reduced assignments and defer the testing until she recovers. Ask the girl if she is in danger of failing and ask the mother if her daugh- ter might be trying to avoid taking the tests for fear of a poor performance. He has been strictly following your orders of physical and cognitive rest and has been asymptomatic for 2 days. Allow him to start the graduated return to play protocol with his athletic trainer since he has been asymptomatic. Allow him to participate in practice only if he promises not to strike the ball with his head. Second impact syndrome is a rare but potentially lethal complication of sustaining another concussion in close proximity to a prior concussion that is not fully recovered. The earliest an athlete should anticipate returning to play is within 5 days, and this timeframe would presume the symptoms of the concus- sion had already resolved for 24 hours. Even if no loss of consciousness is sustained at the initial injury, a con- cussion requires the athlete to be removed from play that day. Initial management of a concussion includes rest from physical activity, not just the competitive training, and also rest from academic work. A shorter recovery time is expected in a younger child because their concussions are milder because they cannot really hit as hard as older athletes. The patient is still exhibiting symptoms of her concussion which is not unexpected since most take 7 to 10 days to resolve. Standardized testing should be discouraged during the recovery phase because it is not cognitive rest and some studies have documented lower scores result. Nausea, fatigue, and difficulty falling asleep are symptoms of concussion that can last several months but do not require imaging. An asymptomatic period without the use of any medications for over 24 hours suggests a graduated return to play protocol may be initiated. Graduated return to play is best because symptoms of concussion often worsen or can recur with exertion. Because this injury is his first concussion, it is unlikely he would be out for the season. Younger athletes generally require longer recovery time and they are at higher risk for more severe injuries due to a developing brain and less devel- oped cervical and shoulder musculature. An 18-month-old girl is seen by the pediatric nurse practitioner for an episode of cyanosis and a concern for poor eating. The family reports that they are extremely worried that for the previous several months she “refuses to eat enough. Earlier in the day when she was forced to sit at the table to eat she proceeded to scream loudly, turn blue, and then fall off her chair. She was born vaginally at term after an uncompli- cated pregnancy to a 28-year-old gravida 1 woman; birth weight was 3900 g (8. She was exclusively breast-fed until about 4 months of age when solids were introduced, and she was switched from breast to whole milk at 1 year of age. Her mother reports that she is able to climb, throw a ball, and walk up and down stairs with assistance. The family has no complaints other than his being a picky eater choosing to drink about 48 oz of whole milk daily instead of eating other foods. He was a term infant born to a 22-year-old woman whose pregnancy was com- plicated by gestational hypertension. He has had neither previous serious illness nor hospitalization and takes no medications.
On physical examination generic malegra dxt 130mg without a prescription, palpation of the peripheral pulses may be diminished or absent below the level of occlusion; bruits may indicate accelerated blood flow velo cit y a n d t u r b u len ce at the sit es o f st en o sis order 130mg malegra dxt with mastercard. Br u it s m ay b e h ear d in the ab d o m en wit h aortoiliac stenosis and in the groin with femoral artery stenosis malegra dxt 130mg sale. Elevation of the feet above the level of the h eart in the supine pat ient oft en induces pallor in the soles. If the legs are t h en placed in the depen dent posit ion, they frequ ent ly develop rubor as a result of reactive hyperemia. Chronic arterial insufficiency may cause hair loss on the legs and feet, t h icken ed an d br it t le t oen ails, an d sh iny at roph ic skin. Syst olic blood pressur es are measur ed by D oppler u lt r ason og- raphy in each arm and in the dorsalis pedis and posterior tibial arteries in each ankle. N ormally, blood pressures in the large arteries of the legs and arms are similar. In fact, blood pressures in t he legs often are higher t han in t he arms because of an artifact of measurement, so the normal rat io of ankle to brachial pressures is more t han 1. Further evaluation with exercise treadmill test ing can clarify the diagnosis wh en sympt oms are equivocal, can allow for assessment of funct ional limit at ions (eg, maximal walking distance), and can evaluate for concomitant coronary artery disease. Smoking is, by far, the single most important risk factor impact ing bot h claudicat ion symptoms and overall cardiovascular mort ality. Besides slowing the progression to critical leg ischemia, tobacco cessation reduces the risk of fatal or nonfatal myocardial infarc- tion by as much as 50%, more than any other medical or surgical intervention. In addit ion, t reat ment of hypercholest erolemia, cont rol of hypert ension and diabet es, and use of ant iplatelet agent s such as aspirin or clopidogrel all have been shown to improve cardiovascular healt h and may have an effect on peripheral art erial circu- lat ion. Carefully super vised exercise programs can improve muscle st rengt h and prolong walking distance by promoting the development of collateral blood flow. Specific medications for improving claudication symptoms have been used, wit h some benefit. Pentoxifylline, a subst ituted xant hine derivat ive t hat increases eryt hrocyt e elast icit y, has been report ed t o decrease blood viscosit y, t hus allowing improved blood flow to t he microcirculat ion; however, result s from clinical t rials are conflict ing, and t he benefit of pentoxifylline, if present, appears small. It has been shown in randomized controlled trials to improve maximal walking dist ance. This can be accomplish ed by percut an eou s an gioplast y, wit h or without placement of intra-arterial stents, or surgical bypass grafting. Angiog- raphy (either conventional or magnetic resonance arteriography) should be per- formed t o defin e the flow-limit ing lesion s pr ior t o any vascu lar procedure. Ideal can did at es for ar t er ial r evascu lar izat ion are t h ose wit h discr et e st en osis of lar ge vessels; d iffu se at h er o scler o t ic an d sm all- vessel d isease r esp o n d p o o r ly. Less common causes of chronic peripheral arterial insufficiency include throm- boangiitis obliterans, or Buerger disease, wh ich is an in flammat or y con dit ion of small- and medium-sized arteries t hat may affect t he upper or lower ext remit ies and is found almost exclusively in smokers, especially males younger t han 40 years. Fi bro mus cul ar dys pl as i a is a h yper plast ic disorder affecting medium and small arter- ies that usually occurs in women. Takayasu arteritis is an inflammatory condition, seen primarily in younger women, t hat usually affect s branches of t he aort a, most com m on ly the subclavian ar t er ies, an d cau ses arm claudication and Raynaud phenomenon, alon g wit h con st it ut ion al sympt oms su ch as fever and weight loss. The heart is the most common source of emboli; condit ion s that may cau se cardiogen ic emboli in clude at r ial fibr illat ion, dilat ed car- diomyopathy, and endocarditis. Artery-to-artery embolization of atherosclerotic debris from the aorta or large vessels may occur spontaneously or, more often, after an intravascular procedure, such as arterial catheterization. Emboli tend to lodge at the bifurcat ion of two vessels, most often in the femoral, iliac, popliteal, or tib- ioperoneal arteries. Arterial thrombosis may occur in atherosclerotic vessels at the site of stenosis or in an area of aneurysmal dilat ion, which may also complicate atherosclerotic disease. Patients with acute arterial occlusion may present with a number of signs, which can be r emembered as “six Ps”: pain, pallor, pulselessness, paresthesias, poikilother- mia (coolness), and paralysis. T h e first five sign s occur fairly quickly wit h acut e ischemia; paralysis will develop if t he arterial occlusion is severe and persistent. Rapid restoration of arterial supply is mandatory in patient s wit h an acute arterial occlusion that threatens limb viability. In it ial man agem ent in clu d es ant icoagu lat ion with heparin to prevent propagat ion of the thrombus. Conventional arteriography usually is indicated to ident ify the locat ion of the occlusion and to evaluat e potent ial met hods of revascularizat ion. Surgical removal of an embolus or arterial bypass may be performed, part icularly if a large proximal artery is occluded. Alternatively, a cath- et er can be used t o deliver int ra-art erial t hrombolyt ic t herapy direct ly int o t he thrombus. In comparison with systemic fibrinolytic therapy, localized infusion is associated with fewer bleeding complicat ions. Which of the following therapies might offer him the greatest benefit in symptom reduction and in overall mortality? Which of the following is the most likely cause of arterial insufficiency in this patient? W hich of the following is the most likely cause of arterial insufficiency in this patient? W hich of the following is the most likely cau se of this pat ient ’s fin din gs? She is evaluated by the cardiovascular surgeon but not felt to be a surgical can did at e. Which of the followin g con dit ion s is likely t o be pr esent in this patient? Cilost azol may help with clau dicat ion sympt om s but will n ot affect car d iovascu lar mor t alit y. T h r om b oan giit is oblit er an s, or Bu er ger d isease, is a d isease of you n g m ale smokers and may cause sympt oms of chronic art erial insufficiency in eit her legs or arms. Ch olest erol embolisms are most likely t o occur aft er a cardiac cat h et er izat ion or ot h er vascu lar pr ocedu r e. Locat ion of ar t er ial in su fficien cy is also import ant for different iat ion. Fibromuscular dysplasia is more likely to involve t he renal art eries and ext racranial cerebrovascular art eries rat her t han peripheral arteries of the extremities. Lastly, Takyasu arteritis is a large vessel vascu lit is p r im ar ily affect in g the ao r t a an d the p r im ar y b r an ch es. Takayasu aortitis is associated with symptoms of inflammation such as fever, and most often affect s the subclavian arteries, producing stenot ic lesions that may cause unequal blood pressures, diminish ed pulses, and isch - emic pain in the affect ed limbs. Embolism of cholesterol and other atherosclerotic debris from the aorta or other large vessels to small vessels of skin or digits may complicate any int ra-art erial procedure.
Frederick Sertürner order 130mg malegra dxt with amex, a German apothecary buy malegra dxt 130 mg cheap, iso- tionship cheap malegra dxt 130mg free shipping, which is the relationship among the drug molecule, lated the frst pure drug from a natural source when he its target receptor, and the resulting pharmacologic activity. The subsequent isolation of many other drugs dimensional conformation of the receptor are synthesized. Drug preparations include crude drug preparations obtained from natural sources, pure drug compounds isolated from Pharmaceutical Preparations natural sources or synthesized in the laboratory, and phar- Pharmaceutical preparations or dosage forms are drug prod- maceutical preparations of drugs intended for administra- ucts suitable for administration of a specifc dose of a drug tion to patients. The relationship among these types of drug to a patient by a particular route of administration. By far, the most common formulation of drugs is for the oral route of administration, followed by Drug formulations used for injections. Tablets and capsules are the most common preparations for oral administration because they Osmotic agent are suitable for mass production, are stable and convenient to use, and can be formulated to release the drug immedi- ately after ingestion or to release it over a period of hours. In the manufacture of tablets, a machine with a punch and die mechanism compresses a mixture of powdered drug and inert ingredients into a hard pill. The inert ingredients include specifc components that provide bulk, prevent stick- ing to the punch and die during manufacture, maintain H2O tablet stability in the bottle, and facilitate solubilization of A the tablet when it reaches gastrointestinal fuids. These ingredients are called fllers, lubricants, adhesives, and dis- Transdermal skin patch integrants, respectively. A tablet must disintegrate after it has been ingested, and then the drug must dissolve in gastrointestinal fuids Drug before it can be absorbed into the circulation. Variations in reservoir the rate and extent of tablet disintegration and drug dissolu- tion can give rise to differences in the oral bioavailability of drugs from different tablet formulations (see Chapter 2). Enteric coat- ings consist of polymers that will not disintegrate in gastric acid but will break down in the more basic pH of the intes- tines. In the sustained-release tablet (A), water is attracted by an osmotic agent in the ucts, release the drug from the preparation over many hours. In the transder- The two methods used to extend the release of a drug are mal skin patch (B), the drug diffuses through a rate-controlling membrane controlled diffusion and controlled dissolution. Controlled dissolution is done by inert polymers that forms, however, because the liquid must be measured each gradually break down in body fuids. Sweet- case, the drug is gradually released into the gastrointestinal ened aqueous solutions are called syrups, whereas sweetened tract as the polymers dissolve. Alcohol is Some products use osmotic pressure to provide a sus- included in elixirs as a solvent for drugs that are not suff- tained release of a drug. Sterile solutions and suspensions are available for par- The attracted fuid then forces the drug out of the tablet enteral administration with a needle and syringe, or with an through a small laser-drilled hole (Fig. Many drugs are formulated as Capsules are hard or soft gelatin shells enclosing a pow- sterile powders for reconstitution with sterile liquids at the dered or liquid medication. Hard capsules are used to time the drug is to be injected, because the drug is not stable enclose powdered drugs, whereas soft capsules enclose a for long periods of time in solution. The gelatin shell quickly dissolves in gas- tions and suspensions are suitable for administration with an trointestinal fuids to release the drug for absorption into the eyedropper into the conjunctival sac. Drug solutions and parti- tions in which the drug is slowly released from the patch for cle suspensions, the most common liquid pharmaceutical absorption through the skin into the circulation. Most skin preparations, can be formulated for oral, parenteral, or patches use a rate-controlling membrane to regulate the other routes of administration. Such provide a convenient method for administering drugs to devices are most suitable for potent drugs, which are there- pediatric and other patients who cannot easily swallow fore effective at relatively low doses, that have suffcient lipid pills or tablets. They are buccal administration are given in a relatively low dose and particularly useful for treating respiratory disorders because must have good solubility in water and lipid membranes. Some likely be washed away by saliva before the drug could be aerosol devices contain the drug dispersed in a pressurized absorbed. Two examples of drugs available for sublingual gas and are designed to deliver a precise dose each time they administration are nitroglycerin for treating ischemic heart are activated by the patient. The oral topical application of a drug to the skin or mucous mem- route of administration is convenient, relatively safe, and the branes. Lotions are liquid prepara- and the varying rates of gastric emptying, intestinal transit, tions often formulated as oil-in-water emulsions and are and tablet disintegration and dissolution. Suppositories are drugs are inactivated by the liver after their absorption from products in which the drug is incorporated into a solid base the gut, called frst-pass metabolism (see Chapter 2), and that melts or dissolves at body temperature. Suppositories oral administration is not suitable for use by patients who are are used for rectal, vaginal, or urethral administration and sedated, comatose, or experiencing nausea and vomiting. Rectal administration of drugs in suppository form can result in either a localized effect or a systemic effect. They and common parenteral routes compared in Table 1-2, can also be administered for localized conditions such as are intended to elicit systemic effects and are therefore hemorrhoids. Other routes of administration, undergo relatively little frst-pass metabolism in the liver. Parenteral administration refers to drug administration with a needle and syringe or with an intravenous infusion pump. Enteral Administration The most commonly used parenteral routes are the intrave- The enteral routes of administration are those in which the nous, intramuscular, and subcutaneous routes. These Intravenous administration bypasses the process of drug include the sublingual, buccal, oral, and rectal routes. In buccal administration, the drug is Because the drug is delivered directly into the blood, it has placed between the cheek and the gum. Cannot be used for drugs that are inactivated by gastric acid, for drugs with a large frst-pass effect, or for drugs that irritate the gut. Can cause bleeding if the patient is receiving an rapid from solutions and is slow and sustained from anticoagulant. Absorption is Cannot be used for drugs that irritate cutaneous tissues or for similar to that in the intramuscular route but is drugs that must be given in large volumes. Poses more risks for toxicity and tends to be more expensive than Allows for rapid titration of drug. Chapter 1 y Introduction to Pharmacology 7 physiologic response, such as agents used to treat hypoten- example, the chemical name of aspirin is acetylsalicylic acid. The intravenous route Others are long and hard to pronounce owing to the size is widely used to administer antibiotics and antineoplastic and complexity of the drug molecule. For most drugs the drugs to critically ill patients, as well as to treat various types chemical name is used primarily by medicinal chemists. The intravenous route is potentially The nonproprietary name, or generic name, is the type the most dangerous, because rapid administration of drugs of drug name most suitable for use by health care profes- by this route can cause serious toxicity. Solutions are absorbed more rapidly the chemical names of drugs, provide some indication of the than particle suspensions, so suspensions are often used to class to which a particular drug belongs. For example, oxacil- extend the duration of action of a drug over many hours or lin can be easily recognized as a type of penicillin. In cases of meningitis, the intrathecal the same as the International Nonproprietary Name and route is useful in administering antibiotics that do not cross the British Approved Name. Epidural administration, common for drugs can vary with the language in which they are used.
Nonetheless order discount malegra dxt, because there is a small risk with sublingual Suboxone buy 130mg malegra dxt otc, treatment is initiated with Subutex purchase malegra dxt 130mg visa, thereby allowing substitution of buprenorphine for the abused opioid. Naltrexone After a patient has undergone opioid detoxification, naltrexone [ReVia, Vivitrol], a pure opioid antagonist, can be used to discourage renewed opioid abuse. By preventing pleasurable effects, naltrexone eliminates the reinforcing properties of opioid use. When the former addict learns that taking an opioid cannot produce the desired response, drug-using behavior will cease. Naltrexone is not a controlled substance, and hence prescribers require no special training or certification. At this time, Vivitrol is the only long-acting drug for managing opioid addiction. With the exception of the benzodiazepines, all of these drugs are more alike than different. Depressant effects are dose dependent and range from mild sedation to sleep to coma to death. The abuse liability of the barbiturates stems from their ability to produce subjective effects similar to those of alcohol. The barbiturates with the highest potential for abuse have a short to intermediate duration of action. Tolerance Regular use of barbiturates produces tolerance to some effects, but not to others. As a result, progressively larger doses are needed to produce desired psychological responses. Consequently, as barbiturate use continues, the dose needed to produce subjective effects moves closer and closer to the dose that can cause respiratory arrest. Physical Dependence and Withdrawal Techniques Chronic barbiturate use can produce substantial physical dependence. When physical dependence is great, the associated abstinence syndrome can be severe—sometimes fatal. In contrast, the opioid abstinence syndrome, although unpleasant, is rarely life threatening. One technique for easing barbiturate withdrawal employs phenobarbital, a barbiturate with a long half-life. Because of cross-dependence, substitution of phenobarbital for the abused barbiturate suppresses symptoms of abstinence. After the patient has been stabilized, the dosage of phenobarbital is gradually tapered off, thereby minimizing symptoms of abstinence. Acute Toxicity Overdose with barbiturates produces a triad of symptoms: respiratory depression, coma, and pinpoint pupils—the same symptoms that accompany opioid poisoning. Treatment is directed at maintaining respiration and removing the drug; endotracheal intubation and ventilatory assistance may be required. Naloxone, which reverses poisoning by opioids, is not effective against poisoning by barbiturates. Benzodiazepines are much safer than the barbiturates, and overdose with oral benzodiazepines alone is rarely lethal. If severe overdose occurs, signs and symptoms can be reversed with flumazenil [Romazicon, Anexate ], a benzodiazepine antagonist. As a rule, tolerance and physical dependence are only moderate when benzodiazepines are taken for legitimate indications but can be substantial when these drugs are abused. In patients who develop physical dependence, the abstinence syndrome can be minimized by withdrawing benzodiazepines very slowly—over a period of months. The abuse liability of the benzodiazepines is much lower than that of the barbiturates. In addition, cocaine can produce local anesthesia as well as vasoconstriction and cardiac stimulation. According to the National Survey on Drug Use and Health, cocaine use has declined. Forms Cocaine is available in two forms: cocaine hydrochloride and cocaine base (alkaloidal cocaine, freebase cocaine, “crack”). Cocaine hydrochloride is available as a white powder that is frequently diluted (“cut”) before sale. Cocaine base is sold in the form of crystals (“rocks”) that consist of nearly pure cocaine. Cocaine base is widely known by the street name “crack,” a term inspired by the sound the crystals make when heated. Routes of Administration Cocaine hydrochloride is usually administered intranasally. Cocaine hydrochloride cannot be smoked because it is unstable at high temperature. Subjective Effects and Addiction At usual doses, cocaine produces euphoria similar to that produced by amphetamines. In a laboratory setting, individuals familiar with the effects of cocaine are unable to distinguish between cocaine and amphetamine. As with many other psychoactive drugs, the intensity of subjective responses depends on the rate at which plasma drug levels rise. When crack cocaine is smoked, desirable subjective effects begin to fade within minutes and are often replaced by dysphoria. In an attempt to avoid dysphoria and regain euphoria, the user may administer repeated doses at short intervals. Acute Toxicity: Symptoms and Treatment Overdose is frequent, and deaths have occurred. Severe overdose can produce hyperpyrexia, convulsions, ventricular dysrhythmias, and hemorrhagic stroke. Angina pectoris and myocardial infarction may develop secondary to coronary artery spasm. Psychological manifestations of overdose include severe anxiety, paranoid ideation, and hallucinations (visual, auditory, and/or tactile). Although there is no specific antidote to cocaine toxicity, most symptoms can be controlled with drugs. Diazepam may also alleviate hypertension and dysrhythmias because these result from increased central sympathetic activity. Although beta blockers can suppress dysrhythmias, they might further compromise coronary perfusion (by preventing beta -mediated coronary2 vasodilation). Reduction of thrombus formation with aspirin can lower the risk for myocardial ischemia.