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By I. Boss. San Diego State University. 2018.

Valproic acid inhibits the metabolism of several drugs discount 60 caps lasuna mastercard, including phe- Several benzodiazepines are used in the management of nobarbital buy lasuna 60 caps without prescription, primidone order lasuna 60caps on line, carbamazepine order lasuna 60caps line, and phenytoin order lasuna 60 caps without prescription, epileptic seizures quality lasuna 60caps, although only a few are approved for leading to an increased blood level of these compounds. At high doses, valproic acid can inhibit its own metabo- Since the benzodiazepines share many properties, they lism. It can also displace phenytoin from binding sites will be discussed as a class; individual members will be on plasma proteins, with a resultant increase in un- mentioned for specific indications. In The primary action of the benzodiazepines as anti- this instance, the dosage of phenytoin should be ad- convulsants is to enhance inhibition through their inter- justed as required. These examples reinforce the need action with the GABAA receptor at the benzodiazepine to determine serum anticonvulsant levels in epileptic binding site. It is highly effective against absence but is likely a factor in their use in the treatment of sta- seizures and myoclonic seizures. In the treatment of clonic epilepsy and for partial seizures with complex status epilepticus, the preferred route is usually intra- symptoms. Benzodiazepines are extensively metabolized The most serious adverse effect associated with val- by the microsomal drug-metabolizing system; fre- proic acid is fatal hepatic failure. Fatal hepatotoxicity is quently an active compound is broken down to another most likely to occur in children under age 2 years, espe- agent that is also active pharmacologically. This is the cially in those with severe seizures who are given multi- reason for the long duration of action of several benzo- ple anticonvulsant drug therapy. As and therefore, valproic acid should not be administered AEDs, they have their major usefulness in the treat- to patients with hepatic disease or significant hepatic ment of absence, myoclonic, and atonic seizures and in dysfunction or to those who are hypersensitive to it. Valproic acid administration has been linked to an in- Drowsiness occurs readily and unfortunately is usu- creased incidence of neural tube defects in the fetus of ally a problem at therapeutic doses. The other limiting mothers who received valproate during the first side effect of the benzodiazepines is the rapid develop- trimester of pregnancy. Although all of the benzodiazepines are similar, cer- Valproic acid causes hair loss in about 5% of pa- tain ones are employed more for the treatment of tients, but this effect is reversible. Clonazepam was the first benzodi- testinal effects are common, and some mild behavioral azepine approved in the United States specifically for effects have been reported. Clonazepam is a hyperglycemia, hyperglycinuria, and hyperammonemia, very long acting compound with potent anticonvulsant have been reported. Drooling and hypersalivation may but its administration may lead to increased depression be troublesome in children and in infants. The intravenous route is preferable for emer- is related to its effect of facilitating GABA inhibition. The latter metabolite has anticonvul- Tiagabine (Gabitril) blocks the reuptake of GABA into sant activity, but most of the anticonvulsant efficacy of neurons and glia, thereby resulting in higher levels of primidone is due to the phenobarbital that is produced. The ability to increase The major untoward effect of phenobarbital and GABA concentrations is presumed to be involved in primidone, when used as anticonvulsants, is sedation. It is primarily used in the treatment of partial ularly in children, is a possible disturbance in cognitive complex seizures. Even when the serum concentration is within tration include dizziness, somnolence, nervousness, nau- the therapeutic range, apparently the ability to concen- sea, and confusion. At present, phenobarbital and primidone are con- Vigabatrin sidered as alternative drugs for the treatment of partial Vigabatrin (Sabril) is a relatively specific irreversible in- seizures and for generalized tonic–clonic epilepsy. They hibitor of GABA-transaminase (GABA-T), the major are judged to be less effective than carbamazepine and enzyme responsible for the metabolism of GABA in the phenytoin. As a result of inhibition of GABA-T, Phenobarbital and primidone are classic agents ca- there is an increase in the concentration of GABA in the pable of inducing microsomal drug-metabolizing en- brain and consequently an increase in inhibitory neuro- zymes (See Chapter 4), and this fact must be considered transmission. Vigabatrin is well absorbed orally and is when using either drug singly or in combination with distributed to all body systems. Consequently, many interactions can oc- nation for vigabatrin is renal excretion of the parent com- cur between phenobarbital and primidone and a variety pound; no metabolites have been identified in humans. If valproic acid is administered with It should not be used in patients with absence epilepsy either phenobarbital or primidone, striking increases in or with myoclonic seizures. Phenobarbital and Primidone (Mysoline) Agents That Block T-Calcium Channels Phenobarbital and primidone are quite similar both Ethosuximide chemically and pharmacologically, and much of the an- ticonvulsant activity of primidone may be ascribed to its It is now generally accepted that the specific antiepilep- metabolic conversion to phenobarbital.

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This sac may become closed off and distended with fluid either from perforation of a posterior gastric ulcer or from the outpouring of fluid in acute pancreatitis buy discount lasuna 60 caps online, forming a pseudocyst of the pancreas order lasuna 60 caps on-line. Passing from it are the gastrosplenic ligament to the greater curvature of stomach (carrying the short gastric and left gastro- epiploic vessels) and the lienorenal ligament to the posterior abdominal wall (carrying the splenic vessels and tail of the pancreas) buy lasuna 60caps overnight delivery. The tail of the pancreas abuts against the hilum of the spleen through which vessels and nerves enter and leave this organ generic lasuna 60caps amex. Blood supply The splenic artery is one of the three main branches of the coeliac axis purchase lasuna 60 caps without a prescription. The fibrous tissue of the capsule extends into the spleen to form a series of trabeculae between which lies the splenic pulp lasuna 60caps free shipping. Clinical features 1In performing a splenectomy the close relation of the pancreatic tail to the hilum and splenic pedicle must be remembered; it is easily wounded. Sim- ilarly, a stab wound of the posterior left chest may penetrate the diaphragm and tear the spleen. The spleen, with its thin tense capsule, is the common- est intra-abdominal viscus to be ruptured by blunt trauma. They occur in about one in ten subjects and, if left behind, may result in persistence of symptoms following splenectomy for congenital acholuric jaundice or thrombocytopenic purpura. The urinary tract The kidneys The kidneys lie retroperitoneally on the posterior abdominal wall; the right kidney is 0. Relations (Figs 80, 81) •Posteriorly—the diaphragm (separating pleura), quadratus lumborum, psoas, transversus abdominis, the 12th rib and three nerves—the subcostal (T12), iliohypogastric and ilio-inguinal (L1). In front of the left kidney lie the stomach, the pancreas and its vessels, the spleen, and the descending colon. The medial aspect of the kidney presents a deep vertical slit, the hilum, which transmits, from before backwards, the renal vein, renal artery, pelvis of the ureter and, usually, a subsidiary branch of the renal artery. Lymphatics and nerves also enter the hilum, the latter being sympathetic, mainly vasomotor, fibres. If a calculus is lodged in the pelvis of the ureter, its removal is comparatively simple when this is extrarenal, and it is correspondingly difficult when the pelvis is hidden within the substance of the kidney. Within the kidney, the pelvis of the ureter divides into two or three major calyces, each of which divides into a number of minor calyces. Each of these, in turn, is indented by a papilla of renal tissue and it is here that the collecting tubules of the kidney discharge urine into the ureter. The kidneys lie in an abundant fatty cushion (perinephric fat) contained in the renal fascia (Fig. Above, the renal fascia blends with the fascia over the diaphragm, leaving a separate compartment for the suprarenal The urinary tract 107 Fig. Only infe- riorly does it remain relatively open — tracking around the ureter into the pelvis. The kidney has, in fact, three capsules: 1fascial (renal fascia); 2fatty (perinephric fat); 3true— the fibrous capsule which strips readily from the normal kidney surface but adheres firmly to an organ that has been inflamed. The left renal vein passes in front of the aorta immediately below the origin of the superior mesenteric artery. Clinical features 1Blood from a ruptured kidney or pus in a perinephric abscess first distend the renal fascia, then force their way within the fascial compart- ment downwards into the pelvis. The midline attachment of the renal fascia prevents extravasation to the opposite side. To a lesser degree, it is in this plane that the normal kidney moves during respiration. Note that CT scans, by convention, are viewed from below, so that the aorta, for example, is seen on the right side. An oblique incision is usually favoured midway between the 12th rib and the iliac crest, extending laterally from the lateral border of erector spinae. Latissimus dorsi and serratus posterior inferior are divided and the free posterior border of external oblique is identified, enabling this muscle to be split along its fibres. Internal oblique and transversus abdominis are then divided, revealing peritoneum anteriorly, which is pushed forward.

Garlic may promote vasodilation by relaxing smooth muscle buy lasuna 60caps cheap, and it may reduce low- Conclusion density lipoprotein (LDL) oxidation buy generic lasuna 60 caps. Fresh garlic may have some cardiovascular benefits discount 60 caps lasuna mastercard, but Indications it is unclear whether it lowers blood lipids or blood pressure as much as originally thought discount lasuna 60 caps fast delivery. Aged prepara- Some studies support garlic having a modest but signif- tions and cooked garlic are likely to be less effective de- icant effect on lowering total cholesterol safe 60 caps lasuna, LDL choles- spite being better tolerated discount 60caps lasuna with amex. More recent studies have found Ginkgo Biloba Leaf Extract no significant effect, even though similar preparations and doses were used. Therefore, the effectiveness of Ginkgo, or maidenhair tree (Ginkgo biloba), is thought garlic for this indication remains unresolved. Likewise, to be the most ancient of living tree species, and it is 790 VII DRUGS AFFECTING THE ENDOCRINE SYSTEM now also one of the top selling herbs in Europe and the likely to occur with the leaf extract. The malodorous United States because of its reputed ability to improve ginkgo fruit cross-reacts with poison ivy (urushiol) and cognitive function. This reduces the risk of allergic reactions cooked ginkgo kernels have had seizures, and conse- to the leaves if they are consumed directly. Ginkgo leaf quently there is some concern about using high doses of extract contains 24% flavone glycosides (including the ginkgo in seizure patients. However, most patients tol- antioxidant rutin, which improves capillary fragility) erate gingko extract very well, with only occasional GI and 6% terpene lactones. Mechanism of Action Bleeding complications are an infrequent but seri- ous concern, with subdural hematomas, subarachnoid Ginkgo leaf extract appears to act primarily as a mild hemorrhages, hyphema (bleeding of the iris), and surgi- cerebral vasodilator that increases cerebral blood flow cal bleeding occasionally reported. Ginkgolides inhibit platelet ministration prior to surgery and the avoidance of its activating factor, and this may improve microcircula- use with anticoagulant drugs and perhaps with aspirin is tory blood flow in atherosclerotic disease with slightly recommended. There appears to be an an- in pregnant women and children, since at least one study tioxidant effect that may be neuroprotective. Although showed in a ginkgo preparation small amounts of some studies suggested a monoamine oxidase inhibitor colchicine, a compound that can block cellular division (MAOI) effect, this is considered to have questionable and cause abortion; however, it is unclear whether this clinical relevance. Ginkgo may reduce the effectiveness of thiazide di- Indications uretics for blood pressure control and at least theoreti- Ginkgo leaf extract is most popular for cognitive disor- cally should be avoided with MAOIs. There is also a ders, including memory loss, dementia, and cerebrovas- suggestion that ginkgo may decrease male and female cular insufficiency. At least one Dose large (214 patient) study, however, failed to show a For cognitive function, total daily doses of 120 to 240 mg memory improvement in dementia patients. Studies are divided into 2 or 3 doses of ginkgo leaf extract are rec- now under way to see whether ginkgo use will protect ommended. Intermittent claudication appears to benefit from ginkgo therapy: many studies demonstrate improved Conclusion walking distance and decreased pain. One meta-analysis of eight studies documented statistically significant im- The preponderance of evidence indicates that ginkgo is provement but questioned its clinical relevance. In some an effective mild cerebral and perhaps general va- studies, the high doses (240 mg) appeared more effective. Ginseng Adverse reactions, Contraindications, Panax ginseng describes the root from two species of and Interactions plants, Asian ginseng (Panax ginseng) and American gin- Allergic reactions are a significant concern with un- seng (Panax quinquefolius), popularly used for improv- processed ginkgo leaf (ginkgolic acid) but are much less ing stamina and providing a sense of well-being. The 69 Herbal Medicine 791 terms red and white ginseng refer to how the root is ginsengs should definitely be avoided in any patient processed, not the species of origin. Dizziness, steam-cured prior to drying, while white ginseng is headache, diarrhea, and nausea have also been re- bleached and dried. A controversial ginseng abuse syndrome con- saponins called ginsenosides (also called panaxosides), of sisting of tremor, elevated blood pressure, insomnia, which up to 18 types are recognized as having differing and anxiety may also occur. Diabetic patients have had hypoglycemia on ginseng, Siberian ginseng (Eleutherococcus senticosus) so sugars must be monitored, and insulin or other hypo- should not be confused with Panax ginseng.

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Volume Limited: A preset volume of air is delivered regardless of the opposing pres- sure buy 60 caps lasuna amex. Several forms of this type of ventila- tion exist cheap lasuna 60 caps on line, including high-frequency jet ventilation buy generic lasuna 60caps line, high-frequency positive pressure ventila- tion cheap 60caps lasuna free shipping, and high-frequency oscillation purchase 60 caps lasuna fast delivery. Controlled Ventilation: The patient gets a breath only when it is delivered by the ma- chine purchase lasuna 60 caps otc. Assist Controlled: The patient gets a full mechanical tidal volume each time he or she attempts an inspiratory effort. The respiratory frequency is determined by the patient, al- though a backup rate is set to ensure a minimum minute ventilation. Agitation may also lead to “breath stacking,” in which the ventilator delivers a second tidal volume before completing the expiratory phase of the first breath. Fortunately, this is rarely a clinical problem because the patient often feels more comfortable and consequently less agitated because of the decreased work of breathing on AC. Synchronous IMV: The respirator delivers a set number of breaths each minute and al- lows the patient to supplement ventilation with his or her own inspiratory efforts between machine breaths. As the ventilator 20 rate decreases progressively, the patient assumes more of the work of breathing. This is the most commonly used type of ventilatory mode in conjunction with pressure support and PEEP. Assist-controlled ventilation (AC) 0 Each inspiratory attempt triggers a mechanical breath. Synchronous intermittent mandatory ventilation (SIMV) 0 Patient is allowed to breathe spontaneously in between synchronized mechanical breaths. Pressure support ventilation (PSV) + SIMV 0 Patient triggers positive pressure support during inspiration of spontaneous breath - - in between SIMV mechanical breaths. The patient controls the rate and inspiratory time while augmenting tidal volume and inspiratory flow. The higher the pressure support, the less work the patient expends to take a breath. Thus, PSV is comfort- able because the patient has more control of his or her ventilation. PSV serves as an ideal weaning mode because the pressure can be turned down slowly, with changes as small as 1 cm H2O. PSV is often integrated with SIMV as a backup to ensure a minimum minute ventilation. It represents the supraatmospheric pressure remaining in the airways at the end of expiration. PEEP increases alveolar ventilation by preventing small airway collapse, thereby increasing FRC. PEEP also is often used prophylactically against atelectasis, particularly in the postop- erative period. Increasing lev- els of PEEP is typically used to decrease the FiO2, in an attempt to limit oxygen toxicity. One disadvantage of PEEP, however, is that it may decrease the cardiac index by decreasing left ventricular end-diastolic volume and should be used cautiously in patients at risk for myocardial ischemia. Pressure Regulated Volume Control: This mode of ventilation is used in the setting of increased airway pressure. A microprocessor in the ventilator adjusts the pressure needed to achieve the proper tidal volume. Continuous Positive Airway Pressure: Positive pressure throughout inspiration and expiration without mechanical assistance during ventilation. Despite the marked reduction in flow rates, oxy- genation and CO2 exchange are still achieved. HFV may be ideally suited to treat such conditions as bronchopleural fistulas or may serve as a more desirable form of ventilation during surgeries requiring a minimum of lung movement. Ventilator Management Ventilator Orders Once the decision has been made to place a patient on a ventilator, the patient must be intu- bated with an appropriate endotracheal tube (see Chapter 13, page 268).

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