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Maxillary antrum Infratemporal bone (which is fused with the posterior wall of the antrum) fossa anteriorly and the pterygoid process of the sphenoid posteri- Nasal cavity orly (Fig purchase actoplus met overnight diabetes prevention quiz. It also contains the sphenopalatine ganglion and transmits the maxillary nerve and internal maxillary (Fig proven 500mg actoplus met blood sugar machine. Note the maxillary The oral cavity antrum anteriorly and the orbital apex superiorly connected by the inferiorThe oral cavity and the oropharynx are separated by a line of orbital fssure 500 mg actoplus met overnight delivery diabetes insipidus renal failure. It consists largely of the lingual tonsils, which form the posterior third of the tongue. The tongueThe contents of the oral cavity are the hard palate, maxil-The tongue is a muscular organ made up of intrinsic transverse, lary and mandibular alveolar ridges, retromolar trigone, buccal vertical, inferior and superior fbres visible on ultrasound mucosa, foor of mouth and anterior two-thirds of the tongue. The vestibule is the space between the cheek and lips exter- It is supported by three paired extrinsic muscles. The larg- nally and the teeth and gums internally and contains the supe- est of these is the genioglossus, which arises anteriorly from rior and inferior gingival sulci. The it from the nasal cavity, with the maxillary alveolus and teeth hyoglossus arises from the hyoid and extends superiorly and forming the anterior and lateral boundaries of the hard palate. Note the horizontal intrinsic muscle, the midline lingual septum and the paramedian genioglossus muscles. A pyramidal glossopharyngeal nerve on its medial aspect and the lingual lobe may extend superiorly, usually arising from the lef side vein, submandibular duct, lingual and hypoglossal nerves on of the isthmus. During development the thyroid gland descends from the A midline fbrous septum divides the tongue and is an foramen caecum in the midline of the tongue base on the end important radiological landmark when staging oral cancer of the thyroglossal duct. More frequently a thyroglossal sinus or cyst may persist, the latter presenting as an anterior cervical Sublingual space swelling. The sublingual space is lateral to the genioglossus muscles and separated from the submandibular space by the mylohyoid Parathyroid glands muscle. There are usually four but occasionally up to six parathyroidThe sublingual space contains the following; anterior glands, which measure approximately 6×2×2mm and are hyoglossus muscles, lingual, glossopharyngeal and hypoglossal most frequently found in the tracheo-oesophageal groove nerves, lingual artery and vein, sublingual and deep portion of posterior to the mid to inferior lobes of the thyroid. The thyroid gland consists of two lobes on either side of theThe normal parathyroid glands are not seen routinely on trachea separated by an isthmus. The thyroid gland (continuous white line) and the trachea (interrupted white line). The cervical lymphatic system squamous cell carcinomas of the tonsil, lateral tongue base and There are approximately 300 lymph nodes within the neck (of supraglottic larynx. A palpable lymph node Level 5 nodes are those within the posterior triangle, is a frequent presentation of head and neck malignancy. Tese nodes likely site of malignancy and their involvement infuences are also known as the spinal accessory and transverse cervical prognosis adversely. Level 5 is divided into 5a (above) and 5b (below) rela-The cervical nodes are commonly classifed clinically into tive to the course of the accessory nerve. Levels 1a and b are submental and submandibular, respec- Level 6 comprises the anterior cervical nodes, which include tively, and drain the lips, anterior foor of mouth and anterior the pre- and paratracheal and the less frequently involved tongue. When a prelaryngeal node is involved in Levels 2 to 4 are synonymous with the upper, mid and a patient with laryngeal squamous cell carcinoma, subglottic lower deep cervical chains and follow the internal jugular vein involvement should be sought. The most important node Level 7, the superior mediastinal nodes, should be assessed of this chain is the jugulodigastric node in the upper deep in cervical oesophageal, thyroid and subglottic laryngeal cervical region as it is the most frequently involved node in cancers. Separated into upper (Va) from skull base to lower border of cricoid and lower (Vb) lower border cricoid to clavicle. From hyoid to manubrium including pre- and paratracheal and prelaryngeal (Delphian) nodes. Superior aspect of manubrium to inominate vein between carotid arteries (not highlighted on this fgure). Note that there are other head and neck nodal groups not included in this classifcation, including intra- and periparotid, facial and retropharyngeal nodes. The retropharyngeal and parotid nodes are not included inThe lymph drains ultimately into the thoracic duct on the the above classifcation. The parotid nodes can be around or actually within the gland and drain the adjacent scalp, external auditory canal and pinna and nasopharynx. A major advantage of radiography is that it can be obtained in the erect position, allowing accurate assessment of spinal alignment and overall spinal balance in the coronal and sagittal planes. Terefore, the radiographic anatomy of the spinal column is A major limitation is the inability to assess the sof tissues essentially limited to assessment of the vertebrae, the joints and of the spinal column, which include the intervertebral discs, spinal alignment. The vertebral columnThe vertebral column commences at the craniocervical junction (C0–C1 articulation) and terminates at the tip of the coccyx. It comprises seven cervical, 12 thoracic, fve lumbar, fve sacral and three to fve coccygeal vertebrae ( Fig. Spinal alignment is assessed in the coronal and sagittal planes: • in the coronal plane, the C7 spinous process should lie vertically above the mid-sacral line • in the sagittal plane, the C2 body should lie vertically above L4 and the hips. The atlanto-axial articulation (C1–C2) comprises four synovial joints between the atlas (C1) and the axis (C2): • the atlas is a bony ring arising from three primary ossifcation centres, the anterior arch and two neural arches · the neural arches fuse by age 3 years to form the posterior arch and fuse with the anterior arch by age 7 years – failure of fusion of the anterior and/or posterior arches may result in congenital defects which can mimic fractures Lumbar spine · the atlas thus comprises an anterior arch, which fuses at the anterior tubercle, the posterior arch and two lateral masses ( Figs. Anterior atlanto-dens • thoracic kyphosis; from T2 to T12, ranging from 20 to 40° interval • lumbar lordosis; from L1 to L5, ranging from 20 to 40° Anterior tubercle of C1 • sacrococcygeal kyphosis (pelvic curvature); from the Odontoid lumbosacral junction to the tip of the coccyx. Each vertebral body is composed of a shell of outer cortical · a secondary ossifcation centre forms at the tip of the bone and superior and inferior fbro-cartilaginous end-plates, dens, fusing by age 12 years, with failure of fusion which enclose a meshwork of internal primary and secondary resulting in an os odontoideum trabeculae formed of cancellous bone and bone marrow. The transverse processes in the thoracic and lumbar regions arise at the junction of the pedicle and lamina and extend Craniometry of the cranio-cervical junction laterally ( Fig. The superior articular processes extend upwards from the A number of lines have been described: pedicle-lamina junction and articulate with corresponding • Chamberlains line; runs between the posterior tip of inferior articular processes arising from the neural arch above the hard palate and the posterior margin of the foramen to form the facet joint (Fig. The sacrum is a curved triangular bone formed by the fusion The canal is divided anatomically into the central canal, lateral of fve sacral vertebrae (Fig. A B Left iliac blade Lumbosacral (L5/S1) disc Left sacral ala Sacral Arcuate line of promontary left S1 ventral root foramen S2 sacral Right sacroiliac segment joint Sacrum S5 sacral Coccyx segment Sacrococcygeal symphysis Coccyx Fig. The morphology of the sacrum difers between males and The occipito-atlantal (C0–C1) joint females, the female sacrum being shorter, wider and moreThe occipito-atlantal joints are synovial joints formed by the posteriorly tilted, thus increasing the capacity of the pelvic articulations between the occipital condyles and the atlas. The occipital condyles project from the inferior aspectThe coccyx is the terminal portion of the vertebral of the occipuThat the anterolateral margins of the foramen column, being formed by three to fve individual vertebrae magnum and articulate with the concave superior articular ( Fig. Foramen transversarium Anterior Left transverse tubercle process Right anterior neural arch Right transverse Left lateral process mass Left foramen Left lamina transversarium Dens Transverse Spinous atlantal process ligament insertion Left posterior neural arch Fig. The facet jointThe facet (zygoapophyseal) joints are paired joints extend- ing from C1/C2 to L5/S1 and are formed by the superior and The atlas inferior articular processes:The atlas has a ring confguration in the axial plane (Fig. The posterior arch forms ~2/5 of the ring and has a sulcus • the articular surfaces are covered by hyaline cartilage and on each side just posterior to the lateral mass for transmission surrounded by a synovium-lined fbrous capsule. In the cervical region, the articular surface lies in the coronalThe lateral masses are bulky and articulate with C0 and C2: plane on axial images (Fig. In the thoracic region, the articular surface also lies in the coronal plane (Fig. In the lumbar region, the articular surface is curved, with The cervical neural arch the superior articular process facing posteromedially and theThe transverse processes of the cervical vertebrae arise from inferior facing anterolaterally ( Fig. Thoracic A B vertebral body Superior articular Thoracic process vertebral Facet joint end-plate Right superior Intervertebral articular disc process Inferior articular Left facet joint process Right inferior articular Pedicle process Left lamina Intervertebral Spinous foramen process Fig. L4 vertebral A B body L4/L5 intervertebral foramen Inferior L5 superior end-plate articular process L4/L5 intervertebral disc L4/L5 facet joint Left L5 pars intervertebral interarticularis foramen L5 inferior articular process Left superior articular process Sacral promontary Left facet joint Left inferior articular process Spinous process Fig. The costovertebral and costotransverse jointsThe costovertebral joints are paired synovial joints formed between the rib head and the costal facets of two adjacent thoracic vertebrae, the inferior aspect of the vertebra above and the superior aspect of the vertebra to which the rib corresponds numerically ( Fig.

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Bastin K et al (1992) Meningeal hemangiopericytoma: defning Dufour H et al (1998) Meningeal hemangiopericytomas purchase 500mg actoplus met visa metabolic disease obesity. Feb;39(1):36-41 (Review) Filippi С еt al (2001) Appearance of meningiomas on difusion Buetow M buy 500 mg actoplus met amex diabetes medications that cause swelling, Burton P generic actoplus met 500 mg blood sugar gold for dogs, Smirniotopoulos J (1991) Typical, atypi- weighted images: correlating difusion constants with histopatho- cal and misleading features in meningioma. Neurosurg 25:514-522 Tumours of the Meninges 805 Haddad F еt al (1997) Cranial osteomas: their classifcation and Naidich T (1990) Imaging evaluation of meningiomas: categorical management. Clin Imaging 27:2204–2209 26:243–249 Hope J, Armstrong D, Babyn P (1992) Primary meningeal tumours Orrison W, Hart B (2000) Intraaxial brain tumors. J Comput Assist Tomogr 16:366-371 ings of a highly aggressive malignant meningioma. Radiology 161:369–375 Konovalov A, Kornienko V (1985) Computed tomography in the Sheporaitis L, Osborn A, Smirniotopoulos J (1992) Radiologic patho- clinics of neurosurgery. In: Kobayashi S (ed) Neurosurgery of com- Tamiya T еt al (2001) Peritumoural brain oedema in intracranial plex vascular lesions and tumours. Tieme, Stuttgart, pp 244–248 meningiomas: efects of radiological and histological factors. Clin Stud 58:1:28–36 ogy 45:129–136 Zimmerman R D et al (1985) Magnetic resonance imaging of men- Martinez-Lage J, Poza M, Martinez M (1991) Meningiomas with ingiomas. On the other hand, rapid craniography cannot re- veal brain damage and may lead to delay in diagnosis. Confusion, neurological defcit, penetrating brain injury, and a palpable impressed fracture, etc. The study acquires images in bone, and mortality in young and middle-aged people, and it is a sof tissue, and intermediate regimens (adequate to diagnose major social and economic problem. Car accidents, falls from important component of the diagnostic complex in head height, assaults, etc. Ultrasound is a portative and cheap technique that does not expose patients to radiation. Secondary injuries are brain oedema and swelling, impactions, ischaemic events and infarctions, formation of aneurysms, and arteriovenous fstules. Haemorrhagic imbibition of contusions in the lef frontotemporal–basal region is observed on 3 days afer injury Head Trauma 813 Fig. It looks hypointense afected, especially its splenium and posterior portions of its on T1-weighted imaging and hyperintense on T2-weighted corpus (Figs 9. When deoxyhaemoglobin transforms into intracel- present, then involvement of corpus callosum should be sus- lular paramagnetic methaemoglobin, the interaction between pected, with concomitant damage to subependymal capillaries protons and paramagnetic centres of methaemoglobin leads along the ventricular surface of corpus callosum, fornix and to hyperintense signal on T1-weighted imaging, which ini- septum pellucidum (Fig. If brainstem is afected, then lesions riphery do not have tight endothelial connections, as in intact are usually found in the white matter (of cerebral lobes) and blood–brain barrier, which is why accumulation of contrast corpus callosum (Fig. Basal starts from the centre to the periphery and depends on the cisterns are usually poorly visualised afer brainstem injury, size of haemorrhage. Several shear, acceleration, and breaking, resulting in displacement of days later haemorrhagic lesions may appear in a nonhaemor- grey and the white matter (they have diferent density). It appears as a hyperintense lesion on T1-weight- why the term shear injury is used. Tis shearing leads to rup- ed imaging and hypointense lesion on T2-weighted imaging, ture of axons and their swelling and impairment of axoplasmic which refects intracellular methaemoglobin transformation fow. Axonal rupture may be incompletely (partial) marked on into extracellular methaemoglobin with typical characteristics the microscopic level and complete in combination with acute (bright signal on Т1- and T2-weighted imaging). Factors of poor prognosis are low scores on the Glasgow tense on T2-weighted imaging (Fig. About two ly sensitive when detecting axonal injuries (lesions are hyper- thirds of lesions are found in the white matter at the junc- intense), whereas they are iso- or hypointense on T1-weighted tion of grey and white matter in the frontoparasagittal region, imaging (Fig. Acute haema- toma in the projection of the corpus callo- sum, blood extension into lateral ventricles. Haemorrhagic lesion in the projection of the lef superior cerebellum peduncle and upper aspect of pons. Combination of temporal lobe contusion, lesion of the corpus callosum and subdural haematoma. In several cases, the Lac peak may be seen, thus refecting ac- tivation of anaerobic glycolysis due to hypoxia and ischaemia. If an increase in Cho peak is seen, then it means cell loss in the damage area and destruction of cell membranes with release of Cho-containing components in a lesion (Kuzma et al. We studied changes of ratios between metabolite peaks and compared them with patient condition, assessed by the Glas- gow coma scale. Such a spectrum means that hypoxia, ischaemic fractures in adults, but accompanied by subarachnoid haem- changes, cell loss with membrane destruction (i. Using their own hemisphere and the internal cranial bone lamina, extending material they showed that there existed a correlation between from the frontal region backwards around the hemisphere survival, disability, and level of brainstem damage: (Fig. Rupture of veins feeding the superior sagittal sinus leads cording to the Glasgow coma scale), level of brain damage, to accumulation of blood in the subdural space along one falx and outcome, which was confrmed by several other studies side. The density of sub- the most frequently seen extracerebral traumatic injury, ofen acute subdural haematoma 7–20 days afer trauma is close to leading to fatal outcomes. Blood is accumulated between dura mater and arach- the help of indirect features such as displacement of the grey noid membrane. Subdural haematoma may cross sutures, falx, and the white matter from the internal cranial bone lamina or tentorium. Subdural haematoma is frequently caused by and by smoothening of subarachnoid fssures homolaterally. However, rupture haemorrhage capsule or in cortical veins, helping to identify of superfcial veins and the superior longitudinal sinus is also the borders of brain surface. No patho- images (e,f) demonstrate clear asymmetry of the projection tracts logical changes are identifed on T1-weighted imaging. Usually, isodense haematomas are difcult mater is usually characterised by abundant vascularisation to diagnose. Bilateral subdural haematoma Two hundred eighty-one patients with chronic subdural is seen in 25% of cases; when it is large, it may lead to marked haematomas have been treated at the Burdenko Neurosurgery compression of lateral ventricles without midline shif (Figs. More frequently, the content of chronic identifed in the haematoma-adjacent structures as well as a subdural haematomas were hypodense compared with brain blood fow asymmetry between two hemispheres (Fig. However, they may expand beyond dural pro- marked in the elderly and children; approximately in 20% cesses like falx. Epidural haematomas are more frequently of cases they are accompanied by other brain damage (Bab- seen in young people, they are usually unilateral (95%), and in chin et al. Hypodense areas inside haematoma are admixture of free blood and serum separated from a blood clot. Connective tissue trabeculae are marked in the haematoma weighted imaging (b) reveal a large extra-axial haematoma of the structure 842 Chapter 9 Fig.

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By a subtle change or addition to the brand name of the bioavailability discount 500mg actoplus met visa diabetes type 2 how to lower blood sugar, are reduced purchase actoplus met online pills blood glucose without blood. There is substance in this original medicine buy cheap actoplus met line diabetes medications for dogs, the manufacturer aims to establish argument, though it is often exaggerated. This unsavoury practice is called ‘umbrella It is reasonable to use proprietary names when dosage, branding’. In addition, with Formulary provides a regularly updated and comprehensive the introduction of complex formulations, e. And, we creases profits for the company who first invented the drug, would add, worthwhile. There are no absolute rights or clear handwriting is shown by medicines of totally different wrongs in this. Serious events have occurred quires inventions, but wishes a healthy generic market in as a result of the confusion of names and dispensing the order to restrain costs. It will to minimise the risk of confusion, but the use of accepted be noted that non-proprietary names are less likely to be prefixes and stems for generic names works well and the av- confused with other classes of drugs. The search for proprietary names is a ‘major problem’ for 7Pharmaceutical companies increasingly operate worldwide and are pharmaceutical companies, increasing, as they are, their liable to find themselves embarrassed by unanticipated verbal output of new preparations. For example, names marketed (in some countries), such new preparations (not new chemical entities) a year, an- as Bumaflex, Kriplex, Nokhel and Snootie, conjure up in the minds of other warning of the urgent necessity for the doctor to cul- native English speakers associations that may inhibit both doctors and patients from using them (see Jack & Soppitt 1991 in Guide to further tivate a sceptical habit of mind. Lancet 2000 image meet – the argument for (2004)1: change in names of 355: 316–317). Knowledge of the requirements for success and the expla- The practice of drug therapy entails more than remember- nations for failure and for adverse events will enable the ing an apparently arbitrary list of actions or indications. Sci- doctor to maximise the benefits and minimise the risks entific incompetence in the modern doctor is inexcusable of drug therapy. Pharmacokinetics • Time course of drug concentration: drug passage across Understanding how drugs act is not only an objective cell membranes; order of reaction; plasma half-life and of the pharmacologist who seeks to develop new steady-stateconcentration;therapeuticdrugmonitoring. The starting point is to consider what drugs do and how Individual or biological variation they do it, i. The body functions • Pharmacogenomics: variability due to inherited through control systems that involve chemotransmitters or influences. Such drugs neither they nor the water in which they are dissolved is are structurally specific in that small modifications to their absorbed by the cells lining the gut and kidney tubules chemical structure may profoundly alter their effect. Mechanisms Receptors An overview of the mechanisms of drug action shows that Most receptors are protein macromolecules. When the ago- drugs act on specific receptors in the cell membrane and in- nistbindstothereceptor,theproteinsundergoanalteration terior by: in conformation, which induces changes in systems within • Ligand-gated ion channels, i. Manykindsofeffectorresponseexist, act on such receptors in the postsynaptic membrane of but those indicated above are the four basic types. When tissues are continuously exposed to the cell membrane and coupled to intracellular effector an agonist, the number of receptors decreases (down-regula- systems by a G-protein. For instance, catecholamines tion) and this may be a cause of tachyphylaxis (loss of effi- (the first messenger) activate b-adrenoceptors through a cacy with frequently repeated doses), e. This increases the activity of who use adrenoceptor agonist bronchodilators excessively. Indeed, one explanation for modulator of the activity of several enzyme systems the worsening of angina pectoris or cardiac ventricular ar- that cause the cell to act. Drugs that have no activating effect whatever on the used to protect against the nephrotoxic effects of receptor are termed pure antagonists. Some drugs, in addition to blocking ac- penicillin interferes with formation of the bacterial cell cess of the natural agonist to the receptor, are capable of a wall; or by showing enormous quantitative differences low degree of activation, i. A patient may be as extensively ‘b-blocked’ by proprano- Restoration of the response after irreversible binding re- lol as by pindolol, i. Some substances produce effects that are specifically opposed to those of the agonist. The agonist action of benzodiazepines on the benzodiazepine receptor Physiological (functional) antagonism in the central nervous system produces sedation, anxiolysis, muscle relaxation and controls convulsions; substances An action on the same receptor is not the only mechanism called b-carbolines, which also bind to this receptor, by which one drug may oppose the effect of another. Ex- cause stimulation, anxiety, increased muscle tone and treme bradycardia following overdose of a b-adrenoceptor convulsions; they are inverse agonists. If the forces that bind Adrenaline/epinephrine and theophylline counteract drug to receptor are weak (hydrogen bonds, van der Waals bronchoconstriction produced by histamine released from bonds, electrostatic bonds), the binding will be easily and mast cells in anaphylactic shock by relaxing bronchial rapidly reversible; if the forces involved are strong (covalent smooth muscle (b2-adrenoceptor effect). A sufficient in- crease of the concentration of agonist above that of the an- tagonist restores the response. For example, abolish exercise-induced tachycardia, showing that the de- enalapril is effective in hypertension because it is structur- gree of blockade is enhanced, as more drug becomes avail- ally similar to the part of angiotensin I that is attacked by able to compete with the endogenous transmitter. Carbidopa competes with levodopa for dopa decarbox- When receptor-mediated responses are studied either in ylase, and the benefit of this combination in Parkinson’s isolated tissues or in intact humans, a graph of the loga- disease is reduced metabolism of levodopa to dopamine rithm of the dose given (horizontal axis) plotted against in the blood (but not in the brain because carbidopa does the response obtained (vertical axis) commonly gives an not cross the blood–brain barrier). S-shaped (sigmoid) curve, the central part of which is a Ethanol prevents metabolism of methanol to its toxic me- straight line. If the measurements are repeated in the pres- tabolite, formic acid, by competing for occupancy of the en- ence of an antagonist, and the curve obtained is parallel to zyme alcohol dehydrogenase; this is the rationale for using the original but displaced to the right, then antagonism is ethanol in methanol poisoning. The above are examples of said to be competitive and the agonist to be surmountable. Drugs that bind irreversibly to receptors include phenoxy- Irreversible inhibition occurs with organophosphorus in- benzamine (to the a-adrenoceptor). Some toxins act in this way; for synthesising new protein; this is why low doses of aspirin example, a-bungarotoxin, a constituent of some snake are sufficient for antiplatelet action. The approach is the basis of Dose–response relationships modern drug design and it has led to the production of Conventionally, the horizontal axis shows the dose and adrenoceptor antagonists, histamine receptor antagonists the response appears on the vertical axis. A steeply rising and pro- cer drugs that act against rapidly dividing cells lack selectivity longedcurveindicatesthatasmallchangeindoseproducesa because they also damage other tissues with a high cell largechangeindrugeffectoverawidedoserange,e. Selective targeting of drugs to less accessible sites Dose–response curves for wanted and unwanted effects of disease offers considerable scope for therapy as technol- can illustrate and quantify selective and non-selective drug ogy develops, e. Drug molecules are three-dimensional Drug A Drug B and many drugs contain one or more asymmetrical or chiral1 centres in their structures, i. For drugs as single enantiomers rather than as racemic mixtures drug A, the dose that brings about the maximum wanted effect is less than the lowest dose that produces the unwanted effect. The difference in weight of drug adminis- Tolerance tered is of no clinical significance unless it is great. Pharmacological efficacy refers to the strength of re- Continuous or repeated administration of a drug is often sponse induced by occupancy of a receptor by an agonist accompanied by a gradual diminution of the effect it pro- (intrinsic activity); it is a specialised pharmacological con- duces. But clinicians are concerned with therapeutic efficacy, to increase the dose of a drug to get an effect previously as follows. By contrast, the term tachyphylaxis describes the phenomenon Therapeutic efficacy or effectiveness, is the capacity of a of progressive lessening of effect (refractoriness) in re- drug to produce an effect and refers to the maximum such sponse to frequently administered doses (see Receptors, effect. Differences in therapeutic efficacy are of great sary to maintain pain relief in terminal care; the effect is due clinical importance, usually more than potency. Tolerance is ac- more than 5% of the sodium load filtered by the glomeruli; quired rapidly with nitrates used to prevent angina, possi- there is no point in increasing the dose beyond that which bly mediated by the generation of oxygen free radicals from achieves this, as this is its maximum diuretic effect. Bend- nitric oxide; it can be avoided by removing transdermal ni- roflumethiazide (moderate efficacy) can effect excretion of trate patches for 4–8 h, e. Furosemide can effect excretion of Accelerated metabolism by enzyme induction (see p.

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