The compro- and thioxanthenes are best avoided unless the mise is incomplete relief on the grounds of safety purchase 50mg fildena mastercard erectile dysfunction muse. Benzodiazepines are safe if use is brief but prolonged use may cause somnolence or Dosing schedules are simply schemes aimed at achieving a poor suckling purchase 25 mg fildena fast delivery erectile dysfunction treatment in sri lanka. Neonatal hypoglycaemia may sion assumes that drug effect relates closely to plasma con- occur generic fildena 150mg visa erectile dysfunction exercises dvd. Sotalol and atenolol are present in the highest centration, which in turn relates closely to the amount of amounts in this group. Oestrogens, progestogens and androgens continuing effect is required are: suppress lactation in high dose. Oestrogen– progestogen oral contraceptives are present in amounts To specify an initial dose that attains the desired effect too small to be harmful, but may suppress lactation if it rapidly without causing toxicity. On repeated dosing, however, it takes Caffeine may cause infant irritability in high doses. The ef- fect may be achieved earlier by giving an initial dose that is Drug dosage larger than the maintenance dose; the initial dose is then called the priming or loading dose, i. The effect that is desired can be obtained at well below the toxic dose (many mydriatics, analgesics, To specify a maintenance dose: amount and frequency. Whether or not ments make comparatively insignificant differences and this approach is satisfactory or practicable, however, the therapeutic endpoint may be hard to measure (depres- depends very much on the t½ itself, as is illustrated by sion, anxiety), may change only slowly (thyrotoxicosis), or the following cases: may vary because of pathophysiological factors (analgesics, 1. In this instance, replacing half the adrenal corticosteroids for suppressing disease). Here a vital function satisfactory solution because dosing every 6–12 h is (blood pressure, blood sugar level), which often changes acceptable. Adjustment of (which is desirable for compliance), giving half the dose must be accurate. Adrenocortical replacement therapy priming dose every day means that more drug is falls into this group, whereas adrenocortical pharmacother- entering the body than is leaving it each day, and the apy falls into the group above. The Maximum tolerated dose is used when the ideal therapeu- solution is to replace only the amount of drug that tic effect cannot be achieved because of the occurrence of leaves the body in 24 h, calculated from the inital dose, unwanted effects (anticancer drugs; some antimicrobials). Dosing at intervals equal to the t½ • Delayed excretion is seldom practicable, the only would be so frequent as to be unacceptable. The answer important example being the use of probenecid to is to use continuous intravenous infusion if the t½ is block renal tubular excretion of penicillin for single- very short, e. Intermittent which a drug is presented by modified-release22 administration of a drug with short t½ is nevertheless systems can achieve the objective of an even as well as a reasonable provided large fluctuations in plasma prolonged effect. Benzylpenicillin has a t½ of frequency of medication to once a day, and compliance be- 30 min but is effective in a 6-hourly regimen because comes easier for the patient. The elderly can now receive the drug is so non-toxic that it is possible safely to give a most long-term medication as a single morning dose. In ad- dose that achieves a plasma concentration many times dition, sustained-release preparations may avoid bowel in excess of the minimum inhibitory concentration for toxicity due to high local concentrations, e. Some sustained-release for- mulations also contain an immediate-release component A uniform, fixed drug dose is likely to be ineffective or toxic to provide rapid, as well as sustained, effect. It is usual then to calculate the dose cause the environment in which they are deposited is more according to body-weight. Adjustment according to body constant than can ever be the case in the alimentary tract, surface area is also used and may be more appropriate, and medication can be given at longer intervals, even for this correlates better with many physiological phenom- weeks. They include phenothia- curvilinear, but a reasonable approximation is that a 70-kg 2 zine neuroleptics, the various insulins and penicillins, human has a body surface area of 1. A combination of preparations of vasopressin, and medroxyprogesterone (in- body-weight and height gives a more precise value for sur- tramuscular, subcutaneous). Tablets of hormones can be face area (obtained from standard nomograms) and other 21 implanted subcutaneously. Reduction of absorption time A soluble salt of the drug may be effective by being rapidly Prolongation of drug action absorbed from the site of administration. In the case of Giving a larger dose is the most obvious way to prolong a subcutaneous or intramuscular injections, the same objec- drug action but this is not always feasible, and other mech- tive may be obtained with hyaluronidase, an enzyme that anisms are used: depolymerises hyaluronic acid, a constituent of connective • Vasoconstriction will reduce local blood flow so that tissue that prevents the spread of foreign substances, e. Delayed release: available other than immediately after administration (mesalazine in the colon); sustained release: slow release as governed 21For example, Livingston E H, Lee S 2001 Body surface area prediction in by the delivery system (iron, potassium); controlled release:ata normal-weight and obese patients. American Journal of Physiology constant rate to maintain unvarying plasma concentration (nitrate, Endocrinology and Metabolism 281:586–591. Therapeutic aims should If the body successfully restores the previous steady state or be clear. Combinations are logical if there is good reason to rhythmthenthesubjecthasbecometoleranttothedrug,i. Fixed-dose drug combinations are suppression of ovulation occurs and is desired, but persis- appropriate for: tence of other effects, e. Single-drug treatment of tuberculosis why a diuretic is commonly used together with a vasodila- leads to the emergence of resistant mycobacteria and is tor in therapy. Glands are therefore capable either of in- (Rifinah, Rimactazid) ensures that single-drug creasing or decreasing their output by means of negative treatment cannot occur; treatment has to be two drugs (usually) feedback systems. An oestrogen and progestogen hormone analogue activates the receptors of the feedback combination provides effective oral contraception, for system so that high doses cause suppression of natural pro- the same reason. Levodopa combined hormone, restoration of the normal control mechanism with benserazide (Madopar) or with carbidopa takes time, e. The number (density) of recep- tors on cells (for hormones, autacoids or local hormones, Chronic pharmacology and drugs), the number occupied (receptor occupancy) and the capacity of the receptor to respond (affinity, effi- The pharmacodynamics and pharmacokinetics of many cacy)canchangeinresponsetotheconcentrationofthespe- cific binding molecule or ligand,23 whether this be agonist drugsdifferaccordingtowhethertheiruseisinasingledose, or over a brief period (acute pharmacology), or long term or antagonist (blocker). Prolonged high population take drugs continuously for large portions of concentrations of agonist (whether administered as a drug their lives, as tolerable suppressive and prophylactic reme- or over-produced in the body by a tumour) cause a reduc- dies for chronic or recurrent conditions are developed; e. In general, the dangers of a drug therapy are not ity and the prolonged occupation of receptors antagonists markedly greater if therapy lasts for years rather than lead to an increase in the number of receptors (up-regula- months, but long-term treatment can introduce significant tion). At least some of this may be achieved by receptors hazard into patients’ lives unless management is skilful. The exact mechanisms may remain ministration, so that, on withdrawal, an above-normal obscure but clinicians have no reason to be surprised when number of receptors suddenly become accessible to the they occur, and in the case of rebound they may wish to use normal transmitter, i. Unmasking of a disease process that has worsened during prolonged Metabolic changes over a long period may induce dis- suppressive use of the drug, i. Drugs may also enhance their own metabolism, and that of The rebound phenomenon is plainly a potential hazard other drugs (enzyme induction). The term means the deliberate interrup- rence at intensified degree of the symptoms for which the tion of long-term therapy in order to restore sensitivity drug was given) and withdrawal syndrome (appearance of (which has been lost) or to reduce the risk of toxicity. The distinction is quantitative Plainly, the need for holidays is a substantial disadvantage and does not imply different mechanisms. Patients sometimes initiate their own drug Rebound and withdrawal phenomena occur erratically. In general, they are more likely with drugs having a short Dangers of intercurrent illness.
These consist of triangular liga- noted fildena 100mg without prescription erectile dysfunction injections cost, however best fildena 100mg erectile dysfunction late 20s, that the majority of free disk fragments ment extensions with a broad base along the lateral margin will lie immediately adjacent to buy fildena overnight delivery erectile dysfunction pills that work, and be inseparable from, of the cord and their apex attaching laterally to the dura. Disk herniations have signal intensity sim- As previously discussed, but worth repeating, there are ilar to, on both T1- and T2-weighted scans, the native disk. The focal nature of a disk herniation is used to diﬀerentiate The cervical nerves exit through the foramina above the this process from a disk bulge, with the latter often deﬁned corresponding numbered vertebrae, with C8 exiting in the as a process involving 180 degrees or more of the disk cir- foramen below the C7 vertebra. In older patients, and those also involved long foraminal disk herniation at C6–7 will cause compression term in activities associated with marked motion of the cervical spine, asymptomatic chronic disk herniations are commonly observed (Fig. Although often diﬃcult in an individual patient to dif- ferentiate from an acute disk herniation, the presence of associated bony spurs extending from the vertebral body endplates can be used to identify a chronic disk herniation (Fig. These bony spurs occur due to bone remodel- ing, with elevation of the periosteum by a disk herniation and subsequent bone deposition. Myelopathic symptoms are more common with chronic disk herniations, with radicular symptoms common in acute disk herniations (Fig. Given how frequent these are—most older patients have at least mild multi- level disease—it is not surprising that these do not corre- late well with symptoms. Disk-osteophyte complexes are felt to be the end result of a disk bulge, which is deﬁned as circumferential expansion of the disk, speciﬁcally greater than 180 degrees (and not focal, as with a chronic disk herniation). Oblique foraminal views oﬀer a further improvement cial area of note in the cervical spine involves the unco- in depiction and detection of cervical foraminal disease, although vertebral joints. These small synovial lined joints (also unfortunately not performed by most sites. Sagittal and axial images reveal presumed acute (recent) disk herniations at C3–4 and C5–6. The herniation at C3–4 is central in location, thaThat C5–6 paracentral with some extension into the foramen on the left. Although seldom used in this application, foramen on gradient echo T2-weighted scans. Careful image inspec- post-contrast scans allow exquisite visualization of cervical forami- tion, including all sequences and planes, is mandatory, together nal disk herniations, which appear as nonenhancing soft tissue easily with a high sensitivity to abnormal soft tissue (disk material) within diﬀerentiated from the intense enhancement of the abundant ve- the foramen. The presence of an osteophyte just superior or inferior to a disk herniation, often visual- ized best on sagittal images, implies that the herniation is chronic. On the axial gradient echo T2-weighted scan, at C5–6, a left paracentral and foraminal herniation is visualized with high signal intensity disk material surrounded by a thin low signal intensity rim. Disk space narrowing is an addi- tional cause of foraminal narrowing, decreasing the height of the neural foramen, with the end result of all these fac- tors being nerve root compression. Asymptom- Degenerative foraminal narrowing is common in older atic small and large chronic cervical disk herniations are a common patients. With a large osteophyte lying in the mid-portion of the foramen, unless axial imaging is performed with very thin sections, partial volume imag- processes of the lower cervical vertebrae posteriorly and ing will lead to poor visualization of the encroachment. Uncovertebral joints are present from for evaluation of the neural foramina include thin section C3 to C7, with encroachment upon the foramina anteri- T2*-weighted gradient echo imaging in the axial plane orly due to degenerative involvement occurring from (Fig. There is mild to moderate ﬂat- tening of the cord (versus its normal elliptical appearance in cross- section), at the C4–5 level, a ﬁnding well seen on axial images. There is moderate sac), and hypertrophy of the facet joints (posterior to the narrowing of the foramen on the left, degenerative in nature and un- thecal sac). The cord is deformed (compressed), with focal abnormal high signal intensity (small white arrows) consis- population, and to some degree thus diﬀerentiated from tent with gliosis seen on both scans. Symptoms are myelopathic and include progressive/intermittent numbness, weakness of the upper extremities, pain, abnormal reﬂexes, muscle Ossiﬁcation of the posterior longitudinal ligament is an uncommon cause of acquired cervical spinal steno- sis. Other, more common etiologies of cervical spinal stenosis include ligamentous infolding and facet joint hypertrophy. As with all cases of spinal stenosis, patients are at greater risk for traumatic spinal cord injury. The posterior longitudinal ligament is prominent, with low signal intensity on both T1- and T2-weighted scans (Fig. Degenerative (acquired) spinal stenosis, previously dis- cussed in general terms, is caused by advanced degenera- Fig. Degeneration of the uncover- tive disk disease, with the latter process also referred to by tebral joint is common, leading to a broad osteophyte (*) in a char- the term spondylosis (Fig. This process can lead clude decreased disk height with thickening and buckling both to foraminal narrowing and mild eﬀacement of the thecal sac, of the intraspinal ligaments, prominence of the posterior the latter in a paracentral location. On this gradient echo axial T2-weighted scan, the right neural fora- men is widely patent, with moderate neural foraminal narrowing on the left. Mild facet osteoarthritis and disk degenerative disease (an osteophyte) contribute in this instance to the foraminal narrowing. Although commonly not quantiﬁed, deﬁned measurements are established for spinal stenosis, with evaluation best on axial images. Osteophyte may experience symptoms), and 10 mm diagnostic of distribution within the cervical spine directly varies with spinal axis cervical spinal canal stenosis. The more mobile lower cervical spine is aﬀected initially levels are C4–5, 5–6, and 6–7, with multilevel involvement with superior spread as disease worsens. Exams from two patients are illustrated, with the ﬁrst demonstrating moderately advanced degenerative disease with disk osteophyte complexes at the C3–C7 levels. Additional common degenerative ﬁndings, present in this patient, include disk space height loss at the C4–5 and C5–6 levels and a slight anterolisthesis of C2 on C3. In advanced disease, myelo- malacia, speciﬁcally edema, gliosis, and cystic changes can be present. Thoracic Spine Disk herniations in the thoracic region are less common, as compared to their counterparts in the cervical and lumbar regions. From published lit- erature series, symptomatic thoracic disk herniations are most commonly present in the lower thoracic spine, from Fig. There is multilevel eﬀacement of the thecal sac, with cord compression, T9–10 to T11–12. Diagnosis requires thin sections with high lustrated (C2–3) produces marked cord deformity and moderate to image quality, and speciﬁcally implementation of strategies severe central spinal canal stenosis. With excellent image qual- ity, sensitivity is high even to very small disk herniations. Deformity of the cord contour is also common, often in the absence of any clinical symptoms and occurring even with very small herniations. Concentric tears (type I) are parallel to the curvature of the outer mar- gin of the disk. There is a tendency to interpret any focus of abnormal high signal intensity within the annulus as a tear. Enhancement of annular tears is noted following intravenous contrast administra- tion, due to enhancement of granulation tissue that forms as part of the normal reparative process.
This 2-month-old The sagittal midline reformatted scan reveals that this prevertebral infant presented with staphylococcus aureus septicemia best purchase fildena erectile dysfunction 70 year olds. There is an enhancing mass lesion order fildena without a prescription erectile dysfunction grand rapids mi, in this 18-year-old patient purchase 25 mg fildena impotence causes cures, with its epicenter in the left parapharyngeal space. There is mild hyperintensity of the and enhancement typical in the acute and subacute phases (part 1). There are grossly enlarged lymph nodes bi- laterally throughout the neck, at essentially all levels. This appearance is nonspeciﬁc, with diﬀerential diagnosis including the viral lymphadenitises and the lymphopro- liferative disorders (speciﬁcally lymphoma and leukemia). Ultrasound and nuclear dication is atherosclerotic disease, with evaluation, in par- medicine remain the primary imaging modalities for the ticular, focused on the carotid bifurcation. Critical to this evaluation of thyroid disease, with ﬁne-needle aspiration assessment is evaluation of stenosis involving either the used to evaluate palpable nodules and speciﬁcally to ex- distal common carotid artery or the proximal internal ca- clude malignancy. Papillary and follicular thyroid carcinomas are preferably using cross-sectional area measurements, rela- the most common malignant thyroid neoplasms, and have tive to (percentage wise) a more distal normal section of a favorable prognosis. A large, well-deﬁned, hyperintense thyroid nodule is noted on the right, on a T2-weighted axial image. For example, papillary carcinoma, the most thyroid gland, seen on axial scans, with a mildly heterogeneous, common thyroid cancer, can present either as a benign appearing nodular appearance. A prominent ulcerated plaque (arrow) is present involving the proxi- mal right internal carotid artery, 1 cm distal to the bifurcation. There is a string sign (arrow) at the origin of the right internal carotid artery, indicating greater than 95% stenosis. There is mild ath- right internal carotid artery at the bifurcation, resulting in a 90% or erosclerotic narrowing presenThat the origin of the left vertebral greater stenosis. A crescent of abnormal high signal intensity (white arrow), partially en- casing the internal carotid artery, is noted, at the skull base, on a precontrast T1-weighted scan, consistent with a mural (methemoglobin) hematoma. The latter is important for evaluation of in the hematoma will be seen as a hyperintense crescent vascular malformations and other vascular lesions such as adjacent to the residual patent lumen. The latter occurs in 30%, typically or malignant disease, hypercoagulable states, and infec- immediately prior to the internal carotid artery entering tion. The thrombosed vein is typically enlarged in the the carotid canal at the skull base. The dissection itself can acute and subacute time frame, with peripheral enhance- extend for a variable length, usually originating a few cm ment of the vessel wall and surrounding inﬂammation. The bony parts of the lumbar and Common Variants vertebrae include the pedicles, transverse processes, ar- ticular pillars (pars interarticularis, superior and inferior articular facets), laminae, spinous processes, and vertebral Anatomy of the Normal Spine body. The facet joints are diarthrodial synovial-lined and There are seven cervical vertebral bodies and eight cervi- richly innervated. C2 is the axis, with On axial imaging the superior articular facet forms a the dens extending superiorly. From C3 to C7 there is a “cap” anterolaterally with the inferior articular facet pos- gradual increase in size of the vertebral bodies. The ligamenta ﬂava nate processes are bilateral superior projections from the (bilateral paired ligaments, which connect the lamina of C3 to the C7 vertebral bodies that indent the disk and ver- adjacent vertebrae, and are present from C2 to S1) extend tebral body above (posterolaterally), forming the uncover- from the anterior aspect of the upper lamina to the pos- tebral joints. In There is a normal slight increase in spinal cord size ex- regard to dermatomes, the foot is innervated by L4 (me- tending from C4 to C6. The neural foramina course antero- dial big toe), L5 (midfoot), and S1 (little toe). In the cervical region, the epidural venous numerically to the level above—for example, the L4 nerve plexus is prominent, with sparse epidural fat, the opposite lies within the foramen at L4–5. In regard to the lumbosacral junction are quite common, with an inci- dermatomes, the hand is innervated by C6 (the thumb), dence near 10%. Within A single anterior spinal artery and two paired posterior any speciﬁc neural foramen, the nerve within the foramen spinal arteries supply the spinal cord. These vessels are fed is that corresponding numerically to the level below—for by anterior and posterior radiculomedullary arteries. The ribs articu- and lumbar region is the artery of Adamkiewicz, which late with the vertebrae both at the disk level and at the usually arises between T9 and L1. There are typically no transverse process (although for the latter only at T1–T10). In the thoracic region, speciﬁcally at the location of the tip of the conus, from epidural fat is often prominent posterior to the thecal sac published studies, this ranges in normal individuals from and dura. Transitional type vertebrae are not uncommon 10% occurring at the upper third of L1 to 10% occurring aThat the thoracolumbar junction. For improved visualization of soft tissue On oﬀ-midline sagittal images, the dorsal root ganglion and marrow abnormalities on the basis of T2 changes, fat (and ventral root) is seen to lie in the superior portion of saturation should be employed in combination with T2- the neural foramen. The thecal sac is well as- sagittal plane is important for evaluation of foraminal nar- sessed on T2-weighted images, with this scan technique rowing, equal or greater in value than the axial plane. In also important for detection of spinal cord abnormalities regard to the neural foramen, the margins are composed (edema, gliosis, demyelination, and neoplasia). Good gray–white matter diﬀer- Imaging Technique entiation is seen within the cord. These there is a conversion from red to yellow marrow, which is structures can also be diﬀerentiated in a similar fashion reﬂected by higher signal intensity on T1-weighted scans on axial T2-weighted scans. With increasing age, both diﬀuse (obtained without any obliquity) depict the neural foram- and focal replacement of red by yellow marrow occurs. T1-weighted scans typically can be high signal intensity), and commonly encountered, on T1- acquired in a short scan time (2 to 4 minutes), with high weighted scans. In the thoracic spine, cardiac motion can oth- in normal disks, best visualized in the lumbar region due erwise be a substantial problem. This structure, the “intranuclear motion artifacts originate from the aorta, vena cava, in- cleft,” is due to ﬁbrous transformation and is observed in ternal organs, and anterior abdominal fat (with respira- all normal disks in patients over the age of 30. For spine imaging the maximum slice thickness that sualization of the intranuclear cleft should be considered should be acquired in any plane and any portion of the 3 Spine 151 spine is 3 mm (Fig. When the window and center are cho- sen for display of the spinal canal, the posterior soft tissue structures are often obscured, being depicted with very high signal intensity due to their proximity to the surface coil. Image normalization is a post-processing feature that takes into account the sensitivity of the coil, and enables the visualization of structures both close and distant rela- tive to the receiver coil, providing more homogeneous sig- nal intensity across the ﬁeld of view. It is important also to realize that today receiver coil coverage is integrated and continuous, allowing imaging of the spine in its entirety without gaps or image registration problems. Signal inten- sity drop oﬀ at the edge of the ﬁeld of view, in the cranio- caudal dimension, should not occur, and is indicative of an operator error. Thus, anatomic regions that were diﬃcult to image in the past due to technical issues, including spe- ciﬁcally the cervicothoracic and the thoracolumbar junc- tions, are well visualized on modern scanners (Fig.
C. Kurt. Judson College, Elgin IL.