Condet

Jeffrey Crawford, MD

• Professor of Medicine
• George Barth Geller Distinguished Professor
• Member of the Duke Cancer Institute

https://medicine.duke.edu/faculty/jeffrey-crawford-md

It has been used primarily as antihypertensive: may be advantageous in patients who develop marked bradycardia with propranolol pulse pressure emedicine 0.25mg digoxin overnight delivery. Metoprolol It is the prototype of cardioselective (1) blockers; nearly 50 times higher dose is needed to block isoprenaline induced vasodilatation hypertension journals ranking discount digoxin 0.25mg online. Some measure of inverse agonistic activity on 1 receptors has also been demonstrated blood pressure eyes buy digoxin 0.25mg on line. Patients who complain of cold hands and feet while on propranolol do better on metoprolol arteria tibial posterior purchase 0.25 mg digoxin otc. Esmolol It is an ultrashort acting 1 blocker devoid of partial agonistic or membrane stabilizing actions. Celiprolol It is a selective 1 blocker having additional weak 2 agonistic activity which reduces vascular resistance and holds promise of safety in asthmatics. Acebutolol Another cardioselective agent with significant partial agonistic and membrane stabilizing properties. Absence of deleterious effect on plasma lipids and on carbohydrate metabolism is another advantage. In contrast to older blockers, hypotensive response to nebivolol has a rapid onset. They are one of the first choice drugs because of good patient acceptability and cardioprotective potential (see Ch. Taken on a regular schedule they decrease frequency of attacks and increase exercise tolerance. High doses, however, may worsen angina in some patients by increasing ventricular size and reducing coronary flow. Cardiac arrhythmias blockers (mainly propranolol) suppress extrasystoles and tachycardias, especially those mediated adrenergically (during anaesthesia, digitalis induced)-may be used i. Propranolol controls ventricular rate in atrial fibrillation and flutter, but only occasionally restores sinus rhythm. Esmolol is an alternative drug for paroxysmal supraventricular tachycardia (see Ch. High risk patients (those who had large infarcts) should be put on blockers (if there are no haemodynamic contraindications) for at least 2 years. However, blockers can be given to only those patients not in shock or cardiac failure and who have heart rate > 50/min with not higher than first degree heart block (P-R interval < 0. Congestive heart failure Although blockers can acutely worsen heart failure, several studies have reported beneficial haemodynamic effects of certain blockers including metoprolol, bisoprolol, nebivolol, carvedilol over long-term in selected patients with dilated cardiomyopathy. The benefit may result from antagonism of deleterious effects of sympathetic overactivity (invoked reflexly by heart failure) on myocardium. Overactivation of cardiac 1 receptors has been found to exert toxic effects on the heart by accelerating myocyte apoptosis and promoting functionally unfavourable remodeling. However, they should not be given to patients with marked fluid retention and to those requiring i. Dissecting aortic aneurysm blockers help by reducing cardiac contractile force and aortic pulsation. Thyrotoxicosis Propranolol rapidly controls the sympathetic symptoms (palpitation, nervousness, tremor, fixed stare, severe myopathy and sweating) without significantly affecting thyroid status. It also inhibits peripheral conversion of T4 to T3 and is highly valuable during thyroid storm. Major use, however, is preoperatively and while awaiting response to antithyroid drugs/ radioactive iodine. Migraine Propranolol is the most effective drug for chronic prophylaxis of migraine (see p.

Stones in the calyces from infundibular stenosis produce pain and infection but do not produce obstructive uropathy prehypertension hypertension order 0.25mg digoxin with mastercard. The location of the infundibulum deep within the renal parenchyma makes open surgical management difficult blood pressure and stroke generic digoxin 0.25 mg visa. Endoscopic laser ablation of the calyx may be considered with obliteration of the calyx and resulting loss of function of that portion of the kidney to prevent future obstruction causes 0f hypertension discount digoxin 0.25 mg amex, infection arteria magna order digoxin 0.25 mg with visa, and pain. Once within the renal pelvis, a small calcification can form a nidus to create a larger obstructing stone. The retroperitoneal location of the kidney, away from other vital structures and bowel gas, allows for shock waves to penetrate the kidney and fragment the stone. Larger stones require prolonged and repetitive shock-wave treatment, which may damage the surrounding parenchyma. Ureteroscopy is a very effective technique (greater than 85% success) in selected cases. It treats the stone and allows for direct visualization of the ureter and renal pelvis. This ensures there is no structural pathology that may have predisposed the patient to produce the original stone. The rate of diuresis is based on the severity of volume overload, urea accumulation, and electrolyte disturbances that occurred during obstruction. Before release of the obstruction, there is a downregulation of the Na+ transporters, and the inability to reabsorb Na+ diminishes the osmotic gradient necessary for urinary concentration. In the distal tubule, downregulation and reduced aquaporin activity promote aquaresis. In the postsurgical patient who is unable to drink, approximately 75% of the urine volume is replaced with 0. Ureteroscopy becomes the treatment of choice for the majority of mid- and lowerureteral stones. Retrograde access is again the preferred choice, but antegrade access through the renal pelvis and down the ureter can be performed. Balloon dilation with a simultaneous full-thickness wall incision of the stricture is a good option. Postprocedure, temporary stenting facilitates drainage and minimizes extravasation of acidic urine, which can impair healing and result in restenosis. Extensive stricture disease of the ureter or urethra from tuberculosis, infection, or malignancy may require open surgical resection of the diseased portion with reanastomosis. It is a friable, frondular tumor with a solid stalk found primarily in older patients with a history of tobacco use. Treatment of obstruction is dependent on tumor location; those that fill the renal pelvis can be treated initially with a ureteral stent. Initial treatment includes an attempt with local cystoscopic excision or unroofing the orifice. When unresectable by cystoscopy, a temporizing stent or nephrostomy tube can be placed until surgical reconstruction with ureteral reimplantation and possible cystectomy can be completed. Retroperitoneal adenopathy along the aorta or vena cava adjacent to the ureter can also produce obstruction. Large pelvic masses may obliterate the normal anatomy of the bladder and ureteral orifices. The relatively slow and gradual prostatic enlargement can come from benign or malignant causes. The chronic increase in voiding pressure produces a hydrostatic stress to the smooth muscles of the bladder, resulting in bladder muscle hypertrophy. A subsequent increase in fibroblast and smooth muscle results in bladder wall trabeculations and eventual bladder wall deterioration. The loss of muscle tone culminates in bladder dysfunction with the ultimate cause of the uropathy being urinary retention. It is this bladder deterioration that produces the functional obstruction and uropathy. Chronic elevated bladder resting pressures above 40 cm H2O can also produce obstructive uropathy from disrupted ureteral peristalsis. This increases the size of the urethral lumen and allows voiding pressures to decrease.

Repeated use is more likely to produce long lasting behavioural abnormalities; psychosis may be precipitated pulse blood pressure normal discount digoxin 0.25 mg with mastercard. Tolerance to central actions and toxic effects of amphetamine develops hypertension jnc 8 summary digoxin 0.25mg with amex, and is both pharmacokinetic as well as pharmacodynamic blood pressure medication for asthmatics cheap 0.25 mg digoxin. Starvation due to suppression of appetite produces acidic urine; amphetamine is ionized more at acidic pH and is excreted more rapidly blood pressure kiosk locations generic digoxin 0.25mg without prescription. Treatment of amphetamine toxicity includes administration of chlorpromazine which controls both central as well as peripheral adrenergic effects. The central effects include alertness, increased concentration and attention span, euphoria, talkativeness, increased work capacity. The reticular activating system is stimulated resulting in wakefulness and postponement of sleep deprivation induced physical disability. But this is shortlived and may be accompanied by anxiety, restlessness, tremor, dysphoria and agitation. Use before examinations to keep awake can be counter productive and needs to be condemned. Hunger is suppressed as a result of inhibition of hypo- Phenylephrine It is a selective 1 agonist, has negligible action. Topically it is used as a nasal decongestant and in the eye for producing mydriasis when cycloplegia is not required. Phenylephrine tends to reduce intraocular tension by constricting ciliary body blood vessels. It is also a frequent constituent of orally administered nasal decongestant preparations. The most important side effect is muscle tremor; tachycardia and arrhythmias are less likely. Isoxsuprine It is an orally effective long-acting receptor stimulant which has direct smooth muscle relaxant property as well. It has been used as uterine relaxant for threatened abortion and dysmenorrhoea, but efficacy is poor. Beneficial effects in peripheral and cerebral vascular diseases are disappointing. It crosses blood-brain barrier to some extent-may produce excitatory effects at higher doses. It is used to prevent and treat hypotension due to spinal anaesthesia and surgical procedures, shock in myocardial infarction and other hypotensive states. They cause bronchodilatation, vasodilatation and uterine relaxation, without producing significant cardiac stimulation. The imidazoline compounds- naphazoline, xylometazoline and oxymetazoline are relatively selective 2 agonist (like clonidine). Regular use of these agents for long periods should be avoided because mucosal ciliary function is impaired: atrophic rhinitis and anosmia can occur due to persistent vasoconstriction. It has been used orally as a decongestant of upper respiratory tract, nose and eustachian tubes. Combined with antihistaminics, mucolytics, antitussives and analgesics, it is believed to afford symptomatic relief in common cold, allergic rhinitis, blocked eustachian tubes and upper respiratory tract infections. On the other hand, serotonergic agents have mild sedating property and primarily affect the satiety centre. Fenfluramine and dexfenfluramine reduce food seeking behaviour by enhancing serotonergic transmission in the hypothalamus. They were extensively used by slimming centres, though tolerance to the anorectic action develops in 2-3 months. In the late 1990s ecocardiographic abnormalities, valvular defects, pulmonary hypertension and sudden deaths were related to the use of a combined preparation of fenfluramine + phentermine. These drugs caused weight loss in obese people and were routinely used by slimming centres. Vascular uses (i) Hypotensive states (shock, spinal anaesthesia, hypotensive drugs) One of the pressor agents can be used along with volume replacement for neurogenic and haemorrhagic shock; also as an expedient measure to maintain cerebral circulation for other varieties of shock. They should not be used in secondary shock when reflex vasoconstriction is already marked. Accordingly they may be grouped into: * the ban order is presently under court stay. Because of the rapidity and profile of action Adr is the only life saving measure.

Syndromes

• General discomfort or uneasiness (malaise)
• Posterior urethral valves in infant boys
• High blood pressure in the lungs
• Serum luteinizing hormone (LH)
• Cryoglobulinemia type II
• Septic shock
• Anti-Mullerian hormone levels
• Graves disease
• Stage II cancer has spread to lymph nodes in the abdomen.

The observed mitochondrial uncoupling would consume calories and dissipate the energy as heat blood pressure chart systolic diastolic pulse generic digoxin 0.25mg with mastercard, which would facilitate weight loss arteria alveolaris superior posterior cheap digoxin 0.25 mg without prescription. However blood pressure high in the morning discount digoxin 0.25mg on line, such mitochondrial impairment yields cytotoxic oxidative and bioenergetic stress that induce irreversible mitochondrial failure blood pressure 220120 digoxin 0.25 mg generic, and hence the hepatotoxicity associated with usnic acid. Principal component analysis showed a clear age-dependent separation in expression profiles between young and old hepatic transcripts in males and females. We identified 370 genes that were altered between young and old men and 1163 genes that were altered between young and old women. The expression of solute carriers increased with age in men, and the majority decreased with age in women. Liver slices have emerged as a model of toxicity that bridge between simpler in vitro cell culture models and fully integrated in vivo models of toxicity. Finally selected slices were analyzed histologically to determine the extent of toxicity and to correlate findings with the biochemical and genomic data. For both compounds, the gene expression results could be categorized into early transient changes, early persistent changes, and late changes. We compared the liver profiles with a mouse tissue microarray dataset which included adult tissues involved in hematopoiesis. These results indicate that there are extensive gene expression differences between early (fetal, neonatal) and adult liver and that the fetal/neonatal liver exhibits transcriptional similarities with the pancreas. Numerous studies support the fact that a genetically diverse mouse population may be useful as an animal model to understand and predict toxicity in humans. We hypothesized that cultures of hepatocytes obtained from a large panel of inbred mouse strains can produce data indicative of inter-individual differences in in vivo responses to hepato-toxicants. In order to test this hypothesis and establish whether high-throughput in vitro studies using cultured hepatocytes from genetically distinct mouse strains are feasible, we aimed to standardize cell isolation and culture conditions and determine whether near-physiological maintenance of the cells isolated from different mouse inbred strains can be achieved. The cells have been assessed for viability and functionality on a daily basis by measuring production of lactate, pyruvate, and urea, as well as leakage of lactate dehydrogenase as a measure of membrane integrity. We also employed calcein and ethidium fluorescence staining to assess cell viability at 1, 3, 5 and 7 days of culture. Our data shows that high yield (48 to 87 million hepatocytes/mouse) and viability (86 to 98%) can be achieved across a panel of strains. Furthermore, we conclude that cell function of hepatocytes isolated from different strains and cultured under standardized conditions is comparable and cells remain viable and metabolically active as indexed by lactate, pyruvate and urea production. These experiments open new opportunities for high-throughput and low-cost in vitro assays that may be used for studies of toxicity in a genetically diverse population. Once absorbed they are poorly eliminated from the body and have been shown to be hepatotoxic and cause developmental, reproductive, immunological and endocrine effects in rodents and non-human primates. Precision-cut rat liver slices were prepared with a Brendel/Vitron tissue slicer and incubated in media for up to 48 hours in a high oxygen environment. Slices exposed to the vehicle were found to be ~ 30% viable at 48 hours, while no viable cells were observed at either 24 or 48 hours in D. These adverse reactions are not predictable using standard pre-clinical strategies and therefore are unrecognized until the very late stages of clinical evaluation. Uncovering common hepatotoxic mechanisms that link distinct classes of compounds would add great value to the fundamental understanding of late-stage adverse reactions. Subsequently, these cell systems were analyzed for transcriptomic changes using Affymetrix human genome microarrays. Each of the three test items invoked a dose-dependent increase in the total number of gene expression changes. Taking the metabolism of compounds into account is essential not only to drug development, drug safety and environmental health issues, but also to evaluate the risks associated with injury to the liver. The ability to screen compounds to assess hepatoxicity is crucial, but has been traditionally limited to in vivo testing for accurate evaluation, which is not desirable for ethical and efficiency reasons. In vitro testing, which reduces animal use, has become a viable option with the advent of specific markers and sensitive reagents.

Purchase digoxin 0.25 mg without prescription. Accurate Blood Pressure Measurement.

References

• Setola, S.V., Catalano, O., Sandomenico, F. et al. Contrastenhanced sonography of the kidney. Abdom Imaging 2007; 32:21-28.
• Engellau L, Albrechtsson U, Dahlstrom N, et al: Measurements before endovascular repair of abdominal aortic aneurysms. MR imaging with MRA vs. angiography and CT, Acta Radiol 44:177-184, 2003.
• Marr KA, Carter RA, Boeckh M, et al. Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood. 2002;100:4358-4366.
• Haffner MC, Mosbruger T, Esopi DM, et al: Tracking the clonal origin of lethal prostate cancer, J Clin Invest 123:4918n4922, 2013.
• Pitman SD, Huang Q, Zuppan CW, et al. Hodgkin lymphomalike posttransplant lymphoproliferative disorder (Hodgkin-like PTLD) simulates monomorphic B-cell PTLD both clinically and pathologically. Am J Surg Pathol. 2006;30:470-476.