Drug Aging
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The deficiency in cholinergic neurotransmission in Alzheimer's disease has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. The clinical benefits of these agents include improvements, stabilisation or less than expected decline in cognition, function and behaviour. The common mechanism of action underlying this class of agents is an increase in available acetylcholine through inhibition of the catabolic enzyme, acetylcholinesterase. ⋯ Despite these differences in pharmacology, a review of clinical data, including head-to-head studies, has not demonstrated differences in efficacy, although they may have an impact on tolerability. It seems clear that whatever the subsidiary modes of action, clinical evidence supporting acetylcholinesterase inhibition as the mechanism by which cholinesterase inhibitors treat the symptoms of Alzheimer's disease is accumulating. Certainly, as a class, the currently approved cholinesterase inhibitors (donepezil, galantamine, rivastigmine and tacrine) provide important benefits in patients with Alzheimer's disease and these drugs offer a significant advance in the management of dementia.
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Neurodegenerative diseases are increasingly common in elderly patients, who present a particular anaesthetic challenge. The majority of people over the age of 70 years have some degree of cerebral atrophy. The pathogenesis of neurodegenerative diseases is due to alterations in the transport, degradation and aggregation of proteins. ⋯ This is particularly relevant to the timing of levodopa in Parkinson's disease, as missed treatment can be detrimental. Regional anaesthesia may, however, have significant advantages in patients with Parkinson's disease, who can continue to take oral levodopa preoperatively, during surgery, if required, and early in the postoperative period. Anti-emetic drugs such as phenothiazines, butyrophenones and metoclopramide should be used carefully in the postoperative period in these patients as their antidopaminergic effects may induce or exacerbate parkinsonian effects.
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Colonic diverticula are protrusions of the mucosa through the outer muscular layers, which are usually abnormally thickened, to form narrow necked pouches. Diverticular disease of the colon covers a wide clinical spectrum: from an incidental finding to symptomatic uncomplicated disease to diverticulitis. A quarter of patients with diverticulitis will develop potentially life-threatening complications including perforation, fistulae, obstruction or stricture. ⋯ Laparoscopic surgery may be associated with less pain, less morbidity and shorter hospital stays, but its exact role is yet to be defined. Diverticular disease of the colon is the most common cause of acute lower gastrointestinal haemorrhage, which can be massive. Although the majority of patients stop bleeding spontaneously, angiographic and surgical treatment may be required, while the place of endoscopic haemostasis remains to be established.
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Apomorphine, a short-acting dopamine D1 and D2 receptor agonist, was the first dopamine receptor agonist used to treat Parkinson's disease. Subcutaneous apomorphine is currently used for the management of sudden, unexpected and refractory levodopa-induced 'off' states in fluctuating Parkinson's disease either as intermittent rescue injections or continuous infusions. Other indications include the challenge test for determining the dopaminergic responsiveness and finding the appropriate dose of the drug in intermittent subcutaneous administration. ⋯ Based on the results of these studies it is recommended that subcutaneous apomorphine either as intermittent injections or continuous infusions should be offered to any suitable Parkinson's disease patient who has difficulties in his/her management with conventional therapy. Low-dose levodopa therapy in combination with waking-day hours subcutaneous apomorphine infusion would probably be the most efficient treatment. Continuous subcutaneous apomorphine infusions should be evaluated before more invasive measures or neurosurgical interventions are contemplated.
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The number of elderly patients presenting for anaesthesia and surgery has increased exponentially in recent years. Regional anaesthesia is frequently used in elderly patients undergoing surgery. Although the type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality in any age group; it intuitively makes sense that elderly patients would benefit from regional anaesthesia because they remain minimally sedated throughout the procedures and awaken with excellent postoperative pain control. ⋯ Epinephrine also can prolong the duration of peripheral nerve blocks. However, caution must be exercised as epinephrine has the potential for causing ischaemic neurotoxicity in peripheral nerves. Regional anaesthesia appears to be safe and beneficial in elderly patients; however, every anaesthetic administered must be assessed on a case-by-case basis and particular consideration should be given to the health status of the patient, the operation being performed and the expertise of the anaesthesiologist.