Current research in Parkinson's disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active. Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.
Compared to studies performed in urban hospitals in other countries, (1) the annual rate of poisoning-related Accident & Emergency Department visits was substantially lower, (2) psychoactive drugs were less frequently incriminated in intentional ingestions, and (3) we found a significantly higher frequency of poisoning by animals and traditional remedies than reported by urban hospitals in other Middle Eastern countries. The limitations of our study (Accident & Emergency Department-based data collection in an urban hospital) do not permit extrapolation to the rest of the country.
Sterile neurogenic inflammation within cephalic tissue, involving vasodilation and plasma protein extravasation, has been proposed as a pathophysiological mechanism in acute migraine. The action of 5-hydroxytryptamine (5-HT1B/1D) agonists--so-called triptans--on receptors located in meningeal arteries (5-HT1B) and trigeminovascular fiber endings (5-HT1D) has an inhibitory effect on this neurogenic inflammation. Recently, a series of second-generation 5-HT1B/1D agonists (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and zolmitriptan) have been developed and are reviewed in this article. Their in vitro pharmacological properties, pharmacokinetics, clinical efficacy, drug interactions, and adverse effects are evaluated and compared to the golden standard in the treatment of acute migraine, sumatriptan.
Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNb) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNb are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.
While most nurses were aware of the purpose of CR formulations, little was known about the different codes used by drug companies and the consequences of crushing these preparations. Interactions with enteral feeds and feeding tubes were mostly overlooked. A 2 day training course followed by continuous in-service training, a lecture to pharmacy staff, and provision of supportive educational material greatly improved the overall medicine administration process in patients with swallowing problems and feeding tubes.
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. Except for a rapid on- and offset of the antiparkinsonian response with subcutaneous apomorphine, the magnitude and pattern of the motor response to single dose of subcutaneously administered apomorphine is qualitatively comparable to that of oral levodopa. Seventy-five percent of patients achieve a clinically significant improvement with a dose of apomorphine 4mg. The efficacy of intermittent subcutaneous apomorphine injections as an add-on to levodopa therapy in advanced Parkinson's disease was explored in one short-term, randomised, double-blind, placebo-controlled trial, one short-term and six long-term, open-label, uncontrolled studies, including a total of 195 patients. These studies provide evidence that this mode of administration was successful in aborting 'off' periods and improving Parkinson's disease motor scores, but tended to increase dyskinesias. No levodopa-sparing effect was observed. Eleven long-term, open-label, uncontrolled studies, including a total of 233 patients evaluated the efficacy of continuous subcutaneous apomorphine infusions in monotherapy or as an add-on to levodopa therapy in advanced Parkinson's disease. These studies proved that subcutaneous apomorphine infusions are successful in aborting 'off' periods, reducing dyskinesias and improving Parkinson's disease motor scores with the added benefit of a substantial levodopa-sparing effect. The apomorphine challenge test has at least 80% overall predictive ability to clinically diagnose Parkinson's disease across the different stages of the disease and parkinsonian syndromes. Similarly, those data also indicate that the apomorphine challenge test has a >80% ability to predict dopaminergic responsiveness across all stages of Parkinson's disease. Adverse events are usually mild and consist predominantly of cutaneous reactions and neuropsychiatric adverse effects. The incidence of adverse effects is higher in patients receiving continuous infusion than in those receiving intermittent pulsatile 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 ...
Despite the higher number of patients receiving ASM upon admission, the multi-approach strategy used in our institution resulted in a significant improvement in the appropriate usage of ASM in medical inpatients.
Unlike the results in most other studies, generalized seizures represented the majority of epileptic seizures. The selection of the AEDs corresponded well with their known efficacy profiles for specific epileptic seizure types. Monotherapy was the type of therapy most frequently used, and sodium valproate and carbamazepine were the most commonly used AEDs.
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