What are the current treatments and their limitations? Existing drugs have serious drawbacks in terms of safety, resistance, stability, and cost. They have low. What are the current treatments for Chagas disease and their limitations? Drawbacks include long treatment periods ( days), dose-dependent toxicity, and a high drop-out rate of patients due to side-effects. There is currently no approved treatment for the chronic form of the. What are the current treatments for sleeping sickness and their limitations? Disease is caused by two subspecies of Trypanosoma brucei (T. b.) gambiense.
Combination medications that contain short-acting anticholinergic and a short-acting beta-agonist. There are two main ways to get inhaled medications into the lungs: A nebulizer is a device that changes liquid medication into a fine mist that can be inhaled into the lungs.
This mist can be breathed in through a mouthpiece or face mask. There are two main types of nebulizers: The jet nebulizer is the most common. In jet nebulizers, pressurized gas from a small air compressor or pressurized oxygen at the hospital is forced through a narrow opening, combining it with the liquid medication to create a mist. Electronic nebulizers are another type of nebulizer.
Two main types are ultrasonic and vibrating mesh. Electronic nebulizers work by using electrical energy to cause very fast vibrations of a mechanical part that turns the liquid medication into a mist. There are two main types of handheld inhalers: A pMDI releases medication in the form of a fine mist that can be inhaled into the lungs. Each spray has a precisely measured dose of medication mixed with a propellant. The spray comes out by pushing down on the canister to release the medication.
Use a slow deep breath. DPIs do not contain a propellant, so the powder is inhaled by taking a fast, deep breath through the mouthpiece. With the DPI it is the user who provides the force to get the medication out of the device and into the lungs. Studies have shown that respiratory medications delivered by nebulizer, metered-dose inhaler MDI and dry-powder inhaler DPI have similar results.
However, these are dependent on proper technique. To decide which system is best for you, talk with your health care provider. Here are some things to consider:. Your doctor can measure the oxygen in your blood by using a pulse oximeter ox-im-eh-ter. This is a small device that fits snugly on your finger. It measures how many red blood cells are carrying oxygen.
If the level of oxygen in your blood is too low, it can be confirmed by an arterial blood gas test ABG. If so, your doctor may prescribe oxygen therapy for you. Shortness of breath does not necessarily mean you need to be on oxygen. Many patients who have severe shortness of breath do not have low oxygen levels in their blood.
Also, many patients who have low oxygen levels do not always feel breathless. Learn more about Oxygen Therapy. Pulmonary rehabilitation is a treatment program. It provides exercise training, education about COPD, tips on how to complete everyday activities without becoming so short of breath and advice on how to live better with your disease. Many different types of medical professionals work with you in the program.
These include doctors, nurses, physical therapists, exercise specialists and dietitians. Dietitians dye-ah-ti-shuns are individuals who can teach you about healthy food choices.
You will work with this team to create a special program for you. Pulmonary rehab programs are available in most communities and often paid for by insurance.
Learn more about Pulmonary Rehabilitation. All medicines can have side effects. Tell your health care provider about all the medicines you take so you can talk together about them. The COPD Foundation offers resources such as COPDsocial , an online community where you can connect with patients, caregivers and healthcare providers and ask questions, share your experiences and receive and provide support.
It is not our intention to serve as a substitute for medical advice and any content posted should not be used for medical advice, diagnosis or treatment. While we encourage individuals to share their personal experiences with COPD, please consult a physician before making changes to your own COPD management plan.
Current treatments for COPD cannot repair the damage to your lungs. However, some treatments may reduce your risk of exacerbations flare-ups. This makes it easier for you to breathe and feel better. Using medicines from different groups may help: Controllers Short-acting Anticholinergic Bronchodilators Controller Recent studies reveal inferior control of symptoms compared to long-acting anticholinergic agents. Long-acting Anticholinergic Bronchodilators Controller Inside our bodies, there is a constant stream of messages being sent to keep us safe and well.
Long-acting Beta-agonist Bronchodilators Controller These medicines also work to relax the muscles in your airways and keep them from squeezing.
These work very well especially for people with night-time symptom Corticosteroids Controller: Combination Long-acting Anticholinergics and Long-acting Beta-agonists Controller For the first time ever, we have a new medication that combines two long-acting bronchodilators into one inhaler.
Phosphodiesterase-4 Inhibitor PDE-4 Inhibitor, Controller This is a new class of controller medication that helps control airway inflammation. Rescue Inhalers Short fast -acting Beta-agonist Bronchodilators Rescue Reliever These medicines work to relax the muscles in your airways from squeezing. Combination Combination medications that contain short-acting anticholinergic and a short-acting beta-agonist.
Nebulizers and Handheld Inhalers. Nebulizers A nebulizer is a device that changes liquid medication into a fine mist that can be inhaled into the lungs. Jet nebulizers The jet nebulizer is the most common. Electronic nebulizers Electronic nebulizers are another type of nebulizer. Therapeutic approaches are mainly aimed at acute ischaemic stroke. The two major drug classes thrombolytic and antiplatelet agents, which also are used to treat myocardial infarction are less effective and sometimes detrimental in ischaemic stroke relative to myocardial infarction.
Current drug treatments are problematic because of their small therapeutic window and the risk of haemorrhage, as well as the difficulty in ensuring correct diagnosis, selecting the most suitable patients and making use of the small time window available for treatment.
Currently, the only approved drug for ischaemic stroke treatment is the tissue plasminogen activator t-PA alteplase Actilyse , which produces reperfusion by dissolving or breaking the thrombus. The effectiveness of thrombolytic drugs depends on the effectiveness of their delivery to the damaged vessel. Recently, according to a recommendation from the European Stoke Organisation based on findings from a randomised trial, ECASS 3 , Alteplase can be given up to four and a half hours after onset of ischaemic stroke rather than three hours PJ , 7 February , p In addition, this time window could be extended up to six hours, although evidence for this is being collected eg, IST-3 trial.
Extension of this window and provision of a higher local drug concentration could be achieved by intra-arterial administration of the thrombolytic agent proximal to the offending thrombus. Initial results from trials using intra-arterial prouroukinase showed significant improvements compared with tPA alone.
Secondary treatment of stroke patients often involves anticoagulants. Traditionally, both heparin and warfarin are used, but low molecular weight heparins bemiparin, dalteparin, enoxaparin and tinzaparin are increasingly employed due to their longer action and lower risk of inducing thrombocytopenia or osteoporosis compared with unfractionated heparin.
Stroke can cause infarction of brain tissue with resultant irreversible neurological damage associated with reductions in neuronal adenosine triphosphate and cell death. This area of infarction is termed the core region. The surrounding area, or penumbra, contains a collateral circulation that continues to perfuse the brain, although the supply of oxygen will be decreased, and evidence shows the presence of inflammatory cascades and cell death in this area.
Much work has focused on the cellular and biochemical pathways of stroke, revealing profiles of gene activation. Indeed, targeting the molecular and cellular penumbra may reveal drug targets for stroke intervention.
Excitotoxicity a process that damages and kills nerve cells occurs when the neurotransmitter glutamate, released in response to ischaemia, overactivates its receptors eg, N-methyl-D-aspartic acid [NMDA] receptor and a-aminohydroxylmethylisoxazole-propionate [AMPA] receptor.
This allows an influx of calcium ions, which, in turn, activates enzymes, such as endonucleases, proteases and phospholipases, causing damage. Most neuroprotectant therapies, such as NMDA antagonists, appear to have been unsuccessful and, in some cases, have worsened the outcome in ischaemic stroke but, when co-administered with a thrombolytic agent, appear to have shown a positive effect in transient ischaemia.
Complexin genes complexin I and II differentially expressed in human brain are regulators of neurotransmitter release and may provide the reason underlying the excessive sustained release of glutamate after acute stroke. It is well accepted that an inflammatory response is triggered after an ischaemic stroke. Inflammation during ischaemic stroke may occur due to thrombus of large eg, carotid, middle cerebral and basilar arteries or small eg, lenticulostriate, basilar penetrating and medullary arteries or due to an embolus.
Many studies have shown the presence and active state of leukocytes neutrophils and monocytes, which can be recruited as early as 30 minutes after ischaemia and reperfusion and resident cells eg, microglia, astrocytes and endothelial cells following stroke. The involvement of resident brain cells versus blood-borne cells remains unknown. Upregulation of cytokines and adhesion molecules occurs and this can induce damage to the blood-brain barrier and extracellular matrix, leading to oedema a major clinical complication in stroke and the further recruitment of leukocytes and platelets.
Endothelial cells are important in the pathophysiology of stroke. During the hypoxic stage of the stroke, endothelial cells swell and form microvilli. This reduces the vessel size and increases the plugging by erythrocytes, leukocytes and platelets. Endothelial cells are also involved in vascular tone of a vessel, which becomes disrupted. Activation of the endothelial cells upregulates a variety of adhesion molecules that recruit platelets and leukocytes, increasing the inflammatory response.
Many drug candidates have been considered for targeting a specific aspect of the inflammatory cascade, such as adhesion molecules. These have led to failed clinical trials eg, enlimomab and Leukarrest.
An interleukin-1 antagonist IL-1RA has been administered to patients within six hours of stroke, although the clinical benefits remain unknown. However, no major side effects were observed and inflammatory cells were reduced. The area of inflammation is an active one in terms of potential targets for stroke patients, although results to date have been highly disappointing. Sadly, most drugs showing beneficial effects in animal stroke models go on to fail in clinical trials.
For example, exogenous administration of growth factors eg, brain-derived neuro-trophic factor has promoted recovery from stroke in rodents but, in humans, the trial was stopped. This questions the usefulness of animal models in understanding the pathophysiology of stroke and the potential development of therapeutic agents for stroke. However, these studies have often been conducted in healthy, young animals. Moreover, these models have focused on single targets in the hope that this provides the key to stroke treatment.
Clearly, this is not the answer to a dynamic pathology and we should be revisiting failed drug targets along with new targets for potential combination therapies for this complex disease. Despite the failure of many animal models to predict success in the clinic, they provide further evidence for the biology of stroke and the response to these therapies, enabling us to learn more about this disease. The use of animals for obtaining targets of stroke particularly when stroke itself is a multifactorial disease is a constant debate.
Animal models have included transient global brain ischaemia in gerbils, rats and mice. These correlated reasonably well with clinical findings and all show selective and delayed neuron death in the hippocampus, which matches that seen in the human. However, careful interpretation will always be needed.
Many animal models focus on the occlusion of the middle cerebral artery MCA. Focal ischaemic models are generated using a filament that is guided up the cerebral artery until it occludes the MCA. Other stroke models include the placement of homologous blood clots in the MCA, which may prove more relevant clinically.
Advances in neuroimaging, such as positron emission tomography and magnetic resonance imaging MRI; perfusion weighted and diffusion weighted , have aided the assessment of patients. Neuroimaging in animals is now being recognised as an important step in helping to understand the pathophysiology of stroke and develop potential therapeutic drugs. Despite further potential glutamate receptor drug targets being produced NPS and Traxoprodil , none has proved successful, possibly due to the hyperacute release of glutamate.
Compounds that target the excitotoxicity associated with stroke, in particular the enhancement of glutamate transport function, may be valuable. Recently, ceftriaxone pretreated animals were shown to induce ischaemic tolerance in focal ischamia mediated by the astrocytic glutamate transporter protein, GLT-1 EAAT2. The application of ex vivo gene therapy is also being investigated with potentially fewer side effects. Combination therapy of caspase inhibitors with MK has been used in rodent models of stroke to block NMDA receptors or fibroblast growth factor, both of which have shown neuroprotection.
AMPA receptor antagonists have also been tried in humans but, to date, none has been successful, again, due to their side effects eg, kidney toxicity. Recent improvement of a non-competitive AMPA receptor antagonist 2,3-benzodiazepine appears to have few side effects, although it is in its early stages. Recent in vivo studies have indicated that acid sensing ion channel blockers might provide neuroprotection, as seen in rodent models of cerebral ischaemia.
This requires further investigation. Hypothermia has also been suggested as a possible treatment in transient ischaemia, although there is debate on whether the activity of tPA may be reduced on cooling, as observed in vitro. Hypothermia may also be beneficial in reducing the activities of matrix metalloproteinases, which play a role in blood-brain barrier function and possible angiogenesis and remodelling after stroke, but evidence is still being collected.
Many advances have been made in stem cell research. Cell therapies for the treatment of myocardial infarction and stroke are being tested in early clinical trials. Small trials have already been performed using haematopoeitic stem and progenitor stem cells, although outcomes have been mixed. These studies showed several significant findings as assessed by the European stroke scale, indicating the safety and feasibility of neuron transplantation for patients with motor stroke.
Another group, the ReNeurob Group, has developed a fetal neural stem cell line CTX0E03 that can differentiate into mature cells with the characteristics of the cells from which they were derived. These cells have already been tested in rodent models and a non-human primate model, and a proposal is with the US Food and Drug Administration for a potential phase I trial. Clearly, this is an exciting time in stem cell research and although further studies are clearly needed, it may provide potential treatments and therapies for stroke.
This article focuses on several areas, although this is by no means an exhaustive list. From a preclinical point of view, a better understanding and interpretation of results from in vivo animal studies is required.
Currently, there is an unmet need for better drug treatments for this complex disease. In this article, Felicity N. E. Gavins discusses current treatments and the . Alzheimer's treatments – learn about drug and non-drug treatments that may help cognitive and behavioral symptoms of Alzheimer's and other dementias. Researchers believe successful treatment will eventually involve a combination of medications aimed at several targets, similar to current treatments for many.