Memantine
Description: Namenda Offers New Hope for More than a Million Alzheimer's Disease Patients The recent FDA approval of Forest Laboratories' Namenda Memantine ; is being heralded by many as the best news for Alzheimer's disease AD ; patients in over five years. The drug's action is quite different from existing AD medications and will be the first drug approved for the moderate to severe patient population. Namenda's ability to improve patient conditions in key areas such as cognition, activities of daily living, and global functioning provides hope to the over one million patients that suffer from moderate to severe form of AD. The drug could reach blockbuster status faster than Aricept touched billion in sales. This research examines the U.S. Alzheimer's disease medication markets with specific focus on markets for medication that are either currently used or are being developed. It provides key market challenges, drivers, and restraints affecting growth and offers a detailed competitive market analysis. The report has been segmented based on disease severity into mild-to-moderate, moderate-to-severe, and mild cognitive impairment MCI ; treatment. Namenda Approval Generates Greater Revenues for Aricept and Other Approved AD Treatments Apart from the revenues generated by Namenda, clinical studies supporting its use as a combination treatment are expected to generate revenues for Aricept and other FDA-approved treatments such as Exelon and Reminyl, states the analyst. Namenda is expected to fulfill the unmet needs of more severe patients in the moderate-to-severe segment, who are unsatisfied with current acetyl cholinesterase inhibitor treatments. Such combination therapies will also improve the compliance of patients currently taking one of the available approved treatments because of their improved action. Patient adherence with drug therapy tends to decline as the disease worsens. Combination therapy should improve this compliance greatly. Since severe AD involves irreversible brain cell death, discovering effective medications for this segment of patient population has been difficult. Namenda's approval has increased optimism of the research community, as the drug's action is more sustained and effective than others'. Patients who have been taken off Aricept are likely to be put back on it along with Memantine. Physicians' experience in using these combination therapies will largely influence sales of Aricept and other acetyl cholinesterase inhibitors in the moderate-to-severe segment. Expected Sanction of Aricept, Exelon, and Reminyl for MCI Treatment to Widen Market Owing to the significant inconveniences of this disease, any medication which shows potential to delay its onset will become increasingly accepted by FDA regulators and the medical community. Aricept is likely to be approved for MCI indication by 2005, and Exelon and Reminyl by 2006. The market for MCI medication is likely to expand considerably since an approved indication will enable companies to conduct significant educational activities, which improve physicians' abilities to diagnose the disorder, notes the analyst. In the long term, these efforts could help drug companies penetrate the lucrative age-related memory impairment market and thereby, gain additional revenue. There is likely to be a paradigm shift that involves taking more of a preventative as opposed to a treatment approach to Alzheimer's disease.
Memantine drug
Match perfusion Fig. 2C ; at the left frontal region and there was no more decoupling arrows in Figs. 2B and 2D ; . The anatomical imaging by MRI Figs. 1C and ID ; revealed exuberant bidirec tional flow through the floor of the third ventricle consistent with widely patent third ventriculostomy. There are no changes noted in the ventricular size when compared to preshunting MRI. In order to detect the global changes in cerebral perfusion and metabolism, the mean and standard deviation of count densities of the entire brain were calculated using the method described previously 24 ; . For local quantification, 20 different 4X4 pixel ROIs were placed on the transverse images Figs. 2E and 2F ; to extract count densities. All count densities were then normalized to the maximal count in the cerebellum. The cerebellum was chosen as reference region, because the mean regional cerebral perfusion was shown not to be different from normal controls 25 ; and hydrocephalus is not known to be associated with structural abnormalities in the cerebellum. The mean count ratios in cerebral perfusion and metabolism improved significantly, respectively, from 0.80 0.11 and 0.88 0.11 preoperatively to 0.83 0.14 and 0.91 0.12 postoperatively two-tailed p 0.00001 in both perfusion and metabolism ; . The asymmetric indices, defined by Right " Left ; Right + Left ; , in the frontal and nonfrontal regions were tabulated in Table 1. The table showed significant reversal of the asymmetric index in frontal metabolism but not in frontal perfusion. This concurred with our visual observation of luxury perfusion, a form of mismatch in perfusion and metabolism. However, although the neurologic symptoms bilateral leg numb ness and weakness, ataxia and frontal headache ; that the patient experienced before endoscopie third ventriculostomy were re solved, paralleling the observations in the pre- and postshunting perfusion and metabolic imaging just described, there are no localizing focal neurologic signs or symptoms to relate to the major site of luxury perfusion. Thus, the clinical improvement was most likely related to global improvement of metabolism and perfusion. DISCUSSION Quantitative PET studies have demonstrated coupling be tween cerebral blood flow, oxygen consumption and glucose utilization 13, 14 ; . Shin et al. 9 ; had demonstrated reversible hypoperfusion in human cerebral cortex after shunting in a single patient with normal pressure hydrocephalus by using a three-dimensional display 01 mTc-HMPAO cerebral perfusion SPECT images. But the status of metabolism, which might not be coupled to perfusion as illustrated in our case, was unknown. Friedland et al. 12 ; demonstrated reversible hypometabolism in human cerebral cortex after shunting in a single patient with normal pressure hydrocephalus by using I8F-FDG PET images during the management of dementia. However, there were no accompanying perfusion images presented to illustrate perfu sion and metabolism mismatch or match. Clearly, the ability of the neurons in a brain region to regain metabolism after surgery but not just perfusion indicates the presence of viable neurons in that particular region. However, reduced metabolism could be due to neuronal cell loss, neurons at crisis ischemia ; or deafferentation diaschisis ; . Thus, in order to identify neuronal.
Until recently, no head-to-head trials compared the efficacy of cholinesterase inhibitors for treating Alzheimer's disease, but limited comparative data is now available. Comparative data is not available for memantine, the only NMDA receptor antagonist, although memantine has been studied in combination with donepezil. Memantine has also been studied in Europe during the last decade for the treatment of dementia and was approved in the European Union in May of 2002 for the treatment of moderately severe to severe AD. In the U.S., the completion of two large Phase III clinical trials confirmed earlier European findings showing that memantine is effective for the treatment of moderate to severe AD. A small number of efficacy trials are available for memantine, and FDA approval was granted based on data from limited placebo-controlled studies. Many patients do not benefit from the first agent they receive, or the medication loses its therapeutic benefit. Other patients discontinue treatment because of safety or tolerability issues. Often, no alternative treatment is offered, so the duration of treatment is short compared to the time patients suffer from this chronic disease. A number of studies evaluating the effect of switching from donepezil to rivastigmine indicate that approximately 50% of patients who experience lack or loss of efficacy with donepezil respond to treatment with rivastigmine. The same studies also indicate that safety and tolerability problems with donepezil do not predict similar problems with rivastigmine.
SIGNATURE OF PATIENT: I understand the need for these questions to be answered truthfully. To the best of my knowledge, the answers I have given are accurate. I also understand it is very important to report any changes in my medical or dental status to the dentist at the earliest possible time, and I agree to do so. I give my permission to the dentist to obtain from my physician or dentist, any additional information regarding my medical history needed to provide me the best dental treatment possible. PERSON COMPLETING FORM: Signature: Date: If other than patient, indicate relationship.
In the field. In conducting such an analysis, a lawyer should: 1 ; Understand the type of regulatory information relied upon by an expert and the process used to generate it. When regulatory agencies make findings or conclusions, they will explain both the purpose of those findings, and the basis for those findings. By carefully evaluating such information, a lawyer will know whether an agency decision is based on reliable evidence of the type that a court might independently admit e.g., reliable epidemiological research showing a doubling of the risk of disease from a particular exposure ; , or uncertain evidence that still suggests the need for regulatory action given broader public health concerns. This kind of critical analysis is especially important where an organization's mission includes scientific research. For example, the IARC has a forward-looking mission.
Memantine treatment in patients with moderate to severe alzheimer's disease already receiving donepezil and meperidine.
Rivastigmine, memantine diabetes diabetes type ii ; automated dosing for elderly patient compliance!
Some people have said that so-called "super responders" exist with prolonged responses to treatment. But again, these are uncontrolled trials, and we don't have Phase III data yet. Chemotherapy plus trastuzumab is also an option based on evidence of a survival advantage compared to chemotherapy alone Slamon 2001 ; . Personally, in these cases, I tend to use an aromatase inhibitor first, depending on the volume of the liver disease. If the patient progresses, which many of them do fairly rapidly, I will go on to chemotherapy with trastuzumab. DR LOVE: Can you talk a little bit about the extent of her liver disease and symptoms? DR PROVATAS: Essentially, she was asymptomatic in terms of weight loss, and she didn't have right upper quadrant pain. On CT, she had four to five lesions in the liver, and an MRI confirmed that she had at least five. DR LOVE: Bob, can you talk about your approach to first-line therapy of women with ER-positive, HER2-positive tumors? Also, would you have FISHed the tumor? DR CARLSON: With a HER2 overexpression 3 + by the Dako test, I would not normally have done a FISH analysis. I pretty much exclude FISH analysis except for the HER2 2 + by IHC. For the treatment pick list, I would have looked at it exactly the same way as Tom just outlined -- hormonal therapy alone, trastuzumab alone, hormones plus trastu26 and mephenytoin.
A 47-year-old man reports a six-month history of intermittent chest discomfort while playing squash. He describes lower substernal tightness with numbness of the left upper arm only during exertion. He does not smoke. His father died suddenly at the age of 49 years. His blood pressure is 138 84 mm Hg. The level of total cholesterol is 261 mg per deciliter, low-density lipoprotein cholesterol 172 mg per deciliter, and high-density lipoprotein cholesterol 50 mg per deciliter, and the triglyceride level is 113 mg per deciliter. An exercise test is positive, with pain and 1.5 mm of horizontal ST-segment depression at stage 4 of the Bruce protocol. How should the patient's case be managed?.
Memantine prices
HSV-03: Treatment modalities for patients diagnosed with genital herpes vary between the USA, France, Germany, Italy and Brazil Minshall ME1, Poliakova TB2, Smith W2, Sevald C2, Christensen KE1, Culp SM1, Rose SD1, Plate H2, Braun DK1. 1Eli Lilly and Company, Indianapolis, IN, USA; 2NFO Migliara Kaplan, Baltimore, MD, USA. Objectives: Evaluate treatment modalities for patients diagnosed with genital herpes in the USA, France, Germany, Italy and Brazil. Methods: Subjects were recruited and screened for this market research survey through mail panels in the USA, France and Germany who were representative of the general population in terms of age, gender, etc. Mass mailing panels were not available in Italy and Brazil, so potential respondents were contacted by telephone using random dialling. The survey consisted of nine questions that focused on the symptoms, diagnosis, and treatment of genital herpes and meprobamate.
National Institute for Health and Clinical Excellence. Social value judgements: guidelines for the institute and its advisory bodies--draft for consultation. London: NICE, 2005. Harris J. It's not NICE to discriminate. J Med Ethics 2005; 31: 373-5. National Institute for Health and Clinical Excellence. Social value judgements: principles for the development of NICE's guidance. London: NICE, 2005. nice page x?o 283495 accessed 16 Dec 2005 ; . Mayor S. NICE says that patients' age should affect treatment. BMJ 2005; 330: 1102. NICE. Appraisal consultation document: Alzheimer's disease--donepezil, rivastigmine, galantamine and memantine review ; . 2005. nice page x?o 245908 accessed 19 Nov 2005 ; . Royal College of Physicians. Response from the Faculty of Old Age Psychiatry of the Royal College of Psychiatrists to the NICE appraisal consultation document: donepezil, rivastigmine, galantamine and memantine for the treatment of Alzheimer's disease. 2005. rcpsych.ac members membership responseNICE March05 accessed 19 Nov 2005 ; . National Institute for Clinical Excellence. Guide to the methods of technology appraisal. London: NICE, 2004. National Institute for Clinical Excellence. Technology appraisal No 58. Guidance on the use of zanamivir, oseltamivir and amantadine for the treatment of influenza. 2003. nice pdf 58 Flu fullguidance accessed 19 Nov 2005 ; . Rawlins MD, Culyer AJ. National Institute for Clinical Excellence and its value judgments. BMJ 2004; 329: 224-7.
Early application is advised as Numbers for workshops may be limited. Examination candidates will be given priority and mercaptopurine.
Our main story focuses on the visit to the CAPRISA Vulindlela Clinical Research Site by several high ranking US officials who were in South Africa to assess some of the US funded programmes being implemented in Africa. August was Women's Month. To commemorate the occasion two Women's Day celebrations were hosted by CAPRISA ; one in Vulindlela see page 2 ; and one at the eThekwini site See page 3 ; . We also introduce a twopage spread focusing on microbicides. In this issue we introduce the exceptional women running the microbicide study at the two Clinical Research Sites, provide an update of new results in HIV prevention science, and the highlight the CAPRISA 004 team's innovative approach to informed consent see page 4 and 5.
Identification & or early detection by screening should be done as early as possible to allow for starting early intervention programs to enhance motor development and prevent complications. Suitable times for screening and identification are at birth 1st week of life ; , 2- 3 months, 9- 12 months, 1.5 2 years, 2.5 3 years and 5- 6 years as well as whenever a child is seen for examination or follow up. as adopted by the screening tool developed by MOH and meropenem.
On the basis of previous studies in rodent models of cerebral ischemia, we administered memantine at a dose of 20 mg kg and clenbuterol at 0.3 mg kg, and evaluated the respective therapeutic windows of the individual compounds in a model.
ONL OPL FIGURE 1. Thickness of retinal layers in the ischemic eye as a percentage of the thickness of the nonischemic fellow eye. The error bars indicate the standard error of the mean. Control group, white bars; memantine before ischemia, black bars; memantine 0.5 and 3 5 hours after reperfusion, dark, hatched bars; and memantine 3 5 and 7.5 hours after reperfusion, light, hatched bars. ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer. * , P 0.05 and mesna.
References 1. World Health Organization. International statistical classification of diseases and related health problems. 10th revision. Geneva: World Health Organization; 1994. 2. Stahl SM. Psychopharmacology of reward and drugs of abuse. In: Stahl SM. Essential psychopharmacology: neuroscientific basis and practical application. Cambridge, UK; New York, NY, USA: Cambridge University Press; 2000. p. 499-538. 3. Kosten TR, Stine SM. Introduction and overview. In: Stine SM, Kosten TR. New treatments for opiate dependence. New York: The Guilford Press; 1997. p. 1-12. 4. National Institute on Drug Abuse NIDA ; . Epidemiological trends in drug abuse series online ; 1999 [cited 1999 June]. Available from: : drugabuse.gov CEWG AdvancedRep 699ADV 5. O'Connor PG, Spickard A Jr. Physician impairment by substance abuse. Med Clin North Am. 1997; 81 4 ; : 1037-52. Review. 6. Pullen D, Lonie CE, Lyle DM., Cam DE, Doughty MV. Medical care of doctors. Med J Aust. 1995; 162 9 ; : 481, 484. 7. Cadman M, Bell J. Doctors detected self-administration opioids in New South Wales, 1985-1994: characteristics and outcomes. Med J Aust. 1998; 169 8 ; : 419-21. 8. Carlini EA, et al. I Levantamento domiciliar sobre o uso de drogas psicotrpicas no Brasil: estudo envolvendo as 107 maiores cidades do pas 2001. So Paulo: CEBRID UNIFESP; 2002. 9. Gold MS. Opiate addiction and the locus coeruleus.The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Psychiatr Clin North Am. 1993; 16 1 ; : 61-73. Review. 10. Fernandez H. Heroin. Minnesota: Hazelden; 1998. 11. Melo ALN. Toxicomanias. In: Melo ALN. Psiquiatria. Rio de Janeiro: Guanabara Koogan; 1986. p. 165-178. 12. Baltieri DA. Opiides: aspectos gerais. In: Focchi GRA, Leite MC, Laranjeira R, Andrade AG. Dependncia qumica: novos modelos de tratamento. So Paulo: Roca; 2001. p. 109-16. 13. Langendam MW, van Brussel GH, Coutinho RA, Ameijden EJ. The impact of harm-reduction-based methadone treatment on mortality among heroin users. J Public Health. 2001; 91 5 ; : 774-80. 14. Francis RJ, Franklin JE. Transtorno por uso de alcohol y otras substancias psicoativas. In: Hales RE, Yudofsky SC, Talbott JA. Tratado de Psiquiatria. Barcelona: Ancora; 1995. p. 373-434. 15. Dickenson AH. Peptides. In: Webster RA. Neurotransmitters, drugs and brain function. New York: John Wiley & Sons; 2001. p. 251-64. 16. Nestler EJ, Hope BT, Widnell KL. Drug addiction: a model for the molecular basis of neural plasticity. Neuron 1993; 11 6 ; : 995-1006. Review. 17. Krupitsky EM, Masalov DV, Burakov AM, Didenko TY, Romanova TN, Bespalov AY, et al. A pilot study of memantine effects on protracted withdrawal syndrome of anhedonia ; in heroin addicts. Addict Disord Treat. 2002; 1 4 ; : 143-46. 18. Nestler EJ. Basic neurobiology of opiate addiction. In: Stine SM, Kosten TR. New treatments for opiate dependence. New York: The Guilford Press; 1997. p. 34-61. 19. Rang HP, Dale MM, Ritter JM. Frmacos analgsicos. In: Rang HP, Dale MM, Ritter JM. Farmacologia. Rio de Janeiro: Guanabara Koogan; 2000. p.485-505. 20. Simon EJ. Opiates: neurobiology. In: Lowinson JH, Ruiz P, Millman RB, Langrod JG. Substance abuse: a comprehensive textbook. Baltimore: Willians & Wilkins; 1991. p. 195-204. 21. Narita M, Funada M, Suzuki T. Regulations of opioid dependence by opioid receptor types. Pharmacol Ther. 2001; 89 1 ; : 1-15. Review. 22. Pittamn AM. Cuidados gerais em medicina interna. In: Woodley M, Whelan A. Manual de teraputica clnica. Rio de Janeiro: MEDSI; 1994. p. 1-34. 23. Martin PR, Hubbard JR. Substance-related disorders. In: Ebert MH, Loosen PT, Nurcombe B. Current diagnosis & treatment in psychiatry. New York: McGraw Hill; 2000. p. 233-59. 24. Diagnostic and statistical manual of mental disorders: 4th ed revised. Washington: American Psychiatric Association; 2000 and memantine.
Figure 3 Neuroprotection by ASIC1 blockade and ASIC1 in brain ischaemia in vivo A ; TTC-stained brain sections show infarct area image ; and volume histogram ; in brains from rats injected with aCSF n 7 ; , amiloride n 11 ; or PcTX venom n 5 ; . * 0.05 and * P 0.01 compared with aCSF-injected group. B ; Reduction in infarct volume in brains from ASIC1 mice n 6 for each group ; . * P 0.05 and * P 0.01 compared with ASIC1 + + group. C ; Reduction in infarct volume in brains from mice injected intraperitoneally with 10 mg kg memantine Mem ; or injected intraperitoneally with memantine accompanied by intracerebroventricular injection of PcTX venom 500 ng ml ; . * 0.01 compared with aCSF injection and between memantine and memantine + PcTX venom n 5 in each group ; . D ; Reduction in infarct volume in brains from either ASIC1 + + or ASIC1 mice injected intraperitoneally with memantine n 5 in each group ; . * P 0.05 and * P 0.01. WT, wild-type. Reprinted from [7] with permission. c 2004 Elsevier and mesoridazine.
This is very much in the range which NICE have considered cost-effective for other indications. For example, the HTA on use of riluzole for motor neurone disease estimated cost per QALY to be 34, 000 to 43, 500, but still allowed the treatment as they considered the illness and patient issues much more fully than in the current HTA. The HTA reports that "the Committee took account of the severity and relatively short life span of people with ALS and in particular, as directly reported to it, of the values which patients place on the extension of tracheotomy free survival time. With these considerations in mind, the Committee considered that the net increase in cost for the NHS of the use of riluzole in this indication was reasonable when set against the benefit, assessed as extended months of an acceptable to patients ; quality of life". In the Appraisal Determination of trastuzumab, approval was given even though the estimate per QALY was 37, 500. In the Appraisal Determination of imatinab for CML, approval was given even though incremental cost over existing treatment hydroxyurea ; was above 60, 000 per QALY. There are many, many other examples. As such, it is clear that the Committee have dealt with cholinesterase inhibitors and memantine in a particularly harsh and unfair way in relation to other treatments recently assessed, suggesting that people with dementia are not valued in the same way as those with other illnesses and laying itself open to claims of ageism. 5. Other cost-effectiveness measures are more accurate, more appropriate and more meaningful, e.g. cost per week of stabilisation improvement The main benefits seen, as stated in the 2001 HTA, are "improvements in patient's cognitive and other functioning". An important question is how this should this is best assessed, if the QALY is not a validated tool for use in dementia. Again, the Appraisals Committee has treated other appraisal determinations in a quite different way. For example, in the determination of temozolomide for malignant brain tumour the HTA states that "estimating cost per QALY is difficult because the extension of mean survival time is not statistically significant and quality of life data are limited". This applies equally well, indeed even more so, to Alzheimer's disease. The appraisal continues "the main benefit of temozolomide is that a proportion of patients benefit from a longer progression-free survival time. Therefore, the most useful measure of cost-effectiveness is cost per progression-free week". This has direct parallels with the symptomatic treatments for Alzheimer's disease. The main benefit of cholinesterase inhibitors and memantine is that a proportion of patients benefit from an effective reversal, or at least stabilisation, in the relentless cognitive decline and other elements of dementia for a period of between 6-12 months depending on whether all cases treated or only responders are taken into account ; . Taking data showing that the 2 3 of responders who stay on treatment experience an average of 1 year's stabilisation improvement, a very realistic assumption when responders are taken in to account, and stay on treatment for 3 years, then the following calculations would apply: 100 patients started on treatment. Initial costs, 3 12 drug supply for 100 people mean drug cost 1000 year 250 patient ; and 2 outpatients visits -baseline and efficacy SHTAC figures: 216 per patient ; . Total cost 46, 600 65 patients are deemed responders; the remaining 35 come off treatment at no further cost and no benefit. The remaining 65 stay on treatment for mean of 3 years, costing an additional 2 years and 9 months of drug supply 2750 ; and 5 further OP attendances at 9, 15, 21, and 36 months 540 ; . Total cost 213, 850. Total cost of treating 100 patients is therefore 260, 450. Benefit accrued is that 65 patients obtain 52 weeks stabilisation improvement 3380 weeks improvement stabilisation. Cost per week of stabilisation improvement 77 per week, which includes the full costs of non-responders and all monitoring but does not include any othe r benefits of the.
Blood which the animals had received. This information has been supplemented by a dilution curve measuring the effect of various concentrations of sinus gland extract, and by a measure ment of typical blood volumes of the crabs average 26.4% of body weight ; . This additional information permits calculation of the circulating hormone in sinus gland units and metamucil.
Able to establish some background clinical work that has been done, I think we need to expand on that to continue to document as baseline assessment in FD patients what is actually wrong, so that when the time comes to give definitive treatments we will be able to measure effectiveness. At the same time, I think we have to go further with the genetic research and identifying these IKAP mutations at elongator changes -- would you agree with that, Dr. Rubin? -- and then eventually go forth with definitive therapies. DR. RUBIN: The only thing I would add, which has already been said, which is, is I think the fact that there can be modulation of the efficiency of splicing requires that we seriously examine a panel of drugs as has been done to see whether there are any compounds that are currently FDA-approved which can be used to facilitate the production of the correct IKAP in these patients. DR. GUTTMACHER: Let me just, in followup to that, mention one thing particularly in reaction to that comment, I think which is a very good one, that I can tell you there is talk certainly that I see at the NIHI and I know at other NIH institutes about seeing whether one of the things that we might be able to do in the next few years that would be useful to move a lot of science forward is to create more access for academic researchers to libraries of small molecules and other kinds of potential targets that would to some degree expand what's available sometimes now in fairly small ways, sometimes only to people who are in industry, and try to make those tools more available to researchers in general in academia and outside of academia. We see that as a potential -- and I seeing heads nodding -- for the people who might use those things, not surprisingly, so that's something that we have on our plate. Another thing that I heard both of you talking about that made me think a little bit about is, I know our institute is looking very carefully at the idea of in the not too distant future creating a new type of K-23 award that would support researchers for 5 years, basically, who are clinician researchers. This is really research not just involving human specimens, that would actually have to involve human beings, but there would be clinical researchers who would be trying to apply the tools of genomics and genetics to diseases with a genetic component, and I could certainly see some careers here perhaps involving familial dysautonomia, for instance, as being very appropriate for that. So a couple of things that I know the NIH is thinking about seriously at the moment that might help move this forward. Other thoughts? VOICE: I applaud the concept. There are enormous numbers of people who would use these. I think and meperidine.
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