American Chinese Pharmaceutical
Association Newsletter
Editor: James W. Shaw, Pharm.D., M.S.
January, 2000
Shiew-Mei Huang
Happy New Year! Hope that you all had a relaxed holiday. Under the leadership of Francis Lam, last year saw many major accomplishments and new initiatives to achieve ACPA's mission. This year, we would like to continue this momentum and build on our members' strengths to further our short- and long-term objectives. As I indicated during my brief remarks last October at the ACPA 4th International Conference in Bethesda, Maryland, ACPA will strive to continue to serve its members to fulfill the following goals in YR 2000:
- Promote global communication and networking between academia, industry, health care, government, and local and overseas Chinese communities
- Provide quality programs, conferences, and workshops, including local and international conferences, as well as new programs (e.g., mentoring and focus-groups)
- Improve Internet and e-mail communication with our members and potential members
At the dinner meeting held last November during the 1999 AAPS Annual Meeting, I met many old acquaintances as well as new faces. Many were excited about being able to listen to and interact with Dr. Roger Williams following his presentation on “Global Drug Development in the 21st Century.” In addition, the forum provided an excellent opportunity for Chinese professionals with different backgrounds and training to interact with one another. At this meeting, half of the attendees were new to ACPA. Many were enthusiastic about joining and serving the organization.
Officer elections were held last December at the 1999 ASHP Midyear Clinical Meeting in Orlando, Florida. Ballots were counted by Francis Lam and Chester Lau in the presence of witness Peter Tam. With the election of Marina Chang and Anna Lee, we now have the following executive committee members to serve the organization in YR 2000.
President: Shiew-Mei Huang (Huangs@cder.fda.gov)
President-Elect: Marina Chang (Changm@cder.fda.gov)
Immediate Past-President: Francis Lam (LamF@uthscsa.edu)
Executive Director: Chester Lau (clau@chsnj.org)
Treasurer: Bing-Bing Yang (byang@amgen.com)
Secretary: Anna Lee (anna_lee@mail.wsu.edu)
The following members have either volunteered or agreed to serve on ACPA’s standing committees. We welcome others who have not had a chance to express their interest in participating on a committee to contact either the executive committee or the appropriate standing committee chair.
Scholarship Committee: Veronica Young (Chair, youngv@uthscsa.edu); Anne Lin; Alan Lau; Mary Ensom; Ken Lem
Communications (Newsletter) Committee: Francis Lam (Chair); James W. Shaw (newsletter editor); Sam Can; Grace Hsu (web site); Ming Hu
Finance Committee: Peter King (Chair, KINGSP@war.wyeth.com); Jane Hsiao; Francis Lam; Lawrence Yu; Diana Wu; Tony Yu
Membership Committee: Bing-Bing Yang (Chair); Chester Lau; Anna Lee; He Sun; Elaine Chong; Jack Chen; Jeff Wong; Wei Yin
Program Committee: Jinn Wu (Chair, jwu@xbl.com); Shiew-Mei Huang; James Fann, Kanyin Zhang, Homer Lin
Nominations Committee: Wendy Chou (Chair, chouw@cder.fda.gov); He Sun; Lan Ni; Marina Chang
We are looking forward to working with these individuals to serve our members in this coming year.
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Francis Lam
It has been a pleasure, a privilege, and a challenge to serve as the President of ACPA in 1999. Like any financial portfolio with “winners” and “losers,” we had our successes and failures. I am pleased that in addition to our regular event held this past November in conjunction with the 1999 AAPS Annual Meeting, we were able to organize two regional conferences and the 4th International Conference. While these programs required an intense effort from many dedicated members, and at times presented a financial burden to the organization, I hope that the momentum can be carried forward. Let these efforts be the beginning of a long-term planning process for programs that meet the needs of our members.
Over the past year, we initiated steps to address communication issues among the leadership and our members. The most important task was to improve the content and delivery of the newsletter, the primary channel of communication with our members. Thanks to the dedicated effort of James Shaw, who was appointed as editor last year, I could not be any happier with the outcome. I am sure we all agree that the newsletter content is significantly improved. James has worked diligently on adhering to a schedule for timely delivery of the newsletter. However, at times the delivery of the newsletter has been hampered by various newsletter contributors being “overworked,” as well as the time-consuming processes of printing and mailing (unselfishly performed by Chester Lau).
With the technology available, as well as the passing of a non-eventful Y2K, my personal opinion is that we should distribute the newsletter exclusively by electronic mail (e.g., a generic PDF file), in addition to posting it in the member section of the web site. Of course, we would still maintain paper copy delivery for members who either do not have an e-mail address or do not have Internet access. The Executive Committee will discuss this, and your input is important. Please e-mail our secretary, Anna Lee, with your comments. Anna and I will be working on updating members’ e-mail addresses, so please direct any new address to my attention. The electronic medium proved to be very useful in facilitating communications between members last year.
Speaking of the web site, Santa Claus delivered a nice present to me this year. Sam Chan and Grace Hsu graciously volunteered just before Christmas to work on updating the web site. We have discussed the process and logistics of keeping the current ACPA domain name. Once we get the domain logistics out of the way, there are numerous ideas in terms of improving the web site that Sam, Grace, and I want to implement. Stay tuned. If you have ideas, expertise, and/or would like to volunteer as well, please e-mail me.
We have continued our scholarship program for pharmacy students. One of our recipients, Elaine Chong, will be helping us to expand our membership base in Western Canada this year. In addition, we have volunteers for similar efforts in the Bay area, as well as the greater LA area. If you would like to volunteer to establish regional/student chapters, please e-mail Chester or Shiew-Mei. Finally, in early December we received the first check for establishing the Gerald Shiu Memorial Graduate Student Scholarship. I hope that ACPA will have sufficient funds in place this year to start this specific scholarship and would like to take this opportunity to again request donations for the scholarship in Gerry's name. Please make your check payable to ACPA, specifying its purpose, and mail to Chester Lau at P.O. Box 2623, Cherry Hill, NJ 08034.
Over the last year I have been enlightened regarding the cost of running ACPA programs and the organization in general. Our treasury is primarily built on member dues, and to a very limited extent, corporate and personal donations. At the beginning of last year, I had a vision as well as a plan to improve our long-term financial viability. Alas, that goal was never achieved, and I share some responsibility for its “non-accomplishment.” However, every year there are more and more organizations sharing the same pot of corporate money, and our M & O budget (production and mailing of the newsletter, ballot mailing, meeting and phone expenses) continues to rise. Under the leadership of Shiew-Mei, we will continue to address the most effective ways of raising and using funds for ACPA activities and needs. I am sure Shiew-Mei would welcome your suggestions and ideas.
I was blessed this past year with help not only from friends but also from members and non-members that I have never met before. For this, I am deeply grateful. I would like to ask that you show the same dedication to Shiew-Mei this year as well as to ACPA’s future leaders. Again, thanks for the opportunity and the trust to serve you. Have a wonderful year.
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More than 100 individuals attended the 1999 ACPA Annual Dinner Meeting, which was held in New Orleans on Tuesday, November 16 during the 1999 AAPS Annual Meeting and Exposition. Roger Williams, M.D., gave a presentation entitled “Global Drug Development in the 21st Century.” The photographs included in the insert mailed with this newsletter were taken at the meeting. ACPA would like to thank all those who worked so hard to make this event possible, as well as those who provided financial support.
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Jack J. Chen, PharmD, BCPS
As the new millennium approaches and as the geriatric population expands, general practitioners and pharmacists will become increasingly involved with the care of patients with Parkinson’s disease (PD). This report provides a brief overview of PD and new trends in its therapy.
Sporadic or “household” PD is characterized by irreversible and progressive degeneration of the substantia nigra with subsequent emergence of motor and non-motor deficits.1 The classic clinical features include resting tremor, rigidity, bradykinesia, and postural instability. Other features include depression, masked facies, altered speech quality and odor detection, constipation, urinary incontinence, and joint pain. The disease affects men and women equally and is found in all ethnic groups. Epidemiological studies have shown a lower incidence in residents of China and Africa.2 However, differences in health care access, life expectancy, and diagnostic criteria must be considered. The typical age at diagnosis is approximately 60 to 65 years, although PD can be diagnosed in early adult life, as in the case of celebrity Michael J. Fox. A genetic form of PD, autosomal recessive juvenile Parkinsonism (AR-JP), has been well described in several clusters of Japanese families and is characterized by early onset (before age 40), good response to levodopa, sleep benefit (improvement in Parkinsonism after sleep), hyperactive tendon reflexes, and dystonia of the feet. Through linkage analysis, Japanese researchers have mapped the AR-JP gene locus to chromosome 6q25.2-q27 and have identified a novel gene, Parkin, from this region.3 The cause of sporadic PD has yet to be identified, although environmental and genetic factors are suspected. Other less common forms of PD include the atypical Parkinsonisms, such as multiple system atrophy and progressive supranuclear palsy, which have received pubic attention due to their recent diagnosis in celebrities such as Johnny Cash and Dudley Moore.
Although the combination of levodopa with a peripheral decarboxylase inhibitor, such as carbidopa or benserazide, remains the cornerstone of symptomatic therapy, many neurologists and movement disorder specialists now favor “levodopa-sparing” therapies that delay the initiation of levodopa or allow for levodopa dosage reduction. The motor and neuropsychiatric complications of long-term levodopa therapy often become the most frustrating and vexing issues to address as the disease progresses (particularly in young-onset patients who experience greater exposure to levodopa). After two to five years of levodopa therapy, most patients begin to experience “wearing-off” or “end-of-dose” phenomena. These are characterized by loss of symptom relief toward the end of the dosing interval. Levodopa-induced dyskinesias are also common and are characterized by involuntary movements of the extremities, neck, and torso. Both complications are partially amenable to pharmacologic manipulation (e.g., increased fractionation of levodopa daily dosage, use of long-acting levodopa formulations, addition of direct dopamine agonists, or addition of COMT [catechol-O-methyl-transeferase] inhibitors). Less commonly, neuropsychiatric complications, such as psychosis, confusion, or visual hallucinations, may arise from levodopa therapy. These are often associated with deteriorating performance of activities of daily living. In most cases, a dosage reduction or discontinuation of concurrent anticholinergic agents, amantadine, selegiline, or direct dopamine agonists will result in improvement. In some cases, patients will benefit from the addition of a low-dose atypical antipsychotic agent. Clozapine (Clozaril®) at doses less than 100 mg/day is very effective. However, routine laboratory monitoring is required as a precautionary measure against clozapine-induced leukopenia. Of the newer atypical antipsychotics, quetiapine (Seroquel®) appears to be effective and well tolerated. Olanzapine (Zyprexa®) is effective but may worsen Parkinsonism, and risperidone (Risperdal®) is poorly tolerated. Interestingly, ondansetron (Zofran®) 10-14 mg/day may also provide relief from hallucinations, indicating that central serotonergic mechanisms may play a role.
Clinicians may also be swayed toward “levodopa-sparing” strategies in light of the controversial issue of levodopa-induced neurotoxicity. The evidence for levodopa-induced neurotoxicity arises from in vitro studies but has never been replicated in vivo in animals or humans. However, the mere fact that levodopa causes in vitro neurotoxicity is worthy of serious consideration, and clinicians (as well as informed patients) may elect to delay or minimize levodopa therapy until more definitive data are available.
Two direct dopamine agonists have recently been introduced that offer an alternative means of “levodopa-sparing” therapy. Pramipexole (Mirapex®) and ropinirole (Requip®) are non-ergoline dopamine agonists that offer a “cleaner” receptor profile and improved tolerability. Both of the new dopamine agonists are efficacious as monotherapy in early-stage PD and may delay the need for levodopa by several years. Results from a recently completed five-year clinical trial demonstrate that ropinirole therapy is associated with a significantly reduced risk of developing dyskinesias as compared to levodopa therapy.4 Because of the non-ergoline structure, serious side effects, such as retroperitoneal and pulmonary fibrosis, are not expected. However, other side effects, such as nausea, constipation, insomnia, somnolence, orthostatic hypotension, confusion, and hallucinations, are similar to those of the older ergot-derived agonists. “Sleep attacks” involving a sudden, overwhelming onset of daytime sleep have been reported with both pramipexole and ropinirole in patients receiving levodopa.5 Subsequently, the manufacturers of Mirapex® have revised the product labeling and now recommend appropriate patient education.
The COMT inhibitors, tolcapone (Tasmar®) and entacapone (ComtanÒ) are novel enzyme inhibitors indicated for use in conjunction with levodopa therapy. These agents have no clinical effect in the absence of levodopa. The purpose of the COMT inhibitors is analogous to that of peripheral decarboxylase inhibitors. In the plasma, levodopa is metabolized to inactive compounds via two major enzymatic pathways, dopa decarboxylase and COMT. Inhibition of these enzymes results in a reduction of levodopa clearance from the plasma and increased availability to the brain. Because the addition of a COMT inhibitor extends the action of a given dose of levodopa, patients experiencing “wearing-off” phenomena can derive significant benefit. The adverse effects of COMT inhibitors result mainly from excess dopamine activity (nausea and dyskinesias) and are easily managed with levodopa dosage reduction. Non-dopaminergic-related adverse effects of COMT inhibitors include reversible elevations in liver function enzymes and diarrhea. Subsequent to reports of fatal hepatic failure, use of tolcapone was suspended in Europe and restricted in Canada. In the US, therapy with tolcapone requires frequent monitoring of liver enzymes. Preclinical and clinical data suggest that liver toxicity is not a class effect of the COMT inhibitors. As a result, entacapone therapy does not require routine liver enzyme monitoring.
As alluded to earlier, PD is associated with a host of features that are often more troublesome than its motor symptoms. Therefore, the introduction of new agents for the management of non-motor complications is always welcomed. For example, cisapride (Propulsid®) for gastroparesis, midodrine (Proamatine®) for orthostatic hypotension, sildenafil (Viagra®) for erectile dysfunction, and serotonin (5-HT3) receptor antagonists for nausea. In many countries, except the US, domperidone (Motilium®) for gastroparesis/nausea and ZelaparÒ, a rapidly disintegrating oral selegiline formulation, are available. Transdermal delivery systems are currently in development for selegiline and novel dopamine agonists. Surgical procedures include site-specific ablative techniques and deep brain stimulation. However, such procedures are reserved only for medically refractory patients who meet well-defined criteria.
Although not discussed in this report, non-pharmacologic interventions are vital. Proper physical therapy, occupational therapy, psychosocial support, diet, and hearing, dental, and vision care are crucial for optimizing the quality of life in patients with PD. With an increased awareness of the Parkinsonian patient’s needs and a familiarity with pharmacology, pharmacists can collaborate with patients, caregivers, and health care professionals to optimize therapy and avoid preventable adverse outcomes.
Patient-oriented educational materials are available in Chinese and may be obtained by contacting:
Taiwanese-American Parkinson’s Association
Jack J. Chen, PharmD, BCPS
7854 Calmcrest Drive, Downey, CA 90240
Email: jackchen@flash.net
Taiwan Parkinsonian
c/o Saudi Aramco
PO Box 5214, Dhaharan 31311, Saudi Arabia
E-mail: kuolonhuang@hotmail.com
Tel/Fax: 966-3-8786461
The Parkinson Foundation of Canada
55 Bloor St. West, Suite 230, Toronto, Ontario, M4W 1A5
Tel: 416/964-1155
1) Chen J, Shimomura S. Parkinson’s disease. In: Herfindal ET, Gourley DR, editors. The textbook of therapeutics: drug and disease management. 7th ed. Baltimore (MD): Williams & Wilkins (in press).
2) Zhang ZX, Roman GC. Worldwide occurrence of Parkinson’s disease: an updated review. Neuroepidemiology 1993;12:195-208.
3) Hattori N, Kitada T, Matsumine H, et al. Molecular genetic analysis of a novel Parkin gene in Japanese families with autosomal recessive juvenile Parkinsonism: evidence for variable homozygous deletions in the Parkin gene in affected individuals. Ann Neurol 1998;44:935-41.
4) Rascol O, Brooks DJ, Korczyn AD et al. Ropinirole reduces risk of dyskinesias compared to L-dopa when used in early Parkinson’s disease [abstract]. XIII International Congress on Parkinson’s Disease, Vancouver, Canada, July 24-28, 1999.
5) Frucht S, Rogers JD, Greene PE et al. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999;52:1908-10.
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