Tricks and Tips

Wednesday, July 13, 2016

Which Drug Interactions Matters a lot in Older Adults?

Conventional wisdom has it that the elderly are at greater risk for adverse drug interactions, and the published evidence supports this view. Older patients take more medications and experience physiologic changes that may affect drug disposition, making them potentially more susceptible to the adverse outcomes from drug interactions. 
Over the past decade or so, we have also accumulated some useful data on which specific drug interactions increase the risk of serious reactions in older patients. In a recent paper, Hines and Murphy from the University of Arizona reviewed population-based studies over the past 10 years, and discussed those that detected serious adverse outcomes due to particular drug interactions. The Table lists the interactions found to result in either increased risk of hospitalization or death. It is important to remember that the interactions in the Table are the ones that were chosen for study, and other related interactions involving these drugs are also likely to increase the risk of serious adverse outcomes. For example, angiotensin receptor blockers may also increase the risk of hyperkalemia when combined with potassium-sparing diuretics or co-trimoxazole; combining calcium-channel blockers with cytochrome P450 (CYP) 3A4 inhibitors other than macrolides may increase the risk of hypotension or shock; digoxin toxicity may occur with concurrent use of many P-glycoprotein inhibitors other than macrolides; and phenytoin toxicity can be produced by CYP2C9 inhibitors other than co-trimoxazole.


Clinical evidence also suggests that a number of other oral antidiabetic agents are metabolized by CYP2C9 and CYP3A4, and hypoglycemia may occur when inhibitors of these isozymes are given concurrently; CYP2D6 inhibitors other than paroxetine may inhibit the efficacy of tamoxifen in breast cancer; CYP1A2 inhibitors other than ciprofloxacin can cause theophylline toxicity; and any CYP2C9 inhibitor would be expected to increase the anticoagulant response to warfarin. Moreover, the elderly may take many other drugs that have substantial risk of drug interactions, especially psychotherapeutic drugs, but also drugs such as colchicine, statins, drugs for Parkinson’s disease, cholinesterase inhibitors for Alzheimer’s disease, and nonsteroidal anti-inflammatory drugs. The vast majority of publications on drug–drug interactions are either case reports or pharmacokinetic studies in healthy subjects. Such data provide evidence that a drug interaction exists, but seldom give us information on how often adverse consequences occur or how severe they are likely to be. The value of the population-based studies discussed above is that they help us determine which drug interactions actually can result in severe adverse consequences, and give us some idea of the incidence of the adverse outcomes. 

References:
  1. Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. 
  2. For an electronic version of this article, including references if any, visit www.hanstenandhorn.com.

Drug Interactions : An addition to Beer's Criteria

In 1991, the first “Beers Criteria” were published to alert clinicians to drugs that are potentially inappropriate for use in older adults. Updates to the list have appeared periodically, and the most recent (November 2015) includes drug– drug interactions (DDIs) for the first time. The expert panel included primarily pharmacists, physicians, and nurses, and they used a modified Delphi method to compile the criteria. 

Criteria for the Inclusion of DDIs:

The panel members made it clear that the DDI list is not intended to be comprehensive, and that individuals should not assume that these are the only DDIs worth considering in older adults. The panel selected DDIs it felt were particularly problematic in the elderly, regarding the potential for adverse outcomes. The panel did not include anti-infective agents or address drug therapy in individuals receiving palliative and hospice care. 

Drug Interactions that Were Included:

The DDIs the panel added to the Beers Criteria fell into several categories, but the most prevalent was an increased risk of falls due to combined use of 2 or more central nervous system (CNS) drugs (eg, antidepressants, antipsychotics, benzodiazepines, hypnotics, opioid analgesics). 
Unfortunately, despite the fact that these additive pharmacodynamic effects are well known and predictable, they are still too often overlooked in the elderly. Also included in the list were the following: 
• Lithium toxicity from concurrent angiotensin-converting enzyme (ACE) inhibitors or loop diuretics 
• Hyperkalemia from ACE inhibitors with amiloride or triamterene • Cognitive decline from multiple anticholinergics 
• Peptic ulcers and gastrointestinal (GI) bleeding from nonsteroidal anti-inflammatory drugs (NSAIDs) plus systemic corticosteroids 
• Urinary incontinence in older women from peripheral alpha-1 blockers plus loop diuretics 
• Theophylline toxicity due to cimetidine 
• Increased bleeding risk from warfarin when combined with amiodarone or NSAIDs 

Evaluation:

The expert panel appears to have achieved its goal of preparing a list of DDIs that can be particularly dangerous in the elderly. It would not be difficult for pharmacists to commit these to memory given that there are only 13 DDIs on the list. When alerted to these DDIs by a computerized screening system, pharmacists could pay particular attention to the alert for elderly patients. In general, the DDIs on the list should be avoided in older adults when possible; therefore, action by a pharmacist may well be warranted. It is important to keep in mind that this list is not comprehensive. The risk of GI bleeding due to NSAIDs can be increased by drugs other than corticosteroids (eg, spironolactone). The risk of lithium toxicity can be increased by drugs other than ACE inhibitors or loop diuretics (eg, angiotensin receptor blockers, NSAIDs). Many drugs other than cimetidine inhibit CYP1A2 and can cause theophylline toxicity. In addition, dozens of drugs other than amiodarone and NSAIDs can increase the risk of bleeding in patients on warfarin, usually through inhibition of CYP2C9 or by inhibitory effects on platelet function. Moreover, many other important DDIs were not included, as the expert panel pointed out. Leaving out antiinfective agents was probably prudent, but many anti-infectives have properties that result in clinically important DDIs. It is important to note that the new Beers Criteria DDIs are not intended to be applied to patients in palliative and hospice care. These patients, for example, may well need therapy with various combinations of CNS-active drugs that can be problematic in other older adults. For most of the 13 DDIs on the list, the expert panel recommended that they should be avoided if possible, but for one of the interactions (theophylline plus cimetidine), the panel simply said “Avoid.” This is appropriate because other histamine2 -receptor antagonists have little effect on theophylline and there is no reason to use cimetidine. 

Summary:

The American Geriatrics Society 2015 Updated Beers Criteria included DDIs for the first time. The panel listed 13 DDIs that may be particularly dangerous in older adults. It would be prudent for pharmacists to pay particular attention to these DDIs in all patients, but especially in the elderly. 

References: 
  1. Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy. 
  2. For an electronic version of this article, including references, visit hanstenandhorn.com.

Drug–Disease Interactions : Lot to Know

This column usually deals with interactions that occur when one drug directly affects the pharmacokinetics or pharmacodynamics of a second drug. It is possible, however, for a precipitant drug to indirectly affect the object drug. A common example would be drug-induced renal or hepatic dysfunction that reduces the elimination of another drug. It is also possible for effective drug therapy to enhance the elimination of an object drug by treating a disease that inhibits drug elimination.

Effect of Disease on Drug Metabolism:

The activity of several cytochrome P450 enzymes (eg, CYP1A2, CYP3A4, CYP2C19, CYP2C9) can be inhibited by disease states that are characterized by infection or inflammation. These disease states increase cytokine concentrations in response to infection, trauma, ischemia, immune-activated T cells, and toxins. Cytokines associated with this CYP inhibitor effect include interleukin-6 (IL-6), IL-1, tumor necrosis factor, and interferon. During active disease periods, the metabolism of drugs may be reduced by the elevated cytokine concentrations; however, it is unknown if these cytokines reduce CYP activity in the liver or the intestinal enterocytes, or both. 

Treatment of the disease may reduce cytokine production and the suppressant effect on CYP enzymes. Schmitt et al reported on the simvastatin plasma concentrations in 12 patients with rheumatoid arthritis (RA) before and after treatment with tocilizumab (Actemra). Patients were administered a single 40-mg dose of simvastatin before and at 7 and 35 days after a single dose of tocilizumab 10 mg/kg. Following treatment with the IL-6 antagonist, the mean simvastatin peak plasma concentration and area under the concentration time curve (AUC) were reduced by close to 60% compared with baseline values. The reduction in simvastatin AUC following tocilizumab administration correlates to approximately a doubling of its oral clearance. At 35 days after the tocilizumab dose, simvastatin plasma concentrations were still 40% less than levels prior to the tocilizumab dosing. The inhibition of CYP3A4 activity by cytokines is likely responsible for the increased simvastatin concentration observed prior to tocilizumab treatment. There was no observable change in the half-life of simvastatin after treatment, suggesting that the change in simvastatin AUC may have been due to increased first-pass effect rather than a change in systemic clearance. It appears that cytokine inhibition of metabolism is rapidly reversed by agents that reduce the inflammatory response (Table). 


A decrease in omeprazole plasma concentration was noted following tocilizumab administration to patients with RA.5 The decrease was about 40% in extensive metabolizers of CYP2C19, but less than 20% in poor metabolizers. These data suggest that the activity of both CYP2C19 and CYP3A4 is reduced in patients with RA and this inhibition is reversed by IL-6 inhibition. Clinical Perspective The magnitude of the change in a drug’s elimination following the administration of a cytokine inhibitor will likely be limited to the degree of cytokine-induced inhibition of the CYP enzymes. Based on the limited data available, cytokine induced inhibition may approach a 50% reduction in drug clearance. In disease states with chronic inflammation, drug dosages may be adjusted downward to avoid adverse events. Treating the inflammation with a cytokine inhibitor will result in an increase in drug clearance and reduction in drug concentration. For drugs with a narrow therapeutic range (eg: warfarin, theophylline, cyclosporine) or in cases in which low plasma concentrations pose a risk of therapeutic failure (eg, antivirals, immunosuppressants, antineoplastics), the increase in clearance may result in an altered patient response. Drug dosage may require an increase when cytokine inhibitors are administered. Patients treated with tocilizumab or other cytokine inhibitors should be monitored for altered response to long-term medications that undergo CYP metabolism. 

References: 
  1. Drs. Horn and Hansten are both professors of pharmacy at the University of Washington School of Pharmacy.
  2. For an electronic version of this article, including references, visit hanstenandhorn.com.

Tuesday, July 12, 2016

UNICEF Internship Programme 2016 - Generic Vacancy Announcement

Purpose of the UNICEF Internship Programme

If you are a committed, creative professional and are passionate about making a lasting difference for children, the world's leading children's rights organization would like to hear from you.

The UNICEF Internship Programme offers qualified and eligible students at both Headquarters (HQ) and Country Offices (CO) the unique opportunity to acquire direct practical experience in UNICEF's work and the United Nations system under the direct supervision of experienced UNICEF staff.

Internships are offered depending on the availability of meaningful assignments and the needs and capacity of units/offices to receive and supervise interns. UNICEF is active in various functional areas related to its mandate, which can be categorized in three main pillars: Programme and Policy, External Relations and Operations. 
Eligibility Requirements
  1. At the time I would like to start my internship with UNICEF, I will be enrolled in a graduate (Master's) degree or undergraduate (Bachelor's) degreel; and
  2. I will have completed at least two years of full-time studies towards completion of my undergraduate degree.
  3. I have excellent academic performance and can demonstrate it by my recent university or other academic institution records.
  4. I am proficient in at least one of UNICEF's working languages (English, French or Spanish) and fluent in the working language of the office I am interested to work in.
Please note: Additional consideration will be given to any past professional experience.

If you could answer 'yes' to all the above listed requirements, you are highly encouraged to apply now to UNICEF's internship database!

If you would like to be eligible to start your internship in 2017, please apply between 1 November 2016 and 30 September 2017.

Please keep in mind: Even if you meet these qualifications, there is no guarantee of placement. Qualified candidates will be placed in UNICEFs Internship database which is accessed by UNICEF managers globally. If you are applying for more than one location, the online application will allow you to choose the New York Headquarters location as well as up to three other field locations outside New York. If an exciting opportunity matching to your profile and interests arise, you will be contacted directly.

Internship dates and duration

To be eligible for an internship with UNICEF, you have to apply to its internship database. When completing your application, you will be asked to indicate:
  1. A time period in the current year when you are available to start your internship,
  2. Your preferred functional areas; and
  3. The location you would like to be considered for.
Please make sure to always keep the information in your profile up-to-date, as the database is being refreshed every year.

Incomplete applications will not be considered.

The duration of an internship with UNICEF is between six weeks and six months.

More information : For more details on the Internship Programme, please see the section's FAQ.

Advertised: 04 Apr 2016 Eastern Standard Time
Applications close: 30 Sep 2016 Eastern Standard Time

Work type: Internship (Apply Here)

Location: United States of America

Sunday, July 10, 2016

Vacancies as Drug Safety Associate


Career Guidance Counselling Centres for Women

Career guidance counselling centres set up in Delhi-NCR will provide dedicated career services to young women seeking employment in the region.

The Counselling Centres, a first of its kind for women, builds on the findings of a UNDP commissioned study which revealed that almost 80 percent of young women in Delhi did not have access to accurate and timely information on educational and job opportunities.

According to Jaco Cilliers, Country Director, UNDP India, “By bridging the information gap, career counselling centres that address the specific needs of women and girls seeking employment, can play an important role in empowering women and building their confidence to secure jobs in the formal labour market.” 

The Centres will be run by the Self Employed Womens Association- Bharat, the All-India Federation of SEWA within the Pankh Program of the SEWA Yuva Shakti Kendras in Delhi. The first such centre was inaugurated today by Sairee Chahal, co- founder of Sheroes.in.

Dr. Sanjay Kumar, Director, SEWA Bharat said, “This programme will help many young women across the city learn more about options available to them and how best to take advantage of these opportunities. We believe this programme will change many lives by providing a vital and desperately needed service in a systematic and holistic manner.”

The career counselling centres are set up as part of a collaboration between UNDP, the IKEA Foundation, Xyntéo, and the India Development Foundation which aims to impact the lives of women in India through training, entrepreneurial skill development and employment.

In order to bridge the information gap, the Pankh Program will address three key factors in the community that hold back women from securing employment opportunities: 
(i.) community presence, 
(ii.) information, 
(iii.) support structures. 
By having a strong community presence, the project aims to change local perspectives on the public and professional spaces that young women can occupy. The programme will host all-female career fairs, and organize graduation ceremonies in the community. In order to increase access to information, underprivileged girls across the city who enter the center will be able to access comprehensive career counseling opportunities, advice from career counselors, psychometric mock-testing, information on job and educational opportunities. The last pillar of the SYSK is a community-based support programme. All together, these programs will equip young women with the tools to navigate the professional workspace, as well as with the knowledge on how to maintain a work-life balance.

The physical centres will be complemented by a cloud-based platform which provides services such as work readiness e-learning, comprehensive mapping of the opportunities existing in the vicinity of the center (job opportunities, availability of skill development courses, training institutes and government schemes, etc.) and direct links with the private sector (job vacancy announcement, mapping of the private sector in the area, possibility for internship / apprenticeship / immersion, job fairs, etc.) The goal of these programmes is to assist young women in pursuing careers rather than simply jobs.

SEWA Bharat will be opening three centres across the Delhi-NCR region. Two of the centers will be based in SEWA Bharat’s existing communities: New Ashok Nagar and Sunder Nagri. These community centers will act as hubs and resource centers within the local communities. The third center, a central counseling unit, will be accessible to any woman across the Delhi-NCR region who is interested in learning more about careers, and other work-related information. This center is being initiated in collaboration with the All India Women’s Conference who has generously donated their premises for the cause. 
Contact Information

For SEWA: Divya Sooryakumar, divya@sewabharat.org, +91 8288913563

For UNDP: Nandita Surendran, nandita.surendran@undp.org; +91-9810084776

Friday, July 8, 2016

Invitations from Subject Experts for various Scientific Activities of IPC

The Indian Pharmacopoeia Commission (IPC) is an Autonomous Body, set up under the Ministry of Health & Family Welfare primarily with the objective of periodically updating of the Indian Pharmacopoeia, the book of standards for the drugs; the National Formulary of India, the book of reference on the drugs; and other related tasks such as preparing, certification and distribution of Reference Substances; National Co-ordination centre for the Pharmacovigilance Programme of India; testing of the new drugs and review of Technical dossier of Drugs for purpose of monograph development for the Indian Pharmacopoeia; and skill development of professions involved relevant fields. It promotes rational use of generic medicines. The IPC is on path of evolving as a modern scientific institution. 


Applications are invited, from experts from various disciplines of science and technology connected with standards setting, who have the relevant merit, competence and willingness to devote their time to the work as Members in the Scientific Body and other Scientific Committees of Indian Pharmacopoeia Commission for a tenure of five years.

Sunday, July 3, 2016

Tina Bayuse - First Pharmacist at NASA

After hearing a presentation about drugs in space, Tina Bayuse thought there might be a role for pharmacists in the space programme. She now runs the pharmacy at Johnson Space Center in Houston, Texas.


For a pharmacist who works as a contractor with Wyle for the National Aeronautics and Space Agency (NASA), Tina Bayuse is surprisingly down to earth. “Getting to work with the astronauts!” she exclaims when asked what the most exciting part of her job is. “But, outside of that, being able to witness the change in pharmacy practice. We have a long way to go, but it’s amazing to see where we’ve come in the space programme since I first started in 2000 to where we are today.”

Bayuse was the first pharmacist ever to work for NASA and now heads a team of four in its own pharmacy at Johnson Space Center (JSC) in Houston, so she has certainly seen change during her career. Much of the team’s work now focuses on preparing the ‘med kits’ for astronauts at the International Space Station, of which there are two types: ‘convenience’ and ‘contingency’. The convenience kit contains medicines that one would usually take on a trip, whereas the contingency kit is made up of drugs such as antibiotics and cardiac life support. “We have an entire group of people who are responsible for the design,” Bayuse expains, “but the contents of the kits actually come from the pharmacy here at JSC. We’re responsible for preparing them for flight and then also packing them into the flight kits with the engineers.”


Medicines in space

Sending medicines into space is much like dispensing medicines terrestrially, but with a few additional concerns. “If there is a shortage of a drug, it affects what the astronauts are trained on and what the biomedical engineers understand to be in the med kit,” she emphasises.

Medicines also have to be selected based on volume and mass on board the space station, which can prove problematic with certain formulations, such as soluble powders or drinks. “Most of our veteran fliers understand this, but sometimes we’ll get somebody who’s never flown before or, more importantly, a doctor who has not been on a mission before,” she says. “On the rare occasions that something like that would be requested, we try to take care of those questions prior to preparing the medicines for packing. Because at the time of packing it’s too late.”

Additionally, there are limits on what the environmental systems in orbit can handle — managing alcohol levels in medicines, for example, can be a challenge. Astronauts may need to take medicines while wearing their suits, outside the space station, so this also needs to be taken into account. “We also make sure that we try to advocate a drug tolerance testing for our crews for medicines that they may not take routinely, in case something they take in orbit affects their cognitive abilities or produces unwanted side effects,” she says.

Planning for missions to the space station is fairly routine for Bayuse, but she is currently considering additional challenges that may be introduced when astronauts begin flying to Mars. “We’re not going to have resupply like we do for the station,” she highlights. “In the [United States] we have a rule where, once you take something out of the manufacturer’s packaging, it is only good for one year.” At the moment, this means that items in the convenience kit are repackaged, but those in contingency pack remain in their original packaging. The effect of radiation on medicines outside lower Earth orbit is also unknown.

It is imperative that quality control is enforced, so a triple-check process is in place, with a different pharmacist checking each time. “We haven’t had a mistake that leaves the door because, if it’s going on orbit, it could be national headlines. International headlines,” she emphasises.

Getting into NASA

Bayuse was interested in space flight since she was a child, but knew that she could not be an astronaut for various health reasons. She began working in her local pharmacy and, after a couple of false starts reading physics and biology, started studying pharmacy. “When I was in my first year of pharmacy school, I attended a presentation about the fact that drugs may not work the same in space,” she remembers. “This presentation was after school in a completely different location I had to drive to. I was in a new city, I wasn’t really comfortable with that, but I thought, heck, I’m going to go anyway and see this speaker.”

After the meeting, Bayuse approached the speaker and asked if there was an opportunity to be involved in any way. “She put me in contact with the person who was running the pharmacology lab at the time and, through years of talking back and forth with this person, I was able to create a rotation to come to Houston and look at what it meant to be part of the space programme with pharmacology as a focus.

“I spent a month at Houston, working in the lab, not doing anything in depth but getting a cursory glance at the work they were doing. Then I did a couple of pharmacy-related projects, working on some drug monographs for the space shuttle — the content of the space shuttle med kit.”

Her work intrigued the medical and pharmacological teams at NASA — so much so that they decided to create a pharmacy position at the lab. “That took quite a long time to come to fruition,” Bayuse recalls, “I actually almost gave up on it, I was in the match programme for residencies. But then I got the phone call that they had created the position and they wanted to know if I would apply for it. So here I am.”
Finding a place at the table

Although Bayuse started work in the pharmacology lab, a review of NASA’s medication management revealed that practices were out of date. “The decision was made that they would have an on-site pharmacy with pharmacy staff to manage everything that we do here terrestrially. We opened the pharmacy on 31 March 2003,” she says.

“It’s not like there’s a training programme for this,” she explains. “I had good mentors who were willing to help me understand things. A lot of it is self taught.” She adds that a good understanding of how to read literature — “not my favourite thing” — is important for the role, as are excellent writing and speaking skills.

“My particular position has morphed into educating people outside the healthcare discipline about what pharmacy does and why we should be involved,” says Bayuse. “Most pharmacists are going to be working with other healthcare providers like physicians and nurses on a routine basis, so you all have the same common language. When you step outside that, and you’re working with non-healthcare providers such as engineers and programme managers who bring a different perspective to the table, being able to communicate with people in those disciplines is imperative.”

She is proud of how far pharmacy at NASA has come. “Before we had to beg to be able to sit at the table, or we would find out after [work had already begun] and then have to do some quick work to make [a project] feasible. But now we’re actually being included from the ground floor and that would probably be my greatest professional achievement,” she enthuses.

Despite these advances, Bayuse says she has to continue to champion the role of pharmacy, particularly to those monitoring the bottom line. “Nobody likes metrics!” she notes. “But choose metrics that will help to prove your point, especially to budget people. And then stay on top of it. Pharmacy is more proactive than a lot of medical professions because being reactive in the pharmacy profession is a bad day.”

For example, with regard to the potential advent of commercial space flight, Bayuse explains that initially pharmacy was not included in the conversation. “It’s not because they are trying to leave you out intentionally, it’s just because they haven’t thought about it from that perspective yet,” she says philosophically, adding that the department is now involved in the plans because of her persistence.

However, her patients do appreciate the work she does — one of the astronauts recently called her from the space station to thank her for helping him get ready for his flight. “Actually having your work recognised by a patient — let alone an astronaut on a space station — is something that pharmacists in general don’t see… so having that recognition for all the work that you do accomplish on their behalf is rewarding,” she adds.

Seeking out a role

Bayuse does not yet see a role for an expanded pharmacy team at NASA, but says that the advent of commercial space flight may present new opportunities, for both pharmacy research and practice. “The health of the general public is not going to be as pristine as our astronaut corps so there will be a role for pharmacists in managing those kinds of disease states and the medicines that come along with that,” she explains.

For any pharmacist looking to work in a pioneering area, Bayuse recommends being persistent. “Along with that, if you have an interest in an area, learn as much as you can about it,” she says. “Understand the rules and regulations that go along with that particular area because that’s a big deal. If you’re interested in something outside the box and there are organisations tied to that interest — such as, in my case, the Aerospace Medicine Association — reach out to them and find out when they are having meetings so you can attend.”