Current global population and impact of growing population in developing countries

As global populations expand and shift, the healthcare sector is coming under increased pressure. In the developed world, aging populations and extended life expectancy have led to an increasing prevalence of chronic, expensive to treat diseases and disabilities and a growing shortage of healthcare workers to cope with the rising demand.1

In the developing world, rapid economic growth and an emerging middle class have dramatically increased demand for health services, even while governments struggle to bring social services to underserved populations.1 The World Health Report for 2006 identified 57 countries facing a critical health workforce crisis. Each of these countries had less than 23 health workers (doctors, nurses and midwives) per  10000 people the minimum required to achieve 80% average rate for deliveries by skilled birth attendants of for measles immunization. Sub Saharan Africa faces the greatest challenges; it has 11% of the world’s population and carries 25% of the global disease burden yet the region has only 3% of the global health workforce. 2In India, for example it is projected that the government will need to train some 800000 new clinicians if they hope to match the proportion if doctors to population as seen in developed countries like UK.1

In Africa, Asia and Latin America, urbanisation has resulted in vast shanty towns with little or no access to health services such as fresh water and sanitation. As urban population swell, so too does the incidence of illness such as heart disease, obesity, diabetes and asthma.1

Current status and gaps in MDGs and the impact on developing countries

Many developing countries especially in Africa continue to make progress towards the achievement of Millennium Development Goals (MDGs), but progress remains uneven across sub regions. Africa is the world’s fastest growing region, and extreme poverty has declined faster since 2005 than over the period between 1990 and 2005, but not fast enough to reach the target by 2015.3 In addition, inequality is undermining efforts to reduce poverty. High gender, income and rural-urban inequalities have tempered the nexus between growth and poverty reduction. In Africa, a 1% increase in inequality increases poverty by 2.16%. Wages remain unequal by gender, with women making as little as half that men make for the same work in Mauritania, Algeria and Ivory Coast.3 Whether in the public or private sphere, from the highest levels of government decision-making to households, women continue to be denied equal opportunity with men to participate in decisions that affect their lives.4

Attending primary school is becoming a norm, but the quality of education remains a challenge. 3Most countries have achieved universal primary enrolment (rates of 90% and higher) as is expected to achieve Goal 2, however low completion and high grade repetition remain a challenge. Reasons include late entry, poverty, and poor quality of education and lack of awareness of education importance.3

Despite good progress, Africa still has the greatest burden of child and maternal deaths. In sub Saharan Africa, one in nine children die before the age of five. 3Environmental sustainability is under severe threat, demanding a new level of global cooperation. The growth in global emissions of carbon dioxide (CO2) is accelerating, and emissions today are more than 46 per cent higher than their 1990 level. Forests continue to be lost at an alarming rate. Overexploitation of marine fish stocks is resulting in diminished yields. More of the earth’s land and marine areas are under protection, but birds, mammals and other species are heading for extinction at an ever faster rate, with declines in both populations and distribution.5

Gains in sanitation are remarkable but not good enough. From 1990 to 2011, 1.9 billion people gained access to a latrine, flush toilet or other improved sanitation facility. Despite these accomplishments, more rapid progress is needed to meet the MDG target. Stopping open defecation and instituting the right policies are significant.4

Health as a critical pathway to human rights and equity

Health is central to sustainable development, health is a beneficiary of development, a contributor to development and key indicator of what people centred, right based inclusive, and equitable development seeks to achieve. Health is important as an end in itself and as integral part of human well-being, which includes material, psychological, social, cultural, educational, work, environmental, political and security dimensions.5

Health is critical to achieving equity. Equitable access to quality health care underpins equitable access to employment, engagement with economic activity and quality of life.4 Poor health and poor health outcomes as well as disease related stigma and discrimination can marginalize entire groups of people. For example, stigma promotes a culture of secrecy that can create barriers to diagnosis, treatment, employment, and marriage and prevent people from playing an active part in society.6Eliminating financial exclusion and non-discrimination are priorities and key principles in human rights and are crucial to the enjoyment of the right to the highest attainable standard of health.6 Human rights are interdependent, indivisible and interrelated. This means that violating the right to health may often impact the enjoyment of other human rights such as rights to education or work, and vice versa.5

Post 2015 health agenda

Health is the integral part of sustainable development. The post-2015 health agenda focuses on health and wellbeing, it builds on the Millennium Development Goals (MDGs) where health for all is a core component. One of the development goals is to decrease the burden of non-communicable diseases (NCDs) because they are the leading causes of death and disability. NCDs are a growing threat to human health especially in Africa and have a negative effect on health. Through their effect on the societal, economic, and the environmental domains they impair the sustainability of development. Post 2015 health agenda is an opportunity to reflect and assess on the MDGs. It considers the role of health in the development agenda beyond 2015 so that there will be progress in improving human health. Goals are thus interventions in their own right, shaping the meaning of development and influencing resource transfers within and between nations .although much has been done in relation to the set out goals, many countries will not meet the MDG targets by 2015 therefore  much still remains to be done beyond 2015. This is so particularly in the lowest income countries for example sub-Saharan Africa. The cost of inaction in relation to non-communicable diseases is now recognized as a global risk requiring action in all countries that extends well beyond the health sector alone. A human rights-based approach to health is essential. Despite their socio-economic and financial status, every human being has the right to enjoy the highest attainable standard of physical and mental health. This approach is recognized in numerous global, regional and national treaties and constitutions. It underpins action and provides part of the rationale for including health in the post-2015 development agenda. Irrespective of where one lives, gender, age or socio-economic status being healthy and having access to quality and effective health care services is of fundamental importance for all people. Healthy populations are essential for the advancement of human development, well-being and economic growth. Global health agenda concerns the need to address the social, economic and environmental determinants of health, not just the proximal causes of illness and disease. Clearly, all these elements are linked.7 Addressing social determinants and inequalities has been shown to be an effective way of increasing equity of access to quality healthcare and outcome within countries thereby tackling the burden on non-communicable diseases in developing countries.8

Global burden of diseases

Global Burden of Disease (GBD) is an essential tool for evidence-based policymaking. Many countries have made remarkable progress in preventing child deaths. As a result, disease burden is increasingly defined by disability instead of premature mortality. The leading causes of death and disability have changed from communicable diseases in children to non-communicable diseases in adults. Between 1990 and 2010, disease burden from many non-communicable causes increased, particularly stroke and hypertension among upper-middle-income countries.9 Hypertension affects one billion people worldwide, leading to heart attacks and strokes. Researchers have estimated that hypertension currently kills 9 million people every year.Hypertension is accountable for approximately 45% of deaths due to heart disease. The numbers of people who suffer from heart attacks and strokes in developing countries due to undiagnosed and uncontrolled risk factors such as hypertension is on the rise. This contributes to the burden of heart disease, stroke and kidney failure and premature mortality and disability. It disproportionately affects populations in low- and middle-income countries. All patients diagnosed with hypertension require medication, but those at medium to high risk will need one or more of eight essential medicines to lower their cardiovascular risk (a thiazide diuretic, an angiotensin converting enzyme inhibitor, a long-acting calcium channel blocker, a beta blocker, metformin, insulin, a statin and aspirin). The cost of implementing such a programme is low, at less than US$ 1 per head in low-income countries, less than US$ 1.50 per head in lower middle-income countries and US$ 2.50 in upper middle-income countries. The cost of implementing such a package amounts to 4% in low-income countries, 2% in lower middle- income countries and less than 1% in upper middle-income countries. In 2008, worldwide, approximately 40% of adults of ages 25 and above had been diagnosed with hypertension; the number of people with the condition has increased from 600 million in 1980 to 1 billion in 2008. The African Region has the highest hypertension prevalence rate of 46% of adults aged 25 and above, while the lowest at 35% is America. Not only is hypertension more prevalent in low- and middle-income countries, they are larger populations than in high-income countries. Due to poor health systems, the numbers of people with hypertension who are undiagnosed, untreated and uncontrolled are also higher in low- and middle income countries compared to high-income countries.10

South Africa and Eastern Cape’s burden of disease

The burden of disease of a country is the impact a health problem has on the country. It is measured by financial cost, mortality, morbidity and other indicators.11 Non-communicable diseases are estimated to account for 29% of all deaths in South Africa.12The occurrence of non-communicable diseases in South Africa is a growing threat to the population in the urban areas. Men are more heavily affected by NCDs because they are more prone to smoking, alcohol use, high salt-intake and lack of physical exercise.  In 2010, the burden of NCDs was a third of the burden of HIV by the number of deaths. In 2008 the non-communicable diseases death toll was estimated to be 92 400 in males and 98 100 in females. The prevalence of smoking tobacco daily in 2008 was 14% with men exhibiting a higher prevalence of smoking daily at 21.2%. South Africa has a 51.1% prevalence rate of physical inactivity therefore owing to the widespread occurrence of hypertension.12 In South Africa, the number of people suffering from  NCDs is also increasing  and this has been attributed to the increase in the contributing risk factors such as a change from traditional to a Westernized diet which includes consumption of food low in fruit and vegetables, rich in refined carbohydrates and saturated fat; lack of physical activity; alcohol abuse and smoking.13 According to the South African National Burden of Disease study done in 2000,in the eastern cape province there were 55 000 deaths per  100 000 among males and it was even higher in females at a rate of approximately 79 000 deaths per  100 000.14

Challenges of NCDs- and Hypertension

The increasing burden of chronic non communicable diseases (NCDs), particularly in the WHO African Region is threatening to overwhelm an already over-stretched health services. Non communicable diseases such as cardiovascular diseases, cancer, diabetes mellitus, mental health problems, chronic respiratory disease, injuries and disabilities, musculoskeletal conditions and genetic disorders challenge the health systems and absorb substantial amounts of resources.15 In Africa non communicable diseases accounted for 28% of morbidities and 35% of mortalities in 1990, these figures are projected to rise to 60% and 65% respectively by 2020, adding to the already high burden of these communicable diseases. Recent studies carried out, such as one countrywide survey of persons seeking health services above 50 years of age in Botswana have revealed that 67% and 12.4% of respondents had hypertension and diabetes respectively. This double burden of disease necessitates concomitant approaches and simultaneous interventions.15

Non communicable diseases have a huge impact on the economy which goes beyond the costs to health services. Indirect costs, such as lost productivity, can match or exceed the direct costs. A significant proportion of the total cost of care falls on patients and their families. People die from all chronic diseases at dramatically younger ages in the countries of the Region. Non communal disease in Africa, are underappreciated as development issues and underestimated as diseases with profound economic effects and many governments take little interest in their prevention and control thus the NCDs do not receive the priority attention in public health policies and programs commensurate with their disease burden.15 Progress in implementing comprehensive NCDs strategies and policies has been hampered by the lack of resources. The key challenges in the region include scarce resources and lack of policies and strategies for controlling NCDs. There is the need for a strong advocacy in favor of prioritizing NCDs and also for assisting in implementing and monitoring cost-effective and integrated approaches for the early detection and management of cardiovascular diseases, cancers, diabetes, sickle cell disease, chronic respiratory diseases, oral health and establish standards of health care for common conditions.15

Non-communicable diseases mainly cancers, diabetes, chronic respiratory diseases and cardiovascular diseases – account for the majority of death and illness in almost every region of the world and they affect both men and women. This can be prevented by tackling poor diet, tobacco use, and harmful use of alcohol and lack of physical activity.16

Health financing in South Africa- resources available for essential medicines

The WHO Model Essential Medicines List provides an internationally recognizable set of selected medicines to help countries choose how to treat their priority health needs. Scaling up the use of zinc sulphate could dramatically reduce the number of the 760 000 children under 5 who die from diarrhoea worldwide, every year.  Zinc can reduce the severity of childhood diarrhoea episodes, and reduce mortality if it is used with oral rehydration salts. This made the World Health Organization add a 20mg zinc tablet to its 2011 Model Essential Medicines List (EML).17

The World Health Organization created the first Essential Drugs List in 1977, which contains about 220 drugs which had their names changed later on. Since then the EML Expert Committee has met every two years to update the Model List, using a transparent process. Any entity may propose an addition including individuals, governments, pharmaceutical companies, or medical associations but they must provide evidence of the proposed drug’s safety, efficacy and cost-effectiveness. They also need to show that the medicine is essential to meeting priority health care needs and is also available in adequate amounts to the people. Each application is reviewed by two members of the Committee’s experts, drawn from a larger expert advisory panel. Their reviews are posted on the WHO web site but the reviewer is not identified so as to avoid any kind of influence and is open to comments. Finally, the whole Committee meets for five days to compile the revised Model List, before submitting it for final approval from the Director-General, WHO.17

The careful selection of a limited range of essential medicines leads to a higher quality of care for patients, better management and use of medicines and more cost-effective use of health resources. Clinical guidelines and lists of essential medicines also help in improving the availability and proper use of medicines in the health care systems. Selection of medicines follows the market approval of a pharmaceutical product which defines the availability of a medicine in a country. An essential medicines list will then be developed according to the disease prevalence, evidence on efficacy and safety, and comparative cost-effectiveness. National reimbursement/health insurance schemes may also use the same approach. WHO is the secretariat for the Expert Committee on Selection and Use, the group of experts responsible for revising and updating the Model List of Essential Medicines.18

SA’s Human Development Index – implication on health

The Human Development Index is an average measure of basic human development achievements in a country. Like all averages, the Human Development Index masks inequality in the distribution of human development across the population at the country level. The Human Development Index is a summary measure for assessing long-term progress in three basic dimensions of human development are, a long and healthy life, access to knowledge and a decent standard of living. As in the 2011 HDR a long and healthy life is measured by life expectancy.19 The number of years a new born infant could expect to live if prevailing patterns of age-specific mortality rates at the time of birth stay the same throughout the infant’s life.20 Life expectancy at birth can be expressed as an index using a minimum value of 20 years and observed maximum value over 1980-2010.20 The Human Development Index is also useful to see the probability of dying between birth and exactly age 5.20

South Africa’s Human Development Index value for 2012 is 0.629—in the medium human development category thus South Africa takes the position of 121 out of 187 countries and territories, sharing the rank with Indonesia and Kiribati. Between 1980 and 2012, South Africa’s Human Development Index value increased from 0.57 to 0.629, an increase of 10 percent or average annual increase of about 0.3 percent.20 The rank of South Africa’s Human Development Index for 2011 based on data available in 2012 and methods used in 2012 was– 122 out of 187 countries. In the 2011 South Africa was on position 123 out of 187 countries. However, it is misleading to compare values and rankings with those of previously published reports, because the underlying data and methods have changed.19The 2010 HDR introduced the Inequality Adjusted HDI (IHDI), which takes into account inequality in all three dimensions of the HDI by ‘discounting’ each dimension’s average value according to its level of inequality. The HDI can be viewed as an index of ‘potential’ human development and the IHDI as an index of actual human development. The ‘loss’ in potential human development due to inequality is given by the difference between the HDI and the IHDI, and can be expressed as a percentage. Due to a lack of relevant data, the IHDI has not been calculated for this country.19

Prevention and control of NCDs for primary health care in low resource settings

The implementation plan of the Global Strategy for Prevention and Control of Non Communicable diseases (2008) is a policy aimed to prevent the four common NCDs and 25% relative reduction in premature mortality from cardiovascular diseases, cancer, diabetes or chronic respiratory diseases by 2025.  The major aim is to provide guidance to countries in incorporating cost effective interventions against major NCDs into their health systems, it suggests that countries involved should use and monitor cost effective methods for early detection of the most common NCDs.

WHO came up with cost effective methods which can be used in resource-poor settings, although there are guidelines on NCDs management, they may be not be applicable in primary care in these areas. For example, type 2 diabetes diagnosis and management in primary health care in low resource settings is a guideline that recommends that fundamental methods be applied in the management of diabetes in primary health care. This targets health care professionals who are in charge of developing diabetes treatment protocols which will be used in primary health care in low-resource settings. This is funded by WHO and has made recommendations of the guideline in type 2 diabetes and also Asthma and chronic obstruction pulmonary diseases which are suitable in low resource settings. 21

Essential medicines are those that meet the needs of the primary health care of the population. Essential medicines are intended to be available in health systems all the time, in adequate amounts, correct dosage forms, assured quality and an affordable to all people. The Essential drug concept can be useful in poor resource settings because an individual can get medicines even if they are limited resources.22

HIFA 2015 has made it a goal for every person worldwide to be able to get access to an informed healthcare provider because people are dying because health care workers do not have access to the information they need.23

Cost effective medicines for NCDs are available in generic forms, though people who need them especially in low-income and middle income countries are not able to access or afford them, and therefore prevalence of NCDs are increasing even with effective interventions made. 60% of all deaths in 2005 were caused by chronic diseases, and 80% of these diseases were in low income and middle income countries.  Burden of chronic NCDs cannot be decreased without good access to essential medicines .24

Role of pharmacy and Therapeutics Committee- Selection of essential medicines (WHO guidelines)

Appropriate use of medicines reduces the burden of NCDs up to 80% in many countries.  Medicines remain inaccessible especially in the low- and middle income countries, as a result of the delivery and utilization issues, which can be solved by planned strategies.25

Many non-communicable diseases have common risk factors and common health systems related constraints that limit access to needed essential medicines. Effective medicines listed in the WHO Model List of Essential medicines, are often unavailable in public facilities, because of deficiency in public resources due to under- funding, inaccurate demand forecasting and inefficient public sector procurement and distribution of medicines. Medicines found in the private sectors, may be unaffordable to the majority. Selection of originator brand products increases the price by two to three times, making treatment less affordable, this is due to a mistaken belief by the health care providers that branded medicines are better than the generics. Pharmaceutical staff particularly in the developing countries remains a challenge, affecting the safe, effective and sensible distribution.25

Affordable medicines can be made more available by improving public procurement, generic medicines being sold in the private sector and promoted by different policies, splitting prescribing and dispensing functions since this will lead to prescribing medicines that will promote their sales, making options available for patented medicines. National guidelines can be implemented to recommend essential medicines which have generic products which are available. Local production of medicines can be promoted by providing voluntary licenses. Quality use of medicines can be encouraged by proven methods including the national body monitoring this, and using essential medicines lists and formularies for supply and training.25

Choosing the most effective, cost effective and safe treatment requires knowledge of the patient’s health condition, life state, and access to impartial, comparative information. The international pharmaceutical industry plays a role in the development, production and distribution of medicines. New drugs are promoted greatly, a new drug does not mean it is better but companies need to regain their investments, and make profits. Promotion may affect treatment decisions; promotion may be used as an information source on a new drug. A major challenge facing health care professionals is the impact of pharmaceutical promotion on prescribing and dispensing medicines.26

HIFAs vision is for every prescriber and user of medicines to have access to the information and knowledge needed to use medicines effectively, since prescribers and users particularly in low resource areas lack such information, and if they do have it, it will be commercially biased.27

Role of current and future healthcare professionals

Heath care professionals are all encouraged to take part in the WHO campaigns for example on World Health day, Ministries of health and health authorities are encouraged to organise clinics to measure blood pressure and inform on the related health risk, and also to distribute posters and leaflets about high blood pressure and consequences.28

BRICS is a group used for economic, cultural and political co-operation between five countries, Brazil, Russia, India, China and South Africa. This group is taken to be on top of emerging economics which have a huge influence on global and regional affairs. BRICS has the potential to be the most influential group in global initiatives on access to affordable and quality of medicines. The BRICS countries have significant pharmaceutical systems and are key manufacturers of active pharmaceutical ingredients for the world and the majority have a high number of pharmaceutical exports, especially of generic medicines. This alliance is a peer -to- peer network that will enable individuals to take part in significant projects, share works and ideas and contribute ground-breaking solutions towards resolution of their indigenous as well as inter-country problems, medicines quality, access and use.29

E-drug is a group of essentialdrugs.org, it targets health workers in developing countries and is centred on off-line email technology. The essential drug concept is very important in poor resource settings because it allows access to the best medicines using the resources that are there. Use of essential drugs lowers prices, due to economics of scale.30

HIFA is a global campaign aimed to provide access to an informed heath care provider by 2015, its vision is for every person who is a prescriber and user of medicines to have access to the information needed to use medicines effectively.31 The focus is on the information and learning needs of healthcare providers in developing countries, especially where the needs are greatest: households and communities, primary health workers, and health professionals working in small district hospitals.32

The Young professionals Chronic Disease Network and The Policy Depot for the National Forum for Heart disease and Stroke prevention are recent social networks that connect people to professionals, events and resources that are connected to ones NCD policy experience and interests.33 NCDFREE is a global social movement against NCDs which are the leading causes of death and kill more than thirty five million people every year. NCDFREE need support to bring attention to inspiring people and their local action.34

Pharmaceutical promotion: need to respond to this crucial problem

Medicines are the core part of the health-care services. Over the years, growing concern has focused attention on the relationship between health-care professionals and the pharmaceutical industry – particularly the industry’s influence on prescribing and dispensing decisions through a range of promotion tools, which can influence treatment choices.35

Pharmaceutical promotion’s huge role in shaping the nature of these treatment decisions seem to go unnoticed by most health-care professionals who seem to be ignorant on how to access pharmaceutical promotion and how to understand its influence on their behaviour.36 The influence of pharmaceutical promotion on health-care professionals’ behaviour and treatment choices can often result in less than optimum medication decisions being made which sometimes result in the deterioration of the patient’s health.35

An international survey of education initiatives on pharmaceutical promotion conducted by the WHO/ Health Action International(HAI) cross-sectional in 2005 found out that most medical and pharmaceutical faculties spent little time if not at all, on the subject although its included in their curriculum.35 There is therefore greater need for health-care professionals take issues of pharmaceutical promotion seriously and to critically analyse information on medicines in order to make better decisions that will positively affect their patients’ health.

Need for evidence based medicine (Revision of STG and EML every two years)

The ability to track down, critically appraise (for its validity and usefulness), and incorporate the rapidly growing body of evidence into one’s clinical practice has been named ‘evidence-based medicine’ (EBM).37 When allocating resources, the strength and weight of scientific evidence on clinical practices and cost-effectiveness, is of great importance.

The use of Evidence based medicine has improved the level of commissioning and provision of health services around the world. It is being applied not only to pharmaceutical treatments but also increasingly to surgical interventions, diagnostic tests and medical devices all over the world.38

The Standard Treatment Guidelines (STG) and Essential Medicines List (EML) aim to provide all prescribers with a set of treatment guidelines covering most of the common disease conditions found in a country so that prescribing practices can be standardised.37 Their revision, every 2 years of great importance not only to the pharmaceutical industry but also to the general public as well. Most disease causing agents like bacteria become resistant to certain drugs over time, thus newer innovative medicines are then required to replace these medicines.

Awareness of TRIPS and its impact on public health

The TRIPS Agreement is an important comprehensive international agreement on intellectual property rights which outlines several important trade related aspects of intellectual property.40 All member countries of the WTO are bound to this agreement and are required to modify their national regulations to accord with the rules of outlined in the agreement.

Under the TRIPS Argument, pharmaceutical companies are to be granted patents to any of their inventions for a minimum of 20 years.39 This gives the companies the time to enjoy maximum profits from their inventions as they will be the sole supplier of the specific patented product.

However, these patents are of great disadvantage to the public sector. Developing countries are affected mostly as the majority of people cannot afford the high prices of the drugs. Generic companies cannot produce and the government on the other hand cannot subsidise the patented drug, hence the price of the drug remain high.39

Fenoldopam

Drug Nomenclature

Synonyms: Fenoldopam Mesylate; Fenoldopam                                                              41

Chemical name: 6-Chloro-2, 3, 4, 5-tetrahydro-1-(p-hydroxyphenyl)-1H-3-benzazepine-7, 8-diol methanesulfonate41

Fenoldopam Mesylate is a white to off-white powder, soluble in water. It must be stored in airtight containers at a temperature of 25 degrees, excursions permitted between 15 degrees and 30 degrees. It must be protected from moisture as well.

Physicochemical Characteristics

Incompatibility (Latest modification: 22-Jun-2005)

Physical incompatibility has been reported42with fenoldopam 80 micrograms/mL (as the mesilate) in 0.9% sodium chloride injection and the following drugs during simulated Y-site administration: aminophylline; ampicillin sodium; amphotericin B; bumetanide; cefoxitin sodium; dexamethasone sodium phosphate; diazepam; fosphenytoin sodium; furosemide; ketorolac tromethamine; methohexital sodium; methylprednisolone sodium succinate; pentobarbital sodium; phenytoin sodium; prochlorperazine edisilate; sodium bicarbonate; and thiopental sodium42

Stability (Latest modification: 22-Mar-2004)

Fenoldopam mesilate, at concentrations ranging from 4 to 300 micrograms/mL in glucose 5% or sodium chloride 0.9%, has been reported2 to be stable for 72 hours when stored at temperatures of 4 degrees or 23 degrees.

Interactions (Latest modification: 30-Jun-2005)

The hypotensive effects of fenoldopam may be improved by other drugs with hypotensive actions. Beta blockers may block fenoldopam-induced reflex tachycardia and use of the drugs together is not recommended.41

Pharmacokinetics (Latest modification: 20-May-2010)

Steady-state plasma concentrations of fenoldopam occur about 20 minutes after starting continuous intravenous infusion. Fenoldopam is extensively metabolised with only about 4% of a dose being excreted unchanged. It is metabolised by conjugation (mainly glucuronidation, methylation, and sulfation). Fenoldopam and its metabolites are excreted mainly in the urine, and the remainder in the faeces. The elimination half-life of fenoldopam is about 5 minutes.42

Uses and Administration (Latest modification: 21-May-2010)

Fenoldopam is a dopamine agonist that is reported to have a selective action at dopamine D1-receptors, leading to vasodilation. It is used in the short-term management of severe hypertension and has also been tried in heart failure.41

Fenoldopam is given intravenously as the mesilate, although doses are expressed in terms of the base; 1.31 micrograms of fenoldopam mesilate is equivalent to about 1 microgram of fenoldopam. 41

In the management of hypertensive crises, fenoldopam mesilate is given by continuous intravenous infusion for up to 48 hours, as a solution containing 40 micrograms/mL of fenoldopam. The dose should be adjusted according to response, in usual increments of 50 to 100 nanograms/kg per minute at not less than 15-minute intervals. The usual dose range is from 100 to 1600 nanograms/kg per minute.41

Administration in children (Latest modification: 02-Jan-2011)

Fenoldopam has been used to induce hypotension in children undergoing surgery. A placebo-controlled study41 in 76 children aged between 3 weeks and 12 years found that infusion at rates below 200 Nano grams/kg per minute was ineffective, and that a dose of 800 Nano grams/kg per minute was the most effective and well tolerated.41 Dose increases beyond this were associated with tachycardia but no further blood pressure reduction.

Fenoldopam has also been investigated to protect renal function and improve urine output in neonates undergoing cardiopulmonary bypass43 (for example by infusion of 100 Nano grams/kg per minute over 72 hours43) and in critically ill children44, but as in adults the extent of any benefit is unclear. Fenoldopam is a rapid-acting, effective agent for intravenous control of blood pressure in children. The effective dose range is significantly higher in children undergoing anaesthesia and surgery (0.8–1.2 mcg/kg/min) than as labelled for adults (0.05–0.3 mcg/kg/min). The PK and side-effect profiles for children and adults are similar.

Hypertension (Latest modification: 05-Jan-2011)

Fenoldopam has a rapid onset of action and short elimination half-life and may be used as an alternative to sodium nitroprusside in the management of hypertensive crises. Its use has been reviewed.43 Comparative studies with sodium nitroprusside in patients with acute severe hypertension have shown fenoldopam to be equally effective in rapidly lowering blood pressure. Additionally, in contrast to nitroprusside, urine output, creatinine clearance, and sodium excretion may be increased by fenoldopam. Fenoldopam may therefore be particularly useful in patients with renal impairment, although this remains to be established.44

Sodium Nitroprusside

Drug Nomenclature (Latest modification: 30-Jan-2013)

Chemical name: Sodium nitrosylpentacyanoferrate (III) dihydrate1

Molecular formula: Na2Fe (CN)5NO,2H2O =298.0

CAS: 14402-89-2 (anhydrous sodium nitroprusside); 13755-38-9 (sodium nitroprusside dihydrate)

Chemical Structure of Anhydrous sodium nitroprusside

Sodium Nitroprusside-A reddish-brown crystals or powder. It is freely soluble in water; and slightly soluble in alcohol. It must be protected from light.41

Incompatibility (Latest modification: 22-Mar-2004)

Sodium nitroprusside has been reported to be visually incompatible with cisatracurium besilate45and with levofloxacin46during simulated Y-site administration.

Stability in solution (Latest modification: 11-Jul-2005)

Solutions of sodium nitroprusside decompose when exposed to light and must be protected during infusion by wrapping the container with aluminium foil or some other light-proof material. Nitroprusside will react with minute quantities of organic and inorganic substances forming highly coloured products. If this occurs the solution should be discarded. Solutions should not be used more than 24 hours after preparation.

The instability of sodium nitroprusside solutions has been the subject of considerable investigation. Although stated to be more stable in acid than in alkaline solution, 47a later study5 found that whereas the initial light-induced darkening of a 1% solution was independent of pH, further degradation leading to the development of a blue precipitate required an acid pH. If protected from light by wrapping in aluminium foil, sodiumnitroprusside 50 or 100 micrograms/mL was found to be stable in 5% glucose, lactated Ringer’s, and normal saline solutions for 48 hours.48

Pharmacokinetics (Latest modification: 22-Mar-2004)

Sodium nitroprusside is rapidly metabolised to cyanide in erythrocytes and smooth muscle and, in vivo, this is followed by the release of nitric oxide, the active metabolite. Cyanide is further metabolised in the liver to thiocyanate, which is slowly excreted in the urine; this metabolism is mediated by the enzyme rhodanase and requires the presence of thiosulfate. The plasma half-life of thiocyanate is reported to be about 3 days, but may be much longer in patients with renal impairment.41

Uses and Administration (Latest modification: 05-Jan-2011)

Sodium nitroprusside is a short-acting hypotensive drug with duration of action of 1 to 10 minutes. It produces peripheral vasodilatation and reduces peripheral resistance by a direct action on both veins and arterioles. It has been termed a nitro vasodilator because it releases nitric oxide in vivo. Its effects appear within a few seconds of intravenous infusion. Sodium nitroprusside is used in the treatment of hypertensive crises and to produce controlled hypotension during general anaesthesia. It has also been used to reduce preload and afterload in severe heart failure including that associated with myocardial infarction.41

Cost effectiveness:

Treatment of hypertension with Fenoldopam appears to have equivalent efficacy with Sodium Nitroprusside but rather at a greater cost to the patient. Cost of drug therapy with Fenoldopam was $597.60; on the other hand, Sodium Nitroprusside only cost $2.66. Fenoldopam has an acquisition cost 200 times greater than the cost of Sodium Nitroprusside, therefore is unlikely to be cost-effective. Cost of drug therapy was significantly greater with Fenoldopam and thus cost of treating patients with Sodium Nitroprusside is much more cost effective. With the ever-increasing cost of drug therapy, the use of drugs having a high acquisition cost are being strictly restricted to situations where strong efficacy or safety advantages justify use. Although, Fenoldopam has an acquisition cost much greater than that of Sodium Nitroprusside, comparative studies that have been completed to date have failed to demonstrate an efficacy or safety advantage over the latter drug. Therefore, Sodium Nitroprusside is more cost effective as compared to Fenoldopam in treating hypertension.50

Comparative efficacy

METHODS: 183 random patients at 24 academic medical centers were used, 90 were treated using fenoldopam and 93 nitroprusside. These patients were adult patients between the ages of 21-80 years who had supine diastolic blood pressures (DBPs) > or = 120 mm Hg, were capable of written informed consent, and did not have selected exclusion criteria. The subjects were randomized to either fenoldopam or nitroprusside therapy; DBP was titrated to 95-110 mm Hg, or a maximum reduction of 40 mm Hg for very high pressures. Infusions were maintained for at least six hours, then the patients were weaned off the IV therapy and oral medication was started. Measurements included BP, heart rate, and duration of study drug infusion and frequency of side effects or complications.51

RESULTS:  Fifteen patients from each arm were excluded from efficacy analysis due to protocol violation. There was no significant difference in baseline characteristics. The two antihypertensive agents were equivalent in controlling and maintaining DBP. Systolic blood pressure (SBP) was reduced to a slightly greater degree for the nitroprusside-treated patients during the initial (0.5-1-hr) study period, and both SBP and DBP were reduced more for the fenoldopam-treated patients in the subset receiving infusions during the 12-24-hour period. The adverse effect profiles of the drugs were similar, as were the times to achieve target pressure, with no clinically relevant difference.51

CONCLUSIONS: For patients who had acute severe hypertension, fenoldopam and nitroprusside were equivalent in terms of efficacy and acute adverse events. Because of a unique mechanism of action, fenoldopam may have advantages in selected subsets of patients.51

Micromedex®: Fenoldopam

SAFETY

Hypotension is one of the most common adverse effects reported with fenoldopam use occurring in 5% of patients. Intravenous fenoldopam also causes hypotension mainly in patients with severe hypertension.

Use of Fenoldopam mesylate has been reported to cause angina pectoris and atrial fibrillation in a small percentage of heart-failure patients. Peripheral edema has also been reported occasionally in heart failure patients treated with fenoldopam.

Dermatological effects of fenoldopam include flushing and injection site reactions.

Gastrointestinal effects include vomiting, nausea and xerostomia.

Interaction of fenoldopam and acetaminophen raises the concentrations of fenoldopam thus monitoring of potential toxicity is required.

Avoid concomitant use of fenoldopam with beta-adrenergic blocker agents as it causes an exaggerated hypotensive effect.

TOXICITY

Toxicity is generally an extension of the pharmacological effect, primarily hypotension. Hydralazine has an active metabolite that binds to cellular proteins and may trigger an autoimmune response.

Severe toxicity is very rare following isolated overdose from these medications. An adult survived an ingestion of 10 g hydralazine. A toddler developed only tachycardia after ingesting 100 mg Minoxidil. An adult developed hypotension and a non-ST-elevation myocardial infarction after ingesting 1200 mg Minoxidil.

Micromedex®: Nitroprusside

SAFETY:

Nine of 54 patients receiving nitroprusside in doses of 2.54 to 1200 micrograms/minute (mcg/min) for hypertensive emergencies developed some symptoms of nausea and/or vomiting, abdominal cramps and abdominal pain].

Nitroprusside therapy is known to cause hypotension and rebound hypertension. Excessive hypotension may occur with nitroprusside and may be resolved with discontinuation of the drug since the direct effect of the drug clears promptly within 10 minutes of discontinuation. Severe hypotension resulting in death has also been reported with nitroprusside administration.

Dizziness, headaches, raised intracranial pressure and drowsiness have also been reported during nitroprusside infusions.

Nitroprusside has been shown to cause impaired pulmonary gas exchange in patients with heart failure.

TOXICITY:

CYANIDE: Infusion of more than 500 mcg/kg sodium nitroprusside at a rate of greater than 2 mcg/kg/min causes generation of cyanide at a rate faster than most patients can eliminate it.

THIOCYANATE: Toxicity generally does not develop in patients with normal renal function before 7 days of continuous therapy at moderate doses. May develop in 3 days in patients with renal insufficiency who are not undergoing haemodialysis.

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