Importance of Quaternary Prevention in the Frail Elderly

Adverse drug reactions (ADRs) are among the ten principal causes of morbidity and mortality worldwide, being those who cause hospitalization, rehospitalization or prolong hospital stay, those with greater economic and health impact [1]. In the EEUU ADRs are the 4th-6th cause of death, representing between 5 to 10% of all the causes of hospitalization and 15-20% of the total hospital Budget [1,2]. In November 2008, the European Union (EU) published the note “Strengthening pharmacovigilance to reduce adverse effects of medicines” which stated that 5% of the consultations in the emergency department are due to ADRs, what implies €145.000 of the health systems budgets. Furthermore, it is estimated that there are about 197.000 deaths per year in the EU related to ADRs [2]. In Spain, according to the study “Estudio sobre la seguridad de los pacientes en atención primaria” (APEAS) [3], 37% of the reasons for serious consultation in primary health care centres are related to medication. Also, according to the Spanish report “Indicadores de Salud 2017” there was a mortality rate of 0.1 per 100,000 people due to ADRs between 2008 to 2015, being 45% of the total deaths in patients over 75 years [4]. These data do not consider the avoidable adverse effects that did not caused mortality but are usually the result of inadequate prescriptions or over prescription.


Introduction
Adverse drug reactions (ADRs) are among the ten principal causes of morbidity and mortality worldwide, being those who cause hospitalization, rehospitalization or prolong hospital stay, those with greater economic and health impact [1]. In the EEUU ADRs are the 4th-6th cause of death, representing between 5 to 10% of all the causes of hospitalization and 15-20% of the total hospital Budget [1,2]. In November 2008, the European Union (EU) published the note "Strengthening pharmacovigilance to reduce adverse effects of medicines" which stated that 5% of the consultations in the emergency department are due to ADRs, what implies €145.000 of the health systems budgets. Furthermore, it is estimated that there are about 197.000 deaths per year in the EU related to ADRs [2]. In Spain, according to the study "Estudio sobre la seguridad de los pacientes en atención primaria" (APEAS) [3], 37% of the reasons for serious consultation in primary health care centres are related to medication. Also, according to the Spanish report "Indicadores de Salud 2017" there was a mortality rate of 0.1 per 100,000 people due to ADRs between 2008 to 2015, being 45% of the total deaths in patients over 75 years [4]. These data do not consider the avoidable adverse effects that did not caused mortality but are usually the result of inadequate prescriptions or over prescription.
The terms "quaternary risk" and "quaternary prevention" refer to those activities of the healthcare system such as pharmacotherapy or the performance of diagnostic tests that can cause damage, being sometimes unnecessary. Quaternary prevention has the purpose to avoid, reduce and palliate damages caused by these activities [5]. All these data highlight the importance of treatment optimization as an essential part in the follow-up of patient´s pathologies, especially in elderly patients with greater complexity, due to pluripathology and polipharmacy but also because of the pharmacokinetic and pharmacodynamic changes that come with the age. These case emphasizes on the importance of considering drugs as an ethiopathogenic cause to be considered in any diagnostic process, and on the research and application of the available tools to try to avoid under and over prescription and the risk of generating ADRs, or prescribing inadequate medication.

Case Report
Our patient is 90 years old and has been a widower for 7 years, he is totally independent for daily life activities and has lived for years with his schizophrenic son in the family home. His son is stable with antipsychotic treatment prescribed by psychiatry and maintains a good relationship with him. In addition, the patient's daughter visits them weekly and does daily telephone supervision.
In his medical record he suffers from a high blood pressure that is Besides, his son refers that the patient is walking with difficulty due to a balance disturbance. When asked, he does not refer history of infectious symptoms on previous days. We perform a complete examination, where there was normal temperature and glycemia, but he was hypotensive (70 / 50mmHg) and bradycardic (46pm).
We explore the bradypsychia and balance alteration referred by the son and as there was no other relevant data, we considered differential diagnosis between iatrogenic hypotension, confusional syndrome, transient ischemic attack, ADR or dehydration.
We referred the patient to the hospital`s emergency department where a cranial CT scan was performed, in which no acute changes were observed, other than those in relation to the TIA suffered in 2013, a complete blood analysis where there was only a slight normocytic anaemia of 13.1g / dL d and a urine and a chest x-ray without pathological findings. The patient was rehydrated in the emergency department for three hours with clinical recovery, deciding hospital discharge with observation and home control by his general practitioner (GP). Amlodipine was withdrawed, due to low blood pressure levels. That afternoon, the patient clinically improved, but presented next morning, a similar clinical picture. We were alerted on the phone and made a medical home visit where we reviewed the patient's medication exploring what and why he took each of his pills, verifying that he had been taking by mistake, his son´s Paliperidone for his constipation. A bibliographic search was carried out [6] where it was verified that the medication taken by the patient had the following adverse effects: bradycardia, confusion, alterations of balance and dysarthria among other effects.

Treatment
The drug (Paliperidone) was suppressed and information on the use, possible ADRs and the importance of handling and preserving medication was given to the patient, and family members. Other information was provided, such as the usefulness of storing medicine in their original container to reduce the risk of mistakes with other drugs or the avoidance of splitting or crushing drugs without having consulted before about the possibility to do so. Keeping the original leaflet to be able to consult it in case of signs or symptoms that do not appear normal was also suggested.
In addition, keeping medication away from other substances (cleaning products, medicines for animals), protected from light and heat is another useful measure.

Discussion
This case tries to emphasize on the risks of medication, especially in the elderly who are more susceptible to ADRs than other age groups. The elderly is usually a group with pluripathologies, high level of chronicity and polymedication, which is defined as the simultaneous intake of several drugs, with the cut generally set at five. This implies an increase in the probability of drug interactions and posology errors, a probable decrease in therapeutic adherence, and the possibility of generating "cascade prescriptions". This definition refers to the prescription of a drug to treat a symptom considered as primary and not as an adverse effect of another drug.
An example would be to prescribe medication for a parkinsonism that manifests itself in a patient who has initiated metoclopramide, instead of identifying this symptom as an adverse reaction to this drug, whose treatment would consist in the suppression of the drug. The more drugs used, the more likely that adverse reactions occur and the higher the risk of hospitalization (regardless of age). This does not mean that drugs must not be prescribed when they are needed (adequate polypharmacy), but special attention should be paid when doing so, evaluating risks and benefits, as They classify drugs according to the different systems and perform two sections on when to start a drug and when we should suspend it [9]. With all this information the question is: How to optimize the prescription? Being well documented on the drug to be prescribed is an effective tool to try to reduce ADRs.
It is worth knowing a less extensive list of medicines and their indications and adverse reactions than prescribing without knowing the risks and benefits of them, especially paying attention to those drugs marketed for less time, where their adverse effects or behavior are not well known. These have the icon of a black triangle in the box in aim to monitor them and, declare any adverse effects that may occur. It is also convenient to assess on the therapeutic adequacy of drugs that may take a longer time to produce a relevant clinical benefit than the patient's life expectancy.
Health education about possible benefits and risks associated with taking the new drug, as well as the purpose of the prescribed medication, also implies an active involvement of the patient in his treatment, improving therapeutic adherence and reducing possible posology errors. It is important that patients know the drugs by both brand names and trade names and that they avoid classifying them according to appearance, since in many cases the non-isoappearance between drugs can lead to confusion.