Post on 25-Jun-2020
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Strategie per il corretto uso dei farmaci nel
molto anziano
N. Ferrara, MD S. Maugeri Foundation, Telese Terme, IRCCS Dept of Health Science, University of Molise
Seminario di studio del Consiglio Direttivo AIP 21 Gennaio 2012 - Genova
H.W. Kildemoes et al. Health Policy 2006;75:298–311
Projected total Danish drug expenditure 2003- 2030
STRATEGIES FOR CORRECT USE OF DRUGS IN THE ELDERLY
PHARMACOGENETICS EDUCATIVE/INFORMATIVE INSTRUMENTS
STRATEGIES FOR CORRECT USE OF DRUGS IN THE ELDERLY
PHARMACOGENETICS EDUCATIVE/INFORMATIVE INSTRUMENTS
Factors of variability in drug response
PHARMACOCYNETIC
PHARMACODYNAMIC
Physiological - age - gender
Pharmacological response
Genetic - metabolic enzymes - transporters - receptors
Pathological - Liver diseases - Kidney diseases
Enviromental - concomitant therapy - diet - smoking - alcool
DRUG
EFFICACY OF THE PHARMACOLOGICAL TREATMENT: FAILURE OF THERAPY AND ADVERSE REACTIONS
EFFICACY
CAUSES: -Inadequate dosage
Individual genetic variability - Drug interactions
ADVERSE DRUG REACTIONS
OPERATIVE TOOLS - Pharmacological monitoring - Pharmacogenetic analysis - Pharmacovigilance
PHARMACOLOGICAL TREATMENT
Patients
FAILURE OF THERAPY
Variability in drug response
The individual variability in drug response is a
clinical problem of overriding importance
The study of this variability covers an area of research
known as pharmacogenetics.
The genetic variations at specific sites of the genome
are called polymorphisms.
PHARMACOGENETICS: refers to “the role of genetic variation affecting drug response or adverse reactions to drugs” (Weinshilboum, 2003) The likely role of genetics in potentially causing adverse drug reactions was set out in a 1957 paper with the programmatic title “Drug Reactions, Enzymes and Biochemical Genetics” (Motulsky, 1957) The term pharmacogenetics was coined by Friedrich Vogel of Heidelberg, Germany in 1959 (Vogel, 1959)
Motulsky et al. J Zhejiang University SCIENCE 2006 7:169-170
Objectives
• To check subgroups of patients with high probability to response or not to a therapy • To check subgroups of patients with high probability of adverse drug reactions • To optimize the dosage
Personalized Therapy
MAX EFFICACY
+
MINOR TOXICITY
At this time pharmacogenetic label informations are reported for more than 120 drugs, and this number is increasing more and more.
Pharmacotherapy. 2008 Aug;28(8):992-8.
Pharmacogenomic biomarker information in drug labels approved by the United States food and drug administration: prevalence of related drug use.
Frueh FW, Amur S, Mummaneni P, Epstein RS, Aubert RE, DeLuca TM, Verbrugge
RR, Burckart GJ, Lesko LJ. Office of Clinical Pharmacology, Office of Translational Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA), Silver Spring, MD 20993, USA.
Warfarin
Since 50 years it represents the milestone of oral anticoagulant therapy The therapy with warfarin induces liver production of proteins involved in the coagulation process with reduced coagulant activity.
Anticoagulants
Warfarin
In the clinical practice sometime is difficult to mantain a patient at a fixed anticoagulant level. The relation between warfarin prescribed dose and the individual response to the drug is regulated by several factors:
♦ Drug assumption
♦ Diet
♦ Diseases
♦ AGE
Warfarin
The individual response may also be modulated by polymorphisms in genes coding for metabolizing enzymes, transporters, receptors and proteins involved in the drug pathway.
CYP2C9, codifyng for the enzyme responsible of the S-
warfarin catabolism.
VKORC1, codifying for the vitamin K complex eposside
reductase.
Case Report
Pz 76 anni, Maschio Motivo del ricovero Riabilitazione Cardiaca post-chirugica (By-pass Aorto-coronarico) Anamnesi 3 aa prima resezione parziale dell’intestino per cancro ipertensione dislipidemia Terapia all’ingresso Ac. acetilsalicilico Ramipril Lorazepam Spironolattone Pantoprazolo Nitroderivati Esame obiettivo Condizioni cliniche stabili
Case Report Diario clinico Comparsa di episodi di fibrillazione atriale e diarrea Terapia in acuto Amiodarone
Eparina
Terapia in cronico Amiodarone Warfarin Neomicina solfato/bacitracina
Case Report Commento Interazione tra farmaci (neomicina+warfarin – amiodarone + warfarin con incremento INR ) Colectomia parziale (superficie di assorbimento ridotta) Farmacogenetica (metabolizzatore intermedio per warfarin + metabolizzatore rapido per vitamina K)
PHARMACOGENETICS & PHARMACOGENOMICS
- Good response - Insufficient response - Collateral effects
Individual therapy on genotype basis
THE PRESENT THE FUTURE
STRATEGIES FOR CORRECT USE OF DRUGS IN THE ELDERLY
PHARMACOGENETICS EDUCATIVE/INFORMATIVE INSTRUMENTS
Interventions focused on improving patients adherence with prescribed regimens and monitoring may be beneficial in terms of reduction of preventable adverse drug events among older persons.
EVALUATION OF AN EDUCATIVE/INFORMATIVE STRATEGY ON DRUGS USE IN ELDERLY
POPULATION WITH CHRONIC-DEGENERATIVE DISEASES IN SEVERAL CARE SETTING: A
CONTROLLED STUDY
NEW STRATEGY ON DRUGS USE IN ELDERLY POPULATION
AIM OF THE STUDY
To realize educational/informative instrument for doctors operating in residential structures.
To predispose an informative-educational instrument addressed to patients, families and caregivers for the prevention of the ADR in old patients, characterized by multiple chronic-degenerative diseases in polypharmacotherapy.
To reduce the potentially unsuitable drug use and to improve the compliance and the appropriateness.
EVALUATION OF AN EDUCATIVE/INFORMATIVE STRATEGY ON DRUGS USE IN ELDERLY POPULATION WITH CHRONIC-
DEGENERATIVE DISEASES IN SEVERAL ASSISTENTIAL SETTING: A CONTROLLED STUDY
Study Design Controlled multicentre prospective study Study Population Patients ≥65 years old Inclusion Criteria 2 or more chronic diseases + > 3 prescribed drugs Recruitment 790 patients (450 controls and 340 cases)
STUDY DESIGN
Group PRE Group POST
usual care usual care + educative/informative instruments
Caregivers
Relatives Patients
+
N° drugs
22191817161514131211109876543
% p
atie
nts
20
15
10
5
0
post-intervention (Mean=9.3±2.9)
pre-intervention (Mean=8.5±2.6)
p<0.0001
N° drug interactions
14131211109876543210
% p
atie
nts
30
25
20
15
10
5
0
post-intervention (Mean =1.97±2.1)
pre-intervention (Mean= 2.15±2)
p = ns
CONCLUSIONS
In our experience an educative/informative instruments was able :
a) To reduce the incidence of ADR
b) To induce a trend in reduction, whereas not significant, of mean inappropriate drug prescrition number in patients more ill and in treatment with more drugs
CONCLUSIONS
In our experience an educative/informative instruments induced:
The reduction in the number of inappropriate prescription for each patient in POST in respect to PRE, whereas an higher mean number of drugs was found, suggesting an higher attention of doctors to inappropriate prescriptions.
No changes in the drug interactions comparing PRE and postintervention subjects, whereas the mean number of interactions was lower in the POST in respect to the PRE.
CONCLUSIONS
The pharmacogenetic and the educative/ informative instruments for patients and doctors can be considered the possible strategies for the correct use of drugs in the elderly.