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

Data from GIFA, SIGG, Italy

Comorbidity in Italy

Istat, 2010

Class of ages

Pre

va

len

ce (

%)

diseases diseases diseases

Class of ages

Pre

vale

nce o

f F

rail

ty (

%)

Men Women

Cardiovascular Health Study , 2006

H.W. Kildemoes et al. Health Policy 2006;75:298–311

Projected total Danish drug expenditure 2003- 2030

Modified from Brenan, 2004

Years

Pre

vale

nc

e (

%)

Events Negligence

Lazarou et al. JAMA 1998; 279:1200-1205

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

All subjects differ in the drug response

PHARMACOGENETICS

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

Time table of INR values, Warfarin dosage and other drugs administration

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

"Here's my sequence...”

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

+

p=ns

p<0.0001

p<0.0001

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

p < 0.05

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.

THANKS FOR YOUR ATTENTION