Trattamento delle sindromi dolorose di spalla con FANS per ...
Transcript of Trattamento delle sindromi dolorose di spalla con FANS per ...
Perché serve una riflessione sui
FANS topici
• Epidemiologia delle patologie dolorose di
origine muscolo-scheletrica
– Prevalenza crescente della patologia degenerativa
– Progressivo aumento dell’età media dei pazienti
• Drug reactions can be classified into
immunologic and nonimmunologic etiologies
• The majority (75 to 80 percent) of adverse
drug reactions are caused by predictable,
nonimmunologic effects.
FANS FANS –– Effetti gastrointestinaliEffetti gastrointestinali
• Dispepsia
• Erosione gastrica
• Ulcera gastrica
Langford, Clin Rheumatol 2006; Strom et al, Arch Int Med 1997; Tramer et al, Pain 2000
‘However, it should be noted that these
represent a very small minority of the very
many people who have benefited from anti-
inflammatory drugs.’
Incidenza di ricoveri ospedalieri per
sanguinamento GI in seguito a
trattamento con FANS:
-0.012% con Ibuprofene
-0.026% con Naprossene
Topical NSAIDs can ease medication administration and
help address barriers to pain management in older patients,
such as taking multiple medications and inability to swallow,
and are a valuable option for long-term care providers
La via transdermicaPotenziali vantaggi
Assenza di effetti collaterali tipici dei FANS assunti per via sistemica
Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults.
Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD007402. DOI:
10.1002/14651858.CD007402.pub2
Quali farmaci?
• VOLUME MOLECOLARE
• CARATTERISTICHE CHIMICO-FISICHE
• CONCENTRAZIONE
Caratteristiche del principio attivo in grado di influenzare
l’assorbimento cutaneo:
Indometacina
PM 350 dalton
Piroxicam
PM 330 dalton
Diclofenac
PM 325 dalton
Ketoprofene
PM 260 dalton
Flurbiprofene
PM 250 dalton
KETOPROFENE ha un basso Peso Molecolare
% of absorbance of the active principle
0
100
100
- +-
+
Efficacy
Percutaneousabsorbance
within4 hours(%
)KP
DC
FP
IM
KP = ketoprofene
FP = flurbiprofene
DC = diclofenac
IM = indometacine
Absorbance/Efficacyof ketoprofene is higher
than other NSAIDs
Particularly suitable for transdermic application
(Yano et al.)
Relazione tra lipofiliae assorbimento cutaneoRelazione tra lipofiliae assorbimento cutaneo
1 2 3 4 5
2
1
Logaritm
o d
ella
% d
i ass
orb
imento
AUMENTO ASSORBIMENTO
Logaritmo del coefficiente di ripartizione(n-ottanolo/acqua)
AUMENTO LIPOFILIA
Diclofenac
Indometacina
Ketoprofene
Flurbiprofene
KETOPROFENE ha un valore di log p= 2,94 prossimo al valore ottimale ed è quindi uno dei FANS con la più alta permeabilitàpercutanea
KETOPROFENE ha un valore di log p= 2,94 prossimo al valore ottimale ed è quindi uno dei FANS con la più alta permeabilitàpercutanea (Tadanori et al.)
Valore ottimale
Il successo della via transdermicaIl successo della via transdermica
CARATTERISTICHE DEL PRINCIPIO ATTIVO
� Dosaggio� Peso Molecolare dei FANS� % assorbimento del
principio attivo � Grado di Lipofilia� Sede infiammata da
raggiungere
Tecnologiadel sistema transdermico
CARATTERISTICHE DEL PRINCIPIO ATTIVO
� Dosaggio� Peso Molecolare dei FANS� % assorbimento del
principio attivo � Grado di Lipofilia� Sede infiammata da
raggiungere
Passaggio di sostanze dalla superficie esterna della cute agli strati sottostanti
TERAPIA TRANSDERMICATERAPIA TRANSDERMICA
Preparati per uso topico
• Unguenti
• Paste
• Gel
• Pomate/creme
• Schiume medicate
• Cerotti medicati
Preparati per uso topico
PRINCIPIO ATTIVO VEICOLO
ATTIVITA’FARMACOLOGICA (PROMOTORI DI
ASSORBIMENTO)
ECCIPIENTI
TECNOLOGY OF THE TECNOLOGY OF THE
TRANSDERMIC SYSTEMTRANSDERMIC SYSTEM
MOLECULE TRANSDERMIC SYSTEM
Diclofenac Natural rubber based
Flurbiprofene Natural rubber based
Ketoprofen Non aqueous matrix (SIS system = Styrene -
Isoprene- Styrene)
When developing a patch formulation the following objectives
should be kept in mind:
1. Reduction in skin irritation subsequent to long-term use;
2. Improvement of the patch adherence to the various body
areas
3. Enhancement of local NSAID absorption.
Non aqueous matrix topical plaster application - SIS
ketoprofenketoprofen 20 mg 20 mg TopicalTopical plasterplaster applicationapplication
KetoprofenKetoprofen
BaseBase
SustainedSustained releaserelease of the of the activeactive principleprinciple
technology
ketoprofenketoprofen 20 mg 20 mg TopicTopic plasterplaster applicationapplication--ExclusiveExclusive matrixmatrix polimericpolimeric SISSIS
3 component copolymer:- Styrene
-Isoprene
- Styrene
Includes and structures the ketoprofen in a stable
and regular way
Even and steady releaseof the active principle
continuously
Ideal Ideal structuralstructural propertiesproperties
Ketoprofen
ONCE A DAY APPLICATION Sustained release within 24 hours
Kuzumaki N et al
ketoprofen 20 mg topical plaster applicationketoprofen 20 mg topical plaster application––
ExclusiveExclusive polymericpolymeric matrixmatrix SISSIS
ketoprofen 20 mg Topical plaster application:ketoprofen 20 mg Topical plaster application:
AbsorptionAbsorption and action and action speedspeedQuantity
of pro
duct
abso
rbed
by
skin
after
a sin
gle a
pplic
ation
(µg/c
m2)
Hours
Takada Y et al
QuantityQuantity of of activeactive principleprinciple detecteddetected in the in the skinskin after a single after a single topictopic applicationapplication of of KetoprofenKetoprofen, , FlubiprofeneFlubiprofene o o DiclofenacDiclofenac
�High elasticity �Perfect adhesion
Suitable also in flexible areas
ketoprofeneketoprofene 20 mg 20 mg topictopic plasterplaster: : AdvantagesAdvantages
OptimalOptimal AdhesionAdhesion and and flexibilityflexibility
Symptomatic treatment of Pain and inflammation caused byAcute Osteo muscular diseases
such as trauma, strains and bruisings
ketoprofen 20 mg Topic plaster application:ketoprofen 20 mg Topic plaster application:
IndicationIndication ::
Trial utilizing ketoprofen plaster, 1plaster/day for 2 weeks involving 174 patients
suffering different post-traumatic diseases
Improving of 63% in Scapulo Humeralis Periartritis
70% of patients improve in the other diseases
Aoki T e et al
Ketoprofen 20mg topic plaster application:anti-inflammatory and antalgic affect
Ketoprofen 20mg topic plaster application:anti-inflammatory and antalgic affect
Multiple factors have been proposed as contributing to the
development of subacromial impingement syndrome,
including:
•altered shoulder kinematics associated with dysfunction of
the rotator cuff and scapular muscles
•capsular tightness
•poor posture
•overuse secondary to sustained intensive work
Obiettivi del trattamento riabilitativo
• Controllo del dolore
• Ripristino della corretta biomeccanica
articolare
• Rinforzo muscolare
– Cuffia dei rotatori
– Stabilizzatori scapolari
• Correzione di fattori predisponenti
• Prevenzione delle recidive
• Rehabilitation Progression
– Primary goal
• Reduce pain – modalities and NSAID’s
– Rule out faulty mechanics
– Baseline of tolerable activity
• Control frequency and load
• Gradually increase level and frequency of activity
– Continue to engage in cardiovascular oriented activity
– After pain and inflammation have been controlled
• Incorporate dynamic stabilizer strengthening
– Stretching of posterior and inferior joint capsule
• Strengthen scapular muscles and maintain normal
scapulohumeral mechanics
• Maintain normal arthrokinematics of SC and AC joints
Controllo del dolore
• FANS – via sistemica/via topica
• Corticosteroidi intra-articolari
• Terapie fisiche