Farmaci antiulcera gastrica

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Farmaci antiulcera gastrica
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Definizione di ulcera
A peptic ulcer, also known as ulcus pepticum, or
peptic ulcer disease (PUD), is an ulcer (defined
as mucosal erosions equal to or greater than 0.5
cm) of an area of the gastrointestinal tract that
is usually acidic and thus extremely painful. It
is a sore in the lining of the stomach or
duodenum. If peptic ulcers are found in the
stomach, they are called gastric ulcers. If they
are found in the duodenum, they are called
duodenal ulcers.
J Pharm Bioallied Sci. 2011 Apr-Jun 3(2)
236241.
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Definizione di ulcera Ferita che non evolve a
guarigione spontanea. Lulcera gastrica è una
lesione profonda della mucosa gastrica di almeno
3 mm o più di diametro.
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Inibitori di Pompa protonica
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Omeprazole, the first drug in this class, was
introduced in 1989. Since then, 4 other proton
pump inhibitors have been introduced
lansoprazole (1995), rabeprazole (1999),
pantoprazole (2000), and esomeprazole (2001). In
2003 omeprazole became available over-the-counter
in the United States.
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Meccanismo di azione dei PPI
Chimicamente tutti gli inibitori di pompa
protonica sono costituiti da un anello
benzimidazolico e un anello piridinico e variano
tra di loro in base alle sostituzioni presenti in
queste due strutture. Sono piridine facilmente
protonabili. Una volta che hanno raggiunto la
mucosa gastrica dopo assorbimento sistemico si
accumulano selettivamente nei canalicoli
secretori gli spazi altamente acidi della cellula
parietale. Allinterno di questo spazio gli
inibitori di pompa protonica subiscono una
conversione catalitica verso specie altamente
reattive le sulfenamidi tiofiliche che sono dei
cationi permanenti. Queste specie reattive
interagiscono in superficie con una H, K/ATPase
sul lume dello spazio secretorio della cellula
parietale formando un legame disulfidico
attraverso due cisteine localizzate nellunità
alfa dellenzima. Questo è il residuo che è
coinvolto nel trasporto dello ione idrogeno.
Questo legame covalente con lenzima da parte
della sulfenamide tiofilica risulta in un
impedimento della secrezione gastrica specifica e
di lunga durata.
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La comparsa di malformazioni gravi nel gruppo
trattato con omeprazolo non era
significativamente diverso da quelle presenti nel
gruppo di controllo e il controllo con GERD.
Anche gli altri PPI non hanno mostrato gravi
malformazioni durante la somministrazione in
donne gravide. In ogni caso lomeprazolo rimane
il farmaco di elezione nel trattamento della GERD
in donne in gravidanza.
Vol 52 july 2006 Canadian Family Physician
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Crescita batterica da PPI
Sebbene i PPI causano un cambiamento della flora
intestinale nellintestino tenue fino ad ora non
cè evidenza che questo fenomeno interferisca con
i processi digestivi o di assorbimento.
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Farmacocinetica dei PPI
Eur J Clin Pharmacol (2008) 64935951
Il lansoprazolo è il farmaco più biodisponibile
(80-90) mentre lomeprazolo è il meno
biodisponibile (205-40). Lomeprazolo e il
pantoprazolo hanno una clearance inalterata
indipendentemente dalla funzionalità renale.
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Metabolismo dei PPI
Dalla figura si può notare che i PPI vengono
metabolizzati nel fegato tramite il CYP2C19
inizialmente e poi dal CYP3A4 in maggior misurca
rispetto al contrario.
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Uso terapeutico
Gli inibitori di pompa protonica vengono usati
nelle condizioni in cui si richiede la riduzione
della secrezione acida gastrica quali il reflusso
gastro-esofageo, il reflusso non-erosivo, ulcere
gastro-duodenali e nella sindrome di
Zollinger-Ellison . Sono usati nella terapia
delleradicazione dell Helicobacter pylori un
microrganismo patogeno implicato nellosviluppo di
ulcere gastro-duodenali. Il rabeprazolo ha il
vantaggio di non interagire con altri farmaci in
quanto non segue una via metabolica enzimatica
coinvolgente i vari CYP.
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Terapia di eradicazione dell H. pilori
Eur J Clin Pharmacol (2008) 64935951
La terapia di prima scelta nelleradicazione è
luso di un PPI, amoxicillina e claritromicina o
metronidazolo. Il trattamento di seconda scelta è
basata sulluso di bismuto in aggiunta alla
terapia di prima scelta. Il trattamento di terza
scelta è basato sui test di suscettibilità del
microorganismo per luso dellantibiotico.
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Uso di altri antibiotici in caso di precedenti
fallimenti nelleradicazione dellH.pilori
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Anti-istaminici antiulcera
I farmaci antistaminici antiulcera sono diretti
nei confronti dei recettori H2. Questi sono
cimetidina, ranitidina e famotidina.
Lancet 2009 374 11925
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Protonic pump inhibitors in kidney transplant
patients efficacy and safety. Cianciolo
G, Feliciangeli G, Comai G, Stefoni S.U.O.
Nefrologia, Dialisi e Trapianto Renale
Policlinico S. Orsola-Malpighi, Bologna. Kidney
transplant patients show a significantly elevated
incidence of gastrointestinal disorders. Protonic 
pump inhibitors (PPI) are considered to be the
correct therapy in the treatment of peptic
ulcers, as they have proven to be safe and
efficient. The metabolization of the PPIs mainly
occurs on a hepatic level therefore, there is no
need to change the therapy accordingly, as there
is with the inhibitors of the histamine receptors
(anti-H2). The PPIs currently available are
omeprazole, pantoprazole, lansoprazole,
esomeprazole, rabeprazole which present different
pharmacokinetic characteristics and different
metabolic routes which are responsible both for
differences in terms of efficacy between the
different molecules, and for the possible
side-effects they may have. All the PPIs, apart
from rabeprazole, are metabolized through an
oxidization and sulphurization processes which
involves the enzymatic system of the P450
cytochrome. The rabeprazole metabolism is
different from the other molecules of the same
category in that it only moderately involves the
CYP450 (CYP3A4 and CYP2C19) from the moment its
metabolization begins through nonenzymatic routes
and 80 is involved in a thioether non enzymatic
reduction mechanism. Consequently, rabeprazole
represents a) a potentially low pharmacological
interaction with immunosuppressive drugs b) a
pharmacokinetic aspect much less subject to
interindividual differences between one patient
and another, due to genetically determined
polymorphisms of the CYP2C19 and of the CYP3A4.
Moreover, rabeprazole may be administered safely
in standard doses with no need to change the
dosage of the other pharmaceutical drugs taken
simultaneously in nephropathic patients, patients
undergoing dialysis and transplanted patients.
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Pharmacoepidemiol Drug Saf. 2011
Oct20(10)1043-9. doi 10.1002/pds.2202. Epub
2011 Aug 8. Relationship between cardiovascular
outcomes and proton pump inhibitor use in
patients receiving dual antiplatelet therapy
after acute coronary syndrome. Hsiao FY, Mullins
CD, Wen YW, Huang WF, Chen PF, Tsai YW. Graduate
Institute of Clinical Pharmacy, College of
Medicine, National Taiwan University, Taipei,
Taiwan. fyshsiao_at_ntu.edu.tw. Abstract BACKGROUND
There is conflicting evidence regarding the
potential interaction between clopidogrel and
proton pump inhibitors (PPIs), with observational
studies suggesting an increased risk of adverse
cardiovascular (CV) outcomes and clinical trials
suggesting there is no such risk. METHODS We
conducted a retrospective cohort study to assess
CV outcomes of 9753 patients taking dual
antiplatelet therapy of aspirin plus clopidogrel
with or without a PPI after hospitalization for
acute coronary syndrome (ACS). Cox proportional
hazards models were used to assess our primary
endpoint of re-hospitalization for ACS in overall
sample and a propensity score matching
subsample. RESULTS Among patients taking
clopidogrel plus aspirin, concomitant use of PPI
was not associated with the risk of
re-hospitalization for ACS (adjusted hazard ratio
HR 1.12 95CI 0.72-1.73). The findings were
consistent in the propensity score matching
cohort (adjusted HR 0.82 95CI 0.43-1.54).
Compared with PPI nonusers, there is no
significant association between each specific PPI
users and the risk of re-hospitalization for ACS
(adjusted HR omeprazole 0.96 95CI 0.35-2.66,
pantoprazole 1.05 95CI 0.38-2.92, rabeprazole 0
.60 95CI 0.17-2.17, esomeprazole 0.31 95CI
0.10-0.99, and lansoprazole 0.82 95CI
0.32-2.07). CONCLUSION In conclusion, this
population-based cohort study found that
concomitant use of clopidogrel and PPI in
patients who received dual antiplatelet therapy
after ACS was not associated with risk of ACS
re-hospitalization. Together, our study and
findings of recently published clinical trials
suggest that there was no apparent CV interaction
between clopidogrel and PPI in patients who
received dual antiplatelet therapy.
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Proton pump inhibitor-induced hypocalcemic
seizure in a patient with hypoparathyroidism. Milm
an S, Epstein EJ.Department of Medicine, Division
of Endocrinology, Diabetes, and Metabolism,
Montefiore Medical Center, Bronx, New York 10467,
USA. Abstract OBJECTIVE To report a case of
proton pump inhibitor-induced hypocalcemic
seizure in a patient with hypoparathyroidism. METH
ODS We describe the clinical history, physical
examination findings, and laboratory values of
the patient and briefly review the relevant
literature. RESULTS A 48-year-old woman with a
history of postsurgical hypoparathyroidism who
was taking calcium carbonate, 1500 mg 3 times
daily, and cholecalciferol, 1200 IU daily,
presented with a generalized seizure in the
setting of hypocalcemia 12 days after initiating
therapy with the proton pump inhibitor lansoprazol
e. Physical examination revealed a positive
Chvostek sign. Electrocardiogram was notable for
a prolonged QT(c) interval of 576 milliseconds.
Laboratory data were notable for the following
values total serum calcium, 5.3 mg/dL ionized
calcium, 2.51 mg/dL and intact parathyroid
hormone, 5.8 pg/mL. The patient's condition
responded to therapy with intravenous calcium
gluconate, oral calcium carbonate, and
calcitriol. As an outpatient she remained
asymptomatic off lansoprazole, treated with
calcium carbonate and calcitriol. CONCLUSIONS Cau
tion should be exercised in prescribing proton
pump inhibitors to patients with a history of
hypoparathyroidism treated with calcium carbonate
supplementation because severe hypocalcemia is a
potential adverse effect.
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