Transcript Terapia peptického vredu.

Peptic ulcer
• defects of mucosa of the stomach / duodenum
= mucosal damage through the lamina muscularis mucosae
Clinical presentation:
stomach – pain in the epigastrium shortly after meal
(the patient often looses weight), nausea, anorexia
duodenum – pain later after meal (fasting), often
during the night, gets better after eating, the patient can
gain weight
Etiopatogenesis
imbalance:
aggressive factors
mostly- HCl, pepsin
↔
protective factors
mostly- mucus, bicarbonate,
fast regeneration of the
mucosa, adequate perfusion
production ↑ - histamine, of the gastric wall
acetylcholine, gastrin, protective factors ↑ - mostly
the production of
etc.
prostaglandins by
cyklooxygenase
Etiopatogenesis - causes
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Helicobacter pylori (Hp)
drugs- most frequently NSAIDs, then corticoids etc.
smoking
dietary mistakes (questionable)
psychosocial stress
genetical factors
conditions with shock, burns, head traumas
Zollinger- Ellison sy.
..........
Diagnosis and
Nonpharmacologic treatment
• ezophagogastroduodenoscopia
histologic check of nature of the ulcer lesions
presence of Hp = microscopy histo-morfology
rapid urease test breath test testing of Ab (in
plasma and in stool)
• nonpharmacol. therapy:
lifestyle (sleep, ↓ stress)
diet (often in smaller amounts, ↓ spicy, ↓ caffeine)
no smoking
Peptic ulcer in the stomach
Peptic ulcer in the duodenum
Peptic ulcer in the duodenum
Helicobacter pylori – black bacteria on the
surface of the gastric mucosa
Pharmacotherapy of
peptic ulcer
Antisecretory drugs (↓ production of HCl):
proton pump inhibitors (PPI)- omeprazole
H2 receptor antagonists- famotidine
anticholinergics (Pslytics)- pirenzepine
Drugs neutralising HCl:
coloidal antacids- compounds of Al a Mg
reactive antacids- NaHCO3 a CaCO3
Mucoprotectives:
prostaglandines, sucralfate, compounds of bismuth
ATBs:
amoxicillin, claritromycin, metronidazole, doxycycline; in case of
failure of therapy- levofloxacin, rifabutin
Antisecretory drugs
(↓ production of HCl)
Proton pump inhibitors
• MA – irreversible blockade of H/K-ATPase
(proton pump)
• most effective antisecretory drugs (inhibit the last
phase of HCl secretion → effect independent from
the stimulus for HCl secretion)
• elevated pH in the stomach decreases the
conversion - pepsinogen → pepsin
• “prodrugs“ - converted into active metabolite in
the parietal cells of gastric mucosa
• good safety profile, good tolerance
• basic pharmacotherapy for peptic ulcer
Proton pump inhibitors
omeprazole: nearly complete blockade of HCl secretion at
rest and after stimulus, high therapeutic effectivity
drug interactions: diazepam, phenytoin, warfarin
clopidogrel??- some studies- might ↓ effectivity of
clopidogrel because of inhibition of CYP450- administer
rather pantoprazole
pantoprazole, lanzoprazole: less interactions, suitable in
polymorbid and older patients esomeprazole: inovated
omeprazole with faster onset and longer duration of action
Newer drugs:
ilaprazol
tenatoprazol: strongest effect, longest duration of effect
H2 receptor antagonists
- MA - selective blockade of H2 histamine receptors →
inhibition of histamine mediated HCl production (indirect
effect on secretion mediated by Ach and gastrin)
- ↓ effectivity than proton pump inhibitors
Examples – cimetidine, ranitidine, famotidine (more
effective), nizatidine
- good safety profile, good tolerance
- drugs of 2nd choice for treatment of peptic ulcer; loosing
therapeutic role in most indications (↓ effectivity)
Anticholinergics
- MA – inhibition of M1 receptors → inhibition of
acetylcholine mediated HCl production
- ≈ same effectivity as H2 antagonists
- ADRs – consequences of ↓activity of PS – for
example dry mouth, problems with vision and
urination, constipation
- example- pirenzepine
- they lost their therapeutic role – ADRs, ↓
effectivity than proton pump inhibitors
Drugs neutralising HCl:
(antacids)
• coloidal antacids:
aluminum and magnesium hydroxide
MA: weak bases → bind HCl; slightly ↑ the production of
prostaglandines
ADRs: - Al hydroxide: constipation, ↓ resorption of
phosphates → osteomalacia; - Mg hydroxide: diarrhoea,
hypermagnesemia; both- risk of interactions!!
• reactive antacids:
NaHCO3 and CaCO3
MA: reaction with HCl, during which CO2 is formed
ADRs: - flatulence, ´milk-alkali´ syndrome
(hypercalcemia, nephrolithiasis, renal insufficiency, ...), in
the case of NaHCO3 metabolic alkalosis !!!!
Antacids – only for symptomatic treatment of dyspepsia!!!
Mucoprotectives
Prostaglandines
• misoprostol (analog of PGE1), enprostil (analog
of PGE2)
- cytoprotective and mucoprotective effect improve the microcirculation underneath the
mucosa + ↑ production of mucus and
bicarbonate + ↑ regenerationof defects
ADRs – diarrhoea, stomach pain, abortion,
- can be used in prevention of peptic ulcer formation
during NSAID treatment (for that, we have other, in
most cases better alternatives)
Sucralfate
• salt of sulfonated sucrose
• MA: in an acidic environment it forms a protective
layer on the surface of the mucus membrane and on the
surface of the defect
• probably stimulates the formation of prostaglandines
• well tolerated
• !don´t administer after administration of antisecretory
drugs!
• seldomly used
Bismuth
- ↑ secretion of mucus and bicarbonate, ↓ secretion
of HCl, antibacterial effect
- ADRs – metallic taste in the mouth, black tongue
and stool, !neurotoxicity (confusion,
hallucinations...)
nowadays used less frequently (risk of ADRs),
part of 2nd line of H. pylori eradication therapy
Eradication of
Helicobacter pylori
(needed for long-term success of
pharmacotherapy of peptic ulcer in Hp
positive patients)
1st line treatment: triple therapy
7 or14 day treatment (14
days – better results)
• proton pump inhibitor
• claritromycin
• amoxicillin – if PNC allergy - metronidazole
problem – decreasing effectivity of the treatment (fails
in approximately 25-30 % of patients)
2nd line treatment: quadruple therapy
(in case of failure of triple therapy; in patients treated with
macrolides in the past; can be considered in patients with
PNC allergy)
7 or14 day treatment (14 days – better results)
• proton pump inhibitor
• bismuth
• metronidazole
• doxycycline
problem – decreasing effectivity of the treatment
– possibility of ↓ compliance (dosing scheme)
– ADRs (mostly bismuth)
New possibilities: sequential therapy
10 days (5 + 5), for example:
First 5 days
• proton pump inhibitor
• amoxicillin
Next 5 days
• proton pump inhibitor
• claritromycin
• tinidazole (possibly metronidazole ??)
Failure of the therapy:
Future?? :
Non-steroidal anti-inflammatory
drugs (NSAIDs) and peptic ulcer
NSAIDs – one of the most widely used drug groups
– in roughly 25 % of chronic users can cause erosions and
ulcerations in the GIT, in 2-4 % perforation or bleeding
Possibilities of prevention–
proton pump inhibitors or
misoprostol during NSAID treatment; use of NSAIDs selectively
inhibiting COX-2
Strategy
– small risk of ulcer – NSAID on its own
– moderate risk of ulcer – NSAID + PPI / misoprostol
– high risk of ulcer – a) administer other (non-NSAID) analgesics,
or b) COX-2 selective NSAID + PPI / misoprostol