Transcript Petr Potměšil

Celecoxib, etoricoxib: selective COX-2 inhibitors (p.o.)
(valdecoxib for parenteral use: ac. postoperat. pain )
Celecoxibe (Celebrex)
• Pharm. Form and dosage
cps. 100/200 mg: once/twice daily
• Indications
- osteoarthritis
- rheumatoid arthritis
- pain in dysmenorrhea
• Contraindications
- CAD, heart failure NYHA III or IV,
not controlled hypertension
Etoricoxibe (Arcoxia)
• Pharm. Form and dosage
Tbl. 30/60/90/120 mg: once daily
• Indications
- osteoarthritis
- rheumatoid arthritis
- ac. gout attack
• Contraindications
- CAD, heart failure NYHA III or IV,
not controlled hypertension
Petr Potměšil, Magdalena Šustková
Selected topics in
gastroenterology
Non-specific inflammatory bowel diseases
no clearly discernible 1 aetiological cause of disease
2 most important of these diseases affecting the large bowel:
• Ulcerative colitis = idiopathic proctocolitis
confined to the large bowel (few centimetres of the terminal ileum
may be affected by ileitis)
• Crohn's disease = ileitis terminalis
microscopically affects the whole of the gastrointestinal tract (very
often ileitis or ileocolitis or manifestation in the large bowel)
chronic diseases: try to treat the acute symptoms then maintaining
remission and avoiding complications
Colitis ulcerosa and morbus crohn –
therapeutic options
• Antiinflammatory drugs
• Biological therapy
1/ mesalazin (Pentasa), active
ingredient from sulfasalazine
2/ glucocorticoids
antininflammatory and
immunosuppressive action
1/ inhibitors of TNF – alpha
• Immunosuppressive drugs
2/ inhibition of leucocyte migration
1/ azathioprin (Imuran tbl.+inj.)
2/ methotrexate (Trexane, Metoject)
• Probiotics
a) Infliximab (Remicade), chimeric monocl. antib.
b) Adalimumab (Humira), hum. monoclon. antib.
c) Not etanercept (Enbrel) !!
natalizumab (Tysabri): anti-integrine eff.
• Supplementation
- Vit. B12 inj. (contraind. in cancer)
Non-specific inflammatory bowel disease
A) Regimen approach
• Specific diet
effective, avoiding oranges, grain legumes
B) Influencing of pathophysiological processes
• Bowel antiinflammatory drugs: aminosalicylates
• Biological therapy, immunosuppressive drugs
• Corticosteroids:
• Hydrocortisone: rect. supposit.: local effects
• Prednison: perorally 30-60mg daily if more severe
C) Complications
• Antimicrobial drugs if infection (perianal festering compl.)
Treatment of festering complications with ATB
• Festering (putrefactive) complications:
1) active colitis ulcerosa
2) Crohn´s disease
• Ciprofloxacin: broad-spectrum chinoline ATB that blocks DNA gyrasis
/CIFLOXINAL,CIPHIN, CIPLOX/
• Metronidazole: well passing to CNS, bones etc., anaerobic pathogens +
against - aerobic /EFLORAN, ENTIZOL, METROZOL/
• Clarithromycin: broad-spectrum macrolide /KLACID, FROMILID/
• Rifaximine
• Co-trimoxazole
Aminosalicylates
• the main anti-inflammatory drugs used to treat
ulcerative colitis
• sometimes remission or at least maintaining disease
with these drugs alone
• usually used in combination
• anti-inflammatory action in all these drugs - produced by
5-aminosalicylic acid (5-ASA) = Mesalazine
• 5-ASA is produced from the other pro-drugs in the intestine
MESALAZINE
– absorbed in jejunum – specific drug formes for effect in large
bowel
– Local effect: COX inhibition, inhibition of lipooxygenase …?
free radicals inactivation ?
– p.o. 1-4g daily (2-3x daily 250-500mg); clysma, supp (ASACOL,
PENTASA, SALOFALK)
– acute problems therapy – maintenance therapy (1/2D) months,
years; (success within 4 weeks)
– Adv. Eff.: less than after sulfasalazine – nephrotoxicity,
interactions (↑toxicity p.o. antidiabetics, methotrexate), with
corticosteroids risk of GIT bleeding is increased
Aminosalicylates
• Pro-drugs of mesalazine (5-ASA):
• Sulfasalazine (SALZOPYRIN, SULFASALAZIN)
– 75% non-absorbable, in the large bowel bacterial degradation 5-ASA (+
sulfapyridine)
– 500mg 2-4x daily till 1g 3-4x daily; maintenance d. 500mg 4xdaily
– More ADVE than mesalazine – headache, dyspeptic disorders, allergy,
reduced sperm count and damage of red / white blood cells haemolytic
anemia, hepatotoxicity etc. (patients on high dose of sulfasalazine
require folic supplementation to maintain normal blood cell count)
• Olsalazine and balsalazide (not registered in CZ)
AE: better tolerated, diarrhea – increased GITsecretion
Anatomical localization of effect of
aminosalicylates
Corticosteroids/Glucocorticoids
• supp., enema/clysma, foam – when problem localised near
rectum, mostly individually produced/ magistraliter (např.
methyprednisolon inj. as enema)
• systemic hydrocortison, prednison (60mg – go down to 20mg/day),
prednisolon
• New synthetic derivates – local use – non-absorbable, less ADVE,
for longer-lasting use (also inhalatory antiasthmatics,
dermathologics)
• budesonide /3xdaily, BUDENOFALK cps, controlled release, rectal foam, ENTOCORT
cps, enema/, faster metabolized, fewer side effects
Immunosuppressive drugs
• mostly azathioprin (1-3mg/kg/day, go down), 6merkaptopurine (1 mg/kg/day) - reduce NKcells of immune system – in longer-lasting highly
active inflammation (higher D of corticosteroids)
– haematogenesis control!
• methotrexate (folic acid antagonist) – in non
tolerated (i.m. - than p.o. 10-15mg weekly)
• in severe colitis – corticosterid-resistant – shorttime combination with ciclosporine A (17mg/kg/day – after 6-8weeks effect), recidives
Biotransformation of azathioprine
Indications for operation
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Morbus Crohn
Colitis ulcerosa
Perforation, peritonitis
Ileus
Massive bleeding
Pronounced stenosis
Fistula, abscess
Failure of conservative
therapy
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Perforation, peritonitis
Proven precancerosis
Toxic megacolon
Pronounced stenosis
Long severe disease course
(surgery as prevention of
carcinoma development)
Spasmolytics/
antispasmodic drugs –
smooth muscles
(of GIT, urinary tract)
SPASMOLYTICS: neurotropic
parasympatholytics
- atropine-like eff. – quarternary nitrogen structure hydrophilic – (N-butyl scopolamine)
N-butyl scopolamine, otilonii bromidum, fenpiverinium,
oxyphenonium
Use: used for smooth muscels contraction, especially in
tubular organs of the GIT - to prevent spasms of the
stomach, gall or urinary bladder, GIT dyskinesis
In combinations with analgetic drugs
Spasmolytics: musculotropic
musculotropic – direct effect in the muscle
-papaverine-like
papaverine, drotaverine, alverine, mebeverine, pitofenone,
pinaverine (GIT Ca channel blocker) etc.
Use: prevent spasms of the stomach, intestine or urinary
bladder, GIT dyskinesis..
Combinations with analgetic drugs
Spasmoanalgesics
• A) Combinations of analgesics + spasmolytics
– Pitofenone + fenpiverine + metamizol = ALGIFEN,
ANALGIN, SPASMOPAN
• B) Analgetic drugs with spasmolytic effects – metamizol
/NOVALGIN/, pethidin /DOLSIN/
USE: symptomatic painful spasms of GIT or urinary tract
(bladder, kidney colics), spastic migraine, dysmenorrhea,
instrumental checkup
Probiotics, prebiotics
• Prebiotics nonabsorbable oligosacharides supporting normal
intestinal microflora (e.g. bifidobacteria) – mannan, inulin, lactulosis
• Probiotics – alive bacteria
Lactobac. delbruecki, Acidophilus casei, Enteroc. faecium other bifidobacteria
– competition with pathogenes
– production of substances that inhibit pathogenes
(lactic acid, peroxide)
– intestine immunity support
Prevention – carcinomas, allergy, traveler´s diarrhea
Deflatulents
• Meteorisms – daily production of 1-2 l of gas;
disturbancies – increassed production, limited
absorption in inflammation, venostasis….
• Treatment - reduction of surface tension activity of
liquides in the GIT tube
• Deflatulents:
– Simeticon – activated dimeticon (silicon oil
dispersion) – non-absorbable
– bowel eubiotics - prebiotics and probiotics
Bowel eubiotics
• A) probiotics: alive non-pathogenic bacteria or
candida)
• B) prebiotics: oligofructans – support growth of
physiological microflora
• C) symbiotics: mixture of alive nonpathogenic
bacteria or candida and growth substrates)
Bowel eubiotics
• Escherichia coli – well sensitive on ATB
• Lactobacillus acidophilus
• Lactobacilli acidophili metabolits
(concentrate of metabolic products, no alive
bacteria)
• Saccharomyces boulardii siccatus (alive
probiotic candida supports natural
microflora)
Other possible indications of drugs that are used for
therapy of colitis ulcerosa/ m. Crohn
• Antiinflammatory drugs
1) mesalazin (Pentasa), active ingredient
from sulfasalazine
only indication
for colitis ulcerosa + m. Crohn
• Immunosuppressive drugs
1) azathioprin
- transplantation, severe RA, SLE
- autoimmune hemolytic anemia
- polyarteritis nodosa
- autoimmune chronic act. hepatitis
2) methotrexate: cytostat. + immunosuppr.
2) glucocorticoids
antiinflammatory + immunosuppressive a) oncology
astma – inhal. systems, if severe p.o.
ac. lymfobl. leucaemia, osteosarcoma
dermatology - eczema
b) rheumatology
rheumatology, ophthalmology
severe active rheumat. + psoriat. artritis
Other indications of biological drugs used for
therapy of colitis ulcerosa/ m. Crohn
A/ inhibitors of TNF - alpha
1/ Infliximab: contraindicated in pregnancy + breastfeeding,
severe infection (sepsis, TBC), heart failure, hypersensitivity
- rheumatoid artritis
- psoriatic artritis and psoriasis, ancylosing spondylitis
2/ Adalimumab: contraindicated in pregnancy + breastfeeding,
severe infection (sepsis, TBC), heart failure, hypersensitivity
- rheumatoid artritis, polyarticular juvenile idiopathic artritis
- psoriatic artritis and psoriasis, ancylosing spondylitis
B/ inhib. of leucocyte migration: natalizumab - multiple sclerosis
Intestine infection, diarrhea: possible ther. options
• Cloroxine (ENDIARON)
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bacteriostatic, g+, g-, against Candidas (in dysmicrobia following ATB use)
No resistance
No absorption – local effect, low toxicity, usually well tolerated
+ oxyphenone – spasmolytic; + further combinations with peripheral „opioids“ (loperamide,
difenoxylate)
• Possible risk of neurotoxicity in longterm therapy, appl. for max. 7-10 days
• Rifaximine (NORMIX)
nonabsorbable ATB – inhib. of RNA-synthesis; children from 2 years,
bactericidal eff., g+, g-, risk of resistance
• Nifuroxazide (ERCEFURYL)
nonabsorbable, bacteriostatic chemotherapeutic for ac. infection diarrhea
• Co-trimoxazol = sulfamethoxazol+trimethoprim: from 6 yrs (BISEPTOL)
Antibiotics for ACUTE CHOLECYSITITS and
CHOLANGITIS
Ac. cholecystitis
Ac. cholangitis
• AMP
• TET
• Cotrimoxazole
• AMP
• Chloramfenikol
• Tetracycline