Gastro-Intestinal Drugs by bvishaal


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									 abdominal  discomfort (pain, bloating,
  distention, or cramps)
 alterations in bowel habits (diarrhea,
  constipation, or both).
 predominant   diarrhea, antidiarrheal agents,
  especially loperamide
 predominant constipation, fiber supplements
 For chronic abdominal pain, low doses of
  tricyclic antidepressants (eg, amitriptyline or
 The anticholinergic properties -
  gastrointestinal motility and secretion,
  reducing stool frequency and liquidity.
 dicyclomine   and hyoscyamine
 exhibit significant additional anticholinergic
  effects including-
 dry mouth
 visual disturbances
 urinary retention
 constipation.
 inhibit sensation, including nausea, bloating,
  and pain.
 reduces the central response to visceral
  afferent stimulation.
 inhibits colonic motility, especially in the left
  colon, increasing total colonic transit time.
 Alosetron  is a 5-HT3 antagonist that has been
  for the treatment of patients with severe IBS
  with diarrhea
 Four other 5-HT3 antagonists (ondansetron,
  granisetron, dolasetron, and palonosetron)
 Alosetron  -for the treatment of women with
  severe IBS ("diarrhea-predominant IBS").
 Its efficacy in men has not been established.
 it reduces IBS-related lower abdominal pain,
  cramps, urgency, and diarrhea.
 gastrointestinal   toxicity
 Constipation
 Episodes  of ischemic colitis
Drug Interactions:
being metabolized by a number of CYP
  enzymes, alosetron does not have clinically
  significant interactions with other drugs.
 Chloride Channel Activator
 Serotonin 5-HT4-Receptor Agonists
 Inflammatory   bowel disease (IBD) comprises
  two distinct disorders:
 ulcerative colitis and
 Crohn's disease.
 5-aminosalicylic acid (5-ASA) have been
  used in the treatment of inflammatory bowel
 formulations have been designed to deliver
  5-ASA include sulfasalazine, olsalazine,
  balsalazide, and various forms of
 sulfasalazine,   5-ASA is bound to
 balsalazide, 5-ASA is bound to 4-
  aminobenzoyl--alanine; and
 olsalazine, two 5-ASA molecules are bound
 In the terminal ileum and colon, resident
  bacteria cleave the azo bond by
  azoreductase enzyme, releasing active 5-
 Pentasa is a
 formulation that
 contains timed-
 microgranules that
 release 5-ASA
 Asacol has 5-ASA
 coated in a pH-
 sensitive resin that
 dissolves at pH 7
 Lialda also uses a pH-dependent resin that
  encases a multimatrix core.
 5-ASA delivered in high concentrations to
  rectum and sigmoid colon by means of
  enema formulations (Rowasa) or
  suppositories (Canasa).
 5-ASA  drugs are considered to be the first-
  line agents for ulcerative colitis.
 efficacy in Crohn's disease is unproven
Nausea           GI Upset        Headache         Bone Marrow


                       malaise              Myalgia
 slow acetylators of sulfapyridine
 Hypersensitivity to sulfapyridine - fever,
  exfoliative dermatitis, pancreatitis,
  pneumonitis, hemolytic anemia, pericarditis,
  or hepatitis.
 Oligospermia-reverses
 Sulfasalazine impairs folate absorption
 renal tubular damage in patients receiving
  high doses of aminosalicylates.
 nephritis are reported with high doses of
  mesalamine formulations
 prednisone  and prednisolone are the most
  commonly used oral glucocorticoids.
 Hydrocortisone enemas, foam, or
  suppositories are used - via topical treatment
  of active inflammatory bowel disease in the
  rectum and sigmoid colon.
 Budesonide    rapid first-pass hepatic
  metabolism resulting in low oral
 inhibit production of inflammatory cytokines
  (TNF-, IL-1) and chemokines (IL-8);
 inhibit gene transcription of nitric oxide
  synthase, phospholipase A2, cyclooxygenase-
  2, and NF-B.
 Glucocorticoids are commonly used in the
  active inflammatory bowel disease.
 rectally administered glucocorticoids are
 Oral controlled-release budesonide (used in
  the treatment of Crohn's disease
 azathioprine is rapidly converted by a
  nonenzymatic process to 6-MP.
 6-Mercaptopurine undergoes
  biotransformation via competing enzymes
  that produce inactive metabolites and active
  thioguanine nucleotides.
 Azathioprine and 6-MP -in the induction and
  maintenance of remission of ulcerative colitis
  and Crohn's disease.
 long-term glucocorticoid therapy to control
  active disease
 purine analogs allow dose reduction or
  elimination of steroids
 nausea, vomiting, bone marrow depression
  and hepatic toxicity
 Severe leukopenia may predispose to
  opportunistic infections
 Hypersensitivity reactions to azathioprine
  or 6-MP occur in patients.
 include fever, rash, pancreatitis, diarrhea,
  and hepatitis.
 Allopurinol markedly reduces xanthine oxide
  catabolism of the purine analogs,
 increasing active 6-thioguanine nucleotides
  that may lead to severe leukopenia.
 Methotrexate   antimetabolite that has
  beneficial effects in Crohn's disease and
  rheumatoid arthritis
 Methotrexate may be given orally, S.C, or I.M
 inhibitionof dihydrofolate reductase
 interfere with inflammatory actions of
 stimulate increased release of adenosine also
  stimulate apoptosis and death of activated T
 bone  marrow depression,
 megaloblastic anemia,
 Alopecia
 At the doses used in the treatment of
  inflammatory bowel disease, these events
  are uncommon
 two biologically active forms: soluble TNF
  and membrane-bound TNF.
 The biologic activity is mediated by binding
  to TNF receptors (TNFR) that are present on
  some cells (especially TH1 cells, innate
  immune cells, and fibroblasts).
      Binding of TNF to TNFR
             activates NF-B
transcription, growth, and expansion.
Biologic actions:
release of proinflammatory cytokines
1.T-cell activation and proliferation
2. fibroblast collagen production
3. up-regulation of endothelial adhesion
 infliximab, adalimumab, and certolizumab
 Infliximab and adalimumab are antibodies of
  the IgG1 subclass.
 Certolizumab is a recombinant antibody
 Infliximab is administered as an I.V infusion.
 Adalimumab and certolizumab are
  administered by S.C injection.
 Allthree agents bind to TNF with high affinity,
 suppresses cytokine release.
 When infliximab or adalimumab bind to
  membrane-bound TNF
    - promotes antibody-mediated apoptosis
    - complement activation, and
    - cellular cytotoxicity of activated T
lymphocytes and macrophages.
 Infliximab   also is approved for ulcerative
 Effective in patients with moderate to severe
  Crohn's disease
 including patients been dependent on
  glucocorticoids or not responded to 6-MP or
 infection -bacterial sepsis, tuberculosis,
  invasive fungal organisms, reactivation of
  hepatitis B, listeriosis, and other
  opportunistic infections.
 upper respiratory infections (sinusitis,
  bronchitis, and pneumonia)
 Antibodies to the antibody (ATA) may develop
  with all three agents.
 Infliximab -include fever, headache,
  dizziness, urticaria, or mild cardiopulmonary
  symptoms that include chest pain, dyspnea.
 Severe acute reactions include significant
  hypotension, shortness of breath, muscle
  spasms, and chest discomfort
A  delayed serum sickness-like reaction
  consist of
- myalgia, arthralgia, jaw tightness, fever,
  rash, urticaria, and edema
 Integrins are a family of adhesion molecules
  on the surface of leukocytes
 adhesion molecules on the surface of the
  vascular endothelium known as selectins
 humanized   IgG4 monoclonal antibody
  targeted against the alpha 4 subunit, which
  thereby blocks several integrins on
  circulating inflammatory cells
 shown efficacy in moderate to severe Crohn's
 Drawback:
-progressive multifocal leukoencephalopathy
  due to reactivation of a human polyomavirus
 Exocrine  pancreatic insufficiency is caused
  by cystic fibrosis, chronic pancreatitis, or
  pancreatic resection.
 These Supplements are the mainstay of
  treatment for pancreatic enzyme
 pancreatin  and pancrelipase
 Pancreatin -low concentrations of lipase and
  proteolytic enzymes
 pancrelipase is a preparation
   -pancrelipase has 12 times the lipolytic
activity and
-4 times the proteolytic activity of pancreatin.
 inactivated by gastric acids
 non–enteric-coated - given concomitantly
  with acid suppression therapy (PPI or H2
 Encapsulated formulations contain acid-
  resistant microspheres (Creon) or
  microtablets (Pancrease, Ultrase)
 Capsules should be swallowed, not chewed, -
  cause oropharyngeal mucositis
 Excessive doses -diarrhea and abdominal
 The high purine content -hyperuricosuria
  and renal stones.
 colonic strictures were reported been
  removed from the market.
 Ursodiol makes up the circulating bile salt
  pool in humans
 After oral administration-conjugated in the
 extensive enterohepatic recirculation.
 undergoes dehydroxylation by colonic
  bacteria to lithocholic acid, a substance with
  hepatic toxicity.
Ursodiol decreases cholesterol content by
  -reducing hepatic cholesterol secretion.
-stabilize hepatocyte canalicular membranes
    -a reduction in the concentration of other
endogenous bile acids or
    - inhibition of immune-mediated hepatocyte
 Ursodiolis used for dissolution of small
  cholesterol gallstones -with gallbladder
 prevention of gallstones in obese patients
  undergoing rapid weight loss therapy.
 Ursodiol is free of serious adverse effects.
 diarrhea is uncommon.
 Unlike predecessor, chenodeoxycholate,
  ursodiol has not been associated with
 Portal hypertension is caused by increased
  blood flow within the portal venous system
 increased resistance to portal flow within the
 Ascites
  hepatic encephalopathy
 development of portosystemic collateral
  especially gastric or esophageal varices.
 Varices can rupture, leading to massive upper
  gastrointestinal bleeding.
 Somatostatin & Octreotide
 Vasopressin & Terlipressin
 Beta-Receptor–Blocking Drugs
 Vasopressin  (antidiuretic hormone) it is also
  a potent arterial vasoconstrictor.
 administered I.V by continuous infusion,
 causes splanchnic arterial vasoconstriction -
  reduced splanchnic perfusion and lowered
  portal venous pressure
 Systemic   and peripheral vasoconstriction can
  lead to
 Hypertension
 myocardial ischemia or infarction
 mesenteric infarction
These effects may be reduced by
coadministration of nitroglycerin (by reducing
portohepatic vascular resistance) and
-reduce the coronary and peripheral vascular
vasospasm caused by vasopressin
 Nausea
 abdominal   cramps and
 diarrhea
 theantidiuretic effects of vasopressin
 promote retention of free water, which can
 lead to hyponatremia, fluid retention, and
 pulmonary edema
A   vasopressin analog that has similar efficacy
  to vasopressin
 fewer adverse effects
 it has never been approved for use in the
 reduce  portal venous pressure via a decrease
  in portal venous inflow.
 This decrease is due to a decrease in cardiac
  output (1 blockade) and
 splanchnic vasoconstriction (2 blockade)
  caused by the unopposed effect of systemic
  catecholamines on receptors.
 nonselective  blockers such as propranolol
  and nadolol are more effective than selective
  1 blockers
 Nonselective blockers significantly reduce
  the rate of recurrent bleeding

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