Drugs used in GIT disorders - PowerPoint Presentation

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Drugs used in GIT disorders

Haitham AlwaliPh.D. PharmacologyAl-Nahrain College of Pharmacy

2/12/2018

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A.

Drugs Used in Acid-Peptic DiseasesUlceration and erosion of the lining of the upper portion of the gastrointestinal tract are common problems that manifest as

gastroesophageal

reflux disease (GERD), gastric and

duodenal

peptic

ulcers

, and

stress-related mucosal injury.Drugs used in acid-peptic disease reduce intragastric acidity by manipulating systems controlling acid secretion, promote mucosal defense or, in the case of peptic ulcers, eradicate the bacterium Helicobacter pylori, which is detectable in over 80% of patients with duodenal ulcers.

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1.

Antacids: are weak bases that neutralize stomachacid by reacting with protons in the lumen of the gut and may also stimulate the protective functions of the gastric mucosa.

antacids reduce the recurrence rate of peptic ulcers.

Popular antacids include magnesium

hydroxide

(Mg[OH]2

) and

aluminum hydroxide

(Al[OH]3). Neither of these weak bases is significantly absorbed from the bowel. Magnesium hydroxide has a strong laxative effect, whereas aluminum hydroxide has a constipating action. These drugs are available as single-ingredient products and as combined preparations.2/12/2018Haitham Alwali

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Calcium

carbonate and sodium bicarbonate are also weak bases, but they differ from aluminum

and magnesium hydroxides in being absorbed from the

gut. Because of their systemic effects

, calcium and bicarbonate

salts

are

less popular

as antacids.2. H2-receptor antagonists—Cimetidine and other H2 antagonists (ranitidine, famotidine, and nizatidine) inhibit stomach acid production, especially at night. They are effective in the treatment of GERD, peptic ulcer disease, and nonulcer dyspepsia and in the prevention of stress-related gastritis.

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3.

Proton pump inhibitors—Omeprazole and (esomeprazole, (dex)

lansoprazole, pantoprazole,

and rabeprazole) are lipophilic weak bases that diffuse into

the

parietal

cell canaliculi, where they

become

protonated and concentrated more than 1000-fold. There they undergo conversion to compounds that irreversibly inactivate the parietal cell H+/K+ ATPase, the transporter that is primarily responsible for producing stomach acid.2/12/2018Haitham Alwali6

Oral formulations of these drugs are

enteric coated to prevent acid inactivation in the stomach. After absorption in the intestine, they are rapidly metabolized in the liver, with

half-lives of 1–2 h. However, their durations of action are approximately

24 h, and they may require 3–4 d of treatment to achieve

their

full effectiveness

.

Proton pump inhibitors are

more effective than H2 antagonists for GERD and peptic ulcer and equally effective in the treatment of nonulcer dyspepsia and the prevention of stress-related mucosal bleeding. They are also useful in the treatment of Zollinger- Ellison syndrome. 2/12/2018Haitham Alwali

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Adverse effects of proton pump inhibitors

occur infrequently and include diarrhea, abdominal pain,

and headache

. Chronic treatment with proton pump inhibitors may result

in

hypergastrinemia

.

Proton pump inhibitors may

decrease the oral

bioavailability of vitamin B12 and certain drugs that require acidity for their gastrointestinal absorption (eg, digoxin, ketoconazole).Patients taking proton pump inhibitors may have a small increase in the risk of respiratory and enteric infections.2/12/2018Haitham Alwali

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4.

Sucralfate— An aluminum sucrose sulfate, sucralfate is a small, poorly soluble molecule that polymerizes in the acid environment of

the stomach. The polymer binds to injured tissue and forms a protective coating over ulcer beds.

Sucralfate accelerates the healing of peptic ulcers and reduces the recurrence rate

.

5.

Misoprostol

—An analog of PGE1, misoprostol

increases mucosal

protection and inhibits acid secretion. It is effective in reducing the risk of ulcers in users of non steroidal anti-inflammatory drugs (NSAIDs).2/12/2018Haitham Alwali10

6.

Antibiotics—Chronic infection with H pylori is present in most patients with recurrent non-NSAID-induced peptic ulcers.Eradication of this organism greatly reduces the rate of recurrence of ulcer in these patients. One regimen of choice consists

of a proton pump inhibitor plus a course of clarithromycin and

amoxicillin (or metronidazole in patients with penicillin allergy).

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B.

Drugs That Promote Upper Gastrointestinal MotilityTheir ability to increase lower esophageal sphincter pressures also makes them useful for some patients with GERD

.In the enteric nervous system, dopamine inhibits cholinergic stimulation

of smooth muscle contraction. Metoclopramide

and

domperidone

are D2 dopamine receptor antagonists that

promote gastrointestinal

motility.When used chronically, metoclopramide can cause symptoms of parkinsonism, other extrapyramidal effects, and hyperprolactinemia. Because it does not cross the blood-brain barrier, domperidone is less likely to cause CNS toxicity.The macrolide antibiotic erythromycin promotes motility by stimulating motilin receptors.2/12/2018Haitham Alwali12

C.

Laxatives:Mechanism Examples1-Bulk-forming

Psyllium,

methylcellulose

2-

Stool-softening

glycerin

, mineral oil

3-

Osmotic Magnesium oxide, lactulose, 4-Stimulant Aloe, senna, cascara, castor oil, bisacodyl 5-Chloride channel Lubiprostone activator

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D. Antidiarrheal Agents

Diphenoxylate and loperamide, meperidine

analogs with very weak analgesic effects.

Diphenoxylate is formulated with

antimuscarinic

alkaloids

(

eg

, atropine) to reduce the likelihood of

abuse; loperamide is formulated alone. Kaolin, a naturally occurring hydrated magnesium aluminum silicate, is combined with pectin, an indigestible carbohydrate derived from apples ( absorbs bacterial toxins and fluid, resulting in decreased stool liquidity.these agents should not be used in patients with bloody diarrhea, high fever, or systemic toxicity because ofthe risk of worsening the underlying condition.2/12/2018Haitham Alwali

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E.

Drugs Used for Irritable Bowel Syndrome(IBS) is associated with recurrent episodes of abdominal discomfort (pain, bloating, distention, or cramps)plus diarrhea or constipation (or both).

The pharmacologic strategy includes

antidiarrheal agents OR laxatives

; and

for the treatment of abdominal

pain, low

doses of tricyclic antidepressants

dicyclomine

and hyoscyamine are used as antispasmodics to relieve abdominal painAlosetron, a potent 5-HT3 antagonist, is approved for treatment of women with severe IBS with diarrhea.Lubiprostone, a laxative that activates the type 2 chloride channels in the small intestine.2/12/2018Haitham Alwali15

F. Drugs With Antiemetic

ActionsIn addition to metoclopramide and other D2 dopamine receptor antagonists, useful antiemetics

are drugs with H1 histamine blocking activity (diphenhydramine), and several phenothiazines

; antimuscarinic drugs such as

scopolamine

; the

corticosteroid

dexamethasone

; and the cannabinoid receptor agonists dronabinol.The 5-HT3 antagonists ondansetron, granisetron, dolasetron are useful in preventing nausea and vomiting after general anesthesia and in patients receiving cancer chemotherapy.Aprepitant, a newer antiemetic, is an antagonist of the neurokinin 1 (NK1) receptor, a receptor in the CNS that is activated by substance P and other tachykinins.

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G.

Drugs Used in Inflammatory Bowel Disease (IBD)Aminosalicylates—Drugs containing 5

aminosalicylic acid (5-ASA) are used as topical therapy for IBD.

The precise mechanism of 5-ASA action is uncertain but may involve

inhibiting the

synthesis of prostaglandins and inflammatory

leukotrienes

.

Balsalazide

and sulfasalazine (a combination of 5-ASA and sulfapyridine) has a higher incidence of adverse effects (sulfapyridine moiety) include gastrointestinal upset, headaches, arthralgias, bone marrow suppression, andsevere hypersensitivity reactions2. Other agents: include

antibiotics, glucocorticoids

(budesonide),

immunosuppressive antimetabolites

(

eg

, azathioprine, methotrexate)

antitumor necrosis

factor

[TNF] drugs (

eg

, infliximab,

adalimumab

).

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H. Pancreatic Enzyme

Replacements:Steatorrhea, a condition of decreased fat absorption together with an increase in stool fat excretion, results from

inadequate pancreatic secretion of lipase

.The abnormality of fat absorption can be significantly

relieved by oral administration of pancreatic

lipase (

pancrelipase

or

pancreatin) obtained from pigs.Pancreatic lipase is inactivated at a pH lower than 4.0; the enzyme should be taken as enteric-coated capsules.I. Drugs That Inhibit the Formation of GallstonesThe formation of cholesterol gallstones can be inhibited by the bile acid derivative ursodiol, which decreases the cholesterol content of bile by decreasing hepatic cholesterol secretion.2/12/2018Haitham Alwali

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