Gastrointestinal and Antiemetic Drugs

[Adnano]

بسم الله الرحمن الرحيم

I will discuse here the drugs used to treat three common medical conditions involving the gastrointestinal tract
1. peptic ulcers and gastroesophageal reflux disease (GERD)
2. chemotherapy-induced emesis
3. diarrhea and constipation

Drugs Used to Treat Peptic Ulcer Disease
Causin of peptic ulcer Tretment
Helicobacter pylori infection eradicating the H. pylori infection
increased hydrochloric acid secretion reducing secretion of gastric acid
inadequate mucosal defense providing agents that protect the gastric mucosa from damage,


Antimicrobial agent
Pt with peptic ulcer who are infected with H.pylori reqiure antimicrobial treatment
Triple therapy : proton pump inhibitor(PPI)+metronidazole or ampicillin + clarithromycin
Quadruple therapy : Bismuth subsalicylate + metronidazole + tetracycline + PPI


Regulation of gastric acid sec
Gastric acid secretion is stimulated by acetylcholine , histamine & gastrin
Diminsh by prostaglandin E2 & somatostatin


H2-receptor antagonists
Cimetidine , ranitidine , famotidine , nizatidine
Action
These agents completely
inhibit gastric acid secretion induced by histamine or gastrin. However, they only partially inhibit gastric acid
secretion induced by acetylcholine or bethanechol.
Therapeutic uses
Peptic ulcer
Acute stress ulcer
GERD
Pharmacokinetics
Given orally , distribute widely throughout the body (icluding into breast milk & across the placenta) and excreted mainly in the urine
Adverse effect
The most effect the side effect are headache , dizziness , diarrhea & muscular pain
CNS effect confusion , hallucination
gynecomastia, galactorrhea (continuous release/discharge of milk), and reduced sperm count



will be follow

[Adnano]

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Inhibitors of the H+/K+-ATPase proton pump
Omeprazole , lansoprazole , rabeprazole , pantoprazole , esomeprazole
Actions
These agents are prodrugs, a weak base, are absorbed and transported to the parietal cell canaliculus
There, it is converted to the active form, which reacts with a cysteine residue of the H+/K+-ATPase, forming a stable covalent bond
Therapeutic uses
For treating erosive esophagitis and for long-term treatment of pathologic hypersecretory conditions (for example, Zollinger-Ellison
Syndrome
Pharmacokinetics:
are effective orally and are excreted in urine and feces.
Adverse effect
Increased concentrations of viable bacteria in the stomach have been reported with continued use of these drugs.

Prostaglandins
A deficiency of prostaglandins is thought to be involved in the pathogenesis of peptic ulcers
Misoprostol : for prevention of gastric ulcers induced by NSAIDs
It is less effective than H2 antagonists
and the PPIs for acute treatment of peptic ulcers.
Antimuscarinic agents (anticholinergic agents)
Muscarinic receptor stimulation increases gastrointestinal motility and secretory activity.
dicyclomine can be used as an adjunct in the management of peptic ulcer disease and
Zollinger-Ellison syndrome, particularly in patients who are refractory to standard therapies. However, its many side
effects (for example, cardiac arrhythmias, dry mouth, constipation, and urinary retention) limit its use.


AntacidsTherapeutic uses
used for symptomatic relief of peptic ulcer disease and GERD, promote healing of duodenal ulcers

Adverse effects
some produce contraceptive and other diarrhea

[Adnano]

Mucosal protective agents
Sucralfate
creates a physical barrier that impairs diffusion of HCl and prevents degradation of mucus by
pepsin and acid.

Bismuth subsalicylate
they inhibit the activity of pepsin, increase secretion of mucus, and interact with
glycoproteins in necrotic mucosal tissue to coat and protect the ulcer crater.

[Adnano]

Drugs Used to Control Chemotherapy-Induced Emesis
Mechanisms that trigger vomiting
Two brainstem sites have key roles in the vomiting reflex pathway, The chemoreceptor trigger zone, which is
located in the area postrema ,The second
important site, the vomiting center, which is located in the lateral reticular formation of the medulla

Antiemetic drug

1.Phenothiazines
acts by blocking dopamine receptors.


2.5-HT3 receptor blockers
Are long duration of action ,such as ondansetron , granisetron , palonosetron and dolasetron selectively block 5-HT3 receptors in the periphery and in the brain.


3.Substituted benzamides
Such as metoclopramide , it highly effect . antidopaminergic side effect include sedation , diarrhea & extrapyramidal symptoms


4.Butyrophenones
Droperidol , doperidol & haloperidol act by blocking dopamine receptors

5.Benzodiazepines
Such as lorazepam & alprazolam


6.Corticosteroids
Dexamethasone & methylprednisolone used alone or combination with other agent
The mechanism is not known , but it may involve blockade of prostaglandins


7.Cannabinoids
Such as dronabinol & nabilone


8.Substance P/neurokinin-1 receptor blocker
Aprepitant , it targets the neurokinin receptor of the brain & block action of natural substance
It is adminstrated orally with dexamethasone & palonosetron.


9.Combination regimens
Antiemetic drugs are often combined to increase antiemetic activity or decrease toxicity
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[Adnano]

Antidiarrheals

1.Antimotility agents
diphenoxylate & loperamide. Side effects include drowsiness, abdominal cramps, and dizziness , it is contraindication in young children or in patients with severe
colitis.(bcoz it contribute to toxic megacolon)


2.Adsorbents
Adsorbent agents, such as bismuth subsalicylate, methylcellulose and aluminum hydroxide , They are much less effective than
antimotility agents.


3.Agents that modify fluid and electrolyte transport
NSAID : by inhibition of prostaglandine synthesis
Bismuth subsalicylate : decrease fliud secretion in the bowel



Laxatives
1.Irritants and stimulants

2.Bulk laxatives

3.Stool softeners



تم بحمد لله

[D.insulin]

يعطيك العافية دكتور عدنان وجزاك الله خير وسعيدين بانضمامك للمشروع
بارك الله بك

[Dr.Tariq]

تلخيص جميل و مدروس، جزاك الله خيراً، يعطيك ألف عافية دكتور....

[ilham]

يعطيكم العافيه على مجهودكم.