GI Pharmacology -4 Irritable Bowel Syndrome and Antiemetics. Dr. Alia Shatanawi
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1 GI Pharmacology -4 Irritable Bowel Syndrome and Antiemetics Dr. Alia Shatanawi
2 Drugs used in Irritable Bowel Syndrome Idiopathic, chronic, relapsing disorder characterized by abdominal discomfort (pain, bloating, distension, or cramps) in association with alterations in bowel habits( diarrhea, constipation, or both).
3 Drugs used in Irritable Bowel Syndrome For chronic abdominal pain, low doses of tricyclic antidepressants (eg, amitriptyline or desipramine, mg/d) appear to be helpful. At these doses, these agents have no effect on mood but may alter central processing of visceral afferent information. The anticholinergic properties of these agents also may have effects on gastrointestinal motility and secretion, reducing stool frequency and liquidity. Tricyclic antidepressants may alter receptors for enteric neurotransmitters such as serotonin, affecting visceral afferent sensation. 3
4 Drugs used in Irritable Bowel Syndrome Antispasmodic or Anticholinergic Agents: Dicyclomine Hyoscyamine. Spasm is not an important symptom in IBS. They inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle. At usual low doses, have minimal side effects.
5 Drugs used in Irritable Bowel Syndrome Serotonin 5-HT 3 - Receptor Antagonists: Alosterone: 5-HT 3 receptors are present in the afferent pain fibers in the extrinsic sensory neurons. Also present on the terminals of the enteric cholinergic neurons. Centrally, 5-HT 3 is involved in the central response to visceral afferent stimulation.
6
7 Drugs used in Irritable Bowel Syndrome Serotonin 5-HT 3 - Receptor Antagonists: Alosterone: Selective antagonist of 5-HT 3 receptors. Has long duration of action. Approved for women with severe IBS in whom diarrhea is the prominent symptom. Efficacy in men is not established. Can cause ischemic colitis, severe constipation requiring hospitalization and surgery.
8 Drugs used in Irritable Bowel Syndrome Serotonin 5-HT 4- Receptor Agonists: Tagaserod: Approved for short term treatment of women with IBS who predominantly have constipation. Reduces pain, bloating and hardness of stool. Expensive.
9 9
10 Pathophysiology of Emesis Cancer chemotherapy Opioids Chemoreceptor Trigger Zone (CTZ) (Outside BBB) Dopamine D 2 5 HT 3,,Opioid Receptors Cerebral cortex Smell Sight Thought Anticipatory emesis Vomiting Centre (medulla) Muscarinic, 5 HT 3 & Histaminic H 1 Pharynx & GIT Motion sickness Chemo & radio therapy Gastroenteritis 5 HT 3 receptors Vestibular nuclei Muscarinic Histaminic H 1
11 Which group of drugs can be used as antiemetics? Serotonin 5 HT 3 Antagonists Dopamine D 2 Antagonist Anticholinergics H 1 Antihistaminics Cannabinoids
12 Antiemetic Agents Afferent Inputs to the Vomiting Center: Chemoreceptor trigger zone: DA 2, 5-HT 3, NK1, and opioid receptors. Vestibular system involved with motion sickness through cranial nerve VIII. Rich in M and H 1 receptors. Pharyngeal irritation through the vagus. GIT afferents through the vagus and spinal afferent nerves, rich in 5-HT 3 receptors. Central mechanisms due to psychiatric disorders, stress, and anticipatory vomiting of cancer chemotherapy (5-HT 3).
13 Antiemetic Agents Serotonin 5-HT 3 - Receptor Antagonists: Ondansetron. Granisetron. Dolasetron. Palonosetron. 5-HT 3 receptors are involved in three out of the five inputs involved with vomiting. Activity restricted to vomiting due to vagal stimulation and chemotherapy. Motion sickness is poorly controlled.
14 Antiemetic Agents Serotonin 5-HT 3 - Receptor Antagonists: Ondansetron. Granisetron. Dolasetron. Palonosetron. Used before chemotherapy, activity enhanced by dexamethasone and NK 1 antagonist. Can also be used in postoperative and post radiation vomiting. Safe drugs but can cause headache, dizziness and constipation. Also prolong QT interval.
15 Antiemetic Agents Neurokinin Receptor Antagonists: Apripetant: Central blockade in the area postrema. Used in combination with 5-HT 3 antagonists. Can cause fatigue, dizziness and diarrhea.
16 Antiemetic Agents Antipsychotic drugs: Prochlorperazine. Promethazine. Droperidol. Inhibit dopamine and muscarinic receptors. Can cause extrapyramidal effects, hypotension and prolong QT interval.
17 Antiemetic Agents Antihistamines and anticholinergic Drugs: Diphenhydramine Meclizine. Hyoscine (scoplamine). Particularly useful in motion sickness. Can cause dizziness, sedation, confusion, dry mouth, cycloplegia, and urinary retention. Hyoscine can be used as a transdermal
18 Antiemetic Agents Benzodiazepines: Lorazepam. Diazepam. Reduce anticipatory vomiting caused by anxiety.
19 Antiemetic Agents Cannabinoids: Dronabinol. Nabilone. Delta-9- tetrahydrocannabinol from marijuana useful for chemotherapy-induced vomiting. Mechanism not understood. Can cause euphoria, dysphoria, sedation, hallucinations, dry mouth, and increased appetite. Also, hypotension, tachycardia, and conjunctival injection.
20 Emetic Agents Many drugs. Hypertonic saline. Apomorphine. Ipecac syrup.
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Contents Definition History Aims Qualities of premedicant Drugs used Premedication in associated disorders Premedication in obstetrics patients Premedication in outpatients surgeries. Premedication in
Clinical Policy: Nabilone (Cesamet) Reference Number: ERX.NPA.35 Effective Date:
Clinical Policy: (Cesamet) Reference Number: ERX.NPA.35 Effective Date: 09.01.17 Last Review Date: 08.18 Revision Log See Important Reminder at the end of this policy for important regulatory and legal