GI Disorders 1: Vomiting Flashcards
Reflex Mechanism of Vomiting
purpose?
which stomach cells are involved?
- defensive response to rid toxic material
- toxins and poisonous compounds induce release of mediators (Serotonin) from enterochromaffin cells lining GI tract
- trigger signals in vagal afferent fibers
Reflex Mechanism of Vomiting
where is it regulated?
what are some causes of vomiting with drugs?
- regulated centrally via vomiting/emetic center in medulla
- communication with chemoreceptor trigger zone (CTZ) is important
- vomiting is an unwanted effect of many drugs
- chemotherapy (drugs target health cells)
- opioids
- general anesthetics
- post-surgery
Reflex Mechanism of Vomiting
Pathways
Pain, repulsive sights, smells, emotional stimuli?
Motion sickness?
Toxins in gut?
Pain, repulsive sights, smells, emotional
- higher cortical centers directly relay to vomiting centre
Motion sickness
- vestibular nuclei replays to CTZ to vomiting centre
Toxic chemicals in gut
- enterochromaffin cells secrete seotonin, vagal afferents to CTZ and directly to vomiting center
Reflex Mechanism of Vomiting
Vomiting vs nausea
what is peripheral vs central pathway for vomiting? (in chemotherapy)
- share similar mechanisms
- nausea can be mediated through independent mech
- easier to pharm manage vomiting than nausea
- defined differently from person experiencing it, cannot test
Peripheral Pathway
- acute chemotherapy vomiting involves 5HT/5HT3 receptor signaling (0-24 hrs)
- enterochromaffin cells release serotonin to vagal afferent
Central Pathway
- delayed involves SP/NK1 receptor signaling (>24 hrs, substance P
- signal from vomiting center which release sub P to NK1
5-HT3 Receptor Antagonists
Names?
Specific use?
-SETRON Ondansetron Granisetron Alosetron (original - removed for vomiting) Palonosetron
- prophylaxis and treatment of motion sickness and chemotherapy-induced vomiting
5-HT3 Receptor Antagonists
MOA?
site of action?
channel types?
- primary site of action is CTZ but also acts on GI tract
- 5-HT3 receptors mediate contraction of fundus, corpus, antrum of GI tract
- 5-HT3 receptors sensitize spinal sensory neurons and induce vagal signaling of nausea
- 5HT receptors are G-protein coupled, except 5HT3 which is a ligand gated cation channel (Na+, K+ channels)
- vagal sensory aff neurons project to emetic center in brainstem
- antagonism also slows intestinal transit and secretions of small bowel
5-HT3 Receptor Antagonists
Adverse effects?
- well tolerated
- headache, GI upset (constipation)
- Ischemic colitis (alosetron) - severe contraction in GI tract used for IBS in women
Dopamine Receptor 2 (D2) Antagonists - Phenothiazines
Antipsychotic phenothiazines (4)
Treatment for nausea and vomiting associated with? (5)
Chlorpromazine
Perphenazine
Prochlorperazine
Trifluoperazine
Cancer Radiation therapy Cytotoxic drugs Opioids Anaesthetics
Phenothiazines
type
MOA - site of action?
- primary site of action is D2 receptors in CTZ
D2 is G-coupled receptor - linked to Gi which inhibits adenylate cyclase and reduce cAMP formation and activation of protein kinase A (antagonist reverses this leading to high cAMP and PKA)
D2 Antagonists - Phenothiazines
AE? (4)
- sedation (chlorpromazine), blocking dopamine recepotrs, movemnt
- orthostatic hypotension
- *extrapyramidal syndrom
- *dystonias: movements in face involuntary, irreversible usually
- *tardive dyskinesia
- *hyperprolactinemia: dopamine naturual antagonist of prolactin secretion galactorrhea
-contrainidcation: severe CNS depression
Metoclopramide
type?
Actions?
D2 Antagonists -
- related to phenothiazines
- also block histamine and musc receptors
- also has peripheral actions (increased GI motility) as well as on CTZ (GI tract and CTZ)
- blocks D2 in other CNS areas
D2 Antagonists - Metoclopramide
AE? (3)
- movement disorders, fatigue, motor restlessness
- *spasmodic torticollis: invol. twisting of neck
- *oculogyric crises: upward eye movements
- *prolactin release
Domperidone
type?
special?
AE?
(separate card)
Haloperiodol, droperidol, levomepromazine - use?
D2 receptor ant
- doesn’t penetrate BBB, less CNS effects
- more specific for D2 receptors on CTZ
- *small increased risk for serious cardiac AE, prolong QT interval
- orally
- other D2 antagonists against acute chemotherapy incuded vomiting (acts on GI tract)
Histamine H1 Receptor Antagonist
Name (3)
Cinnarizine
Cyclizine
Promethazine
Histamine H1 Receptor Antagonist
what types of nausea and vomiting is it used for?
- G-protein coupled receptors linked to Gq proteins
- effective for nausea and vomiting due to motion sickness
- drowsiness
- not in CTZ, not for chemo induced or substances acting on CTZ directly
- promethazine for pregnancy morning sickness
