(5) GI & Endo: GI (1.1-1.3) Flashcards
What is the neuroanatomical name for the vomiting center?
nucleus tractus solitarius
Which cranial nerves signal to the nucleus tractus solitarius?
(1) CN X
(2) CN VIII
which serotonin receptor mediates the vagal afferents from the GI tract?
5-HT3
what is the neuroanatomical name for the chemoreceptor trigger zone?
Area postrema
(Located in the fourth ventricle, but outside the BBB)
MOA: Ondansetron
5-HT3 receptor antagonist
(“On -DANCE-atron”)
Adverse Effects (4) : Ondansetron
(1) Constipation
(2) Headache/Dizziness
(3) Torsades
(4) Serotonin syndrome
what type of nausea can first-generation antihistamines (H1 receptor blockers) treat?
vestibular
(motion sickness)
name 2 receptors found in high concentration throughout the vestibular system
(1) H1
(2) M1
name 2 receptors found in high concentration in the area postrema
(1) D2
(2) NK1
* (NK1 = neurokinin 1 receptors, which are activated by substance P)*
MOA: Metoclopramide
D2 receptor antagonist
(In area postrema ∴ Good at treating drug-induced nausea)
what drug can be used to treat delayed gastric emptying (unrelated to cholinergics)?
Metoclopramide
(Notice completely different MOA but many similarities to Bethanochol)
Contraindication: Metoclopramide
Bowel obstruction
(Parkinson’s)
Adverse Effects (7): Metoclopramide
(1) Diarrhea
(2) Drowsiness
(3) Depression
(4) Extrapyramidal effects
(5) Neuroleptic malignant syndrome
(6) Elevated prolactin
(7) Torsades de Pointes
what adverse effect is associated with chronic Metoclopramide use?
Tardive dyskinesia
- (causes repetitive, involuntary movements, such as grimacing and eye blinking;*
- due to long-term use of neuroleptic drugs used to treat psychiatric conditions)*
what is the endogenous ligand for the NK1 receptor?
Substance P
MOA: Aprepitant
NK1 receptor antagonist
(Often preferred over other anti-emetics ∵ it doesn’t affect dopamine or 5-HT ∴ fewer side effects)
what neurotransmitter is released at the mucosa in response to GI irritation?
5-HT
Which gastric cell secretes HCl?
Parietal cell
(Remember it also secretes intrinsic factor for Vit. B12 absorption)
What transporter pumps H+ into the lumen of the stomach?
H+/K+ ATPase
What directly stimulates parietal cells to secrete HCl?
(1) Histamine
(2) Gastrin
(3) Acetylcholine
Which histamine receptor is responsible for increasing HCl secretion?
H2
What paracrine-acting molecule stimulates HCl secretion from parietal cells?
Histamine
(Contrast with gastrin)
What stimulates the release of histamine from ECL cells?
Gastrin
(Endocrine molecule, contrast with histamine)
What secretes GRP?
Vagus n.
(Thus indirectly stimulating HCl release via GRP and directly stimulating HCl via ACh)
Suffix: H2 receptor antagonist
“-tidine”
Indications (2) : PPIs/H2 receptor antagonists
(1) GERD
(2) GI Ulcers
* (PPIs are first line)*
Adverse Effects (4) : Cimetidine
(1) Inhibits CYP450
(2) Gynecomastia
(3) Impotence
(4) Elevated prolactin
MOA: PPIs
Irreversibly inhibit H+/K+ ATPase
Suffix: PPI
“-prazole”
What is the preferred pharmacologic treatment for Zollinger-Ellison syndrome?
PPI
(Otherwise, octreotide can be used)
Adverse Effects (5) : PPIs
(1) C. difficile infection
(2) Respiratory infections
(3) ↓ Absorption of divalent cations
(4) ⇒ ↑ Risk of osteoporosis
(5) ⇒ Hypomagnesemia
How does somatostatin reduced acid production?
By inhibiting the release of:
(1) Histamine from ECL cells
(2) Gastrin by G cells
What type of gastrinomas can be treated with somatostatin?
SST receptor (+)
(… obviously need the receptor to mediate the ligand’s effect)
Which gastric cell secretes histamine?
ECL cells
Name 3 osmotic laxatives
(1) Magnesium salts
(2) Polyethylene glycol
(3) Lactulose
* (Magnesium salt = Milk of Magnesia)*
MOA: Senna
Stimulant laxative
What is the etiology of melanosis coli?
Chronic senna use
Describe how lactulose helps with hepatic encephalopathy
Metabolism of lactulose by GI bacteria ⇒ ↓ pH ⇒ NH3 → NH4<strong>+</strong> ⇒ Prevents absorption of intestinal ammonia
How does liver cirrhosis lead to encephalopathy?
⇒ ↑ NH4+
Describe why Rifaximin is useful in the treatment of hepatic encephalopathy
Kills ammonia producing bacteria
(Poorly absorbed lumenal antibiotic, similar to Neomycin)
MOA: Psyllium
Indigestible material ⇒ Distention ⇒ Promotes peristalsis
MOA: Docusate
Stool surfactant agent
(Facilitates penetration of stool by water and lipid ⇒ Softer)
Which opioid receptor is found in high density in the GI tract?
μ
(mu)
Which μ-opioid agonist does not cross the BBB?
Loperamide
How do μ-opioid agonist reduce GI motility?
Increase colonic phasic segmenting activity
(↑ Activity of GI circular smooth muscle while ↓ activity of GI longitudinal smooth muscle)
Which antidiarrheal agent is combined with atropine to prevent abuse?
Diphenoxylate
Name a contraindication to antidiarrheals
Bloody diarrhea / Fever
Name 2 tumors which can cause secretory diarrhea
(1) VIPoma
(2) Carcinoid tumor
