GI Pharmacology Flashcards
Three important centres affecting nausea and vomiting are the vomiting centre, the chemoreceptor trigger zone, and the vestibular nuclei. These are located in the ____________
Medulla
The __________ contains receptors (opioid mu, kappa, dopamine-type 2 [D2], neurokinin-1 [NK1], and serotonin [5-HT3] that detect emetic agents in the blood and relays information to the vomiting centre
CTZ (Chemoreceptor trigger zone)
Toxic agents, microorganisms, toxins, cytotoxic drugs, and mechanical distension can lead to the release of mediators/neurotransmitters from ___________________ cells in the lining of the GI tract.
Enterochromaffin
Main NT’s/mediators involved in control of vomiting
Acetylcholine
Histamine
5-HT
Dopamine
Substance P
Name three substances that are carried through the bloodstream that directly stimulate the chemoreceptor trigger zone
Opioids
Ketoacids
Urea
Vomiting predominantly in the morning is associated with which three conditions?
Pregnancy
Uraemia
Alcoholic gastritis
Distal intestinal obstruction or gastrocolic fistulas can produce what kind of vomiting?
Feculent emesis
What type of vomiting is associated with increased intracranial pressure?
Projectile vomiting
Vomiting during or shortly after a meal is associated with which gastric condition?
Peptic ulcer disease
MOA of Metoclopramide
D2 receptor antagonist
MOA of Chlorpromazine
D2 receptor antagonist
MOA of Ondansetron
5-HT3 receptor antagonist
MOA of Cyclizine
H1 receptor blocker
MOA of H1 receptor antagonists: The vomiting centre possesses neutrons which are rich in cholinergic and histamine receptors. These types of neutrons are especially involved in the transmission from the vestibular apparatus or periphery to the vomiting centre. _______________ acts to block the histamine receptors in the CNS, thus reducing activity along these pathways.
Cyclizine
Indication for this H1 receptor antagonist include nausea and vomiting caused by:
- Motion sickness
- Narcotic analgesics
- Anaesthetics in the post-operative period
- Vomiting associated with radiotherapy
Cyclizine
Adverse effects of Cyclizine (H1 receptor antagonist)?
Drowsiness
Confusion
Constipation
Urinary retention (possibly d/t anticholinergic effects)
Contraindications for Cyclizine (H1 receptor antagonist)?
Acute alcohol intoxication- may increase the toxicity of alcohol
Primary site of action for 5HT-3 receptor antagonist (Ondansetron)?
Chemoreceptor trigger zone
MOA of 5HT-3 receptor antagonist:
Chemotherapy and radiotherapy —> serotonin from enterochromaffin cells of the small intestine —> presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents. _______________ may block the initiation of this reflex. Activation of vagal afferents —> central release of serotonin from the CTZ. Thus, the antiemetic effect of _____________ is probably d/t the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or CNS, or both.
Ondansetron
Indication for 5HT-3 receptor antagonist (Ondansetron)?
Vomiting d/t cytotoxic drugs or radiation; postoperative
Adverse effects of 5HT-3 receptor antagonist (Ondansetron)?
HA
Dizziness
Constipation
QT prolongation
Contraindication for 5HT-3 receptor antagonist (Ondansetron)?
Arrhythmia having QTc prolongation
Antipsychotic phenothiazines such as _____________ act to antagonist the D2 receptors in the chemoreceptor trigger zone, but they also block histamine and muscarinic receptors
Chlorpromazine
This drug is a D2 receptor antagonist closely related to the phenothiazine group, that acts centrally on the CTZ and also has a peripheral action on the GI tract itself, increasing the motility of the oesophagus, stomach, and intestine. This not only adds to the anti-emetic effect, but explains its use in the tx of GORD
Metoclopramide
MOA of Metoclopramide?
Inhibits D2 receptor in the chemoreceptor trigger zone. Also has prokinetic effects
Indications for _____________ include:
- Delayed chemotherapy induced nausea and vomiting
- Radiotherapy induced N & V
- Symptomatic treatment of N & V, including acute migraine induced N & V
Metoclopramide
Adverse effects of this drug include disorders of movement, fatigue, motor restlessness, spasmodic torticollis (involuntary twisting of the neck). Also stimulate prolactin release, causing galactorrhoea and disorders of menstruation
Metoclopramide
Contraindications for _______________ :
- GI haemorrhage
- GI mechanical obstruction
- History of neuroleptic or ____________-induced tardive dyskinesia
- Parkinson’s disease
- Combination with levodopa or dopaminergic drugs
Metoclopramide
This NT has a direct relaxant effect on the gut by activating muscular D2 receptors in the lower oesophageal sphincter and stomach (fundus and antrum)
Dopamine
_________________ inhibits the release of ACh from intrinsic myenteric cholinergic neurons by activating pre-junctional D2 receptors, which leads to an indirect inhibition of the musculature
Dopamine
This drug promotes gut motility by inhibiting presynaptic and postsynaptic D2 receptors, which leads to an indirect inhibition of the musculature.
Metoclopramide
This drug promotes gut motility by inhibiting presynaptic and postsynaptic D2 receptors, and antagonists presynaptic inhibition of muscarinic receptors, which promotes release of ACh. This in turn leads to increased lower oesophageal sphincter and gastric tone, increased intragastric pressure, and accelerated gastric emptying.
Metoclopramide
What is the primary ligand of NK1 receptor antagonists?
Substance P, a nociceptor NT
Which glucocorticoid can be used for chemotherapy and radiotherapy-induced N&V, postoperative N&V?
Dexamethasone
A patient is receiving highly emetogenic chemotherapy for metastatic carcinoma. To prevent chemotherapy-induced N&V, she is likely to be treated with which of the following?
A. Levodopa
B. Methotrexate
C. Misoprostol
D. Ondansetron
E. Omeprazole
D. Ondansetron (5-HT3 receptor antagonists are highly effective at preventing chemo-induced N&V)
Spasmodic torticollis is a side effect of which antiemetic drug?
A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Nabilone
E. Ondansetron
C. Metoclopramide
The following drugs act on various receptors in the chemoreceptor trigger zone. Identify receptors on which these drugs act?
Aprepitant
Neurokinin 1
The following drugs act on various receptors in the chemoreceptor trigger zone. Identify receptors on which these drugs act?
Cyclizine
Histamine 1
The following drugs act on various receptors in the chemoreceptor trigger zone. Identify receptors on which these drugs act?
Metoclopramide
Dopamine 2
The following drugs act on various receptors in the chemoreceptor trigger zone. Identify receptors on which these drugs act?
Ondansetron
5-HT3 (serotonin)
The following drugs act on various receptors in the chemoreceptor trigger zone. Identify receptors on which these drugs act?
Scopolamine
Muscarinic
A patient is recently diagnosed as having Parkinson’s disease. Which antiemetic drug is contraindicated in this patient?
A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Ondansetron
E. Scopolamine
C. Metoclopramide, as it is a dopamine receptor antagonist
