Upper GI Pharm part 2 Flashcards
how are antiemetics catagorized?
according to the receptor on which they are proposed to act. However, there can be considerable overlap in multiple receptor type activation
treatment and prevention of the nausea and emesis associated with cancer chemotherapy
Use of several anti-emetic agents from different pharmacological classes may be used in combination.
Scopolamine is what type of antiemetic
Anticholinergic agent (muscarinic receptor antagonist)
Historic and effective for the prevention and treatment of motion sickness (prevention of postoperative nausea and vomiting)
Scopolamine (given as a transdermal patch)
Dimenhydrinate is what type of anti-emetic?
Histamine-1 blocker (antihistamine)
MOA for Dimenhydrinate
Histamine H1 antagonist. Some anti-muscarinic activity. Acts at vestibular afferents and within the brainstem.
Use of Dimenhydrinate
prevention and treatment of motion sickness
Granisentron and Ondansetron act on what receptor?
anti-serotoin; 5-HT3 antagonist
most widely used drugs for chemotherapy-induced emesis. These agents areavailable as tablets, oral solution, and intravenous preparations.
Ondansetron and Granisentron
MOA of granisentron and Ondansetron
5-HT3 receptors are present in several sites involved in emesis; vagal afferents, the STN and the area postrema. Serotonin is released by ECL cells of the small intestine in response to hemotherapeutic agents and may stimulate vagal afferents (via 5-HT3 receptors) to initiate the vomiting reflex.
Metabolism of Granisentron and Ondansetron
metabolized in the liver followed by glucuronide or sulfate conjugation
Uses of Granisentron and Ondansetron
Chemotherapy-induced nausea, nausea secondary to upper abdominal irradiation, hyperemesis of pregnancy, and to a lesser degree, postoperative nausea, but not
against motion sickness
Dopamine2 receptor antagonists
Prochlorperazine
MOA of Prochlorperazine
Principal mechanism is D2 receptor antagonism at the CTZ; Also some anticholinergic, antihistamine activity
“general-purpose” anti- emetics. Not uniformly effective in cancer chemotherapy induced emesis.
Prochlorperazine
Where is prochlorperazine metabolized? Side effects?
liver
sides = restlessness
highly lipid-soluble and is absorbed readily after oral administration. It is highly protein bound.
Dronabinol
MOA of Dronabinol
probably relates to neuronal CB1 receptor activation.
Recommended uses for Dronabinol
prophylactic agent in chemotherapy-induced emesis refractory to other treatments, treatment of anorexia associated with weight loss in AIDS patients.
Side effects of Dronabinol (more so in elderly)
palpitations, tachycardia, vasodilation/facial flushing, dysphoria, vertigo, dizziness, lack of concentration, depersonalization, etc
Metabolism of Dronabinol
Liver, active and inactive metabolites are formed
Glucocorticoids such as______ can be useful adjuncts in the treatment of nausea in patients with cancer, possibly by suppressing tumor inflammation and prostaglandin production.
dexamethasone
Substance P receptor (NK1) antagonist
Aprepitant
MOA of Aprepitant
Inhibits substance P/NK1 receptors
Uses of Aprepitant
Used in combination with other antiemetics (5-HT3 antagonist and a corticosteroid) for acute and delayed nausea and vomiting associated with chemotherapy,post-operative nausea
broken down by CYP3A4 and bound exclusively to plasma protein
Aprepitant
Agents that promote gastric emptying and GI motility by enhancing coordination.
Prokinetic agents
What makes a prokinetic agent a useful one?
Useful prokinetic agents act “upstream” of
ACh, at receptor sites on the motor neuron, or indirectly, on neurons or non-neuronal cells one or two orders removed
dopamine2 antagonist, however
may interact with serotonin receptors.
Metoclopramide
suppression of ACh release from myenteric
motor neurons, are mediated by _________receptors.
D2 dopaminergic
How are DA antagonists better then prokinetic agents?
antagonizing the inhibitory effect of dopamine on myenteric motor neurons, DA receptor antagonists are effective as prokinetic agents; they have the additional advantage of relieving nausea and vomiting by antagonism of DA receptors in the chemoreceptor trigger zone.
MOA of DA antagonists like Metoclopramide
In addition to D2 receptor antagonist, its actions may involve 5-HT4 receptor agonism, vagal and central 5-HT3 antagonism and possible sensitization of muscarinic
receptors on smooth muscle.
Where does metoclopramide work best?
upper digestive tract
What can we use to tx diabetic gastroparesis; gastroesophageal reflux
oral metoclopramide
When given parenterally, what does Metoclopramide help with?
gastroparesis and nausea and vomiting
Metabolism of Metoclopramide
sulfation and glucuronide conjugation by the liver
Side effects of metoclopramide
Tardive dyskinesia, dystonias
is a prokinetic agent (complex actions) used for severe GERD and diabetic gastroparesis.
Metoclopramide
are 5-HT3 blockers which attenuate vomiting by both action at CTZ and visceral afferents.
Ondansetron and Granisetron
a dopamine2-antagonist used to treat nausea and vomiting.
Prochlorperazine
is tetrahydrocannabinol (marijuana) used to treat chemotherapy-induced vomiting centrally perhaps acting at the vomiting center in the medulla. Used in cases where other therapiesare ineffective
Dronabinol
is a histamine-1 blocker. Used to treat motion-induced vomiting.
Dimenhydrinate
is an antimuscarinic agent and is the historical treatment for motion sickness. It acts on the cortex & inner ear.
Scopolamine
is a substance P receptor antagonist. Used in combination therapy for the treatment of chemotherapy associated nausea
Aprepitant
useful in the combination of other anti-nausea medications in the treatment of nausea in patients with cancer.
Dexamethasone
