Upper GI Pharm part 2

Question 1

how are antiemetics catagorized?

Answer 1

according to the receptor on which they are proposed to act. However, there can be considerable overlap in multiple receptor type activation

Question 2

treatment and prevention of the nausea and emesis associated with cancer chemotherapy

Answer 2

Use of several anti-emetic agents from different pharmacological classes may be used in combination.

Question 3

Scopolamine is what type of antiemetic

Answer 3

Anticholinergic agent (muscarinic receptor antagonist)

Question 4

Historic and effective for the prevention and treatment of motion sickness (prevention of postoperative nausea and vomiting)

Answer 4

Scopolamine (given as a transdermal patch)

Question 5

Dimenhydrinate is what type of anti-emetic?

Answer 5

Histamine-1 blocker (antihistamine)

Question 6

MOA for Dimenhydrinate

Answer 6

Histamine H1 antagonist. Some anti-muscarinic activity. Acts at vestibular afferents and within the brainstem.

Question 7

Use of Dimenhydrinate

Answer 7

prevention and treatment of motion sickness

Question 8

Granisentron and Ondansetron act on what receptor?

Answer 8

anti-serotoin; 5-HT3 antagonist

Question 9

most widely used drugs for chemotherapy-induced emesis. These agents areavailable as tablets, oral solution, and intravenous preparations.

Answer 9

Ondansetron and Granisentron

Question 10

MOA of granisentron and Ondansetron

Answer 10

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.

Question 11

Metabolism of Granisentron and Ondansetron

Answer 11

metabolized in the liver followed by glucuronide or sulfate conjugation

Question 12

Uses of Granisentron and Ondansetron

Answer 12

Chemotherapy-induced nausea, nausea secondary to upper abdominal irradiation, hyperemesis of pregnancy, and to a lesser degree, postoperative nausea, but not
against motion sickness

Question 13

Dopamine2 receptor antagonists

Answer 13

Prochlorperazine

Question 14

MOA of Prochlorperazine

Answer 14

Principal mechanism is D2 receptor antagonism at the CTZ; Also some anticholinergic, antihistamine activity

Question 15

“general-purpose” anti- emetics. Not uniformly effective in cancer chemotherapy induced emesis.

Answer 15

Prochlorperazine

Question 16

Where is prochlorperazine metabolized? Side effects?

Answer 16

liver

sides = restlessness

Question 17

highly lipid-soluble and is absorbed readily after oral administration. It is highly protein bound.

Answer 17

Dronabinol

Question 18

MOA of Dronabinol

Answer 18

probably relates to neuronal CB1 receptor activation.

Question 19

Recommended uses for Dronabinol

Answer 19

prophylactic agent in chemotherapy-induced emesis refractory to other treatments, treatment of anorexia associated with weight loss in AIDS patients.

Question 20

Side effects of Dronabinol (more so in elderly)

Answer 20

palpitations, tachycardia, vasodilation/facial flushing, dysphoria, vertigo, dizziness, lack of concentration, depersonalization, etc

Question 21

Metabolism of Dronabinol

Answer 21

Liver, active and inactive metabolites are formed

Question 22

Glucocorticoids such as______ can be useful adjuncts in the treatment of nausea in patients with cancer, possibly by suppressing tumor inflammation and prostaglandin production.

Answer 22

dexamethasone

Question 23

Substance P receptor (NK1) antagonist

Answer 23

Aprepitant

Question 24

MOA of Aprepitant

Answer 24

Inhibits substance P/NK1 receptors

Question 25

Uses of Aprepitant

Answer 25

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

Question 26

broken down by CYP3A4 and bound exclusively to plasma protein

Answer 26

Aprepitant

Question 27

Agents that promote gastric emptying and GI motility by enhancing coordination.

Answer 27

Prokinetic agents

Question 28

What makes a prokinetic agent a useful one?

Answer 28

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

Question 29

dopamine2 antagonist, however | may interact with serotonin receptors.

Answer 29

Metoclopramide

Question 30

suppression of ACh release from myenteric | motor neurons, are mediated by _________receptors.

Answer 30

D2 dopaminergic

Question 31

How are DA antagonists better then prokinetic agents?

Answer 31

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.

Question 32

MOA of DA antagonists like Metoclopramide

Answer 32

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.

Question 33

Where does metoclopramide work best?

Answer 33

upper digestive tract

Question 34

What can we use to tx diabetic gastroparesis; gastroesophageal reflux

Answer 34

oral metoclopramide

Question 35

When given parenterally, what does Metoclopramide help with?

Answer 35

gastroparesis and nausea and vomiting

Question 36

Metabolism of Metoclopramide

Answer 36

sulfation and glucuronide conjugation by the liver

Question 37

Side effects of metoclopramide

Answer 37

Tardive dyskinesia, dystonias

Question 38

is a prokinetic agent (complex actions) used for severe GERD and diabetic gastroparesis.

Answer 38

Metoclopramide

Question 39

are 5-HT3 blockers which attenuate vomiting by both action at CTZ and visceral afferents.

Answer 39

Ondansetron and Granisetron

Question 40

a dopamine2-antagonist used to treat nausea and vomiting.

Answer 40

Prochlorperazine

Question 41

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

Answer 41

Dronabinol

Question 42

is a histamine-1 blocker. Used to treat motion-induced vomiting.

Answer 42

Dimenhydrinate

Question 43

is an antimuscarinic agent and is the historical treatment for motion sickness. It acts on the cortex & inner ear.

Answer 43

Scopolamine

Question 44

is a substance P receptor antagonist. Used in combination therapy for the treatment of chemotherapy associated nausea

Answer 44

Aprepitant

Question 45

useful in the combination of other anti-nausea medications in the treatment of nausea in patients with cancer.

Answer 45

Dexamethasone