GI: Emesis

Question 1

the two areas vomiting is triggered and WHERE

*which is sensory and motor ?

Answer 1

BRAINSTEM:
1. chemoreceptor Trigger zone–SENSORY mechanism of vomiting

2. Vomiting Center–now called central pattern generator–MOTOR mechanism of vomiting

Question 2

which zone is outside the BBB

Answer 2

chemoreceptor trigger zone

Question 3

% of patients who experience N/V who undergo chemo

Answer 3

70-80%

Question 4

why is it good that the Chemoreceptor trigger zone is outside the brainstem

Answer 4

it can respond DIRECTLY to chemical stimuli in the blood or CSF

Question 5

the Vomiting Center responds to?

Answer 5

afferent input from:

• vestibular system
• periphery (pharynx/GI tract_
• higher brainstem and cortical structures

Question 6

vestibular system mainly plays a role in?

Answer 6

motion sickness

Question 7

emetic actions of chemotherapeutic agents

• directly activate?
• which NTs are involved
• peripherally?
• reflex response?

Answer 7

• directly activate the medullary Chemoreceptor trigger zone or vomiting center
• dopamine receptor type 2 and serotonin type 3 (5-HT)
• color of the drugs or smells can even trigger vomit reflex
• act peripherally: damage cells in GI tract–they release serotonin from enterochromaffin cells of SI–serotonin then activates 5-HT3 receptors on vagal and splanchnic afferent fibers–carry signal to medulla–emetic response

Question 8

list common clinic uses for anti-emetics

Answer 8

*post-op
*opiates
*radiotherapy
*chemotherapy induced Nausea and vomiting (CINV)
*

Question 9

which tx regimen works best for CINV

Answer 9

COBMO regimen

Question 10

list the 7 categories of anti-emetics

Answer 10

1. Phenothiazines
2. 5-HT3 rec blockerrs
3. Substituted Benzamides
4. Butyrophenones
5. Benzos
6. Coticosteroids
7. Substance P/Neurokinin-1 receptor antagonists

Question 11

list the drugs under Phenothiazines

*ending?

Answer 11

Prochlorperazine
Chlorpromazine

-AZINE

Question 12

Prochlorperazine

• drug class
• MOA
• routes of admin
• onset of action
• indications
• SE
• BBW?

Answer 12

class: Phenothiazines

MOA: block dopamine receptors in CTZ. Increasing the dose will improve anti-emetic effect

Indications: low or moderately emetogenic (causing vomiting) chemotherapeutic agents (such as fluorouracil and doxorubicin)

Routes: PO, IM, IV, Rectal

OOA: 10-20 mins for IV, IM

SE: dose dep

• extrapyramidal signs
• ECG abnormalities
• hypotension

BBW: in US for eldery–incr rate of mortality

Question 13

which drug classes work good for motion sickness

Answer 13

anticholinergics–esp Scopolamine

and
H1 receptor antagonists–Dimenhydrinate, Meclizine, Cyclizine

Question 14

List the 5-HT3 receptor blockers

*end in?

Answer 14

-setron

dolasetron
granisetron
ondansetron
palonosetron

Question 15

5-HT3 receptor as a class:

• MOA
• inidcations (very effective for? Less effective for?)
• OOA
• DOA/ T1/2
• Routes of admin and timing of admin
• metabolism
• SEs

Answer 15

*MOA: selectively block serotonin or 5-HT3 receptors in periperhy (visceral vagal afferent fibers) AND in brain (CTZ)

• Inds:
  1. very effective in CINV and Post-op N/V both ADULTS AND KIDS can be given as a single dose before chemo*
  2. less effective at suppressing acute nausea (motion sickness)
• OOA: rapid
• DOA and T1/2: Long
• Routes: IV and PO–same effectiveness. can be given as a single dose before chemo session
• metabolism: HEAVILY hepatic… adjust dose for hepatic dz PTs

SE:

• QT Prolongation (high doses of ondansetron + dolasetron)
• HA
• serotonin syndrome
• GI

Question 16

Which 5-HT3 receptor drugs are effective in preventing emesis in PTs treated with Cisplatin (chemo)
*also with post-op N/V

Answer 16

Ondansetron

Granisetron

Question 17

which is the only 5-HT3 rec blocker that needs adjustment dosing for hepatic insuff PTs

Answer 17

ondansetron

Question 18

where is 5-HT3 rec found and what kind of receptor

Answer 18

GI tract

*ligand gated ion channel

Question 19

Metoclopramide (reglan)

• drug class
• MOA (3)
• indications
• routes
• metabolized where
• OOA for all routes
• SEs

Answer 19

*class: Substituted Benzamide

• MOA:
• acts as dopamine antagonist centrally and peripherally aka inhibits dopamine in the CTZ
• it is a weak 5HT3 antagonist at high doses
• stimulates cholinergic receptors on gastric smooth muscle cells (increases gastric motility) and AcH release at NMJ

*Routes: PO, IV

*OOA
IV: 1-3 mins
PO: 30-60 mins

*metabolized in kidneys–renal function impairment need to adjust dose

• indications:
• good/mainly used for gastroparesis
• modest anti-emesis effect for CINV

SE:
-tardive dyskinesia– involuntary movements of the face and jaw.
-dystonia–a state of abnormal muscle tone resulting in muscular spasm and abnormal posture
(movement s/e bc MOA acting on NMJ)****

Question 20

relationship b/w dopamine and serotonin

Answer 20

dopamine is a weak serotonin antagonist

Question 21

list the drugs that are Butyrophenones

Answer 21

Droperiodol
Haloperidol
first gen antipsychotics

Question 22

Butyrophenones as a class:

• MOA
• BBW
• indications
• DOA and T1/2
• SE

Answer 22

MOA:

• dopamine antagonists–1st gen antipsychotics
• they act as tranquillizers that potentiate the effect of opioids

BBW: increased mortality in elderly

INDS:

• pre-anesthetic sedation
• moderately effective anti-emetics (post-op**) BUT not the 1st drug we reach for

DOA:

• droperidol short acting
• Haldol is longer acting bc longer half life (18 hrs)

SE:

• QTc»_space;»
• Torsades

Question 23

name the benzos used as anti-emetics

Answer 23

Alprazolam–xanax

Lorazepam–ativan

Question 24

Benzos as a class:

Indications

Answer 24

Anticipatory vomiting (esp for chemo patients)

• sedative
• anxiolytic
• amnestic

antiemetic potency is LOW*

Question 25

Which corticosteroids are used as anti-emetics

Answer 25

Dexamesthasone | Methylprednisolone

Question 26

Corticosteroids as a class: - MOA - Indications

Answer 26

MOA: suppress peritumoral inflammation and prostaglandin production*** mainly the prostaglandin blockade Indications: AS ADJUNCT TX * alone, very little anti-emetic effect * used as adjunct therapy in nausea and mild/moderate CINV and post-op

Question 27

list the substance P/Neruokinin-1 receptor antagonists ends in??

Answer 27

Aprepitant Rolapitant Netupitant -PITANT

Question 28

substance P/Neruokinin-1 receptor antagonists * MOA * indications * SE * T1/2 * bound to? * contra

Answer 28

MOA: - target the neurokinin receptor in the vomiting center - block actions of substance P INDS: - high-moderately emetogenic chemo regimens ***delayed phase of CINV (24 hrs after tx) ***** - usually admin w/ dexamethasone and 5HT3 Antag like Zofran CONTRA: patients taking Cisapride or Pimozide because can cause QT prolongation SE: - fatigue - abdominal pain - hiccups - diarrhea T1/2: 180 hours * bound to plasma proteins extensively >95% * metabolized in liver

Question 29

what is substance P * found where * involved with? * where does it bind

Answer 29

*NT* and *neuromodulator* -released from nerve terminals of sensory nerves -found in brain and sc involved with pain and inflammation Bind to receptor called NK1 receptor

Question 30

what is best tx for delayed CINV

Answer 30

Substance P/Neurokinin-1 rec antagonists

Question 31

Cannabinoids * end in? * MOA * INDS

Answer 31

- inol * Marinol * Dronabinol--naturally occuring * Nabilone (synthetic) MOA: stimulate of the CB1 (cannabinoid rec 1) subtype of cannabinoid receptors on neurons in and around CTZ and emetic center INDS: *prohylactic agent when other antiemetics not effective

Question 32

which corticosteroid is MC used for antiemetic tx and in combination therapy?

Answer 32

dexamethasone

Question 33

IV administration of which antihistamine can cause gangrene

Answer 33

Promethazine (Phenergan) | **IM route preferred**

Question 34

List the antihistamines * MOA * Indications * SE

Answer 34

-zine (except for diphenhydramine) * Cyclizine * Meclizine * Promethazine * Diphenhydramine Indications: * motion sickness * post-op nausea MOA: act on vestibular afferents and within the brainstem via anti-cholinergic properties SE: ****drowsiness

Question 35

List the anticholinergic drug used for nausea * indication * MOA * route(s) * SE

Answer 35

Scopalamine (Hycosine) INDS: * prev and tx of motion sickness, sometimes post-op anusea * NO ROLE in CINV MOA: muscarinic rec antagonist Routes: MC transdermal patch SE: dry mouth, visual disturbances, drowsiness