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Pharmacology > GI: Emesis > Flashcards

GI: Emesis Flashcards

1
Q

the two areas vomiting is triggered and WHERE

*which is sensory and motor ?

A

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

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

which zone is outside the BBB

A

chemoreceptor trigger zone

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3
Q

% of patients who experience N/V who undergo chemo

A

70-80%

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4
Q

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

A

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

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5
Q

the Vomiting Center responds to?

A

afferent input from:

  • vestibular system
  • periphery (pharynx/GI tract_
  • higher brainstem and cortical structures
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6
Q

vestibular system mainly plays a role in?

A

motion sickness

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7
Q

emetic actions of chemotherapeutic agents

  • directly activate?
  • which NTs are involved
  • peripherally?
  • reflex response?
A
  • 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
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8
Q

list common clinic uses for anti-emetics

A

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

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9
Q

which tx regimen works best for CINV

A

COBMO regimen

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10
Q

list the 7 categories of anti-emetics

A
  1. Phenothiazines
  2. 5-HT3 rec blockerrs
  3. Substituted Benzamides
  4. Butyrophenones
  5. Benzos
  6. Coticosteroids
  7. Substance P/Neurokinin-1 receptor antagonists
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11
Q

list the drugs under Phenothiazines

*ending?

A

Prochlorperazine
Chlorpromazine

-AZINE

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12
Q

Prochlorperazine

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

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

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13
Q

which drug classes work good for motion sickness

A

anticholinergics–esp Scopolamine

and
H1 receptor antagonists–Dimenhydrinate, Meclizine, Cyclizine

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14
Q

List the 5-HT3 receptor blockers

*end in?

A

-setron

dolasetron
granisetron
ondansetron
palonosetron

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15
Q

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
A

*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
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16
Q

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

A

Ondansetron

Granisetron

17
Q

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

A

ondansetron

18
Q

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

A

GI tract

*ligand gated ion channel

19
Q

Metoclopramide (reglan)

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

*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)****

20
Q

relationship b/w dopamine and serotonin

A

dopamine is a weak serotonin antagonist

21
Q

list the drugs that are Butyrophenones

A

Droperiodol
Haloperidol
first gen antipsychotics

22
Q

Butyrophenones as a class:

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

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&raquo_space;»
  • Torsades
23
Q

name the benzos used as anti-emetics

A

Alprazolam–xanax

Lorazepam–ativan

24
Q

Benzos as a class:

Indications

A

Anticipatory vomiting (esp for chemo patients)

  • sedative
  • anxiolytic
  • amnestic

antiemetic potency is LOW*

25
Q

Which corticosteroids are used as anti-emetics

A

Dexamesthasone

Methylprednisolone

26
Q

Corticosteroids as a class:

  • MOA
  • Indications
A

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
27
Q

list the substance P/Neruokinin-1 receptor antagonists

ends in??

A

Aprepitant
Rolapitant
Netupitant

-PITANT

28
Q

substance P/Neruokinin-1 receptor antagonists

  • MOA
  • indications
  • SE
  • T1/2
  • bound to?
  • contra
A

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
29
Q

what is substance P

  • found where
  • involved with?
  • where does it bind
A

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

30
Q

what is best tx for delayed CINV

A

Substance P/Neurokinin-1 rec antagonists

31
Q

Cannabinoids

  • end in?
  • MOA
  • INDS
A
  • 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

32
Q

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

A

dexamethasone

33
Q

IV administration of which antihistamine can cause gangrene

A

Promethazine (Phenergan)

IM route preferred

34
Q

List the antihistamines

  • MOA
  • Indications
  • SE
A

-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

35
Q

List the anticholinergic drug used for nausea

  • indication
  • MOA
  • route(s)
  • SE
A

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

Pharmacology (28 decks)

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