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Clinical Pharmacology Exam 3 > Nausea > Flashcards

Nausea Flashcards

1
Q

What are the five NT receptor sites important in the vomiting reflex?

A
  1. M1: muscarinic
  2. H1: histaminic
  3. D2: dopamine
  4. 5-HT3: serotonin
  5. NK1 receptor: substance P (chemo lecture)

1, 2 - inner ear
3, 4 - GI tract

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2
Q

What is the name of the anticholinergic, M1 receptor AAG? MOA?

A

Scopolamine

MOA: block Ach at PNS sites in smooth muscle, secretory glands, CNS

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3
Q

What are two clinical indications of scopolamine? What is the clinical pearl?

A
  1. px of Motion* sickness
  2. off-label to dry oropharyngeal secretions*

Pearl: takes 6-8hr to work, may last 72hr
- preferred over antihistamines for motion sickness in person desiring wakefulness during travel*

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4
Q

List the drug interactions and ADRs of scopolamine.

A

Interactions: other anticholinergics, CNS depressants

ADRs: xerostomia, sedation, urinary retention, blurred vision

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5
Q

What are the three antihistamine, H1 receptor AAG?

A
  1. dimenhydrinate
  2. meclizine
  3. promethazine
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6
Q

What is the MOA of dimenhydrinate?

A

MOA:

  1. central anticholinergic action by blocking CTZ
  2. DEC excitability of middle ear labyrinth, blocks conduction in middle ear vestibular-cerebellar pathways
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7
Q

What are clinical indications and ADRs of dimenhydrinate?

A

Indications: motion sickness*

Drug interactions, ADRs - same as scopolamine

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8
Q

Meclizine has the same MOA, drug interactions and ADRs as dimenhydrinate. What is special about meclizine clinical indication?

A

motion sickness

vertigo management**

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9
Q

In addition to H1 receptor AAG, what else does promethazine act on?

A

D2 receptor AAG

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10
Q

What are the three MOA of promethazine?

A
  1. DA AAG at D2 in CTZ –> limits emetic input to medullary vomiting center
  2. a-adrenergic blocker, depresses release of hypothalamic hormones
  3. competes w/histamine for H1 receptor (sedation)
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11
Q

What are four clinical indications for promethazine? What is the C.I.?

A
  1. motion sickness
  2. antiemetic*
  3. adjunctive for pain mgmt* (migraines)
  4. tx allergic conditions

C.I. - do not use in kids < 2y (potential fatal respiratory depression)*

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12
Q

Promethazine is substrate of CYP2D6. What are two other bolded drug interactions to be aware of?

A
  • avoid combo w/levodopa (may inhibit antiPD effect)

- QTc-prolongation

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13
Q

What are promethazine and prochlorperazine ADRs?

A
  • EPS*
  • Alter cardiac conduction - life-threatening dysrhythmias*
  • NMS*

other: amenorrhea/gynecomastia, antihistaminc/cholinergic ADRs

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14
Q

List the three classes of dopamine AG and the drugs within that class.

A
  1. Phenothiazines
    - prochlorperazine
    - promethazine
  2. Butyrophenones
    - droperidol
  3. Benzamides
    - metoclopramide
    - trimethobenzamide
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15
Q

Prochlorperazine has the same drug interactions and ADRs as promethazine. What is prochlorperazine indicated for? C.I.?

A

Indications:

  • antiemetic*
  • mild/mod, but not highly emetogenic chemotherapy

C.I.

  • do not use in kids < 2y*
  • avoid in pregnancy - newborn EPS, withdrawal sxs w/3rd tri exposure*
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16
Q

Droperidol antagonizes D1/D2 receptors in the brain and is used as a preanesthetic agent for PONV. Why do we avoid this drug?

A

BBW - QTc prolongation (dose dependent)

17
Q

When would you use trimethobenzamide?

A

Parkinson’s

apomorphine administration

18
Q

What are the 3 metoclopramide MOA?

A
  1. Central/peripheral D2 receptor AAG at low dose
  2. Blocks serotonin receptors in CTZ at high dose
  3. Enhance response to ACh in UGI tissue - enhanced motility w/out stimulating gastric, biliary, or pancreatic secretions
19
Q

What are common clinical uses for metoclopramide?

A
  • prevent/tx CIE w/mild-moderate emetogenic agents
  • prevent/tx PONV
  • DM gastroparesis**
20
Q

What should you not combine with metoclopramide?

A

Levodopa

21
Q

Drowsiness is a dose-related ADR of metoclopramide. Why should you try to use the smallest dose possible and short duration? What is the BBW?

A
  • EPS, especially acute dystonia which may be irreversible
22
Q

What is the class suffix for serotonin AAG? Which is most commonly used?

A

“-setrons”

Ondansetron

23
Q

What is the 2nd generation serotonin AAG?

A

Palonosetron

24
Q

What is the MOA of the serotonin AAG?

A

Inhibit serotonin at 5-HT3 receptor in small bowel, vagus nerve, and CTZ

DEC afferent visceral and CTZ stimulation of medullary vomiting center

** primary tx for variety of causes of nausea d/t diffuse blockade of serotonin **

25
Q

What are labeled indications for serotonin AAGs?

A
  1. Prevention* of CIE (scheduled, do not use PRN)
  2. Nausea r/t irradiation
  3. Prevent/tx PONV
    - repeat doses given in response to inadequate control of NV are generally inadequate**
26
Q

What are two off label uses of ondansetron?

A
  1. Kids w/GE in ED to reduce need for IV fluids and hospitalization
  2. Kids and adults with other serious NV, help avoid dehydration
27
Q

What CYP is ondansetron? What other drug interactions should you know?

A

3A4 substrate

Clean overall, but careful with other QTc drugs

28
Q

Serotonin AAGs are fairly well tolerated. What are two ADRs?

A

MC: HA

All agents have issues with QTc prolongation**

29
Q

Clinical situation:

Vestibular nausea / motion sickness

NT: histamine, Ach

A

Meclizine, scopolamine

30
Q

Clinical situation:

Migraine-associated nausea

NT: DA

A

Metoclopramide, prochlorperazine, promethazine

31
Q

Clinical Situation:

Gastroenteritis

NT: DA, serotonin

A

Promethazine, serotonin AAG

32
Q

What is the stepwise approach for nausea management with pregnancy?

A
  1. lifestyle
  2. vitamin B6 (pyridoxine)
  3. Add H1 AAG to Vit B6
  4. Low dose ondansetron
  5. Phenothiazine (promethazine or metoclopromide)
  6. other: ginger
33
Q

What is first line therapy for NV in pregnancy according to ACOG?

A

Vitamin B6 (pyridoxine)

34
Q

What is the H1 AAG you can add for NV in pregnancy? What is something to be aware of?

A

Doxylamine

Somnolence is common

35
Q

Why are you concerned about using ondansetron in a preggo?

A

1st trimester use linked to slight increased risk of congenital heart defects & cleft palate**

Also prolongs QT interval

36
Q

What med can you use to increase GI motility if needed, for gastroparesis?

A

Metoclopramide

Low dose and short term to decrease risk of tardive dyskinesia

37
Q

If metoclopramide is not appropriate for gastroparesis, what are some other options?

A
  • erythromycin

- domperidone or cisapride (both tightly restricted and used only by GI specialty)

Clinical Pharmacology Exam 3 (19 decks)

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