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PharmacologyII > Emesis (Vomiting) > Flashcards

Emesis (Vomiting) Flashcards

1
Q

Role of GI Tract

A
  • digestion and absorption of food
  • important endocrine organ
  • gastric acid secretion
  • gut motility and defecation
  • formation and excretion of bile
  • vomiting and nausea
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2
Q

True or False?

GI Tract contains its own neuronal network?

A

True.
The GI Tract contains its own neuronal network (enteric nervous system) that contains as many neurons as there are in the spinal cord

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3
Q

Vomiting

A
  • defensive response to rid the host of toxic/irritating material
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4
Q

How is vomiting regulated?

A

Regulated via the vomiting center in the medulla and communicates with chemoreceptor trigger zone (CTZ)

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5
Q

Acute chemotherapy drug-induced vomiting

A
  • vomiting within the first 24 hours of chemotherapy

- Involves 5HT/5HT3 receptor signaling

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6
Q

Delayed chemotherapy drug-induced vomiting

A
  • vomiting after 24 hours of chemotherapy

- involves substance P (SP/NK1) receptor

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7
Q

5-HT3 receptor antagonists

A
  • ondansetron
  • granisetron
  • alosetron - original 5HT3 but removed from market and now used to treat IBS in women
  • palonosetron
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8
Q

5-HT3 receptor

A
  • ligand-gated cation channels that mediates Na+/K+ ions
  • primary site of action is the CTZ
  • 5-HT3 receptors induce vagal signaling of nausea and mediate contraction of the GI tract
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9
Q

5-HT receptors

A
  • 7 families

- all are G-protein coupled, except 5-HT3

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10
Q

5-HT3 receptor antagonists action

A
  • inhibits vagal signaling to vomiting (emetic) center in the brainstem to prevent vomiting from occurring.
  • also slows intestinal transit
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11
Q

Adverse Effects of 5-HT3 receptor antagonists

A
  • Headache and GI upset (constipation)

- Ischemic colitis (alosetron)

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12
Q

5-HT3 Receptor Antagonists Pharmacokinetics

A
  • prolonged half-life that persists even when the drug is removed from the systemic circulation
  • drug can be given orally or through IV/IM
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13
Q

Dopamine Receptor 2 (D2) Antagonists - antipsychotic phenothiazines

A
  • chlorpromazine
  • perphenazine
  • prochlorperazine
  • trifluoperazine
  • work by inhibiting dopamine signaling
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14
Q

Dopamine Receptor 2 (D2) receptor antagonists

A
  • D2 receptor is Gi-protein coupled and inhibits adenylyl cyclase thereby lowering cAMP formation
  • D2 receptor antagonists would reverse the action of D2 receptor and increase cAMP formation and activation of protein kinase A (PKA)
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15
Q

D2 receptor antagonists Pharmacokinetics

A
  • highly lipophilic
  • half-lives range from 12-24 hours
  • available orally and in parenteral formulations
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16
Q

D2 receptor antagonists adverse effects

A
  • extrapyramidal syndrome like dystonias and tardive dyskinesia (involuntary repetitive movements of the face and body)
  • hyperprolactinemia
17
Q

D2 receptor antagonist is contraindicated in patients with?

A

CNS depression

18
Q

Metoclopramide

A
  • D2 antagonist
  • may also block histamine and muscarinic receptors
  • acts centrally on the CTZ, also has peripheral actions (increased GI motility)
  • also blocks D2 receptors in other areas of the CNS
  • primarily given orally
19
Q

Adverse effects of metoclopramide

A
  • spasmodic torticollis
  • oculogyric crises
  • stimulates prolactin release
20
Q

Domperidone

A
  • D2 receptor antagonist (specific for D2 receptor)
  • does not penetrate the blood brain barrier (less CNS side effects)
  • small increased risk for serious cardiac adverse effects
  • primarily given orally
21
Q

D2 receptor antagonists used for acute chemotherapy-induced emesis

A
  • metoclopramide
  • domperidone
  • haloperidole
  • droperidol
  • levomepromazine
22
Q

Histamine (H1) receptor antagonists

A
  • cinnarizine
  • cyclizine
  • promethazine
  • inhibit Gq protein coupled receptor
  • effective against nausea and vomiting due to motion sickness
23
Q

H1 receptors

A
  • G-protein coupled receptors linked to Gq proteins (phospholipase C)
  • activates protein kinase C, and increases Ca2+
24
Q

Promethazine

A
  • H1 receptor antagonist

- can also be used to treat pregnancy-associated morning sickness

25
Q

Muscarinic Receptor Antagonists

A
  • hyoscine (scopolamine)
  • used for the prophylaxis and treatment of motion sickness
  • given orally or via transdermal patches
26
Q

Muscarinic Receptor Antagonists adverse effects

A
  • includes dry mouth and blurred vision

- may also cause drowsiness

27
Q

Aprepitant/Fosaprepitant

A
  • antaognists of substance P receptors (NK1 receptors) in the CTZ
  • antiemetic drug
  • fosaprepitant is a prodrug of aprepitant
28
Q

Nabilone

A
  • antiemetic drug
  • synthetic cannabinol
  • antagonised via naloxone
29
Q

Dexamethasone

A
  • antiemetic drug

- high doses can prevent vomiting caused by sytotoxic drugs (MOA unknown)

PharmacologyII (12 decks)

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