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NUNA 680 - Pharm > Antiemetics > Flashcards

Antiemetics Flashcards

1
Q

Where is the brainstem vomiting center located?

A

In the lateral medullary reticular formation

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2
Q

What are the pharmacologic systems and receptors associated with vomiting? (7)

A

Acetylcholine (muscarinic), histamine H1, serotonin 5-HT3, dopamine, substance P, GABA, and neurokinin-1

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3
Q

The chemoreceptor trigger zone in the 4th ventricle houses which receptors that provide afferent input to the vomiting center?

A

Dopamine, serotonin 5-HT3, opioid receptors

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4
Q

The vestibular system (motion sickness) houses which receptors that provide afferent input to the vomiting center?

A

Muscarinic and H1 receptors

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5
Q

Irritation of the pharynx (______ nerve) initiates a gag and retch response.

A

vagus

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6
Q

Which receptors in the mucosa of the GI tract provide afferent input to the vomiting center?

A

The vagal and enteric afferents - 5-HT3 receptors activated by serotonin released by the mucosa which then stimulate vagal input to CTZ and vomiting center

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7
Q

What are the CNS afferent inputs to the vomiting center?

A

Stress and anticipatory vomiting

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8
Q

The vomiting center sends efferent signals through which cranial nerves through vagal parasympathetic fibers and sympathetic chain to skeletal muscle via alpha motor neurons?

A

V, VII, IX, X, XII

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9
Q

How does efferent output travel from the emetic center?

A

Via the phrenic and spinal nerves of the abdominal wall musculature, producing the act of vomiting

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10
Q

What is the suggested MOA of benzodiazepines as antiemetics?

A

Decreases dopamine input at CTZ; anxiolysis; may decrease adenosine reuptake decreasing production and release of dopamine at CTZ

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11
Q

If benzos are being given solely as an antiemetic, at what point in the case should they be administered?

A

Toward the end

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12
Q

What is the MOA of antihistamines as antiemetics?

A

Anticholinergic effect, histamine receptor blockade

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13
Q

What are three antihistamines that can be used as antiemetics? Their effects are limited to what?

A

Diphenhydramine, meclizine, dimenhydrinate

Weak effects except on motion sickness and blocking “oculoemetic” reflex which occurs in strabismus surgery which tugs on extraocular muscles.

Can cause sedation, dizziness, confusion, dry mouth, urinary retention, and decreased BP.

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14
Q

What phenothiazine antihistamines can be used as antiemetics? What are their doses?

A

Prochlorperazine (2.5-10 mg IV) and promethazine (25 mg IV)

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15
Q

What is the MOA of phenothiazine antihistamines as antiemetics?

A

Inhibition of dopamine and muscarinic (ACh) receptors

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16
Q

What are the limitations of phenothiazine antihistamines as antiemetics?

A

Compounds sedation produced by post-op narcotics; extrapyramidal effects, pseudoparkinson’s (Dopamine blockers should NOT be given to Parkinson’s patients), lowers seizure threshold, hypotension (via alpha blockade)

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17
Q

What is the MOA of scopolamine as an antiemetic?

A

Antimuscarinic (vestibular system), antagonizes histamine and serotonin; blocks transmission to the medulla of impulses from overstimulation of the vestibular apparatus.

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18
Q

What characteristic of scopolamine allows it to be worn as a patch?

A

Lipid solubility; it crosses the blood brain barrier (and the placenta if given IV)

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19
Q

Guidelines for scopolamine patch administration?

A

Apply 60 minutes prior to induction; can provide adequate drug levels (5 mcg/hr) for 48-72 hours with less than 0.5 mg absorbed total

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20
Q

What are some side effects of the scopolamine patch as an antiemetic?

A

Ocular effects (CI for glaucoma; vision disturbances, unilateral pupil dilation on side of patch), restlessness, delirium, sedation, dry mouth, tachycardia (less than IV dose)

21
Q

What butyrophenones are used as antiemetics?

A

Droperidol (Inapsine)

22
Q

Through what mechanism do butyrophenones function as an antiemetic?

A

Dopamine blockade (alpha 1 blockade)

23
Q

What is the dosage of droperidol as an antiemetic?

A

0.625-1.25 mg IV (0.05 mg/kg)

24
Q

What are side effects and limitations of butyrophenones/droperidol as an antiemetic?

A

Hypotension (by vasodilation via alpha blockade), prolongs QT interval (risk of Torsades), extrapyramidal effects (avoid for Parkinson’s, elderly), sedation

25
Q

How can extrapyramidal effects caused by butyrophenones/droperidol be treated?

A

Benadryl

26
Q

MOA of metoclopramide as an antiemetic?

A

Dopamine blockade in CTZ and cholinergic stimulus to GI tract (increased gastric and SI motility)

27
Q

Antiemetic dose of metoclopramide?

A

10-20 mg IV

28
Q

Concomitant use of metoclopramide with phenothiazines or droperidol can increase incidence of what side effects?

A

Extrapyramidal effects (restlessness, dystonias, Parkinsonism)

29
Q

With what mechanical/physical condition should metoclopramide be avoided?

A

Intestinal obstruction (increased pressure can cause rupture)

30
Q

What is serotonin? Where is most of it stored? Name four 5-HT receptors.

A

Serotonin as an endogenous vasoactive substance and neurotransmitter (emesis and pain) and a cerebral stimulant.

90% is stored in the enterochromaffin cells of the GI tract.

1F, 2, 3, and 4

31
Q

What is the function of a 5-HT1 receptor?

A

Cerebral vasoconstriction (agonist for migraines)

32
Q

What is the function of a 5-HT2 receptor?

A

Coronary artery and pulmonary vessel vasoconstriction

33
Q

What is the function of a 5-HT3 receptor?

A

PNS - visceral pain; CNS - emesis, appetite, addiction, pain, and anxiety (antagonism for antiemetic)

34
Q

What is the function of a 5-HT4 receptor?

A

Gastrokinesis (agonist to treat constipation, IBS)

35
Q

What are the indications/MOA of Serotonin 5-HT3 Receptor Agonists?

A

Chemotherapy induced NV, PONV (NOT motion sickness)

Blocks peripheral receptors on the intestinal vagal afferents and central receptors in the vomiting center, CTZ (vagal stimulation)

5-HT3 blockade without effect on dopamine, histamine, adrenergic, or muscarinic receptors

36
Q

Since Serotonin 5-HT3 Receptor Antagonists only target serotonin receptors, what does that mean for the side effect profile?

A

No Parkinsonian, restlessness, hypotension, or sedation; minimal side effects

37
Q

Name 4 5-HT3 Receptor Antagonists

A

Ondansetron, dolasetron, granisetron, palonosetron

38
Q

What is the dosage for ondansetron?

A

4-8 mg (0.15 mg/kg peds) IV

39
Q

What is the dosage for dolasetron?

A

12.5 mg IV

40
Q

What is the dosage for granisetron?

A

1 mg (0.01 mg/kg) IV

41
Q

What is the dose for palonosetron?

A

0.075 mg IV (a newer drug which requires a smaller dose)

42
Q

What are the side effects and limitations of Serotonin 5-HT3 Receptor Antagonists?

A

Headache, constipation, theoretically cardiac arrhythmias (dolasetron)

Cost and prolonged QT interval are limitations; efficacy comparable to droperidol; propofol used for induction and maintenance may not require an additional antiemetic.

43
Q

How do corticosteroids act as antiemetics?

A

Unknown; possibly inhibit prostaglandin synthesis centrally and control endorphin release

44
Q

Antiemetic dexamethasone dose?

A

0.15 mg/kg

45
Q

Corticosteroids can enhance the effectiveness of what other antiemetic class?

A

5-HT3 antagonists

46
Q

Limitations of corticosteroids as antiemetics

A

Chronic therapy: interference with healing, immune suppression, avascular necrosis, increased blood glucose in diabetic and obese patients

47
Q

When is dexamethasone best given if using as an antiemetic?

A

Prior to induction

48
Q

What is aprepitant? Dose?

A

NK1 (Neurokinin) receptor antagonist of substance P found in the area postrema, nucleus of the solitary tract and afferent fibers of the vagus nerve; new drug for PONV prophylaxis; 40 mg PO 1 hour preop

49
Q

What is the antiemetic dose of ephedrine?

A

0.5 mg/kg IM

NUNA 680 - Pharm (8 decks)

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