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Pharmacology TL > Antiemetics: PONV > Flashcards

Antiemetics: PONV Flashcards

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1
Q

What is nausea?

A

Subjectively unpleasant sensation in the epigastrium and throat associated with the urge to vomit.

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2
Q

What is vomiting?

A

Forceful expulsion of upper gastrointestinal contents through the mouth caused by powerful sustained contraction of the abdominal muscles.

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3
Q

What is retching?

A

Labored rhythmic activity of the respiratory muscles, including the abdominal muscles and diaphragm, without expulsion of gastric contents.

Example: dry heaves.

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4
Q

What receptors are found in the Chemoreceptor Trigger Zone (CTZ)?

A

Dopamine (D₂), Serotonin (5-HT₃), Histamine, Muscarinic (ACh)

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5
Q

What is the role of the Vestibular System in motion sickness?

A

Involved in motion sickness via cranial nerve VIII, using histamine and muscarinic receptors.

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6
Q

What signals contribute to the emetic center from the GI tract, pharynx, and higher centers?

A

Signals from stomach stretching (distension), bad smells/tastes, and visual input via the vagus nerve.

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7
Q

Which drug blocks the 5-HT₃ receptor?

A

Ondansetron

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8
Q

Which drug blocks the D₂ dopamine receptor?

A

Droperidol

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9
Q

Which drug blocks the Histamine (H₁) receptor?

A

Promethazine

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10
Q

Which drug blocks the Muscarinic (ACh) receptor?

A

Atropine

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11
Q

What is the function of these antagonists?

A

They prevent nausea/vomiting by blocking specific triggers.

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12
Q

What is the Emetic Center?

A

The final common pathway where all the signals converge and controls the actual act of vomiting.

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13
Q

What happens if the vagus nerve is strongly stimulated?

A

Vomiting can occur instantly even before nausea.

Treat the original cause (the trigger zone or vestibular input) for effective treatment.

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14
Q

Factors influences Etiology of PONV

A

Patient-specific factors, Surgery-related factors, Anesthetic-related factors, Postoperative factors

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15
Q

What age group shows an increase in incidence of PONV?

A

Within the pediatric population, there is an increase in incidence through pre-adolescence.

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16
Q

Which sex is more likely to experience PONV?

A

Women are 2-3 times more likely to have PONV.

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17
Q

How does menstruation affect the likelihood of PONV in women?

A

There is a fourfold increase in PONV during menses.

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18
Q

What personal history increases the risk of PONV?

A

A history of PONV or motion sickness increases the risk.

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19
Q

How does obesity relate to PONV risk?

A

Obesity, defined as a BMI > 30 kg/m2, increases the risk as fat acts as a reservoir for anesthetic agents.

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20
Q

What are Patient-Related Factors

A

Age and sex, gender
History of PONV or motion sickness
Obesity
Nonsmoking status
Anxiety
Decreased gastric motility or emptying

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21
Q

What is the surgery with the highest incidence of postoperative nausea and vomiting (PONV)?

A

Strabismus repair – 76%

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22
Q

What is the incidence range of PONV for gynecologic laparotomy?

A

40% to 77%

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23
Q

What is the incidence range of PONV for adenotonsillectomy?

A

36% to 76%

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24
Q

What types of surgeries promote PONV?

A

Gonadal/Reproductive (highest risk), Abdominal, Oculo-gyric, Pharyngeal

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25
What is the effect of benzodiazepines on PONV?
Benzodiazepines decrease PONV.
26
How do opioid analgesics affect the CTZ?
Opioid analgesics stimulate the CTZ.
27
What is the role of NSAIDs in anesthesia?
NSAIDs help decrease opioid use.
28
Rank the types of anesthesia by PONV risk from highest to lowest.
1. General anesthesia – Highest risk 2. Major regional anesthesia (e.g., spinal, epidural) – Moderate risk 3. Peripheral regional anesthesia (e.g., nerve blocks) – Lowest risk ## Footnote General > major regional (e.g. spinal/epidural) > peripheral regional
29
What is the PONV risk associated with inhalational agents in general anesthesia?
Inhalational agents (e.g., sevoflurane, desflurane, isoflurane) have a higher PONV risk.
30
What is the PONV risk associated with propofol-based TIVA?
Propofol-based TIVA (Total IV Anesthesia) has a lower PONV risk. ## Footnote Propofol has antiemetic properties.
31
What percentage of PONV risk is associated with the duration of anesthetic exposure?
60% of PONV risk is associated with 30 minutes of anesthetic exposure.
32
What factor influences PONV risk related to anesthesia provider?
The experience of the anesthesia provider influences PONV risk.
33
What are some postoperative factors that can affect recovery?
Uncontrolled pain, especially visceral/pelvic pain, opioid administration, dehydration, early ambulation/patient handling, and early oral intake.
34
How does dehydration affect postoperative nausea and vomiting (PONV)?
Adequate IV fluid hydration can decrease PONV.
35
What is the effect of early oral intake on PONV after surgery?
Early oral intake increases PONV after conventional surgery but decreases PONV after laparoscopic surgery.
36
What is the incidence of PONV with general anesthesia?
25% to 30%
37
What is the incidence of PONV with high risk procedures using emetogenic anesthetics?
Up to 80% ## Footnote Emetogenic anesthetics include narcotics and desflurane.
38
How do estimates of PONV compare to actual occurrence?
Estimates of PONV are less than the actual occurrence.
39
What are the Consequences of PONV?
• Patient discomfort (mild to severe) • Decreased ability of patient to care for him/herself • Increased cost – Personnel, supplies, drugs – Unplanned admissions • Wound dehiscence/bleeding • Aspiration pneumonitis • Dehydration and electrolyte imbalance
40
Which patients are considered high risk for PONV? 3 points each
Patients with a history of PONV, history of motion sickness, gynecologic laparoscopy, or breast reconstruction. ## Footnote Each high-risk factor is worth 3 points.
41
Which patients are considered intermediate risk for PONV? 2 points each
Patients undergoing facelift surgery, strabismus or middle ear surgery, neurosurgery, or who are obese. ## Footnote Each intermediate-risk factor is worth 2 points.
42
Which patients are considered low risk for PONV? 1 point each
Preadolescents, females, patients with anxiety, those undergoing laparoscopic cholecystectomy, intraoperative or postoperative opioid use, or with a duration of anesthesia greater than 60 minutes. ## Footnote Each low-risk factor is worth 1 point.
43
What is the threshold for prophylactic antiemetic indication?
A total of 3 points or more indicates that prophylactic antiemetic is indicated. ## Footnote Points are assigned based on risk factors.
44
What is a likely prophylaxis plan for high-risk patients?
1. 10 mg Reglan 2. 8 mg Dexamethasone 3. 4 mg Zofran
45
What are anticholinergics?
Scopolamine blocks muscarinic (M) receptors and is used for motion sickness and PONV.
46
What are antihistamines?
Hydroxyzine, Dimenhydrinate, and Diphenhydramine block histamine (H₁) and muscarinic (M) receptors to help with motion-related nausea.
47
What are benzamides?
Metoclopramide (Reglan) blocks dopamine (D) and increases gastric emptying, which is helpful in GERD or gastroparesis. It also weakly blocks serotonin (S).
48
What are butyrophenones?
Droperidol and Haloperidol are strong dopamine blockers used for severe nausea but have sedation and QT prolongation risks.
49
What are 5-HT₃ receptor antagonists?
Ondansetron, Dolasetron, and Granisetron block serotonin (S) receptors and are very common for PONV and chemo-related nausea.
50
What are phenothiazines?
Promethazine, Prochlorperazine, and Perphenazine block dopamine (D), muscarinic (M), and histamine (H₁) receptors. They are broad-spectrum antiemetics but can be sedating and cause extrapyramidal symptoms.
51
What is a notable use of scopolamine?
Scopolamine is good for motion sickness due to its muscarinic blocking effects.
52
What is a notable use of ondansetron?
Ondansetron is a serotonin blocker that is great for chemo and PONV.
53
What is a notable use of metoclopramide?
Metoclopramide also speeds up gastric emptying, making it good for reflux and gastroparesis.
54
What is a notable characteristic of promethazine?
Promethazine is considered the 'poor man’s' antiemetic because it is affordable and broad acting.
55
What is the bioavailability of Metoclopramide after oral administration?
About 75% due to hepatic first pass effect.
56
How is Metoclopramide distributed in the body?
It is distributed into most tissues and rapidly crosses the blood-brain barrier and placenta.
57
How is Metoclopramide excreted from the body?
Up to 30% is excreted in urine unchanged; the remainder is eliminated in urine and bile as sulfate and glucuronide conjugates.
58
What is the half-life of Metoclopramide?
4-6 hours, but can be up to 24 hours in patients with impaired renal function.
59
What are some side effects of Metoclopramide?
Side effects may include extrapyramidal symptoms and sedation.
60
What is the elimination half-life of butryophenones (droperidol/haldol)?
The elimination half-life is about 100 minutes.
61
What is the minimum effective dose of butryophenones for sedation?
Doses as low as 0.625 mg have provided effects similar to sedation. ## Footnote Maximum dose is 25 mg per Dave.
62
Which phenothiazines are most effective in treating opioid-associated PONV?
Promethazine and prochlorperazine are the most effective.
63
What are the side effects of phenothiazines?
Side effects include extrapyramidal symptoms, hypotension, prolonged tiredness, dysphoria, anxiety, and restlessness that develop after discharge.
64
How does the effectiveness of phenothiazines compare to ondansetron?
They are effective up to 4 mg of ondansetron.
65
What is the black box warning for Droperidol?
It is due to its potential for serious proarrhythmic effects and death.
66
What should all patients undergo prior to Droperidol administration?
All patients should undergo a 12-lead ECG.
67
What are the risks associated with Droperidol?
Cases of QT prolongation and serious arrhythmias.
68
What are the main 5HT3 receptor antagonists?
Ondansetron, Granisetron, and Dolasetron
69
What type of channel is the 5HT3 receptor?
It is a ligand gated cation channel (nicotine/GABA)
70
How are 5HT3 receptor antagonists absorbed?
They are readily absorbed after oral administration.
71
What is the distribution pattern of 5HT3 receptor antagonists?
They have rapid distribution to the CNS.
72
How are 5HT3 receptor antagonists metabolized?
They are metabolized via the Cytochrome P450 system in the liver.
73
How are 5HT3 receptor antagonists eliminated from the body?
They are eliminated via the kidneys.
74
How effective are low doses of 5HT3 receptor antagonists?
They are generally well tolerated and effective even at low doses (ondansetron 1 mg/granisetron 100 mcg).
75
What are some common side effects of 5HT3 receptor antagonists?
May cause headache, dizziness, and constipation.
76
What is the effect of 5-HT3 antagonists at high doses on cardiac conduction?
All have similar effects on cardiac conduction at high doses. ## Footnote This effect was only recognized in package inserts after the introduction of Zofran.
77
How does the effect of 5-HT3 antagonists compare to droperidol?
The effect is similar to the droperidol effect.
78
Why do some people fail prophylaxis with 5-HT3 drugs?
Some people fail prophylaxis with 5-HT3 drugs due to the wrong basic mechanism being attacked, as serotonin comes from the gut, not narcotics.
79
What is a factor contributing to variability in response to 5-HT3 drugs?
Human variability is a factor, as there are gene number and type variations for the primary enzyme CYP2D6.
80
What is the ultrarapid metabolizer phenotype?
It is characterized by overactive CYP2D6 activity.
81
What is the effect of ultrarapid metabolizer phenotype on drug effectiveness?
It leads to reduced effectiveness of the drug. Resulting in more nausea and vomiting with standard doses of CYP2D6 metabolized 5-HT3 RAs.
82
Patient populations of Ultrarapid CYP2D6 metabolizer phenotype and %
– Northern European countries, 2%–4% – Mediterranean area, 7%–12% – Ethiopia, 29% – Saudi Arabia, 21%
83
What patient populations are associated with CYP2D6 deficiency?
5%–10% of whites, significant hepatic impairment and coadministration of potent inhibitors, such as quinidine, fluoxetine, or haloperidol.
84
What may result from CYP2D6 deficiency?
Increased potential for drug interactions and side effects + Accumulation of CYP2D6 metabolized drugs and higher serum drug concentrations of CYP2D6 5-HT3.
85
Which NK-1 antagonist is currently on the market?
Aprepitant is the only drug on the market for CINV
86
What is the role of Substance P in relation to NK-1 antagonists?
It works by blocking Substance P from binding to NK-1 receptors in the central nervous system.
87
How are NK-1 antagonists best used in therapy?
They are best used in combination therapy with 5HT-3 and steroids.
88
What are the Principles of Scuderi’s Multimodal Therapy?
• Use of preoperative anxiolysis preventing air gulping • Three prophylactic anti-emetics (10 mg dexamethasone, 0.625 mg droperidol, and low dose of 5 HT-3) + gastric emptying • TIVA (total intravenous anesthesia) using propofol induction/infusion • non-lingering narcotics (eg. remifentanil) • non-steroidals in place of narcotics (eg. ketorolac) • no nitrous oxide or potent inhaled anesthetics • avoidance of muscle relaxants/necessary reversal • vigorous hydration

Pharmacology TL (11 decks)

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