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2-Pharm Final > Antiemetics > Flashcards

Antiemetics Flashcards

1
Q

Define nausea.

A

subjective feeling of the need to vomit; unpleasant; sometimes emesis isn’t preceded by nausea

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2
Q

Define vomiting.

A

involves contractions of the ileum and jejunum which move their contents back towards the stomach, the glottis closes to protect the airway, and the diaphragm contracts, the pharyngeal sphincters relax, the abdominal muscles contract which creates increased intraabdominal pressure that compresses the stomach; with open upper esophageal sphincters, emesis occurs

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3
Q

Define retching.

A

occurs when the same process happens, but the stomach is empty, no stomach contents are expelled

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4
Q

Define regurgitation.

A

Esophageal sphincters are not completely closed allowing stomach contents to pass into esophagus in setting of elevated abdominal pressure, no forceful expelling of stomach contents (no vomiting)

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5
Q

What is an example of regurgitation?

A

excessive mask ventilation

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6
Q

What is vomiting center?

A

controls vomiting & retching; located within the nucleus of tractus solitarius & parts of reticular formation in medulla oblongata

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7
Q

What are neurotransmitters that are involved in the vomiting center?

A

Neurotransmitters that activate or inhibit vomiting center: acetylcholine, dopamine, histamine, substance P, & serotonin

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8
Q

Review vomiting center components.

A
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9
Q

What is the Chemoreceptor Trigger Zone (CTZ?

A

located in the area postrema on the floor of 4th ventricle in the brain, lies outside the blood-brain barrier

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10
Q

What can the Chemoreceptor Trigger Zone (CTZ) detect?

A

CTZ can detect agents & relay signals to the vomiting center where the mechanical act of vomiting is stimulated

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11
Q

Where does the vomiting center send impulses?

A

Mechanical act of vomiting activated by vomiting center

When activated, vomiting center sends impulses (efferent signals) via CN V, VII IX, X, & XII; transmits efferent signals from the vomiting center to motor fibers GI & spinal nerves to diaphragm & abdomen to elicit vomiting

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12
Q

What are other ways to activate the vomiting center?

A

can also be activated by vestibular apparatus, thalamus, cerebral cortex, & neurons within GI tract

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13
Q

What is the definition of Postoperative Nausea and Vomiting (PONV)?

A

Defined as having nausea or emesis within 24 hours of a surgical procedure

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14
Q

Along with pain, _______ is a major issue that contributes to patient satisfaction

A

PONV

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15
Q

What is the occurance of PONV?

A

Can occur up to 40% of patients untreated, 80% for high-risk patients

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16
Q

What are antiemetics targets of?

A

Numerous neurotransmitters and receptor sites serve as a target for antiemetic medications

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17
Q

What are patient risk factors for PONV?

A
  • Women
  • Nonsmokers
  • Hx PONV
  • Hx of motion sickness
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18
Q

What are surgical risk factors for PONV?

A
  • Surgery > 1 hr
  • GYN, laparotomy/laparoscopy, ENT, breast, plastics, orthopedics
  • Peds: incidence starting at age 3 - herniorrhaphy, T&A, strabismus, male genitalia
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19
Q

What are anesthetia risk factors for PONV?

A
  • Inhaled anesthetics
  • Nitrous oxide
  • Neostigmine
  • Opioids
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20
Q

What are the properties of PONV?

A
  • Prevention easier than treatment
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21
Q

Use __________ for prevention and treatment PONV

A

multimodal approach (multiple drugs targeting multiple receptor sites)

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22
Q

Review components of the multimodal aprroach to PONV prevention and treatment.

A
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23
Q

What is the anticholinergic used for PONV?

A

Scopolamine

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24
Q

What is the drug class of Scopolamine?

A

Anticholinergic (antimuscarinic): tertiary amine (crosses the blood brain barrier)

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25
What is the formulary for Scopolamine?
Antiemetic - transdermal patch
26
What is the use of Scopolamine?
Used as antiemetic for motion sickness & PONV prophylaxis
27
What is the MOA of Scopolamine?
Exerts antiemetic action by blocking muscarinic acetylcholine receptors within the vestibular system near the CTZ
28
What is the administration of Scopolamine?
* Apply 1 patch at least 4hrs before noxious stimulus (remove after 72hrs) * Apply to dry postauricular area
29
What is the half life of Scopolamine?
Long half-life: 4.5 hr
30
What is the amount of Scopolamine delivered by the patch?
1.3 mg delivers about 5mcg/hr
31
What is the main side effect of Scopolamine?
visual disturbances (anisocoria)- wash hands after handling; dry mouth
32
When should Scopolamine be used cautiously?
Caution with glaucoma, seizures, psychosis, people over 65, not studied on peds
33
When is Scopolamine not approved?
Not approved for anyone younger than 18 y/o
34
What are causes of Central Anticholinergic Syndrome?
Can result from atropine and scopolamine (not glycopyrrolate, doesn’t cross blood-brain barrier)
35
What are the s/s of Central Anticholinergic Syndrome?
restlessness, hallucinations, somnolence, unconsciousness
36
What is a mnemonic for Central Anticholinergic Syndrome?
**“atropine fever"** Anticholinergic med overdose: “Blind as a bat, Mad as a hatter, Red as a beet, Dry as a bone, Hot as hell, Full as a flask”
37
What is true about small children and Central Anticholinergic Syndrome?
small children can develop w/therapeutic dose of anticholinergic drug
38
What is the treatment for Central Anticholinergic Syndrome?
physostigmine (lipid soluble tertiary amine) 15-60 mcg/kg IV
39
What is the MOA of Physostigmine?
an anticholinesterase (acetylcholinesterase inhibitor) which increases ACh levels (within CNS) to compete with anticholinergic drugs such as atropine or scopolamine within the CNS
40
Why are Edrophonium, neostigmine, pyridostigmine not effective against Central Anticholinergic Syndrome?
not effective d/t quaternary ammonium structure & not able to enter the CNS
41
What is the repeat does of Central Anticholinergic Syndrome?
Repeat every 1-2 hours
42
What can Central Anticholinergic Syndrome be mistaken for?
This syndrome can be mistaken for delayed recovery from anesthesia and postop delirium
43
What are examples of dopamine-2 antagonists?
* Metoclopramide (Reglan) * Droperidol * Haloperidol * Prochlorperazine (Compazine)
44
What is drug properites of Metoclopramide (Reglan)?
Benzamide with both cholinergic and antidopaminergic properties
45
What are the resulting effects of Metoclopramide (Reglan)?
Results in PONV reduction
46
What are the characteristics of cholinergic stimulation with Metoclopramide (Reglan)?
* Contraction of lower esophageal sphincter (LES) & gastric fundus * Increased gastric and small intestine motility (prokinetic) * Decreased muscle activity in pylorus and duodenum
47
What are the characteristics of antidopaminergic activity of Metoclopramide (Reglan)?
Antagonizes dopamine receptors in CTZ (antiemetic effects)
48
Who should Metoclopramide (Reglan) be used cautionly in?
**Antidopaminergic activity** * Caution with Parkinson’s disease, Restless Leg Syndrome, & those w/movement disorders r/t dopamine inhibition or depletion
49
What can dopamine antagonism from Metoclopramide (Reglan) result in?
Dopamine antagonism in CNS can result in **_extrapyramidal reactions_** (oculogyric crises, opisthotonus, trismus, torticollis)
50
What is the black box warning of Metoclopramide (Reglan)?
**Antidopaminergic activity** ## Footnote 2009 Black Box Warning from FDA: admin. may result in development of tardive dyskinesia
51
Define akathisia.
feeling of unease, restlessness; can result in cancellation of surgery if administered preoperatively
52
What is Metoclopramide (Reglan) implicated in?
Implicated with cardiac dysrhythmias including prolonged QT interval and Torsades de Pointes
53
What are the GI effects of Metoclopramide (Reglan)?
* GI prokinetic activity results from selective cholinergic stimulation of GI tract * Results in accelerated gastric clearance of liquids & solids, decreased gastric emptying time, shortened transit time through small intestine
54
What is the only drug FDA approved for diabetic gastroparesis?
Metoclopramide (Reglan)
55
What effect is on Metoclopramide (Reglan) and atropine?
Atropine opposes metoclopramide-induced increases in lower esophageal sphincter tone & GI hypermotility
56
What is the clinical use of Metoclopramide (Reglan)?
Preoperative decrease in gastric fluid volume, antiemetic effect, tx gastroparesis, tx gastroesophageal reflux, & intolerance to enteral feedings
57
What is the dose of Metoclopramide (Reglan)?
Prokinetic before anesthesia induction: 10-20 mg IV – results in increased LES tone & decreased gastric fluid volume
58
What can rapid push of Metoclopramide (Reglan) cause?
rapid push can cause cramping)
59
When is Metoclopramide (Reglan) benefical?
May be beneficial in patients: recently ingested food, trauma, obese, DM w/gastroparesis symptoms, parturients, GERD
60
What does Metoclopramide (Reglan) not effect?
* Does not affect pH of gastric contents * doesn’t offset opioid-induced hypomotility of the gut
61
What drugs should Metoclopramide (Reglan) not be used with?
Should not be used with these drugs: phenothiazines, butyrophenones, MAO inhibitors, and tricyclic antidepressants or in patients with preexisting extrapyramidal signs or symptoms
62
What are the inhbitory effects of Metoclopramide (Reglan)?
Inhibitory effects on plasma cholinesterase activity
63
What is an absolute contraindication to Metoclopramide (Reglan)?
* Do not administer to patients with mechanical obstructions
64
What are examples of mechanical obstructions?
Bowel obstruction, bowel perforation, pyloroplasty, or intestinal anastomosis
65
Review the black box warning of Metoclopramide (Reglan)?
66
What are the drug classes of Droperidol & Haloperidol?
* Butyrophenone * 1st generation antipsychotic drug class * dopamine receptor antagonists
67
What are the properties of Droperidol & Haloperidol?
Possess antidopaminergic, antinoradrenergic, anticholinergic, & antihistaminergic activity
68
What is the black box warning of Droperidol & Haloperidol?
Block Box Warning due to prolonged QT syndrome
69
What are characteristics of the black box warning of Droperidol?
resulted from higher doses of droperidol than commonly used for antiemetic effect
70
What can Droperidol & Haloperidol cause?
Can cause extrapyramidal symptoms as other dopaminergic blocking drugs
71
What have the side effects of Droperidol & Haloperidol lead to?
Lead to relative non-use despite its effectiveness
72
What is the dose of Droperidol for PONV?
Droperidol 0.625-1.25 mg IV
73
What is the dose of Haloperidol for PONV?
Haloperidol 0.5-2 mg
74
What is the drug glass of Prochlorperazine (Compazine)?
1st generation antipsychotic drugs with antiemetic properties
75
What are the properties of Prochlorperazine (Compazine)?
* Phenothiazine * Antidopaminergic, antiadrenergic, & antihistamine activity (similar to butyrophenone drugs)
76
What are examples of 1st generation antipsychotic drugs with antiemetic properties?
* Chlorpromazine (Thorazine) * Prochlorperazine (Compazine)
77
What are side effects of Prochlorperazine (Compazine)?
dry mouth, sedation, QTc prolongation, extrapyramidal symptoms, agranulocytosis, orthostatic hypotension
78
What corticosteroid has antiemetic properties?
Dexamethasone (Decadron)
79
What is the drug class of Dexamethasone?
Corticosteroid – glucocorticoid (anti-inflammatory, immunosuppressant, anti-emetic activity)
80
Whst is the MOA of Dexamethasone?
Mechanism of antiemetic activity unclear * Proposed mechanism of action: central inhibition of prostaglandin synthesis and control endorphin release
81
What is the efficacy of Dexamethasone?
Efficacy similar to ondansetron & droperidol
82
What is high risk patients Dexamethasone?
Risk of perioperative hyperglycemia with at-risk patients (diabetic patients)
83
What is the dose of Dexamethasone?
Included in multimodal regimens to prevent PONV: Dose 4- 8 mg IV (Nagelhout)
84
When is Dexamethasone most effective?
Some anesthesia sources indicate most effective if given prior to induction
85
What are the different types of 5-HT3 Antagonists with antiemetic properties ?
* Ondansetron (Zofran) * Dolasetron (Anzemet) * Granisetron * Tropisetron
86
What is 5-HT3 receptors?
excitatory ligand-gated ion channels located in brain and GI tract
87
What is the MOA of 5-HT3 Antagonists?
Stimulation via serotonin released by enterochromaffin cells of small intestine: * Stimulation of 5-HT3 receptors by serotonin stimulates vomiting reflex * Antiemetic effect occurs through competitive antagonism of 5-HT3 receptors
88
Where is the highest density of 5-HT3?
Highest density of receptors in area postrema/CTZ
89
What are the clinical uses of 5-HT3 Antagonists?
prevention and treatment of PONV & chemotherapy/radiation-induced N&V
90
Do 5-HT3 Antagonists cross the BBB or not?
Cross the blood-brain barrier
91
What is 5-HT3 Antagonists not effective in treating?
Not effective for motion induced N&V
92
What is Ondansetron (Zofran) related to?
Structurally related to serotonin
93
What is Ondansetron (Zofran) specific to?
Specific to 5-HT3 receptors thus lacks neurologic side effects
94
What are common side effects of Ondansetron (Zofran)?
headaches, diarrhea
95
What is the effect of Ondansetron (Zofran) and metoclopramide given together?
Cardiac dysrhythmias when combined with metoclopramide
96
What can Ondansetron (Zofran) cause?
Can cause slight prolonged QTc interval
97
What is the dose of Ondansetron (Zofran)?
4-8 mg IV administered 2-5 min before induction
98
What is the dose of Ondansetron (Zofran) for pediatrics?
0.05-0.15 mg/kg – decreases incidence of PONV for T&A and strabismus surgery
99
What was the use of Tropisetron/Granisetron/Dolasetron?
Used with chemo/radiation induced N&V but finding way into anesthesia practice
100
What are the properties of Tropisetron?
* Prokinetic properties * 2-5 mg IV
101
What is the duration of action of Tropisetron?
longer acting than ondansetron (7.3 h vs 3.5 h)
102
What is the selectivity of Granisetron?
more selective than ondansetron
103
What is the elimination half time of Granisetron?
9 h elimination ½ time
104
What does Granisetron work best with?
Worked better with coadministration of dexamethasone
105
What is the dose of Granisetron?
0.02- 0.04 mg/kg IV
106
What is Dolasetron (Anzemet) metabolism?
Highly potent: metabolite hydrodolasetron provides antiemetic effect
107
What is the anesthesia dose of Dolasetron (Anzemet)?
Anesthesia dose: 12.5 mg IV

2-Pharm Final (10 decks)

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