Antiemetic Drugs Flashcards
(131 cards)
1
Q
What is the emetic response?
A
A reflex brought about by activating the vomiting center either directly or indirectly
2
Q
Where are the direct-acting stimuli that activate the vomiting center from?
A
The cerebral cortex (anticipation or fear)
Sensory organs (upsetting sights, noxious odors or pain)
Vestibular apparatus of the inner ear
3
Q
What are the indirect stimuli that activate the vomiting center?
A
First activate the chemoreceptor trigger zone (CTZ) which in return activates the vomiting center
4
Q
How does the activation of CTZ occur?
A
By signal from the stomach and the small intestine (traveling along the vagal afferents)
By the direct action of emetogenic compounds that are carried to the CTZ in the blood.
5
Q
What are examples of emetogenic compounds?
A
Anticancer drugs
Opioids
Ipecac
6
Q
What is the result of activation of the CTZ?
A
Once activated, the vomiting center signals the stomach, diaphragm, and abdominal muscles, resulting in a coordinated response of expulsion of gastric contents
7
Q
What are the receptors involved in the activation of CTZ? (7)
A
Serotonin
Glucocorticoids
Substance P
Neurokinin 1
Dopamine
Acetylcholine
Histamine
8
Q
What is the general MOA of antiemetics?
A
Blocking or activating or or more of the receptors
9
Q
What is the prototype drug of serotonin antagonists?
A
Ondansetron
10
Q
What is the prototype drug of glucocorticoids?
A
Dexamethasone
11
Q
What is the prototype drug of substance P/ neurokinin-1 antagonist?
A
Aprepitant
12
Q
What is the prototype drug of benzodiazepine?
A
Lorazepam
13
Q
What is the prototype drug of dopamine antagonists?
A
Prochlorperazine
14
Q
What is the prototype drug of cannabinoids?
A
Dronabinol
15
Q
What is chemotherapy-induced nausea and vomiting? (CINV)
A
Nausea and vomiting due to dehydration, electrolyte imbalances, nutrient depletion and esophageal tears
16
Q
What is the main drawback of CINV?
A
It can be so serious that patients may discontinue therapy rather than endure further discomfort
17
Q
What are three types of emesis associated with chemotherapy?
A
Anticipatory
Acute
Delayed
18
Q
What is the mechanism of CINV?
A
Chemotherapy –> indirect and direct way of activating vomiting center–> serotonin release (GIT) / substance P (CTZ) –> 5-HT3 receptors/NK1 receptors –> CINV
19
Q
What is the anticipatory emesis from chemotherapy?
A
Occurs before drugs are actually given, triggered by the memory of severe nausea and vomiting
20
Q
What is the acute emesis from chemotehrapy?
A
Begins within minutes to a few hours after receiving chemotherapy and often resolves within 24 hours
21
Q
What is the delayed emesis form chemotherapy?
A
Develops a day or more after drug administration
22
Q
What is an example of delayed emetic drug?
A
Cisplatin emesis is maximal 48 to 72 hours after dosing and can persist for 6 to 7 days
23
Q
What are antiemetics most effective for?
A
Most effective at preventing CINV rather than suppressing it once it has already begun
24
Q
What does the antiemetic regimen depend on?
A
On the emetogenic potential of the chemotherapy drugs used:
If highly emetogenic –> 3 drugs
If moderately emetogenic –> 2 drugs
If barely emetogenic –> 1 drug
25
Which are the most effective drugs at suppressing nausea and vomiting caused by anticancer drugs?
Serotonin receptor antagonists
26
What are serotonin receptor antagonists effective against?
Nausea and vomiting associated with radiation therapy, anesthesia, viral gatsritis and pregnancy
27
What are the examples of serotonin receptor antagonists?
Ondansetron (prototype)
Granisetron (10 to 15x more potent than prototype)
Dolasetron
Palonosetron
28
What is Ondansetron approved for?
CINV
Vomiting associated with radiation therapy and anesthesia
Used off-label for other causes
29
What other causes is Ondansetron used for?
Childhood viral gastritis and morning sickness of pregnancy
30
What is the MOA of Ondansetron?
Blocks type 3 serotonin in CTZ and on afferent vagal neurons in the upper GIT
31
What is the effectiveness of Ondansetron like?
Very effective by itself, and even more effective when combined with dexamethasone
32
What is the administration route of Ondansetron?
Oral or parenteral
33
What are the side effects of Ondansetron?
Headache, diarrhea, dizziness
QT interval prolongation and increased risk of Torsades de Pointes
34
Why does Ondansetron not cause extrapyramidal effects?
It does not block the dopamine receptors
35
What are the extrapyramidal effects?
Akathisia, acute dystonia
36
Which kind of drugs cause extrapyramidal effects?
Antiemetic phenothiazines
37
What is the MOA of Granisetron?
Blocks 5-HT3 receptors on afferent vagal neurons and in the CTZ
38
What is Granisetron approved for?
Nausea and vomiting associated with radiation therapy, chemotherapy, and surgery
39
What are the adverse effects of Granisetron?
Headache, weakness, tiredness and diarrhea/constipation
40
What is the administration route of Granisetron?
PO
IV
Transdermal
41
What is Dolasetron approved for?
CINV and postoperative nausea and vomiting
42
What is the administration route of Dolasetron?
PO
IV
43
What are the side effects of Dolasetron?
Same as the other serotonin antagonists
44
What is the important exception when it comes to Dolasetron?
When given in high doses (IV), it poses a significant risk of fatal dysrhythmias
High dose - IV therapy should not be used, oral therapy and low-dose IV therapies are considered safe
45
What is Palonosetron?
A second generation serotonin antagonist
46
What is Palonosetron approved for?
CINV and postoperative nausea and vomiting
47
What is the MOA of Palonosetron?
Same mechanism, efficacy, and side effects as the rest of the serotonin antagonists
48
What are the two main differences of Palonosetron?
Has a much longer half-life
Effective against delayed emesis (as well as acute emesis ), whereas the others are most effective against acute emesis
49
What is the half-life of Palonosetron?
40 hours compared to the 8 hours (another serotonin antagonist)
50
Why is Palonosetron more effective against delayed emesis?
Due to its longer half-life
51
What are the administration routes of Palonosetron?
PO
IV
52
What are the glucocorticoids used to suppress CINV?
Methylprednisolone
Dexamethasone
53
How are glucocorticoids effective in suppressing CINV?
Both on their own and in combination with antiemetics
54
What is the MOA of glucocrticoids?
They bind to the membrane, fuse, and transcribe multiple genes, the mechanism which affects and suppresses emesis though is unknown
55
What is the administration route of glucocorticoids?
IV
56
What are the side effects of glucocorticoids?
Serious side effects are absent; antiemetic use is intermittent and short-term
57
When do serious side effects present with glucocorticoids?
If there is chronic use
58
What are the examples of Substance P/ neurokinin 1 antagonists?
Aprepitant
Fosaprepitant
Rolapitant
59
What is the prodrug of Substance P/ neurokinin 1 antagonists? What happens to it?
Fosaprepitant is the prodrug that undergoes conversion to Aprepitant in the body
60
What is the principal application of Substance P/ neurokinin 1 antagonist?
Prevention of CINV
61
What is the half life of Rolapitant?
180
62
What is Rolapitant approved for and why?
Prevention of chemotherapy-induced delayed emesis because of its longer half-life
63
What are the uses of Aprepitant?
Postoperative nausea and vomiting
CINV (delayed and acute)
64
What is the MOA of Aprepitant?
Blocks neurokinin-1 receptors (for substance P) in the CTZ
65
How can Aprepitant be used?
Alone for managing postoperative nausea nd vomiting
In combination with other antiemetic drugs for managing CINV
66
Which other antiemetic drugs is Aprepitant used with?
Mainly glucocorticoids and serotonin antagonists
67
What are the PK of Aprepitant?
Well absorbed
Plasma levels peak after 4 hours
Extensive hepatic metabolism - primarily CYP3A4, excretion in urine and feaces
Plasma half-life 9 to 13 hrs
68
What are the adverse effects of Aprepitant?
Generally well tolerated
Fatigue and asthenia
Hiccups
Dizziness
Diarrhea
Milf, transient elevation of circulating aminotransferases, indicating possible liver injury
69
What are the drug interactions of Aprepitant like?
It is a substance for, an inhibitor of, and indices of CYP3A4, which means the drug itself can metabolize other cancer drugs
It can save patients from emesis but cancel out the effects of the cancer drugs
70
What other drug-metabolizing enzyme does Aprepitant induce?
CYP2D6
71
What is the effect of Aprepitant indicating CYP2D6?
Wafarin/ethinyl are 2D6 substrates, so inducing CYP2D6 eliminates their efficacy
72
What is Fosaprepitant?
An IV prodrug that undergoes RAPID conversion to Aprepitant
73
What are the indications of Fosaprepitant?
Preventing CINV ONLY
In contrast with Aprepitant which is also indicated for postoperative nausea and vomiting
74
What are the adverse effects of Fosaprepitant?
Similar to Aprepitant PLUS pain and induration at the infusion site
75
What is the example of Benzodiazepines?
Lorazepam
76
How is Lorazepam used?
In combination therapies to suppress CINV, not used as monotherapy
77
What are the 3 principal benefits of Lorazepam?
Sedation,
Suppression of anticipatory emesis
Production of enterograde amnesia
78
How does the anterograde amnesia help with antiemetic drug compliance?
Helps control extrapyramidal reactions caused by phenothiazine antiemetics
79
What is the contraindication of Lorazepam?
Pregnancy
80
What are the examples of dopamine antgonists?
Phenothiazines
Butyrophenones
Metoclopramide
81
What is the MOA of Phenothiazines?
Block dopamine two receptors in the CTZ
82
What are Phenothiazines approved for?
Surgery, cancer chemotherapy, toxins
83
What are the side effects of Phenothiazines?
Extrapyramidal reactions, anticholinergic effects, hypotension and sedation
84
What are other uses of Phenothiazines?
Used in schizophrenia
85
What is the most widely used antiemetic in young children?
Phenothiazines, Phenergan
86
What are the dangers of Phenothiazines?
Respiratory depression and local tissue injury
87
What is a safer alternative of Phenothiazines for antiemetics for children?
Ondansetron
88
What is the contraindication of Phenothiazines?
Children under 2 years of age, and should be used with caution for children over 2.
Respiratory depression can be severe or fatal, sometimes
89
What are examples of Butyrophenones?
Haloperidol & Droperidol
90
What is the MOA of Butyrophenones?
Block dopamine 2 receptors in the CTZ
91
What are Butyrophenones effective against?
Postoperative nausea and vomiting, emesis caused by cancer chemotherapy, radiation therapy, and toxins
92
What are the potential side effects of Butyrophenones?
Similar to those of Phenothiazines PLUS QT prolongation
93
Which Butyrophenone drug is associated with QT prolongation?
Droperidol
94
What is the MOA of Metoclopramide?
Blocks dopamine 2 receptors in the CTZ
95
What is Metoclopramide used for?
Suppresses postoperative nausea, vomiting, and emesis with anticancer drugs, opioids, toxins, and radiation therapy
96
What are examples of cannabinoids?
Dronabinol
Nabilone
97
Where and what are cannabinoids approved for?
US, medical use approval
98
What are cannabinoids related to?
Marihuana
99
What is the principal psychoactive agent in C. sativa (marijuana)?
Dranabinol
100
What is Nabilone?
A synthetic derivative f dronabinol
101
What is Sativex?
Combination of THC and cannabidiol
Available in Canada and UK for treating neuropathic pain
102
What are the therapeutic uses of Cannabinoids?
Suppressing CINV, second-line
103
What is the MOA of Cannabinoids?
Mechanism unknown, most likely via activating cannabinoid receptors in and around the vomiting center
104
What kind of patients should Cannabinoids be reserved for?
Patients who are unresponsive to or intolerant of preferred agents
105
What is Dronabinol approved of that Nabilone is not?
Stimulating appetite in patients with AIDS
106
What are the adverse effects of cannabinoids?
Temporal disintegration, dissociation, depersonalization, and dysphoria
Tachycardia and hypotension
Drowsiness
Abuse potential
107
What is the caution indication of Cannabinoids?
Should be used with caution when it comes to patients with CVD
108
What are the contraindications of Cannabinoids?
Patinets with psychiatric disorders
109
Why is there an abuse potential for Cannabinoids?
It mimics the subjective side effects of marijuana
110
What is a more effective alternative to Dexamethasone and Palonosetron?
Aprepitant and Palonosetron
111
When is nausea and vomiting in preganncy common?
During the first trimester
112
What is hyperemesis gravidarum?
A severe form of NVP, characterized by dehydration, ketonuria, hypokalemia, and loss of 5% or more of body weight
113
How can NVP be managed?
Both pharmacological and non-pharmacological interventions
114
What are the non-drug intervention for NVP?
Eating small portions of food through the whole day
Avoiding foods, odors, and supplements that trigger NVP
Acupuncture and ginger (alternative treatments)
115
What is the first-line therapy for NVP?
Two drug combination: doxylamine and vitamin B6
116
What are the alternative pharmacological treatments for NVP?
Prochlorperazine
Metochlopramide
Ondansetron
117
What si the last resort of pharmacological treatments for NVP?
Methylprednisolone but only after ten weeks of gestation
118
What is the risk associated with Methylprednisolone?
Cleft lip risk increases
119
What are the drugs for motion sickness?
Prophylactically:
1. Anticholinergic
2. Antihistamines
120
What is motion sickness?
Can be caused by sea, air, car and space travel
121
WHat are the symptoms of motion sickness?
Nausea, vomiting, pallor and cold sweats
122
What is the example of anticholinergic drugs used for motion sickness?
Scopolamine
123
What is Scopolamine?
A muscarinic antagonist, the most effective drug for the prevention and treatment of motion sickness
123
What are the examples of antihistamines used for motion sickness?
Dimenhydrinate,
MAclizine,
Cyclizine
124
What is the MOA of Scopalamine?
Suppresses nerve traffic in the neuronal pathway that connects the vestibular apparatus of the inner ear to the vomiting center
125
What are the common side effects of Scopalamine?
Dry mouth, blurred vision, drowsiness, urinary retention, constipation and disorientation
126
What is the MOA of antihistamines?
Blocks ACh receptors & histamine receptors, suppressing of motion sickness due to the blocking of H1R and muscarinic receptors in the neuronal pathway that connects the inner ear to the vomiting center
127
What is the most prominent side effect of antihistamines for motion sickness?
Sedation --> results from blocking H1R
128
What are other side effects of antihistamines?
Dry mouth, blurred vision, urinary retention, and constipation --> muscarinic receptors blocking
129
Which is more effective, antihistamine or Scopolamine?
Scopolamine; sedation further limits antihistamines' utility
130
