Ondansetron Flashcards
What classification does Ondansetron fall under?
Antiemetic
Explain the pharmacodynamics of Ondansetron
Ondansetron is a selective 5-HT3 receptor antagonist (recall that 5-HT3 is serotonin!), that blocks serotonin both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone.
What are the indications for Ondansetron?
Relief of moderate to severe nausea and vomiting
What are the contraindications for Ondansetron
- Known allergy or hypersensitivity to ondansetron
- Congenital long QT syndrome
- Phenylketonuria (PKU)- Ondansetron ODT may contain aspartame which should be avoided in patients with phenylketonuria.
- Relative contraindication in first trimester pregnancy- clinicall consultation REQUIRED in all pregnant patients
- Please note that some Indigenous people may have a higher prevalence of Long QT Syndrome due to a genetic variation. It is advisable to inquire with Indigenous patients whether they or their family have been diagnosed with Long QT Syndrome. If so, dimenhyDRINATE is the recommended antiemetic for this patient population.
What is the ADULT dosing for Ondansetron?
- 4 mg PO as a single dose
- Do not repeat dose
What is the PEDIATRIC dosing for Ondansetron?
- 2 mg PO for ages 6 months - 4 years
- 4 mg PO for ages 4 and up
- Do not repeat dose
What are the age limitations for Ondansetron?
Cannot be administered <6 months
What is the duration of the three pharmacokinetics for Ondansetron?
Parenteral:
- Onset: 15-30 minutes
- Peak: 1 hour
- Duration: > 5 hours
What adverse effects are possible with Ondansetron?
- Headache
- Constipation
- Hypersensitivity reactions
- Hypotension
- Depression or agitation
What stimuli can cause someone to vomit?
- Sensory inputs (emotions, pain, foul smells)
- Gastrointestinal inputs (distention of stomach)
- Vestibular system activation (motion)
- Exposure to drugs/toxins
What five neurotransmitter pathways interact with the nausea/vomiting pathway?
- Muscarinic (M1)
- Dopaminergic (D2)
- Histaminergic (H1)
- Serotonergic (5-HT3)
- Substance (NK1)
What are the two “nausea centers” of the brain?
- Vomiting centre
- Chemoreceptor trigger zone (CTZ)
Define the Vomiting Centre
A complex cluster of neurons, located in the medulla oblongata, serves as the central command for initiating emesis/vomiting. These neurons receive input from the various sources throughout the body
Define the Chemoreceptor trigger zone (CTZ)
It is located outside of the blood-brain-barrier in the medulla. Once it receives input, it stimulates the vomiting center via acetylcholine
Describe the chain of events that occurs once the nausea centres have been triggered
- Lower esophagus sphincter closes
- Diaphragm and abdominal muscles contract to push food up (increases abdominal pressure)
- Salivation increases
- Heart rate increases
- Epiglottis closes to prevent aspiration
What are the higher brain centres?
- Cerebral cortex
- Amygdala
- Limbic system
What sites does the vomiting centre receive input from?
- Higher centres in the brain
- Gastrointestinal tract
- Vestibular system
- Chemoreceptor trigger zone (CTZ)
What triggers the higher brain centres?
Sensory inputs such as:
- Cognition
- Emotion
- Pain
- Foul smells
- Memories such as anticipatory nausea prior to chemotheraphy
- Increased intercranial pressure
Neurotransmitters involved:
- 5-hydroxytrpytamine AKA (5-HT3) AKA Serotonin
- Dopaminergic (D2)
What triggers the gastrointestinal tract?
Sensory inputs such as:
- Irritation
- Inflammation
- Distention/stretching of the somach/intestines
This information is carried by the vagal nerve
Neurotransmitters involved:
- 5-hydroxytrpytamine AKA 5-HT3 AKA Serotonin
- Dopaminergic (D2)
What triggers the vestibular system?
Sensory inputs such as:
- Motion sickness
Neurotransmitters involved:
- Histaminergic (H1)
- Muscarinic (M1)
What triggers the chemoreceptor trigger zone?
The chemoreceptor trigger zone can be directly stimulated since it is located outside of the blood-brain barrier. This allows circulating substances, such as drugs and toxins, access to it.
Neurotransmitters involved: - - 5-hydroxytrpytamine AKA 5-HT3 AKA Serotonin
- Dopaminergic (D2)
- Histaminergic (H1)
- Muscarinic (M1)
These neurotransmitters stimulate the vomiting center via acetylcholine. The opioid mu receptors are also involved which is largely the reason why opioids can cause vomiting.
List common causes of nausea/vomiting
- Infection
- Medication-related nausea
- Pregnancy
- Vertigo
List potentially life-threatening conditions that could cause nausea/vomiting
- Acute infection
- Bowel obstruction
- Diabetic ketoacidosis
- GI bleeding
- Ischemic bowel
- Meningitis
- Migraines/headaches
- Myocardial infarction
- Sepsis
- Stroke
List common medications that could cause nausea/vomiting
- Antibiotics
- Cannabis (hyperemesis)
- Chemotherapy
- Opioids
- SSRIs: Selective Serotonin Reuptake Inhibitors
- Many more…
Describe the chemical composition of DimenhyDRINATE
DimenhyDRINATE is a salt that includes diphenhydrAMINE (Benadryl) with 8-chlorotheophylline which is similar to caffeine.
Describe the chemical composition of DimenhyDRINATE
Ondansetron is one of the medications most commonly used for the empiric treatment of nausea and vomiting. It is only available with a prescription in Canada.
What happens if a patient swallows Ondansetron before it disintegrates?
ODTs are different from conventional sublingual and buccal tablets, which are absorbed directly through the oral mucosa. Ondansetron ODTs will still be effective if swallowed whole as they are absorbed through the GI tract.
What three factors should be considered when treating nausea/vomiting?
- The etiology of the nausea/vomiting and the neurotransmitters involved
- The drug’s mechanism of action, side effects, drug interactions, and contraindications (pharmacologic agent comparison)
- The patient’s characteristics (i.e. elderly, pregnant, etc.)
What are two considerations for treating head injury?
DimenhyDRINATE: Must be used with caution as it may cause further CNS dysfunction.
Ondansetron: Preferred in these patients as control of vomiting is important to limit the increase in intracranial pressure.
What are two considerations for treating geriatrics?
DimenhyDRINATE: Older adults may be more sensitive to the side effects of dimenhyDRINATE, such as drowsiness, confusion, constipation, or trouble urinating.
Ondansetron: Due to these risks, and the American Geriatric Society’s (AGS) Beers criteria, ondansetron should be the antiemetic of choice in the elderly populations, if etiology permits.
What are two considerations for treating pregnant patients?
DimenhyDRINATE: Preference is given to dimenhyDRINATE for nausea and vomiting during pregnancy. Pregnant patients should be reassured that dimenhyDRINATE is safe and low risk of toxicity for the fetus.
Ondansetron: Use of ondansetron in early pregnancy (first trimester) is controversial.
What are two considerations for treating alcohol withdrawal?
DimenhyDRINATE: The preferred antiemetic due to its lack of QT interval elongation side effects, in contrast to ondansetron. This distinction is important, especially when dealing with electrolyte imbalances in alcohol withdrawal.
Ondansetron: Has QT interval elongation side effects unlike dimenhyDRINATE.
