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Example:

alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan) commonly used prior to chemotherapy to reduce anticipatory vomiting

MOA:

The anti-emetic mechanism of action of benzodiazepines is related to the combination effects of sedation, reduction in anxiety, and possibly depression of the vomiting centre. Generally, the antiemetic property of benzodiazepines is weak, primarily depends on relieving psychogenic component. Scientists believe that excessive activity of nerves may be the cause of anxiety and other psychological disorders, and benzodiazepines reduce the activity of nerves in the brain and spinal cord by enhancing the effects of GABA.

Common side effects:

amnesia, sedation, hypotension, perceptual disturbances, urinary incontinence, drowsiness, light-headedness, confusion, dizziness.

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List of drugs:

1. Dronabinol

2. Nabilone

3. Canabidiol (epidiolex)

4. Nabiximol

Mechanism of action:

Interacts with the centrally located CB1 receptors and 5-HT3 receptors which regulate emesis by decreasing the release of serotonin into the synapse hence, will inhibit the nausea and emesis response.

Dronabinol: weakly and partially agonizes activity at CBR1 and CBR2 receptors

Nabilone: strong agonist for the cannabinoid receptor CB1 and CB2

Nabiximol:

Has weak partial agonist activity at cannabinoid-1 (CB1R) and cannabinoid-2 (CB2R).

Common side effects:

1. Drowsiness

2. Dizziness

3. Euphoria

4. Appetite changes

5. Weight loss

6. Fatigue

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Side effects:
severe nausea and vomiting, trouble urinating, dryness of mouth, unwanted and uncontrolled face or body movements that may not go away when you stop taking the medicine.

MOA:
As anti-emetics, their mechanism of action is thought to be as antagonists of 5-HT ( 5-hydroxytryptamine) and dopamine receptors in the chemoreceptor trigger zone. In addition, they act as an alpha-adrenergic antagonist. Phenothiazine appears to exert its anti-emetic activity by blocking the dopamine receptors in the chemical trigger zone (CTZ) in the brain, thereby relieving nausea and vomiting.

Examples:
prochlorperazine,
chlorpromazine,
fluphenazine,
perphenazine,
trifluoperazine,
thioridazine,
mesoridazine

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prepared by Ting, Jeanie, Suaad, Colleen, Adam, Fatin Syazwani, Madihah, Imran, Yan Shan. Ainaa Syamim, Azizah, Hidayah, Syazana

1. What is Butyrophenones

antipsychotic (neuroleptic) agents antiemetic agents

Dopamine receptor antagonist

Examples: Haloperidol (most widly used antipsychotic), Droperidol, Azaperone, Bromperidol, Benperidol, Trifluperidol

2. Mechanism of Action:

Butyrophenones work primarily by blocking dopamine-mediated synaptic neurotransmission by binding to dopamine receptors.It also interferes with GABA-, norepinephrine-, and serotonin-mediated neuronal activity. By interfering the dopamine release, the

Vomiting is induced by the stimulation vomiting centre by dopamine, which releases Ach, which then leads to the feelings of nausea and actions of vomiting. Hence, blocking the dopamine receptors thus exert its antiemetic effects.

3. Side effects:

Common side effects includes  sedation, extrapyramidal symptoms,  drowsiness, restlessness, dizziness, headache, blurred vision

Haloperidol and droperidol: dose-dependent risk of QT prolongation and torsades de pointes. Additional side effects include hypotension, alpha blockade, and acute dystonia.

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List of drugs: dolasetron (Anzemet), granisetron (Kytril), ondansetron (Zofran), tropisetron (Navoban) and palonosetron (Aloxi)

Mechanism: 5-HT3 receptor antagonists prevent serotonin from binding to 5-HT3 receptors in the small intestine thereby reducing the likelihood of nausea and vomiting

Side effects: Headache, fatigue, malaise, dizziness, stomach pain, disturbance of liver function

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Drugs (Examples):

1. aprepitant

2. fosaprepitant

3. rolapitant

4. casopitant

MoA:

Selective high-affinity antagonist of substance P/NK1 receptor

Block activation of substance P involved in vomiting

Exert their strongest antiemetic properties through central inhibition (able to cross BBB)

Thus, having a unique broad antiemetic pharmacological profile of these agents

Side effects:

Diarrhea

Dizziness

Mild anorexia

Headache

Steven johnson syndrome (severe)

Hives And rash (severe)

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Eg: Metoclopramide, Cisapride, Domperidone

MOA: Prokinetic agents are commonly used in intensive care, mainly to aid in early enteral feeding. They can also be used to treat nausea and vomiting, dopamine antagonist, block dopamine, speeds up stomach emptying, help with gastroesophageal reflux disease.

Possible Side Effects: Feeling restless, insomnia, feeling drowsy, low mood
Tiredness, sleep problems, diarrhea, nausea, vomiting, seizure, headache, confusion, dizziness, exhaustion.

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Drugs: promethazine, cyclizine
MOA: Central action, antagonize or inhibit the histamine receptor
Side effects: dry mouth, drowsiness, fatigue

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E.g. Dexamethasone, methylprednisolone

MOA: Underlying pathophysiologic mechanism of antiemetic action unclear. Hypothesis: Inhibits prostaglandin synthesis in the cortex as glucocorticoid receptors are widespread in the brain.

Side effect (Long term use): insomnia, indigestion, agitation, increased appetite, weight gain, and acne.

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