(23) Antiemetics: 5-HT3, D2, NK1, M1, and H1

Antiemetics

drugs that prevent/treat nausea and vomiting.

Nausea/Vomiting Pathways

Neurotransmitter / Signal	Receptor	Where / How it causes N/V
Serotonin	5-HT3	GI tract → GI irritation/chemo-inducd N/V CTZ → chemical/drug-related N/V
Dopamine	D2	CTZ → chemical/drug-related N/V
Substance P	NK1	CTZ → chemical/drug-related N/V
Histamine	H1	Vestibular system → motion sickness
Acetylcholine	M1	Vestibular system → motion sickness

• CTZ = Chemoreceptor Trigger Zone

MASTER CHART

• FOR CORTICOSTEROID USE- ADD Postoperative N/V

• For Diphenhydramine and Meclizine (ADR)

  • CNS

    • Sedation

    • Slower reaction time

    • Confusion

    • Delirium

    • Children can have paradoxical excitation instead of sedation

  • Antimuscarinic effects — MEMORIZE THESE 4

    • Dry mouth

    • Blurred vision

    • Constipation

    • Urinary retention

• For Diphenhydramine and Meclizine - add promethazine too!!!

• For cannabinoids: dronabinol (drug name)

Match the condition to the class

Condition	Treatment
Chemotherapy N/V	5-HT3 + NK1 + corticosteroid
Postoperative N/V	5-HT3 or D2 antagonist or corticosteroid
Motion sickness / vertigo	H1 or M1 blocker
Gastroparesis N/V	D2 antagonist with prokinetic effect
Anticipatory N/V	Benzodiazepine

STOP FLASHCARD HERE!

Master Chart (SKIP)

Drug class / Drugs	MOA	Uses	ADRs	Fun Fact / Other
5-HT3 antagonists Ondansetron (Zofran), Granisetron (Kytril), Palonosetron (Aloxi)	Block 5-HT3 receptors → block serotonin signaling → ↓ N/V	Chemotherapy-induced N/V postoperative N/V postradiation N/V	Headache constipation serotonin syndrome — rare QT prolongation	Palonosetron: long half-life → useful for delayed N/V
NK1 antagonists Aprepitant (Emend)	Blocks NK1 receptor → blocks substance P → ↓ N/V	Mainly chemotherapy-induced N/V	dizziness Fatigue	Often used with 5-HT3 antagonist + NK1 antagonist + corticosteroid DDI: CYP3A4 interactions
D2 antagonists	Block D2 receptors → block dopamine pathway → ↓ N/V	Chemotherapy-induced N/V postoperative N/V general N/V	EPS / movement problems sedation hypotension some drugs → QT prolongation
Substituted benzamides	D2 antagonism some also have a prokinetic effect	Especially gastroparesis-related N/V	EPS restlessness dystonia
H1 antihistamines Meclizine (Antivert) Diphenhydramine (Benadryl)	Block H1 receptors in CNS → block vestibular pathway → ↓ motion sickness	Motion sickness vertigo mild N/V	Sedation dry mouth urinary retention confusion,especially elderly	First-generation antihistamines are useful because they cross BBB and reach CNS
Scopolamine Scopolamine (Scopace)	- Blocks M1 receptors → blocks vestibular pathway → ↓ motion sickness	Motion sickness vertigo mild N/V
Corticosteroids	Antiemetic Mechanism = unclear; enhance effect of 5-HT3 antagonists	Part of chemotherapy-induced N/V combination therapy	Short-term → generally well tolerated long-term → Cushing-like effects
Benzodiazepines		Anticipatory N/V, especially when anxiety/stress is involved How Anxiety/stress → anticipatory N/V Benzodiazepine → ↓ anxiety → ↓ N/V	Sedation dependence
Cannabinoids	Act on cannabinoid receptors; exact mechanism unclear	Refractory chemotherapy-induced N/V	Euphoria dysphoria hallucinations tachycardi sedation

5-HT3 antagonists

topics

• MOA

• Uses

• ADR

• Fun Facts

Main Antiemetic Classes (SKIP)

• 5-HT3 antagonists

  • Ondansetron (Zofran)

  • Granisetron (Kytril)

  • Palonosetron (Aloxi)

• D2 antagonists

• NK1 antagonists

  • Aprepitant (Emend)

• H1 antihistamines

  • Meclizine (Antivert)

  • Diphenhydramine (Benadryl)

• Scopolamine

  • Scopolamine (Scopace)

• Substituted benzamides

• Benzodiazepines

• Corticosteroids

• Cannabinoids

5-HT3 antagonists

MOA

Block 5-HT3 receptors → block serotonin signaling → ↓ N/V

5-HT3 antagonists

Uses:

• chemotherapy-induced N/V

• postoperative N/V

• post-radiation N/V

5-HT3 antagonists

ADRs:

• headache

• constipation

• QT prolongation

• serotonin syndrome — rare

5-HT3 antagonists

Fun Fact

Palonosetron: Long half-life → useful for delayed N/V

NK1 antagonists

topics

• MOA

• Use

• ADRs

• Fun Fact

NK1 antagonists

MOA

Blocks NK1 receptor → blocks substance P → ↓ N/V

NK1 antagonists

Use:

• Mainly chemotherapy-induced N/V

NK1 antagonists

ADRs:

• fatigue

• dizziness

NK1 antagonists

Fun Fact

• DDI: CYP3A4 interactions

• Often used in combination:

  • 5-HT3 antagonist + NK1 antagonist + corticosteroid

D2 antagonists

topics

• MOA

• Uses

• ADR

D2 antagonists

MOA

Block D2 receptors → block dopamine pathway → ↓ N/V

D2 antagonists

Uses

• chemotherapy-induced N/V

• postoperative N/V

• general N/V

D2 antagonists

ADR:

• Important ADR:

  • D2 blockade → EPS (extrapyramidal symptoms): movement problems

• Also:

  • sedation

  • hypotension

  • some drugs → QT prolongation

Substituted benzamides

topics

• MOA

• Use

• ADRs

Substituted benzamides

MOA

• D2 antagonism

• Some also have a prokinetic effect.

Substituted benzamides

Use

• Especially gastroparesis-related N/V

Substituted benzamides

ADRs

• EPS

• restlessness

• dystonia

H1 antihistamines

topics

• MOA

• Uses

• ADRs

• Fun Facts

H1 antihistamines

MOA

Block H1 receptors in CNS → block vestibular pathway → ↓ motion sickness

H1 antihistamines

Uses:

• motion sickness

• vertigo

• mild N/V

H1 antihistamines

ADRs:

• sedation

• dry mouth

• urinary retention

• confusion, especially elderly

H1 antihistamines

Fun Facts

First-generation antihistamines are useful because they cross the BBB and reach the CNS.

Scopolamine

Topics

• MOA

• Use

Scopolamine

MOA

Blocks M1 receptors → blocks vestibular pathway → ↓ motion sickness

Scopolamine

Use:

• motion sickness

• vertigo

• mild N/V

Corticosteroids

topics

• MOA

• Use

• ADR

Corticosteroids

MOA

• Antiemetic mechanism = unclear

• But: enhance the effect of 5-HT3 antagonists

Corticosteroids

Use

• Part of chemotherapy-induced N/V combination therapy

  
  

Corticosteroids

ADR

• short-term → generally well tolerated

• long-term → Cushing-like effects

Benzodiazepines

topics

• Use

• ADR

Benzodiazepines

Use

• Anticipatory N/V, especially when anxiety/stress is involved

• How

  • Anxiety/stress → anticipatory N/V
    Benzodiazepine → ↓ anxiety → ↓ N/V

Benzodiazepines

ADRs:

• sedation

• dependence

Cannabinoids

topics

• MOA

• Use

• ADRs

Cannabinoids

MOA

• Acts on cannabinoid receptors; exact mechanism unclear

  
  

Cannabinoids

Use:

• Refractory chemotherapy-induced N/V

  • Refractory = other treatments did not work well enough.

Cannabinoids

ADRs:

• euphoria

• dysphoria

• hallucinations

• tachycardia

• sedation