93 - Anti-emetics

Question 1

Nausea measurement is subjective. It can be associated with changes in ____ and _________ as a biomarker.

Answer 1

EGG;

vasopressin release

Question 2

______________ is the final destination to cause nausea. _______ and ______ receptors are present.

Answer 2

Vomiting centre (VC);
NK1 and opioids

Question 3

Nucleus tractus solitarius (NTS) may receive signals and send them to the vomiting centre. Which 4 receptors are present?

Answer 3

1. 5-HT3
   - vagal (5-HT3) and sympathetic afferents
2. D2
3. M
   - Glossopharyngeal and Trigeminal afferents (gagging in pharynx)
4. H1

Question 4

What receptors are present in the area of postrema? (AP)

AP receives signals and send them to the vomiting centre.

Answer 4

1. Opioid
2. 5-HT3
   - from blood-borne emetics (cytotoxic drugs, opioids, L-DOPA,…)
   - from stomach, small intestine (5-HT3) due to local irritants (cytotoxic drugs, CUSO4, radiation, bacteria)
3. D2
   - vagal (5-HT3) and sympathetic afferents
4. M

Question 5

2 sources of stimulating the higher centres, thus the vomiting centre.

Answer 5

1. Sensory input (pain, smell, sight)

2. Memory, fear, dread, anticipation

Question 6

Inner ear (motion) aminoglycosides might stimulate H1 and M receptors in the _________, and thus the vomiting centre.

Answer 6

Hypothalamus

Question 7

List the 3 ways to remove toxins from GI tract.

Briefly describe them.

Answer 7

1. Gastric lavage
   - in unconscious patients
2. Emetic drugs
   - in conscious patients with gag reflex within 4 hours of toxin ingestion
   - do not use with distillates or corrosive substances
3. Activated charcoal
   - used as an adjunct to emesis, binds to many toxins

Question 8

What is retching?

Answer 8

Unsuccessful vomiting movements against a closed glottis.

Question 9

Which 2 pharmacological classes of drug are used to inhibit nausea/ emesis due to motion sickness > vestibular nuclei?

Answer 9

1. H1 receptor antagonists

2. M1 Muscarinic receptor antagonists

Question 10

Which 3 pharmacological classes of drug are used to inhibit nausea/ emesis arose from the CTZ (Chemoreceptor trigger zone) = AP (area of postrema)?

Answer 10

1. Dopamine antagonists
2. 5-HT3 antagonists
3. Aprepitant

Question 11

Which pharmacological class of drug are used to inhibit nausea/ emesis arose from visceral afferents due to stimuli from pharynx and stomach?

Answer 11

5-HT3 receptor antagonists

Question 12

Which 2 pharmacological classes of drug are used to inhibit nausea/ emesis arose from the NTS (Nucleus Tractus Solitarius)?

Answer 12

1. Muscarinic receptor antagonists

2. H1 receptor antagonists

Question 13

Which pharmacological class of drug are used to inhibit nausea/ emesis arose from the vomiting centre?

Answer 13

Muscarinic receptor antagonists.

Question 14

Area of postrema is _______ of the BBB, acted by circulating drugs ______.

Answer 14

outside;
directly

Cerebrum, NTS, VC are all inside the BBB.

Question 15

Which 2 kinds of drugs are used to induce emesis in emergency?

Answer 15

1. Apomorphine
2. Syrup of Ipecacuanha

(like choking: Ipe-ca-cuan-haaaaa)

Question 16

How does apomorphine work to induce emesis in emergency?

Answer 16

• Activate D2 receptor at the Area of Postrema (D2 agonist)
• but is blocked by neuroleptics or drugs that block D2 receptors

Same MAO for L-DOPA, and domperidone

Used in Parkinson’s disease as well

Question 17

How does Syrup of Ipecacuanha work to induce emesis in emergency?

Answer 17

• Contains emetine and cephaline that releases 5-HT from ECF cells (5-HT3 involvement)
• Worked in GI via vagus nerve or in Area of Postrema when absorbed

Question 18

5 Major drug classes to antagonize emesis.

Answer 18

1. H1 antagonists (motion/pregnancy sickness)
2. Muscarinic antagonists
   (motion sickness)
3. 5-HT3 antagonists
   (Chemo-radiotherapy-emesis & PONV)
4. NK1 antagonists
   (Chemo-radiotherapy-emesis & PONV)
5. Dopamine antagonists
   - domperidone
   - metoclopramide
   - phenothiazines

Question 19

Cyclizine, cinnarizine and dimenhyrinate are ____________ to stop ____-induced emesis.

Answer 19

H1 receptor antagonists;

opioid

Question 20

Promethazine, meclizine are ___________ to stop ______-induced emesis.

Answer 20

H1 receptor antagonists;
pregnancy

*Diphenhydramine will become promethazine when used in morning sickness (first time pregnancy)

Question 21

Give to examples of muscarinic antagonist.

What are their actions?

Answer 21

Hyoscine, scopolamine;

Block M1 receptor at vestibular nuclei and NTS
For motion sickness.

Question 22

Drugs should be given prior to sickness for motion sickness. Side effects related to muscarinic receptor blockage include:

Answer 22

Blurred vision , sedation (calm?), dry mouth, constipation

Question 23

What and where is the action of dopamine receptor antagonists?

Answer 23

Blocking D2 receptors at the Area of Postrema

Question 24

What are the 3 potential consequences of nausea and emesis? Give examples for each consequence.

Answer 24

1. Physical
   - fatigue
   - esophageal tears
   - gastric herniation
   - rupture of stitches
2. Metabolic
   - loss of K+
   - loss of Na+
   - resulting in alkalosis
3. Psychological
   - aversion to food
   - anticipatory nausea and vomiting
   - discontinuation of therapy.

Question 25

Motion-induced emesis: Vestibular system (semi-canicular canals and otolith orgnas) + Other sensory input like visual memory > ___ and ____ receptors in the vestibular nucleus. ___ and ___ levels increase during motion. > Cerebellum > NTS and Area of Postrema and VC

Answer 25

H1 and M1 receptors Histamine and Acetylcholine

Question 26

Drugs used in motion sickness

Answer 26

1. Hyoscine/ Scopolamine (M) 2. Diphenhydramine (H, weak M) 3. Promethazine (H, weak M)

Question 27

____________ is a broad inhibitory anti-emetics. Give 2 examples of it.

Answer 27

NK1 blockers / receptor antagonists. They inhibit the NK1 receptor at dorsal vagal complex at brainstem. Aprepitant, netupitant

Question 28

CINV = Chemotherapy induced nausea and vomiting. At high dose, it casues ______induced emesis. What are the 2 phases of this type of emesis and briefly explain the mechanisms.

Answer 28

Cisplatin 1. Acute phase - Cisplatin induced the rapidly-dividing and turn over of GI cells, EC cells disrupted and thus high 5-HT3 released, act on the 5-HT3 receptors on vagus nerve (5-HT3 involvement in the intensity of emesis) 2. Delayed phase - Cell breakdown products causes amino acid cascade, potential inflammatory mediator release (Other factors in the intensity of emesis)

Question 29

5-HT3 antagonists can be used in CINV. They are highly selective and have less side effects than metoclopramide. Give examples of them and briefly describe their actions and locations.

Answer 29

- Block 5-HT3 receptor at vagus nerve and Area of Postrema. - Ondansetron, Granisetron - Palonosetron (more potent PA 10.5, longer half time) - High dose metoclopramide - also used for postoperative nausea and and vomiting.

Question 30

What is nabilone? | What is its action?

Answer 30

It is a cannabinoid 1/2 receptor agonist. It is a synthetic cannabinoid, Endogenous cannabinoids inhibit the release of neurotransmitters via multi-step retrograde signalling pathway; while nabilone potentiates this pathway.