The Pharmacological Treatment of Nausea & vomiting

Question 1

Drugs for the management of motion sickness:

Answer 1

I. Anticholinergics:

II. H1 antihistamines:

Question 2

Drugs for the management of motion sickness:

Anticholinergics: Drugs

Answer 2

SCOPOLAMINE: Is prophylactic only for motion sickness arising from short or long exposure to severe motion.

Question 3

SCOPOLAMINE

Mechanism of action:

Answer 3

Cochlear (CN8) sensation of motion is projected via cholinergic fibers of the auditory nerve to the CTZ. Scopolamine is an anticholinergic that blocks the activation of muscarinic receptors by acetyl choline.

Question 4

SCOPOLAMINE

Side effects:

Answer 4

sedation, extrapyramidal (drowsiness, dry mouth)

Question 5

Drugs for the management of motion sickness

H1 antihistamines: Drugs:

Answer 5

1. Ethanolamine derivatives: Dimenhydrinate (Dramamine™)
2. Piperazines: Cyclizine & Meclizine
3. Phenothiazine derivatives: Promethazine (Phenergan™)

Question 6

Ethanolamine derivatives: Dimenhydrinate (Dramamine™) USE:

Answer 6

Available OTC for prophylaxis of MS. Taken 30-60 min prior to a trip & their effect last for 4-6 h.

Question 7

Piperazines: Cyclizine &Meclizine USE:

Answer 7

• Cyclizine is OTC used primarily to counter MS.
• Meclizine, exerts a depressant effect on hyperstimulation of labyrinthine function. Used for vestibular Disturbances ( Vertigo & Menier’s disease).

Question 8

3. Phenothiazine derivatives: Promethazine (Phenergan™) USE:

Answer 8

Primarily used for the management of nausea & vomiting. Side effect: SEDATION.

Question 9

ANTIDOPAMINERGICS AS ANTIEMETICS Classes:

Answer 9

A. Phenothiazines:
B. Butyrophenone derivatives
C. Benzamide derivatives

Question 10

ANTIDOPAMINERGICS AS ANTIEMETICS

Mechanism of action:

Answer 10

They block dopamine receptors in the Chemoreceptor Trigger Zone (CTZ)

Question 11

Phenothiazines: Drugs

Answer 11

1. CHLORPROMAZINE
2. PROCHLORPERAZINE
3. THIETHYLPERAZINE

Question 12

CHLORPROMAZINE

Action/Use:

Answer 12

• Is a centrally acting anticholinergic as well
as antidopaminergic.
• Used for N&V & intractable hiccough.

Question 13

PROCHLORPERAZINE

Action/Use:

Answer 13

Is a poor antipsychotic but highly useful antiemetic .

Question 14

THIETHYLPERAZINE

Action/Use:

Answer 14

Inhibits the CTZ & VC.

Question 15

Butyrophenone derivatives

Answer 15

DROPERIDOL
• Blocks dopaminergic receptors in the CTZ. Clinically used
postoperatively for nausea and vomiting.

Question 16

DROPERIDOL

Action/Use:

Answer 16

Blocks dopaminergic receptors in the CTZ. Clinically used postoperatively for nausea & vomiting.

Question 17

Benzamide derivatives

Answer 17

1. Metoclopramide

2. Trimethobenzamide

Question 18

Metoclopramide

Action/Use:

Answer 18

• Dopamine receptor antagonist that blocks chemotherapeutic induced activation of D2 receptors in the CTZ.
• In addition, it stimulates gastric emptying. Given prophylactically prior to cancer chemotherapy & in prevention of postoperative nausea & vomiting.

Question 19

Trimethobenzamide

Action/Use:

Answer 19

Side effects of these agents are extrapyramidal. Therefore, for short-term use.

Question 20

ANTIEMETIC SEROTONIN ANTAGONISTS Drugs:

Answer 20

1. Ondansetron
2. Granisetron
3. Dolasetron .
4. Palonosetron

Question 21

Ondansetron

Action/Use:

Answer 21

• A selective 5-HT3 receptor antagonist that is effective in preventing emesis by high dose of cytotoxic drugs such as cis-platinum & radiation.
• Given I.V. or oral

Question 22

Granisetron

Action/Use:

Answer 22

More potent than ondansetron. Oral

Question 23

Dolasetron

Action/Use:

Answer 23

Has a longer half-life than other 5HT3-receptor blockers.

Question 24

Palonosetron

Action/Use:

Answer 24

Available as I.V. for N&V associated with chemotherrapy.

Question 25

Concomitant administration of 5HT3-receptor blockers with dexamethasone?

Answer 25

significantly increases their potency.

Question 26

ANTIEMETIC SEROTONIN ANTAGONISTS | MECHANISM OF ACTION:

Answer 26

• Serotonin (5-HT) antagonists block 5-HT3 receptors in the stomach & small intestines. • These organs transmit their stimuli through vagal & sympathetic afferents to the CTZ & to the VC through the solitary tract nucleus. • In addition, they block those 5-HT3 receptors in the CTZ that are intimately involved in stimulating the VC to produce emesis • These agents are the most effective antiemetics available to date. These agents are effective alone or in combination with other drugs, such as glucocorticoids & benzodiazepines.

Question 27

MISCELLANEOUS ANTIEMETIC DRUGS

Answer 27

1. Dronabinol or Delta 9-tetrahydro cannabinol 2. CORTICOSTEROIDS: 3. APREPITANT 4. BENZODIAZEPINE:

Question 28

Dronabinol or Delta 9-tetrahydro cannabinol (Marinol™) Action/Use:

Answer 28

* One of the major active substances in marijuana that acts by stimulating the CB1-subtype of cannabinoid receptors. * Principally used as an antiemetic in cancer chemotherapy ONLY when patients have failed to respond to other antiemetics. * Patients often experience psychomimetic reactions not induced with other antiemetics & require careful monitoring.

Question 29

CORTICOSTEROIDS: | Action/Use:

Answer 29

* Dexamethasone & methyl prensisolone. Corticosteroids have anti-emetic effects. * They enhance the overall antiemetic effect & reduce side effects when combined with other anti-emetics. * Their mechanism of action is thought to occur by preventing the production of prostaglandins associated with chemo- or radiation therapies.

Question 30

APREPITANT: Pharmacology:

Answer 30

Is a substance P/neurokinin 1 (NK1) receptor antagonist, that is used as an adjunct drug for preventing emesis induced by cytotoxic chemotherapeutic agents such as cisplatin. It crosses the BBB & inhibits emesis via central actions.

Question 31

BENZODIAZEPINE: Lorazepam & Alprazolam

Answer 31

* Used as an adjunct to other antiemetic regimens. * They are effective in patients with anticipatory vomiting because they cause somnolence & amnesia lasting for hours. * Usually given one day prior to initiation of chemotherapy.

Question 32

Modern antiemetic therapy utilizes a combination of drugs?

Answer 32

The foundation is the 5-HT3 receptor antagonist, to which dexamethasone, benzodiazepine, NK1 antagonist or D2-antagonists are added as required to achieve high efficacy.