The Pharmacological Treatment of Nausea & vomiting Flashcards
Drugs for the management of motion sickness:
I. Anticholinergics:
II. H1 antihistamines:
Drugs for the management of motion sickness:
Anticholinergics: Drugs
SCOPOLAMINE: Is prophylactic only for motion sickness arising from short or long exposure to severe motion.
SCOPOLAMINE
Mechanism of action:
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.
SCOPOLAMINE
Side effects:
sedation, extrapyramidal (drowsiness, dry mouth)
Drugs for the management of motion sickness
H1 antihistamines: Drugs:
- Ethanolamine derivatives: Dimenhydrinate (Dramamine™)
- Piperazines: Cyclizine & Meclizine
- Phenothiazine derivatives: Promethazine (Phenergan™)
Ethanolamine derivatives: Dimenhydrinate (Dramamine™) USE:
Available OTC for prophylaxis of MS. Taken 30-60 min prior to a trip & their effect last for 4-6 h.
Piperazines: Cyclizine &Meclizine USE:
- 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).
- Phenothiazine derivatives: Promethazine (Phenergan™) USE:
Primarily used for the management of nausea & vomiting. Side effect: SEDATION.
ANTIDOPAMINERGICS AS ANTIEMETICS Classes:
A. Phenothiazines:
B. Butyrophenone derivatives
C. Benzamide derivatives
ANTIDOPAMINERGICS AS ANTIEMETICS
Mechanism of action:
They block dopamine receptors in the Chemoreceptor Trigger Zone (CTZ)
Phenothiazines: Drugs
- CHLORPROMAZINE
- PROCHLORPERAZINE
- THIETHYLPERAZINE
CHLORPROMAZINE
Action/Use:
• Is a centrally acting anticholinergic as well
as antidopaminergic.
• Used for N&V & intractable hiccough.
PROCHLORPERAZINE
Action/Use:
Is a poor antipsychotic but highly useful antiemetic .
THIETHYLPERAZINE
Action/Use:
Inhibits the CTZ & VC.
Butyrophenone derivatives
DROPERIDOL
• Blocks dopaminergic receptors in the CTZ. Clinically used
postoperatively for nausea and vomiting.
DROPERIDOL
Action/Use:
Blocks dopaminergic receptors in the CTZ. Clinically used postoperatively for nausea & vomiting.
Benzamide derivatives
- Metoclopramide
2. Trimethobenzamide
Metoclopramide
Action/Use:
- 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.
Trimethobenzamide
Action/Use:
Side effects of these agents are extrapyramidal. Therefore, for short-term use.
ANTIEMETIC SEROTONIN ANTAGONISTS Drugs:
- Ondansetron
- Granisetron
- Dolasetron .
- Palonosetron
Ondansetron
Action/Use:
- 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
Granisetron
Action/Use:
More potent than ondansetron. Oral
Dolasetron
Action/Use:
Has a longer half-life than other 5HT3-receptor blockers.
Palonosetron
Action/Use:
Available as I.V. for N&V associated with chemotherrapy.
Concomitant administration of 5HT3-receptor blockers with dexamethasone?
significantly increases their potency.
ANTIEMETIC SEROTONIN ANTAGONISTS
MECHANISM OF ACTION:
• 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.
MISCELLANEOUS ANTIEMETIC DRUGS
- Dronabinol or Delta 9-tetrahydro cannabinol
- CORTICOSTEROIDS:
- APREPITANT
- BENZODIAZEPINE:
Dronabinol or Delta 9-tetrahydro cannabinol (Marinol™) Action/Use:
- 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.
CORTICOSTEROIDS:
Action/Use:
- 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.
APREPITANT:
Pharmacology:
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.
BENZODIAZEPINE: Lorazepam & Alprazolam
- 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.
Modern antiemetic therapy utilizes a combination of drugs?
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.
