1. Emetics, Antiemetics and Prokinetics
Dr. Soe Aung Myint

2. EMETICS
AND ANTIEMETICS

3. Emetics drugs which induce vomiting
Therapeutic emesis is rarely required except in cases of poisoning

4. drugs which suppress the vomiting
Antiemetics
drugs which suppress the vomiting
If the cause of vomiting can’t be removed
it may be desirable to attempt to prevent or suppress it by drugs
↓ the consequences of vomiting

5. Vomiting(Emesis)
A protective function which serve to remove unsuitable material that have been swallowed
A symptom of some systemic diseases

6. Mechanism of vomiting
a complex series of movements controlled by vomiting centre (VC) & Chemoreceptor Trigger Zone (CTZ)
Some peripheral signals bypass the trigger zone, reaching the emetic center via the solitary tract nucleus (eg, from pharynx, stomach, & small intestine)

7. Consequences of vomiting are ***-
electrolyte imbalance
exhaustion → collapse
aspiration → pneumonitis
↑ intra-abdominal pressure → hernia & burst PU
↑ ICP

8. Receptors for vomiting*
CTZ - high concentration of 5HT3, D2, opioid receptors, Neurokinin-1 receptors
VC - contains histamine, cholinergic receptors

9. Local Emetics mustard & water, warm hypertonic solution of salt,
salts of heavy metals,
1% Cupric sulphate,
1% Zinc sulphate,
ipecac (alkaloid) syrup
MOA: irritate sensory nerve endings in the
pyloric half of the stomach

10. Apomorphine - selective action on CTZ
Central Emetics*
Apomorphine - selective action on CTZ
Ipecacuanha - locally irritates the gut & centrally acts on CTZ

11. APOMORPHINE
a semisynthetic morphine like alkaloid with pronounced emetic action (> morphine)
Mechanism of action: Structurally related to dopamine & a powerful stimulant of dopamine receptors in the CTZ
Onset of action: within min after mg SC injection
No second dose due to CNS depression

12. Ipecacuanha
Dose-15-30ml oral
Onset min
Can give second dose

13. Indications for Emetics*
Acute poisoning by non-corrosive substances
Acute indigestion due to excessive intake of food

14. Contraindications * for Emetics
Poisoning by corrosives - cause scarring eg, strong acids & alkalis – gastric perforation & damage to esophagus petroleum distillates - chemical pneumonitis due to inhalation
Comatose, stuporous or delirious patients - because of asphyxiation & aspiration pneumonia due to lack of coughing reflex
Pregnancy,hernias,advanced PU,GI erosions
Cardiac decompensate and hypertension patients
Young children,debilitated patient

15. ANTIEMETICS

16. Classification of Antiemetics***
DRUGS
Anticholinergics: Hyoscine
Anti-histamines: Cinnarizine
- Cyclizine
Meclizine
Diphenhydramine (Benedryl)
Dimenhydrinate (Dramamine)
Promethazine (Phenergan)
SITE OF ACTION
Vomiting centre and gut

17. Classification of Antiemetics***
DRUGS
D2 receptor antagonists- Phenothiazines:
Chlorpromazine (Buromazine) Prochlorperazine (Stemetil)
Perphenazine
Butyrophenone : Haloperidol Metoclopramide
Domperidone (Motilium)
SITE OF ACTION
CTZ
CTZ and gut

18. Classification of Antiemetics***
DRUGS
5HT3 receptor antagonists
Ondansetron, tropisetron, granisetron
Cannabinoids: nabilone, pronabilol, dronabinol
Miscellaneous
Pyridoxine (Vitamin B6)
Steroids (dexamethasone)
Benzodiazepines (lorazepam)
Neurokinin-1 antagonists (aprepetant)
SITE OF ACTION
CTZ and gut
CTZ
Vomiting d/t cytotoxics
Cannabis sativa

19. Mechanism of action of anti-emetics
They may act either on VC or on CTZ
Anti-emetic effect
on VC - anticholinergic action, antihistaminic action
on the CTZ - antidopaminergic or 5HT3 antagonist action

20. 1. ANTICHOLINERGICS - HYOSCINE (Scopolamine)
Mechanism of action: block central muscarinic receptor on VC & gut (relaxation of GIT)
Use: motion sickness (given 1 hr before journey, lasts for hrs)
Hyoscine: mg IM

21. 2. ANTIHISTAMINES MOA: inhibition of histamine receptor
& cholinergic receptor in VC
CYCLIZINE - shortest duration of action, 50 mg TDS
MECLIZINE - longest duration of action, 24 hrs or more, single dose 50 mg

22. 2. ANTIHISTAMINES PROMETHAZINE
is chemically a phenothiazine but functionally an antihistamine,
used for morning sickness & space motion sickness,
Dose- 25 mg BD
DIPHENHYDRAMINE & DIMENHYDRINATE- motion sickness & Meniere’s disease,
common side effect is drowsiness
Dose mg TDS

23. 3. D2 RECEPTOR ANTAGONISTS
PHENOTHIAZINE, CHLORPROMAZINE
central inhibition of dopamine receptor on CTZ (with low non sedative dose)
PROCHLORPERAZINE, PERPHENAZINE
with piperazine side chain are more powerful antiemetics
Dose mg 8 hourly IM
Untoward effects - drowsiness, hypotension, extrapyramidal effects

24. METOCLOPRAMIDE
structurally related to procainamide (lacks LA & antiarrhythmic action)
Pharmacological Actions
antiemetic action
prokinetic action-
↑ lower esophageal sphincter tone,
↑ gut peristalsis & emptying ,
relaxation of pyloric antrum & duodenal cap

25. Mechanism of Action
Central - inhibits dopamine D2 r/c on CTZ
Peripheral
– may be due to 5HT4 r/c agonistic action,
– 5HT3 r/c antagonist action,
– D2 r/c blocking action on cholinergic enteric
neurones
– All these facilitate ACh release from enteric neurones

26. METOCLOPRAMIDE Therapeutic Uses
Gastro esophageal reflux disease (together with antisecretory drugs)
patients with delayed gastric emptying due to postgastrectomy, diabetes gastroparesis
Non ulcer dyspepsia (symptomatic improvement in chronic dyspepsia)
small bowel intubation
to empty stomach before emergency anaesthesia & labour
prevention and treatment of vomiting caused by gastrointestinal disorder, cytotoxic drugs, radiation & uraemia

27. METOCLOPRAMIDE Untoward Effects
extrapyramidal dystonia, more common in children & young adults with high dose fatigue, motor restless, spasmodic torticollis (involuntary twisting of neck), occulogyric crisis (involuntary upward eye movement)
gynaecomastia, galactorrhoea (due to ↑ prolactin secretion), menstrual disorder
somnolence, drowsiness, dizziness,
diarrhoea

28. METOCLOPRAMIDE Pharmacokinetic rapidly & completely absorbed,
first pass metabolism present
Bioavailability 75%, T1/2 – 4-6 hr
Contraindication***
intestinal obstruction, perforation, haemorrhage
Dose - 10 mg 8 hourly oral, IM, IV

29. 4. 5HT3 RECEPTOR ANTAGONISTS:
ONDANSETRON
5HT3 antagonist
for cytotoxic drug induced & radiation induced vomiting ,
post-op vomiting
dose – 8 mg TDS

30. 5. Cannabinoids (nabilone)
vomiting due to stimulation of CTZ, used when other drugs failed

31. 6. Miscellaneous PYRIDOXINE (Vitamin B6) no specific action
doubtful efficacy - advantage of being harmless - suitable placebo to support psychotherapy
used alone & with antiemetics in hyperemesis gravidarum

32. 6. Miscellaneous STEROIDS (Dexamethasone) mechanism unknown
by inhibiting PG formation
to control vomiting induced by cytotoxic drugs

33. 6. Miscellaneous NEUROKININ-1 antagonist (Aprepitant)
antagonise substance P which may cause vomiting
adjunct to dexamethasone & 5HT3 receptor antagonist in preventing N & V caused by cytotoxics (eg, cisplatin)

34. CHOICE OF ANTIEMETICS

35. Motion Sickness Hyoscine - best for motion sickness, short lasting
Other drugs- cinnarazine, cyclizine, dimemhydrinate, promethazine
For prophylaxis, an antiemetic is best taken
1 hr before exposure to the motion
Once motion sickness has started, IM, SC or rectal routes are required. Alternatively, hyoscine may be administered as a dermal patch.

36. Vomiting due to Cytotoxic Drugs
5HT3 receptor antagonist (ondansetron) is highly effective.
For severe vomiting, ondansetron plus dexamethasone with or without lorazepam (all given IV) is most effective combination & well tolerated.
Metoclopramide may be substituted for ondansetron.

37. Vomiting after General Anaesthesia
Metoclopramide or
5HT3 receptor antagonist (ondansetron) or
butyrophenone (haloperidol, droperidol)

38. Vomiting in Pregnancy
Occurs at weeks & usually resolves by weeks of gestation.
By reassurance that the problem is transient & discussion of diet.
Rarely, decision is taken to take a drug & then H1 receptor antagonist or phenothiazine (eg, promethazine) is preferable.
Pyridoxine deficiency may occur in hyperemesis gravidarum which requires IV fluids & multivitamin supplement.

39. Vertigo Antimuscarinics & phenothiazines are generally preferable.
Cyclizine or prochlorperazine may be used to relieve an acute attack.
Betahistine (a histamine analogue) is used to improve blood circulation to the inner ear in Meniere’s disease; also cinnarazine.

41. Prokinetics 1..Medication used to
a.Enhance coordinated motility of GIT
b.Enhance transit of foods in GIT
2.Therapeutic uses
a.GERD
b.Gastroperesis (delayed gastric emptying time)
c.Pseudoobstruction ..1.False obstruction(if no intrinsic obstruction if bowel is dissected)
2.may be due to muscle abnormalities,nervous defect,constipation

42. Prokinetic Agents Rapidly Promote Gastric
Emptying By Selectively Duodenal Motility
Esophagus
Gastroesophageal
Sphincter
Fundus
pH 2.3
Stomach
HCL
Mucus
Pyloric Sphincter H+
Duodenum H+ H+ H+ H+
Cholinomimetic will be unselective
Proknetics modulate ACh release to promote opening of the
Gastro-Duodenal Sphincter & Selectively  Duodenal Motility.

43. Categories of Prokinetics
1.Cholinergic agents
a.Cholinergic derivatives ,Bethanechol
b.Acetylcholinesterase inhibitor,Neostigmine
2.Dopamine receptor antagonists
Domperidone,metoclopramide
3.5HT4(serotonin)receptor agonists***
Cisapride,Metaclopromide (maxalon)
4.Motilin- like agent
Macrolide antibiotics..erythromycin
5.Chloride channel activator- lubiprostone

44. 1. METOCLOPRAMIDE (Maxolon)
See antiemetics

45. 2. DOMPERIDONE (Motilium)
Mechanism of Action
blocks dopamine receptor in CTZ (D2)
Pharmacological Actions
↑ tone in lower esophageal sphincter
relax pyloric sphincter
not peneterate well into blood brain barrier
antagonise D2 in pituitary
block α adrenoreceptor (→ ↑ motility by decreasing relaxation)

46. 2. DOMPERIDONE (Motilium)
Use
Chronic dyspepsia of unknown cause
to promote post partum lactation
Untoward Effect
hyperprolactinaemia, galactorrhoea, gynaecomastia
Dose
10-20 mg 4-8 hourly

47. 3. CISAPRIDE (Prepulsid)
Now obsolete due to ventricular arrhythmias & sudden death
(K+ channel blockade & long QT interval)
Mosapride
Tegaserod

48. directly stimulates motilin receptor on GI smooth muscle &
4. ERYTHROMYCIN
directly stimulates motilin receptor on GI smooth muscle &
Promotes onset of a migrating motor complex
↑ lower esophageal pressure & stimulation of gastric & small bowel contractility

49. 4. ERYTHROMYCIN Use: diabetic gastroparesis,
acute upper GI haemorrhage to promote gastric emptying of blood prior to endoscopy
Limited practical use because of rapid development of tolerance due to down regulation of motilin receptor

50. 5. LUBIPROSTONE(prostanoic acid derivative)
MoA-
stimulates Cl- channel opening in intestine → ↑ liquid secretion into the intestine → shortens intestinal transit time
Use - chronic constipation

51. ----- a. prochlorperazine ----- b. ondansetron ----- c. apomorphine
Antiemetic drugs are:
----- a. prochlorperazine
----- b. ondansetron
----- c. apomorphine
----- d. lobelline
----- e. dimenhydrinate Y Y N N Y

52. D2 receptor antagonists used for vomiting: ----- a. nabilone
----- b. ondansetron
----- c. domperidone
----- d. promethazine
----- e. hyoscine N N Y N N

53. The followings are useful for motion sickness: ----- a. hyoscine
----- b. meclizine
----- c. diphenhydramine
----- d. domperidone
----- e. atropine Y Y Y N N

54. Antiemetics acting on CTZ: ----- a. chlorpromazine ----- b. atropine
----- c. metoclopramide
----- d. prochlorperazine
----- e. cyclizine Y N Y Y N

55. ____a. is a prokinetic and antiemetic agent
Metoclopramide
____a. is a prokinetic and antiemetic agent
____b. is potent antidoperminergic with
cholinomimetic properties
____c. is used in vomiting and diarrhea
____d. is used in vomiting due to cytotoxic
drugs
____e. is also used in motion sickness Y Y N Y N

56. Thank You
Thank You