EMETICS AND ANTIEMETICS

Ngatidjan, Prof. MD. M.Sc. Sp.FK(K).

Department of Pharmacology and Therapy

Faculty of Medicine UGM

Lecturer in the Faculty of Medicine UMY

EMETICS AND ANTIEMETICS

• Emetics

drugs or substance induced emesis or vomiting

or induce nausea lead to vomiting

- apomorphine

• Antiemetics

drugs used for therapy of vomiting

- dimenhydrinate, etc.

NAUSEA AND VOMITING

• Gastrointestinal stimulation

• Motion sickness

• Hormone disturbance pregnancy sickness

• Intracranial pathology

• Metabolic disorders

• Psychogenic

• Severe pain cardiac, bile duct or ureteric

• Drug and radiation induced emesis

• Endogenous toxin

(Lullmann et al., 2005)

Gastrointestinal stimulation

• Stimulation of mechanoreceptors by

distension or obstruction in the gut

gstric fullness

• Stimulation of chemoreceptor caused by

endotoxins cholera

• Ingestion of drugs or toxic material ipecac,

carbamates, and inject of morphine, apomorphine

Gastrointestinal stimulation

• Peptic ulcer disease,

• Pancreatic disease,

• Intra-abdominal emergencies :

intestinal obstruction,

acute pancreatitis,

acute pyelonephritis,

acute cholecystitis,

acute viral hepatitis,

• Acute gastroenteritis : viral gastroenteritis,

salmonellosis, shigellosis, staphylococcal (enterotoxins),

(Page et al., 2005)

Motion sickness

• Nausea – and even – vomiting

caused by unwillingness motion

• Centered around the sensory input conflict of

- visual

- vestibular

- proprioceptive

inappropriate reflex sickness

Hormone disturbances

• Pregnancyduring the first trimester

- approximately 85% of pregnancy nausea

- approximately 52% of pregnancy vomiting

- approximately 0,1% hyperemesis gravidarum

caused by delayed gastric emptying, changed in intra-

abdominal pressure, hormonal changes and psychogenic

• Premenstrual nausea cyclic

• Side effect of hormonal contraseptive

(Page et al., 2005)

(Page et al., 2005)

Intracranial pathology

• Associated with severe headache may be

as the consequence of a rise in intracranial

pressure resulting from :

- intracranial hemorrhage head injury

- severe intracranial inflammatory response

• Migraine

Metabolic disorders

• Hypoglycemia

• Uremia

• Diabetes mellitus

diabetic ketoacidosis

• Etc.

Psychogenic

• Chronic psychogenic vomiting

• Nervous dyspepsia- nausea, vomiting, anxiety, irritability and weight loss

• Anoxia nervosa bulimia

• Certain sight, smell, or feeling may trigger revolution of fear nausea vomiting

• Anxiety

Severe pain

• Cardiac pain

• Acute distension of the stomach

• Acute distension of bile duct stone

• Acute distension of ureter stone

EMETICS(drug induced emesis)

Drugs induced nausea and vomiting

• Cancer chemotherapy Cisplatin, cyclophosphamide > 90%,

Mercaptopurine (< 10%),

melphalan oral (< 10%) – iv (60-90%)

• Apomorphine,

• Levodopa,

• Morphine and related opioid analgesics

• Cardiac glycoside

Severely emetogenic in almost all patients

Moderately emetogenic Least emetogenic

Cisplatin

Mustine

Cyclophosphamide

Dacarbazine

Doxorubicin

Mitomycin C

Procarbazine

Nitrosoureas

5-Fluorouracil

Cytarabine

6-Mercaptopurine

Bleomycin

Vinblastine

Vincristine

The number of women who were reported to get sickness with oral contraceptive,

travel or migraine and the relationship to vomiting in pregnancy

Pregnancy

sickness

Oral contraceptive

sickness

Travel sickness Migraine sickness

Vomiting

No vomiting

30 (70%)

13 (30%)

77 (63%)

46 (37%)

45 (65%)

24 (35%)

Emetics

therapeutic induction of vomiting

• Apomorphine

to induce vomitus in alcoholic abuse, or using disulfiram

• Apomorphine or ipecac syrup

to induce emesis in the therapy of acute oral intoxication

ANTIEMETICS

(Page et al., 2005)

Antiemetics

• Dopamine receptor antagonists

• Muscarinic receptor antagonists

• Histamine H1-receptor antagonsits

• 5-HT3-receptor antagonsits

• Sedatives and hypnotics

• Phenothiazines

D-receptors antagonists

Block D-receptors in the brain

in the : area postrema,

dorsal motor nucleus of vagus nerve

nucleus tractus solitarius

decrease stimulation of CTZ

• Haloperidol

• Fluphenazine

• Metoclopramide

M-receptors antagonists

Block M-receptors in the brain

in the area postrema, dorsal vagal complex

in gastrointestinal tract decrease its motility

• Scopolamine

side effects : sedation, blurred vision, urinary retention,

dry mouth (decrease saliva secretion)

contraindicated for airline pilots, bus and car drivers, etc.

H1-receptor antagonists

Antihistamines

Block H1-receptors in area postrema

and M-receptors in related structure

• buclizine

• cyclizine

• dimenhydrinate

• meclizine

• promethazine

5-HT3-receptor blockers

Seritonine antagonists

Block 5HT3-receptors in area postrema, nucleus

tractus solitarius and on vagal afferent nerve endings.

• ondansetron

• granisetron

• tropisetron

adverse effects : headache, constipation, flushing

Phenothiazines

• chlorpromazine

• promethazine

• prochlorperazine

• trimeprazine

mixed pharmacological blocking properties

(muscarinic blockers, antihistaminic, dopaminergic blockers,

adrenergic and serotonergic blockers)

ANTIEMETICS IN CHILDREN

5-HT receptor antagonists

• ondansetron,

• ganisetron,

• dolasetron,

• palonosetron.

blocks presynaptic r-5HT on sensory vagal fibers

(in the gutwall especially in the acute phase of chemotherapy induce)