Emesis & anti emetics medications

Emesis & anti emetics medications

1. Emesis and Antiemetics GMC Jagdalpur

2. Nausea Nausea  is an unpleasant sensation of  wanting to vomit , and is often associated with cold sweat,  pallor , salivation, loss of gastric tone, duodenal contraction, and the reflux of intestinal contents into the stomach. Nausea generally precedes vomiting, but can occur by itself.

3. Retching Retching  is a strong  involuntary effort to vomit , and usually follows nausea. During retching, the abdominal muscles, chest wall and diaphragm all contract without any expulsion of gastric contents.

4. Vomiting Vomiting is the  forceful expulsion  of the contents of the  gastrointestinal system  out through the mouth. From an evolutionary perspective, it is thought to have evolved as a defence mechanism of the body, serving a protective function to rid the body of noxious substances that have been ingested, rather than allowing them to be retained and absorbed by the intestine.

5. Stomach itself does not actively expel its contents during vomiting. The stomach, oesophagus, and their relevant sphincters are all in fact relaxed during vomiting. Most of the force that expels the contents arises from the contraction of the diaphragm , which is the major respiratory muscle, and the abdominal muscles , which are the muscles involved in active expiration.

6. Symptoms of emesis Profuse salivation; Sweating; Elevated heart rate; Pallor; Nausea; and Retching movements.

7. Causes of nausea and vomiting Conditions Reasons Irritation of the stomach and duodenum Indigestion; Allergies ; Bowel obstructions; Gallstones ; Liver problems; Pancreatitis . Infectious causes Viral  labyrinthitis ; Viral gastroenteritis ; Influenza ; Whooping cough ; Food poisoning. Endocrine Pregnancy . Labyrinth causes Motion sickness ; Meniere’s disease . Increased intracranial pressure Haemorrhage. Meningitis ; Lesions in parts of the brain. Drug/treatment induced Cancer  chemotherapy ; Opiates ; Digoxin ; Immunotherapy; Nicotine , Antibiotics ; Radiotherapy ; Alcohol  excess. Central nervous system (CNS) Anticipation; Migraine ; Bulimia nervosa ; Psychogenic stimuli

8. Area Postrema surrounds 4th ventricle outside blood brain barrier & monitors blood

9. Anatomy of Emesis Chemoreceptor trigger zone (CTZ) in the area postrema (AP) at the bottom of the fourth ventricle has high concentration of: • 5-HT3 • D2 • M1 • NK1 • opioid The CTZ has connections to the Nucleus of the Tractus Solitarius (NTS) & Reticular Formation (aka vomiting center ) which contains: • 5-HT3 • M1 • NK1

10. Mechanisms of emesis Afferent  inputs go to the  central nervous system  (CNS), relaying the signals of emetic stimuli; These signals are received, recognised, and centrally processed. They then form integrated emetic  efferent  signals coming from the CNS; These motor and chemical efferent pathways relay signals that lead to the coordinated respiratory, gastrointestinal and abdominal muscle expulsive actions of vomiting.

11. Chemoreceptor trigger zone (CTZ) The CTZ is located in the  medulla  of the  brain . It has a defensive  blood-brain barrier  for detecting circulating toxins in the blood and  cerebrospinal fluid  (CSF), and is sensitive to a number of circulating emetic agents, including  morphine , intravenous copper sulphate , and certain circulating metabolic emetic agents associated with  uraemia , infections and radiation . When activated, the CTZ does not initiate vomiting itself, but relays stimuli to the  integrative vomiting centre  which produces the actual act of emesis.

12. Integrative vomiting centre The integrative vomiting centre coordinates activities of the nearby neural structures to produce a complex patterned response, resulting in the processing and action of the vomiting reflex. The centre is located in the medulla. The motor component of the vomiting centre is controlled by both somatic and  autonomic   systems , meaning that both voluntary and involuntary systems are involved in the process. Their inputs are coordinated by the vomiting centre.

13. Somatic efferent pathways control respiratory and abdominal musculature. Visceral efferent components mediating changes in gastric tone and motility , while salivation, pallor and sweating are autonomic epiphenomena. The autonomic nervous system is not essential for the mechanical act of vomiting.

14. Afferent pathways The vomiting centre is predominantly activated by three different mechanisms: By nervous impulses from the stomach, intestinal tract, and other portions of the body, resulting in a reflexive activation; By stimulation from the higher brain centres; By the chemoreceptor trigger zone (CTZ) sending impulses.

15. Afferent impulses may also arise from other sites, such as unpleasant sights and odours, as well as severe parietal  pain . The most common afferent pathways are in the viscera, or abdominal organs. Vomiting can be provoked by occlusion of the coronary vessels, distension of the intestine, and irritation of the gastrointestinal mucosa. In the gastrointestinal tract,  mechanoreceptors  in the intestinal wall are activated by abnormal contractions, distension or physical damage. Potentially harmful chemical stimuli can also activates chemoreceptors  located in the intestinal wall. These receptors then release information to the vomiting centre.

16. Efferent pathways The vomiting reflex is mediated by both the autonomic and somatic systems, and consists of two phases: Prodomal phase  (pre-ejection): Relaxation of gastric muscles followed by small intestinal retrograde peristalsis; Ejection phase:  Comprises of retching and vomiting including expulsion of gastric contents.

17. Consequences of vomiting

18. Types of emesis (Drug induced) Acute emesis:  symptoms occurring within the first 24 hours after drug therapy; Delayed emesis:  symptoms occurring after 24-48 hours after last dose of drug therapy; Anticipatory emesis:  a conditioned response in patients who have developed significant drug-induced nausea and vomiting during previous cycle of therapy.

19. Post-operative nausea and vomiting (PONV) Age:  M/C in Younger & elderly patients Gender:  Women tend to suffer more than men do. Nutrition:  overweight or obese pts Past history:  H/o motion sickness or previously h/o nausea and vomiting after a surgical procedure Cancer therapy:  Patients undergoing chemotherapy and radiotherapy are more likely to suffer as well; Anaesthetic and surgical factors:   inhalational agents and medications (such as morphine Some surgical factors : such as operations around the ear and inner ear, eyes, mouth and some abdominal surgery.

20. Consequences of vomiting Severe and prolonged vomiting can cause the following harmful consequences: Dehydration, which can be lethal, especially in children; Protracted vomiting may result in starvation, malnutrition and vitamin deficiency; Severe post-operative vomiting can increase bleeding, aspiration  pneumonia , and induce the re-opening of surgical wounds as a result of involuntary muscle contractions associated with vomiting; Metabolic alkalosis .

21. Therapeutic use of Emetic agents

22. Common examples of emetics are: Powdered mustard suspension, strong common salt solution, IPECAC and apomorphine. Mustard and common salt are commonly used household emetics because they are easily available. They are indicated in case of poisonings. They act reflexly by irritating the stomach.

23. Apomorphine It is a semisynthetic derivative of morphine. Acts on CTZ. It is given in a dose of 6 mg i.m ./ s.c. route. It takes minimum 5 minutes for its action. It should not be given in the patients who are having respiratory distress as it also acts as a respiratory depressant. Its action is unpredictable when given by oral route. For induction of vomiting, very high dose is required, which is not safe.

24. Ipecacuanha It is obtained from dried root of Cephaelis ipecacuanha which contains an alkaloid called Emetine . It causes vomiting by irritating the gastric mucosa reflexly as well as by acting on CTZ. To induce vomiting, it is given orally in a dose of 15–30 ml in adults, 10–15 ml in children and 5 ml in infants. It takes minimum 15 minutes for its action. The syrup of IPECAC is safer than apomorphine.

25. Contraindications of emetics use Kerosene poisoning ( aspiration may cause chemical pneumonia ). CNS stimulant drug poisoning ( emetics precipitate convulsions ). Morphine poisoning ( emetics do not works properly ). Corrosive poisoning ( it may lead to G.I. perforation/esophageal erosion ). Unconscious patients ( increases chances of aspiration ). Paediatric patients. ( increases chances of aspiration ).

26. Management of Emesis Lifestyle Pharmacotherapy

27. Dietary management of nausea Avoid foods that: are fatty/greasy/fried; are spicy or hot; have strong odours. Eat small amounts more frequently and eat slowly; Eat before you get hungry, because hunger can make feelings of nausea stronger;

28. Avoid eating in a room that is too warm, or has cooking odors that might disagree with you; Sip cold clear fluids Have foods and drinks at room temperature or cooler; hot foods may add to nausea; Rest after meals, because activity may slow digestion. It’s best to rest sitting up for about an hour after meals;

29. CLASSIFICATION OF ANTIEMETICS Anticholinergics Hyoscine, Dicyclomine H 1 antihistaminics   Promethazine, Diphenhydramine, Dimenhydrinate, Doxylamine, Meclozine (Meclizine), Cinnarizine. Neuroleptics(D2 blockers) Chlorpromazine, Triflupromazine, Prochlorperazine, Haloperidol, etc. Prokinetic drugs   Metoclopramide, Domperidone, Cisapride, Mosapride, Itopride, levosulpride. 5-HT3 antagonists Ondansetron, Granisetron, Palonosetron, Ramosetron NK1 receptor antagonists Aprepitant, Fosaprepitant Adjuvant antiemetic Dexamethasone, Benzodiazepines, cannabinoids

30. Anticholinergics Antiemetic action is exerted by blocking conduction of nerve impulses from the vestibular apparatus to the vomiting centre (which involves cholinergic link). These drugs have poor efficacy in vomiting of other etiologies. Hyoscine and Dicyclomine are the most commonly used anticholinergic drugs in G.I. system.

31. Hyoscine It has shorter duration of action. It is given in a dose of 0.2–0.4 mg oral or i.m . It is very effective for motion sickness. The most common adverse effects are dry mouth and sedation. Transdermal hyoscine patch is applied behind the pinna. It contains 1.5 mg of Hyoscine and delivers the drug for consecutive three days.

32. Dicyclomine It is also used for motion sickness as a prophylaxis . It is given in a dose of 10–20 mg orally. It is used as an antispasmodic agent. Don’t give in lactating mother? The most common adverse effects are dry mouth and sedation.

33. H 1 Antihistaminics H 1 antihistaminic drugs have weak antiemetic property. The antiemetic action is due to antihistaminic, anticholinergic and weak antidopaminergic action. These drugs are useful to prevent motion sickness, morning sickness and postoperative vomiting. The main side effects are dry mouth, sedation, confusion, dizziness, and urinary retention.

34. Drug Dose and Route Main uses Promethazine 25 mg, tablet & i.v. Motion sickness, chemotherapy induce vomiting Diphenhydramine 25–50 mg oral Dimenhydrinate 25–50 mg oral Doxylamine 10-20mg oral Morning sickness Meclozine (Meclizine) 25–50 mg oral Sea sickness Cinnarizine 25–50 mg oral Vertigo, labyrinthitis

35. NEUROLEPTICS (D 2 - BLOCKERS) Phenothiazines, haloperidol are potent antiemetics. They block D2 receptors in the CTZ; antagonize apomorphine induced vomiting and have additional antimuscarinic as well as H1  antihistaminic property.  but less effective in motion sickness ?

36. They have broad spectrum antiemetic action effective in: Drug induced and postoperative nausea and vomiting (PONV). Disease induced vomiting: gastroenteritis, uraemia, liver disease, migraine, etc. Malignancy associated and cancer chemotherapy (mildly emetogenic) induced vomiting. Radiation sickness vomiting (less effective). Morning sickness: should not be used except in hyperemesis gravidarum.

37. S/E M/C sedation. Acute muscle dystonia may seen in children and girls. Not given in undiagnosed cause of vomiting; because its delayed the symptom of intestinal obstruction, appendicitis.

38. Prochlorperazine An D 2 antagonist, given in a dose of 5–10 mg BD/TDS oral, &/or 12.5–25 mg by deep i.m . injection. It is indicated in vertigo and some case of chemotherapy induced vomiting. These drugs are least preferred as antiemetics due to availability of better and safer antiemetics .

39. MIDAZOLAM Short-acting benzodiazepine with a rapid onset of action which has been demonstrated efficacious as antiemetic in postoperative emesis resistant to the usual treatments Midazolam decreases dopamine imput at the CTZ or dopaminergic neuronal activity and 5-HT release by binding to the GABA benzodiazepine complex

40. OLANZAPINE Antipsychotic drug that blocks multiple neurotransmitters: dopamine at D1, D2, D3 and D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3 and 5-HT6 receptors, catecholamines at alpha 1 adrenergic receptors histamine at H1 receptors Used for CINV

41. Gabapentin A g-aminobutyric acid analogue approved in 1994 as an anticonvulsant In an anedoctal report, complete resolution of chemotherapy-induced nausea was seen in a patient with breast cancer, after she was placed on gabapentin for the treatment of hot flushes The mitigation of tachykinin neurotransmitter activity useful to control both hot flushes and emesis has been suggested as possible mechanism of action

42. Ghrelin Stimulates gastric motility Protects gastric mucosa Increases appetite

43.  PROKINETIC DRUGS Metoclopramide, domperidone, cisapride, mosapride, itopride, levosulpride

44. Metoclopramide It is also called gastric hurrying agent. It has both peripheral and central actions. Peripherally: Metoclopramide has more prominent effect on upper GIT; increases gastric peristalsis while relaxing the pyloric sphincter and the first part of duodenum. It also increases the tone of lower esophageal sphincter (LES). Centrally: Metoclopramide blocks the D2 receptors in CTZ.

45.  D 2   antagonism It blocks D 2 receptors — hastening gastric emptying and enhancing LES tone by augmenting ACh release. The central antidopaminergic (D 2 ) action of metoclopramide on CTZ is clearly responsible for its antiemetic property. It also antagonised apomorphine induced vomiting, CPZ like extrapyramidal effects and hyperprolactinaemia.

46. 5-HT4  agonism Metoclopramide acts in the g.i.t . to enhance ACh release from myenteric motor neurones. This results from 5-HT4 receptor activation on primary afferent neurones (PAN) of the ENS via excitatory interneurones . The gastric hurrying and LES tonic effects are mainly due to this action which is synergised by bethanechol and attenuated by atropine.

47. 5-HT3  antagonism At high concentrations metoclopramide can block 5-HT3 receptors present on inhibitory myenteric interneurones and in NTS / CTZ. The central anti 5-HT3 action appears to be significant only when large doses are used to control CINV.

48. Pharmacokinetics It is rapidly absorbed orally. It acts in ½–1 hr when given orally, within 10 min after i.m . and 2 min after i.v. injection. Action lasts for 4–6 hours. It crosses the BBB and placental barrier. It is metabolized in liver and excreted by urine.

49. Indications Vomiting due to different reasons such as drug induced, disease associated, postoperative and radiation sickness, etc. It is not preferred in motion sickness due to poor effectiveness. It can be used for morning sickness only when other drugs fail. It is used as Gastrokinetic agent to accelerate gastric emptying in conditions such as: diabetic gastroparesis associated gastric stasis and when emergency general anaesthesia has to be given and the patient has taken food less than 4 hours before. To facilitate duodenal intubation Dyspepsia and persistent hiccups. GERD

50. Adverse effects The most common side effects are loose stools, sedation , dizziness and muscle dystonias (due to extrapyramidal side effects in children). Long-term use can cause galactorrhoea, gynaecomastia and parkinsonism. Doses Adults: 10 mg TDS oral or i.m . Children: 0.2–0.5 mg/kg TDS oral or i.m .

51. Domperidone Domperidone is a D 2 receptor inhibitor. It acts as metoclopramide but has chemical structure like haloperidol. Pharmacokinetics It is well absorbed orally, but due to first pass metabolism, it has poor bioavailability (15%). It is metabolized in liver and excreted in urine. The plasma t½ is 7.5 hr.

52. Dose Adult: 10–40 mg TDS. Children: 0.3–0.6 mg/kg in three divided doses. Indications These are same as metoclopramide but less effective as gastrokinetic agent. It is not useful in chemotherapy induce emesis. Adverse effects The side effects are less as compared to metoclopramide. Others: headache, loose stools and dry mouth.

53. Cisapride It is 5-HT 4 receptors agonist and promotes Ach release in the gut wall causing prokinetic activity. It is not an antiemetic as it does not act on D 2 receptors. Therefore, no extrapyramidal side effects are seen. The t½ is 10 hours. It was commonly indicated as prokinetic agent, particularly for gastroesophageal reflux disease and gastroparesis. Its clinical use has been banned in India since 2011 due to cardiac side effects like Q-T prolongation etc..

54. Mosapride It is a congener of Cisapride. It is also a 5-HT 4 receptors agonist and poor 5-HT 3 antagonistic action on myenteric plexus. Like cisapride, it does not act on D 2 receptors hence, hyperprolactinemia and extrapyramidal side effects are not seen. The common side effects are abdominal pain, diarrhoea, headache, dizziness, and insomnia.

55. It may also cause Q-T prolongation when co-prescribed with macrolides and azoles. So, it should be given carefully in cardiac patients. It is given in a dose of 5 mg (elderly 2.5 mg) TDS. It is indicated in diabetic gastroparesis, non-ulcer dyspepsia, GERD (as adjuvant to H 2 blockers/PPIs), and some cases of chronic constipation.

56. Itopride It is a safer prokinetic drug. It has D 2 antidopaminergic and anti-cholinesterase activity. Thus, it potentiates the Ach action on GIT causing prokinetic activity. No drug interactions are seen with macrolides and azoles. It can be given safely to cardiac patients as no Q-T prolongation has been recorded yet. The side effects are diarrhoea, abdominal pain, headache. Galactorrhoea and gynaecomastia occur rarely. No extrapyramidal side effects are seen. It is given in a dose of 50 mg TDS before meals.

57. Levosulpride It is a selective antagonist of dopamine D 2 receptor activity on both central and peripheral levels. It is typical neuroleptic and a prokinetic agent. It is used in a treatment of anxiety disorders, dyspepsia, irritable bowel syndrome (IBS), etc. It is metabolized in liver and excreted in urine with a t ½ of 9.7 hr. when given orally and 4.3 hr by i.v. route.

58. It is usually given in combination with PPI (rabeprazole) (rabeprazole 20mg+ levosupride 75mg). It can be given safely to cardiac patients as no Q-T prolongation has been recorded yet. The common side effects are diarrhoea and constipation . (dose dependent) It should not be used to stimulate the GI motility in presence of GI haemorrage, obstruction and perforation. The patients should be advised to avoid driving or work on machinery as it causes dizziness and somnolence in some patients. The newer prokinetic drugs are sultopride and tiapride.

59. 5-HT 3 ANTAGONISTS Ondansetron, Granisetron, Palonosetron, Ramosetron

60. 5-HT 3 ANTAGONISTS These antiemetic drugs were developed to control cancer chemotherapy or radiotherapy induced vomiting and proved their worth. They block the depolarizing action of 5-HT exerted through 5-HT3 receptors on vagal afferents in the GIT as well as in nucleus tractus solitarius (NTS) and CTZ.

61. They are highly effective in postoperative nausea and vomiting (PONV) and disease or drug induced vomiting. They are not effective in apomorphine or motion sickness induced vomiting. Nowadays, these drugs are the most commonly used antiemetics.

62. Ondansetron It is given by both oral and i.v. route. It is metabolized in liver and excreted in urine and faeces . The t ½ 3–5 hrs and duration of action is 8-12 hrs , which may be longer at higher doses.

63. Indications & Dose Cancer chemotherapy (highly emetogenic drugs) induced vomiting ; 8 mg i.v. by slow injection over 15 min ½ hr before chemotherapeutic infusion, followed by 2 similar doses at 4 hours interval. Alternatively, single 24 mg i.v. dose on first day can also be used. To prevent delayed emesis: 8 mg oral is given twice a day for 3–5 days. To prevent postoperative nausea and vomiting (PONV): 4–8 mg i.v. given before induction of anesthesia and given 8 hourly postoperatively if required. For radiotherapy and less emetogenic drugs : 8 mg orally given 1–2 hr prior to the procedure and then at eight hrly interval till required.

64. Granisetron It is ten times more potent than ondansetron. It is more effective during the repeat cycle of chemotherapy. Its t ½ is 8-12 hrs therefore, given in BD doses. The side effects are similar to ondansetron.

65. Indication and Dose Cancer chemotherapy (highly emetogenic drugs) induced vomiting ; 1–3 mg diluted in 20–50 ml saline and infused i.v. over 5 min before chemotherapy, repeated after 12 hr. For radiotherapy and less emetogenic drugs : 2 mg oral 1 hr before chemotherapy or 1 mg before and 1 mg 12 hr after it. To prevent post operative nausea and vomiting (PONV): 1 mg diluted in 5 ml saline and injected i.v. over 30 sec before starting anaesthesia or 1 mg orally every 12 hours.

66. Palonosetron It is the longest acting 5-HT 3 antagonist and given in a single dose only . It is more effective in suppressing delayed vomiting occurring between 2-5 days after chemotherapy. It is given by both oral and i.v. routes. It is metabolized in liver and excreted in urine. It has t½ of 40 hrs.

67. In addition to the common side effects of 5-HT 3 antagonist, it also causes Q-T prolongation, when co-administered with erythromycin, moxifloxacin, anti-psychotics, antidepressants, etc. It should always be given by slow i.v. infusion as rapid i.v. injection may cause blurring of vision. Indications & Dose Cancer chemotherapy (highly emetogenic drugs) induced vomiting: 250 µg by slow i.v. injection 30 min before chemotherapy. Do not repeat before 7 days. To prevent post operative nausea and vomiting (PONV): 75 μg i.v. as a single injection just before induction.

68. Ramosetron It is similar to ondansetron in general properties. It is also indicated for diarrhoea predominant IBS as it has shown potential to normalize disturbed colonic function. Indications & Dose Cancer chemotherapy (highly emetogenic drugs) induced vomiting : 0.3 mg injected i.v. before chemotherapy, and repeated once daily. For low emetogenic chemotherapy : 0.1 mg once daily. To prevent post operative nausea and vomiting ( PONV) : Ramosetron 0.3 mg i.v. equally effective as ondansetron 8 mg i.v.  

69. NK 1 RECEPTOR ANTAGONISTS Aprepitant, fosaprepitant The substance-P released due to emetogenic chemotherapy activates neurokinin (NK1) receptors in CTZ and NTS and plays a role in the causation of vomiting. Aprepitant and Fosaprepitant antagonists block the NK1 receptors and act as antiemetics in chemotherapy induced vomiting.

70. Aprepitant Aprepitant has high affinity to NK1 receptors. It is well absorbed orally. It penetrates BBB and is metabolized in liver and excreted in faeces and urine. t½ is 9–13 hours. It should not be given to the patients who have been already prescribed Q-T interval prolonging drugs. The main side effects are weakness, fatigue, flatulence and rarely rise in liver enzymes.

71. Indications & Dose Cancer chemotherapy (highly emetogenic drugs) induced vomiting : Oral aprepitant (125 mg + 80 mg + 80 mg over 3 days) combined with standard i.v. ondansetron/ palonosetron + dexamethasone regimen significantly enhances the antiemetic efficacy against highly emetogenic cisplatin based chemotherapy. It is highly useful in patients undergoing multiple cycles of chemotherapy. To prevent post operative nausea and vomiting PONV: A single (40 mg) oral dose of aprepitant is well effective in PONV.

72. Fosaprepitant It is a parenterally administered prodrug of aprepitant . It is given as 150 mg running i.v. infusion administered over 20-30 minutes. In Cancer, chemotherapy (highly emetogenic drugs) induced vomiting : It is given in a dose of 150 mg in conjuction with standard i.v. ondansetron/ palonosetron + dexamethasone regimen.

73. CASOPITANT Potent and selective oral NK1 receptor antagonist which has shown activity in preventing chemotherapy-induced nausea and vomiting in preclinical studies

74. ADJUVANT ANTIEMETICS (Corticosteroids, benzodiazepines, cannabinoids)

75. Cannabinoids They are obtained from Cannabis indica , and possesses good antiemetic activity. Tetrahydrocannabinol (THC) is the active principle. They act by agonistic action on cannabinoid receptors (CB-1), which are located in vomiting centre and CTZ. They are also good appetite stimulants. They are metabolized in liver and metabolites are excreted slowly over days to weeks in the feces and urine. They are not commonly used due to availability of better drugs. They are used only in those patients, who do not respond to other antiemetics. The common side effects are euphoria, dysphoria, sedation, hallucinations, and dry mouth.

76. Dronabinol is the purest form of THC and is usually given in a dose of 5 mg/m 2 just prior to chemotherapy and every 2–4 hours as needed. Nabilone It is a man made cannbinoid , having antiemetic property. It has been approved by US-FDA for its clinical use. It is used only in those patients, who do not respond to other antiemetics. It is given in a dose of 1-2 mg before 1-3 hour of chemotherapy; then every 8-12 hours during the course of chemotherapy and for 2 days following cessation of chemotherapy.

77. Benzodiazepines (BZDs) BZDs have sedative action and relieve the psychogenic component of vomiting; thereby used as adjuvant to antiemetics. They also suppress dystonic side effects of metoclopramide. The commonly used BZDs are diazepam, lorazepam (oral/ i.v. ), and alprazolam (oral only).

78. Corticosteroids Corticosteroids (dexamethasone, methylprednisolone) have antiemetic properties, but exact mechanism of action is unknown. These agents enhance the efficacy of 5-HT 3 receptor antagonists. The commonly used corticosteroid is dexamethasone, which is given in a dose of 8–20 mg intravenously before chemotherapy, followed by 8 mg/day orally for 2–4 days.

79. Therapeutic window High Therapeutic Index Low Therapeutic Index – 5-HT 3 antagonists – NK 1 antagonists – corticosteroids (combo) – cannabinoids – dopamine antagonists – benzodiazepines

80. DIGESTANTS These are substances intended to promote digestion of food. Used as appetite stimulants or health tonics. They are occasionally beneficial, only when elaboration of enzymes in g.i.t . is deficient. Their routine use in tonics and appetite improving mixtures is irrational

81. Pancreatin It is a mixture of pancreatic enzymes obtained from hog and pig pancreas. It contains amylase, trypsin and lipase/ Indicated in chronic pancreatitis or other exocrine pancreatic deficiency states. It reduces the Fat and nitrogen content of stools and helps in diarrhoea/ steatorrhoea . It has to be used as enteric coated tablets or capsules. S/E: Nausea, diarrhoea and hyperuricaemia.

82. Pepsin May be used along with HCl in gastric achylia due to atrophic gastritis, gastric carcinoma, pernicious anaemia, etc. Papain It is a proteolytic enzyme obtained from raw papaya. Its efficacy after oral ingestion is doubtful. Diastase and Takadiastase These are amylolytic enzymes obtained from the fungus Aspergillus oryzae . They have been used in pancreatic insufficiency, but efficacy is equivocal.

83. Methyl polysiloxane Dimethyl polysiloxane , Simethicone, Dimethicone It is a silicone polymer, a viscous amphiphilic liquid—reduces surface tension and collapses froth, ‘antifoaming agent’. It is not absorbed from g.i.t . and is pharmacologically inert. It is added with antacid, digestant and antireflux preparations. Mostly indicated for flatus. Also indicated for GERD and peptic ulcer Dose: 40–120 mg 3 to 4 times a day.

84. GALLSTONE DISSOLVING DRUGS