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Year : 2017  |  Volume : 15  |  Issue : 4  |  Page : 305-308

Drug Dialogues – Medication news and new medications

Date of Web Publication17-Nov-2017

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DOI: 10.4103/0973-4651.218651

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How to cite this article:
. Drug Dialogues – Medication news and new medications. Curr Med Issues 2017;15:305-8

How to cite this URL:
. Drug Dialogues – Medication news and new medications. Curr Med Issues [serial online] 2017 [cited 2023 Feb 2];15:305-8. Available from: https://www.cmijournal.org/text.asp?2017/15/4/305/218651

Source: CMC Pharmacy Bulletin, a publication of the Pharmacy Service (DISH), CMC, Vellore.

Choosing the right anti-emetic drug

Choosing the right anti-emetic is cardinal in treating nausea and vomiting of any etiology. As there are multiple potential causes for nausea and vomit-ing, the choice of anti-emetic should be guided at least in part by probable cause. The potential causes include gastric stasis, intestinal obstruction, enteric infections, endocrine/metabolic disease, radiotherapy, chemotherapy, raised intra-cranial pressure, labyrinthine disease, drugs etc.

When stimulated by any of the above mentioned emetogenic causes, the chemoreceptor trigger zone (CTZ) (which monitors blood and CSF for emetogens) and solitary tract nucleus (STN) (which receives signal mainly from the gut) sends impulses to the vomiting centre (VC), which then initiates nausea and vomiting. The VC also receives signal from the vestibular apparatus (in motion sickness). The CTZ has high concentrations of receptors for serotonin (5-HT3), dopamine (D2), and opioids; the STN is rich in receptors for encephalin, histamine and ACh and also contains 5-HT3 receptors. These are the neurotransmitters involved in nausea and vomiting and an understanding of their nature will allow a rational approach to the selection of a suitable anti-emetic agent.

Commonly used anti-emetic drugs inhibit either histamine (antihistamine), ACh (anticholinergic), dopamine (antidopaminergic) or serotonin (5-HT3 antagonist). The other drugs commonly used in specific situations include neurokinin-1 (NK-1) antagonists (aprepitant and fosaprepitant), glucocorticoids (dexamethasone and methylprednisolone) and ben-zodiazepines (lorazepam, for anticipatory nausea and vomit-ing with chemotherapy).

For treatment to be most effective, identifying and targeting the most likely cause(s) are important. As there is often more than one cause of these symptoms, and different anti-emetics have different mechanisms of action, combinations are often required. Anti-emetic that acts in multiple receptors in multiple areas may be useful regardless of cause, or where there are multiple causes.

Different anti-emetics work on different receptors in different areas of the nausea and vomiting pathway. Metoclopramide works on dopamine receptors mainly in the periphery but also in the CNS; domperidone works on dopamine receptors in the periphery. Chlorpromazine works on multiple receptors in the CNS. It has anti-dopaminergic, antihistamine and anticholinergic (M1 receptors) actions in the VC. Drugs acting on the same receptor (e.g. domperidone and metoclopramide) should not be used together as the risk of side-effects will be increased without additional clinical benefit. Steroid anti-emetic is not usually preferred in haematology patients and should be used with caution in diabetic and immunocompromised patients. Dexamethasone is usually given as prophylaxis and not as treatment.

Motion sickness is mediated mainly through histamine and ACh neurotransmission, and thus antihistamines are preferred. Other anti-emetics including ondansetron have been shown to be a poor choice for motion sickness.

Anticipatory nausea and vomiting is said to be mediated by GABA and hence benzodiazepines are preferred.

Acute and delayed chemotherapy induced nausea and vomiting (CINV) have been linked to serotonin release and inflammation caused by serotonin respectively. This finding forms the clinical rationale behind the combination therapy with 5-HT3 antagonists and steroids.

Substance P acting at NK-1 receptors is one of the final common mechanisms involved in activation and coordination of the vomiting reflex and further, NK-1 receptor antagonists (e.g. aprepitant) augment the antiemetic activity of the 5-HT3 antagonist and dexamethasone and inhibit both acute and delayed phases of cisplatin-induced emesis and so are clinically indicated only for cisplatin-induced nausea and vomiting.

Metoclopramide and domperidone are dopamine antagonists and also have prokinetic properties and are used primarily in nausea and vomiting associated with gastric stasis and functional bowel obstruction. The prokinetic effect is blocked by antimuscarinics (Hyoscine butylbromide) and should therefore not be given concurrently.

In summary, the ideal way to treat or prevent nausea and vomiting is to find its most likely causes and then choose the most appropriate anti-emetic depending on site and mechanism of action while simultaneously treating the reversible causes.


  1. Hasler WL. Nausea, Vomiting and Indigestion. In: Harri-son's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  2. Brunton LL. Anti-nauseants and anti-emetic agents. In: Goodman & Gilman's The Pharmacological Basis of Thera-peutics. 12th ed. New York: McGraw-Hill; 2011.
  3. Twycross R. Anti-emetics. In: Palliative Care Formulary. 2nd ed. UK: Radcliffe Medical Press; 2002.
  4. Antiemetic Guidelines for Adult Patients Receiving Chemotherapy and Radiotherapy - antiemetic-guidelines-november-2010.pdf [Internet]. [cited 2017 May 15].

5 Drugs / 5 Points Learning


(Ondansetron, granisetron, palanosetron)

  • Act by inhibiting 5-HT3 receptor in the vomiting center, chemoreceptor trigger zone and in the small intestine
  • Granisetron and ondansetron are used in the management of chemotherapy induced nausea and vomiting (CINV) and in post-operative nausea and vomiting (PONV)
  • Palonosetron is used to prevent nausea and vomiting associated with moderately or highly emetogenic cytotoxic drugs
  • Generally safe with minimal significant side-effects but has been implicated with QT-prolongation
  • Though effective, some patients do not respond well to this group, hypothetically due to allelic variants of CYP2D6 or 5-HT3 receptor subunits


(Aprepitant, fosaprepitant)

  • Act by binding to the NK1 receptors in the CNS and thus inhibits binding of substance P and prevents emetic signal
  • Used to prevent acute and delayed nausea and vomiting associated with cisplatin based chemo-therapy
  • Often combined with dexamethasone and a serotonin antagonist
  • Generally well tolerated; fatigue, dizziness and diarrhoea can commonly occur
  • They are CYP3A4 inhibitors and hence should be used with caution with drugs that are primarily metabolized through CYP3A4


(Metoclopramide, chlorpromazine, prochlorperazine, domperidone)

  • Act by blocking the chemoreceptor trigger zone
  • Used for the prophylaxis and treatment of nausea and vomiting associated with a range of conditions and in breakthrough and refractory emesis
  • Metoclopramide is safe in pregnancy and is licensed for pregnancy associated nausea and vomiting
  • Chlorpromazine is more sedating than the other drugs of this group
  • Severe dystonic reactions sometimes occur, especially in children


(Dexamethasone, methylprednisolone)

  • Used in vomiting associated with cancer chemotherapy and intractable nausea and vomiting during pregnancy
  • Their anti-emetic mechanism of action remains to be elucidated
  • Intrinsically weak antiemetic drugs and is usually used in prophylaxis as an adjunct and not for treatment in CINV
  • May be used alone but often combined with an antiemetic(s) from other groups
  • Side-effects of short courses of steroid are mild, but should be used with caution in diabetes mellitus patients

ANTIHISTAMINES (Doxylamine, promethazine, diphenhydramine)

  • Inhibit the action of histamine at the H1 receptor and limit stimulation of the vomiting center from the vestibular system
  • Primarily used for motion sickness
  • Doxylamine and promethazine are not teratogenic and are preferred in the treatment of pregnancy associated nausea and vomiting
  • They are minimally effective for treating nausea and vomiting associated with gastrointestinal irritation
  • Sedation is a common side-effect with any of these drugs


  1. Hasler WL. Nausea, Vomiting and Indigestion. In: Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  2. Brunton LL. Anti-nauseants and anti-emetic agents. In: Goodman & Gil-man's The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill; 2011.
  3. Characteristics of antiemetic drugs [Internet]. [cited 2017 May 18]. Available from http://cursoenarm.net/UPTODATE
  4. Taylor T. Treatment of nausea and vomiting in pregnancy [Internet]. NPS MedicineWise. [cited 2017 May 18].

Ondansetron dosage for gastroenteritis induced vomiting in children

Ondansetron is a widely used serotonin antagonist antiemetic especially for chemotherapy-induced vomiting and post-operative nausea and vomiting. The drug is not approved in children for vomiting due to other causes and hence the dosage is not available in drug information databases. Acute gastroenteritis is the most common cause of vomiting in children which is often treated with antiemetics. Antihistamines and dopamine antagonists including promethazine, metoclopramide and domperidone oral liquids are generally used. Although rare, adverse effects such as drowsiness, extrapyramidal reactions, hallucinations, convulsions and neuroleptic malignant syndrome may occur with these medications.

Ondansetron, has a favourable safety profile and does not cause drowsiness. A literature search provided 3 randomized controlled trials and 1 observational cohort study on the effectiveness of ondansetron to treat vomiting secondary to gastroenteritis in children.

Roslund et al in 2008 randomized 106 children aged 1–10 years with acute gastritis or gastroenteritis to either receive a single dose of ondansetron (0.15 mg/kg) or placebo orally. The investigators found that children who received ondansetron were less likely to receive IV fluids and admitted to hospital compared with children who received placebo. Yilmaz et al in 2010 randomized 109 children aged 5 months to 8 years who presented to the emergency department with vomiting due to acute gastroenteritis to receive either ondansetron 0.2 mg/kg or placebo every 8 hours. The researchers found that the children who received ondansetron were less likely to vomit both during the first 8 hour follow-up and during the next 24 hour follow-up. Ramsook et al in 2002 randomized 145 children aged 6 month to 12 years with vomiting from acute gastroenteritis to receive a single dose of ondansetron (dose not found) or placebo. The study found that ondansetron was effective in reducing the emesis and in lowering the rates of IV fluid administration. Freedman et al in 2010 did a dose-response study in which 105 children with dehydration due to gastroenteritis were given ondansetron (dose ranged between 0.13 and 0.26 mg/kg) and observed that there was no significant association between the dose of ondansetron and the outcomes of number of vomiting episodes, volume of fluids consumed, increase in body-weight, or number of diarrhoea episodes per hour. The study implicated that the higher doses of ondansetron were not superior to lower doses, nor they were associated with increased side-effects.

In summary, oral ondansetron therapy in a single dose of 0.2 mg/kg or every 8 hours (if needed) may be considered for infants and children over 6 months of age with vomiting due to gastroenteritis.


  1. Roslund G, Hepps TS, McQuillen KK. The role of oral ondansetron in children with vomiting as a result of acute gastritis/gastroenteritis who have failed oral rehydration therapy: a randomized controlled trial. Ann Emerg Med. 2008 Jul;52(1):22–29.e6.
  2. Yilmaz HL, Yildizdas RD, Sertdemir Y. Clinical trial: oral ondansetron for reducing vomiting secondary to acute gastroenteritis in children-a double-blind randomized study. Aliment Pharmacol Ther. 2010 Jan;31(1):82–91.
  3. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D. A randomized clinical trial comparing oral ondansetron with placebo in children with vomit-ing from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397–403.
  4. Freedman SB, Powell EC, Nava-Ocampo AA, Finkel-stein Y. Ondansetron dosing in pediatric gastroenteri-tis: a prospective cohort, dose-response study. Paediatr Drugs. 2010 Dec 1;12(6):405–10.

Steroid inhalers may increase risk of non tuberculous mycobacterial infections

Use of steroid inhalers for asthma and chronic obstructive pulmonary disease (COPD) increases the risk of mycobacterial infections, according to a study published in the European Respiratory Journal.

The researchers carried out a population-based case-control study using linked laboratory and health administrative databases in Canada to examine adults aged 66 years or older being treated for obstructive lung diseases, including asthma and COPD. 417,494 older adults included in the study, there were, 2,966 incidents of nontuberculous mycobacterial pulmonary disease (NTM-PD) and 327 cases of tuberculosis.

The association between NTM-PD and inhaled corticosteroids use was found to be statistically significant for fluticasone but not for budesonide or other inhaled corticosteroids. The association between inhaled corticosteroids use and tuberculosis was not found to be significant.

The findings highlight that the use of inhaled corticosteroids increases the risk of NTM-PD, the authors concluded. NTM-PD is still relatively rare but because it is a chronic infection that is extremely difficult to treat, prescribers should consider the risk when prescribing inhaled corticosteroids, particularly to patients with COPD.


  1. Brode S, Campitelli M, Kwong J et al. The risk of mycobacterial infections associated with inhaled corticosteroid use. Eur Resp J 2017 50: 1700037.

Smoking affects drug dosing

Tobacco use in any form (smoking or smokeless) is very common in India. Six percent of adults in the country smoke cigarette, whereas 9.2% of adults smoke bidi. One in four adults uses smokeless tobacco. The average age at which a person initiates tobacco use has been estimated at 18 years. Moreover, five in ten adults are exposed to second-hand smoke at home and/or at public places.1

Polycyclic aromatic hydrocarbons, found in cigarette smoke, have enzyme inducing properties. This chemical induces mainly the hepatic isoenzyme CYP1A2 (1A1, 2E1, 2B6 are also reported). Therefore, interactions caused by smoking have an effect on all drugs being substrates of and therefore metabolized by CYP1A2.2

Warfarin is a minor substrate of CYP1A2 and its metabolism is known to be affected by cigarette smoking. In an adult who was stabilized on warfarin for his deep vein thrombosis, the INR rose significantly when he decreased his smoking from one pack per day to half pack per day and then subsequently stopped smoking completely. The patient's smoking cessation resulted in a major modification of his required weekly warfarin dose (a 39% dose reduction).3 A 2011 meta-analysis also highlighted the potential smoking-warfarin interaction by increasing warfarin clearance.4

Theophylline is a major substrate of CYP1A2. Theophylline clearance may be decreased in patients following cessation of smoking. This is extremely important, given the therapeutic index of theophylline is narrow. Its elimination half-life is highly variable in patients with smoking history. Psychoactive drugs metabolized by CYP1A2 are known to be affected with smoking. In a case report, a 73 year old woman who was diagnosed with Parkinson's disease did not improve with carbidopalevodopa. Upon reviewing the patient history, the clinicians discovered that the patient was taking olanzapine 30mg daily for bipolar disorder and had a 40-pack-year history of smoking and had stopped smoking 4 months earlier. The results of neurologic evaluation showed that the patient did not have Parkinson's disease but was possibly experiencing olanzapine toxicity secondary to smoking cessation. Olanzapine is a major substrate of CYP1A2. Smoking is also associated with increased clearance of fluphenazine, haloperidol, chlorpromazine and clozapine.5

Smokers might require higher than normal doses of the antidepressant imipramine, however, they do not appear to require dose adjustments of amitriptyline, nortriptyline or clomipramine. Pharmacodynamic drug interactions with tobacco smoke has also been reported largely due to nicotine. The primary pharmacodynamic interactions with smoking are hormonal contraceptives and inhaled corticosteroids. Smoking has been reported to increase the adverse effects of the combined oral contraceptive pill (COCP). The COCP is contraindicated in women aged 35 years or older who smoke 15 or more cigarettes a day. Smokers may require higher doses of inhaled corticosteroids to attain asthma control.6,7

Nicotine activates the CNS and this may explain the attenuated sedation observed in smokers compared to non-smokers taking benzodiazepines, less analgesia from some opioids and reduced efficacy of beta-blockers.

Individuals who are on the above discussed drugs and others known to be affected by smoking should regularly be monitored for their smoking status and dose adjusted accordingly.


  1. Fact sheet: India (2009-2010), Global adult tobacco survey (GATS). Ministry of Health and Family Welfare, Gov-ernment of India
  2. Laki S, Kalapos-Kovács B, Antal I, Klebovich I. [Importance of drug inter-actions with smoking in modern drug research]. Acta Pharm Hung. 2013;83(4):107–20.
  3. Jordan SD, Stone MD, Alexander E, Haley J, McKee A. Patient case: impact of smoking cessation on international normalized ratio. J Pharm Pract. 2014 Oct;27(5):470–3.
  4. Nathisuwan S, Dilokthornsakul P, Chaiyakunapruk N, Morarai T, Yodting T, Piriyachananusorn N. Assessing evidence of interaction between smoking and warfarin: a sys-tematic review and meta-analysis. Chest. 2011 May;139(5):1130–9.
  5. Arnoldi J, Repking N. Olanzapine-induced parkinsonism associated with smoking cessation. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 2011 Mar 1;68(5):399–401.
  6. Arnoldi J, Repking N. Olanzapine-induced parkinsonism associated with smoking cessation. Am J Health-Syst Pharm AJHP Off J Am Soc Health-Syst Pharm. 2011 Mar 1;68(5):399–401.
  7. Kroon LA. Drug interactions with smoking. Am J Health Syst Pharm. 2007 Sep 15;64(18):1917-21.


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