Effects of different serotonin receptor subtype antagonists on the development of cardiac allograft vasculopathy in murine aortic allografts

BackgroundCardiac allograft vasculopathy (CAV) is the main obstacle for long-term survival after heart transplantation. Alloimmune mediated chronic vascular rejection results in several mechanisms like platelet activation, immigration of inflammatory cells through the endothelial layer and proliferation and migration of smooth muscle cells (SMCs). Serotonin (5-HT) promotes these processes via activation of 5-HT₂ receptors. We hypothesized that inhibiting 5-HT₂ receptors ameliorates the development of CAV.MethodsCBA/JRj mice recieved aortic grafts from C57BL/6 mice. After transplantation until recovery of organs, recipients were treated with serotonin receptor antagonists: sarpogrelate (5-HT_2A), SB 204741 (5-HT_2B) or terguride (5-HT_2A+B). Mice were sacrificed after 14 days for qRT-PCR analysis or after 30 days for histological evaluation. Serum serotonin ELISA was done at both time points.ResultsElevated serum serotonin levels were significantly reduced after 5-HT_2A antagonist treatment as was 5-HT_2A receptor expression. This went along with reduced inflammation characterized by significantly fewer infiltrating macrophages and pro-inflammatory intragraft cytokines and with reduced tissue remodeling evident as significantly less neointima formation.ConclusionInhibition of the 5HT/5-HT_2A receptor axis leads to significantly reduced neointima proliferation after aortic transplantation associated with reduced transendothelial migration of macrophages and decreased expression of inflammatory cytokines. These findings have translational implications as inhibitors of 5HT_2A like sarpogrelate are already approved for clinical use.     

Acute Migraine Therapy: New Drugs and New Approaches

The conceptual shift of our understanding of migraine from a vascular disorder to a brain disorder has dramatically altered the approach to the development of new medicines in the field. Current pharmacologic treatments of acute migraine consist of nonspecific and relatively specific agents. Migraine-specific drugs comprise two classes, the ergot alkaloid derivatives and the triptans, serotonin 5-HT_1B/1D receptor agonists. The ergots, consisting of ergotamine and dihydroergotamine (DHE), are the oldest specific antimigraine drugs available and are considered relatively safe and effective. Ergotamine has been used less extensively because of its adverse effects; DHE is better tolerated. The triptan era, beginning in the 1990s, was a period of considerable change, although these medicines retained vasoconstrictor actions. New methods of delivering older drugs include orally inhaled DHE and the transdermal formulation of sumatriptan, both currently under study. Novel medicines being developed are targeted at neural sites of action. Serotonin 5-HT_1F receptor agonists have proven effective in phase II studies and have no vascular actions. Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. Other targets under investigation include glutamate (AMPA/kainate), TRPV1, prostanoid EP4, and nitric oxide synthase. With new neural targets and the potential for therapeutic advances, the next era of antimigraine medications is near.     

The effects of a 5-HT2A receptor antagonist on blood flow in lumbar disc herniation : application of nucleus pulposus in a canine model

Blood vessel clots are found around the nerve root in patients with lumbar disc herniation. Thrombosis formation in the experimental application of nucleus pulposus to the nerve root has been shown in histological studies. In addition, reduction of blood flow and nerve conduction velocity are induced by the application of nucleus pulposus, which mimics lumbar disc herniation. In patients with lumbar disc herniation, nerve root block, which is thought to increase nerve blood flow, improves radiculopathy. 5-HT_2A receptor antagonists are used in chronic arterial occlusive diseases to improve blood flow and have been reported to work as well as nonsteroidal anti-inflammatory drugs in improving radiculopathy due to lumbar disc herniation in clinical studies. This study investigated the effects of a 5-HT_2A receptor antagonist on blood vessel diameter and blood flow in a canine experimental model of lumbar disc herniation. A total of 13 dogs were used. The animals were divided into three experimental groups and surgery was performed 1 week before measurements. In the nucleus pulposus group (NP; n = 5), the nucleus pulposus was applied to the nerve roots from the ventral side. In the sham group (n = 5), nucleus pulposus was not applied. In the naïve group (n = 3), the animals did not undergo surgery. Measurements of vessel diameter and blood flow were done before and after administration of saline and drugs. The diameters and blood flow volume of the observed blood vessels were measured on video-recordings every 10 min for 65 min. In all groups, vessel diameter and blood flow did not change before or after administration of saline. In the NP and sham groups, vessel diameter and blood flow increased significantly after administration of 5-HTRA compared with the naïve group. 5-HTRA improved blood vessel diameter and blood flow in the nerve roots inflamed by the application of nucleus pulposus but not in the intact nerve roots. 5-HTRA might be a potential agent to improve blood flow in the nerve roots of patients with lumbar disc herniation.     

Buspirone--frontrunner of a new genre of anxiolytics

Buspirone (Buspar; Bristol) marks a departure from established concepts of anxiolysis. Differing substantially both in its mode of action and in the clinical expression of its action from agents such as barbiturates and benzodiazepines, it would seem to operate chiefly via the 5-HT1A subtype of serotonin receptor. Such receptor selectivity is likely to be responsible for the novel action of this anxiolytic in that sedation and psychomotor and cognitive dysfunction are minimal, and because dependence is unlikely. The slower onset of full therapeutic benefit further delineates the differences between buspirone and other anxiolytics. However, it is apparent that the benzodiazepines will not readily be displaced from all of their varied applications by buspirone. This review examines buspirone and provides some guidelines for its use.     

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.     

The drug treatment of anxiety and panic disorder

The mainstay of drug treatment of non-psychotic anxiety is the benzodiazepine group of drugs, but major side-effects are sedation and dose-related psychomotor, cognitive and memory impairments. However, tolerance to sedation-related side-effects usually develops, although not to the anxiolytic effects. Buspirone, an azaspiro-decanedione, is the first FDA-approved non-benzodiazepine anxiolytic. Anxiolytic efficacy similar to the benzodiazepines has been established, although the onset of effect is more gradual. Infrequent side-effects are dizziness, nausea, headaches, nervousness and lightheadedness; but it would not appear to cause sedation, memory effects or physical dependence. In a double-blind prospective study to compare buspirone to clorazepate, withdrawal effects occurred with the latter but not with the former. In formulating treatment strategies for anxiety and panic disorders, consideration should be given to the duration of symptoms and likely duration of therapy, and anxiolytics should be titrated to the lowest possible dose consistent with maximal relief of anxiety and the least adverse effects.     

Anxiolytic and anxiogenic drugs: Changes in behaviour and endocrine responses

In order to examine the link between changes in behaviour in animal tests of anxiety and the corticosterone stress response, this article: (1) reviews the changes in plasma corticosterone conentrations when rats are exposed to animal tests of anxiety; (2) describes the effect in animal tests of anxiety of administering CRF, ACTH and corticosterone; (3) describes the effects of the benzodiazepines and other anxiolytic drugs on plasma corticosterone concentrations of stressed and unstressed animals; (4) describes the effects on stressed and unstressed corticosterone concentrations of administering anxiogenic drugs. It is concluded that an antistress effect is not a necessary consequence of an anxiolytic drug action and that a prostress effect may not necessarily predict an anxiogenic drug action.     

5-HT3 receptor antagonists do not alter spontaneous contraction of pregnant myometrium in vitro

Background5-HT3 receptor antagonists are effective antiemetics for perioperative use. However, their effects on myometrial contractility remain unknown. We examined whether three different 5-HT3 receptor antagonists could affect the contraction of human myometrium.MethodsSamples of human myometrium were taken from parturients undergoing elective cesarean delivery. Effects of ondansetron, granisetron and tropisetron (over a range of 1–10⁴ ng/mL) on spontaneous contraction (ratios of amplitude, interval, and duration of the contraction) were examined and compared to saline controls (n=6 for each agent).ResultsNone of the three 5-HT3 receptor antagonists significantly affected myometrial contraction.Conclusion5-HT3 receptor antagonists do not affect the contraction of myometrial strips isolated from term pregnant women.     

Gastric disorders: modifications of gastric content,antacids and drugs influencing gastric secretions and motility

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid-suppressing therapy is widespread in critical care. The aim is to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus, include opioid analgesics, catecholamines and α₂-adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin either alone or in combination. Limited efficacy has been demonstrated with these medications. A range of further medications, with different drug targets, are being investigated as alternatives. These include motilin agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5-HT₄ antagonists and cholinesterase inhibitors.     

Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft

For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT_2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT_1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT_2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency.     

Effekte von Serotonin2Rezeptoragonisten auf Skelettmuskelpräparate von Patienten mit Disposition zu maligner Hyperthermie

In pigs genetically susceptible to malignant hyperthermia (MH), it has been shown that serotonin (5-HT₂) receptor agonists can induce MH and “psychotic” behaviour. Both can be prevented by 5-HT₂ receptor antagonists. Furthermore, free levels of serotonin in plasma increased concomitantly with clinical and laboratory parameters during halothane-induced MH in pigs. In this study the in vitro-effects of the 5-HT₂ receptor agonist1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were investigated in muscle specimens of MH-susceptible (MHS) and normal (MHN) patients. Methods. Muscle biopsies were obtained from 37?patients aged 5–69?years (23.6±5.3?years) with clinical suspicion for MH. The patients were first classified as MHS, MHN or MHE (MH equivocal) by the in vitro contracture test (IVCT) according to the European MH protocol. After MH classification, surplus muscle specimens were subjected to the DOI study. DOI was added to the organ bath in a concentration of 0.02?mmol/l. The in vitro effects on contracture development and muscle twitch were observed for 120?min. Results. Muscle specimens of all patients developed contractures after administration of DOI. However, DOI produced an earlier development of contracture in MHS (17.0±1.8?min; n=17) than in MHN (64.7±5.9?min; n=15) muscles. In MHS muscles, contractures were more distinct than in MHN muscles; at the end of the experiment, contractures had reached a maximum of 12.5±0.9?mN in MHS and 5.1±0.7?mN in MHN muscles. Muscle twitch following DOI administration was reduced significantly in both MHS and MHN muscles. The results of four MHE muscles were comparable with MHS. Conclusion. The present study supports the assumption that an altered serotonin system might be involved in the development of MH. In further studies it should investigated whether 5-HT₂ receptors of skeletal muscles from MHS subjects are disordered in function or structure. 5-HT₂ receptor agonists should be considered as MH-triggering agents.     

Blockade of 5-HT(2A) and/or 5-HT(2C) receptors modulates sevoflurane-induced immobility

Purpose  

Blockade of 5-hydroxytryptamine (5-HT)_2A receptors reportedly mediates or modulates the ability of isoflurane to produce immobility during noxious stimulation and would thereby influence MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimulation in 50% of subjects). However, no data are yet available regarding the role of this receptor in the immobilizing action of sevoflurane. In this study, we examined how prior intraperitoneal administration of either the 5-HT_2A receptor antagonist altanserin or the 5-HT_2C/2B receptor antagonist SB 206553 might affect sevoflurane MAC in rats.     

Current therapy for management of postoperative nausea and vomiting: the 5-HT3 receptor antagonists

The control of postoperative nausea and vomiting (PONV) remains a problem in spite of the improvements achieved with newer anesthetic agents, such as propofol, and newer antiemetics. Management of PONV is difficult, this is most likely due to the multiple receptors and neurotransmitters in the central nervous system that mediate the emetic response, and to the multifactorial etiology of PONV. Studies of the four major 5-hydroxytryptamine (serotonin) subtype-3 (5-HT₃) receptor antagonists suggest that they have similar safety and efficacy for prevention and treatment of PONV. These drugs lack the significant side effects observed with traditional antiemetics. Combination regimens of 5-HT₃ receptor antagonists and traditional antiemetics can improve antiemetic efficacy. Areas of future study include comparing the cost effectiveness of these agents and determining optimal combinations of antiemetics to further reduce the incidence of PONV.     

Modern treatment modalities in anxiety

Developments in the medical management of anxiety tend, over the last two decades, to have clustered around modifications to the early benzodiazepines. These developments have given the psychiatrist a wide range of options in terms of intensity and duration of action but have carried with them the range of penalties associated with the benzodiazepines as a group. These include among others addiction potential and a sometimes inappropriate level of sedation. The need has been for a new drug, unrelated to the benzodiazepines and which is more specifically orientated towards anxiety. Buspirone, it seems, may well be such a drug. This paper discusses the anxiety disorders, the drug management of anxiety, the problems associated with traditional anxiolytics and the recent availability of a new class of drug in this indication.     

Antinociceptive role of 5-HT1A receptors in rat spinal cord

Background. Intrathecal administration of 5-hydroxytryptamine(5-HT) is antinociceptive to noxious heat and electrical stimuli.The contributions of different receptor subtypes to the antinociceptiveeffects of 5-HT are controversial. The main reasons for thisare the poor receptor subtype selectivity of some agonist drugsand the difficulty of restricting drug action to the spinalcord in some experimental paradigms. This study investigatedthe roles of different 5-HT receptor subtypes involved in thespinal cord control of the nociception produced by these twonociceptive testing paradigms. Methods. Tail-flick latency and electric current threshold fornociception were measured in an acute pain model that allowedthe study of the antinociceptive effects of intrathecally administereddrugs that were due to actions of these drugs at spinal cordreceptors. Experiments were performed in male Wistar rats withchronically implanted lumbar subarachnoid catheters. Dose–responsecurves for spinally mediated antinociceptive effects of agonistsselective for 5-HT receptor subtypes were constructed. Results. The 5-HT₁ agonist 1-(3-chlorophenyl)-piperazine dihydrochloridecaused a dose-dependent antinociceptive effect, measured byboth nociceptive tests. However, 8-hydroxy-DPAT (selective 5-HT_1Aagonist) produced antinociception assessed by electric currentbut not tail flick. A 5-HT_1A-selective antagonist, 4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)-piperazine,reversed the antinociception in the electrical test producedby both of these agonists but the tail-flick latency effectsafter intrathecal 1-(3-chlorophenyl)-piperazine were not suppressedby this antagonist. Conclusions. We conclude that 5-HT_1A receptors in the spinalcord are involved in the nociceptive mechanisms assessed bynoxious electrical stimuli. Other 5-HT₁ receptors (non 5-HT_1Areceptors) are involved in the spinally mediated antinociceptionassessed by thermal noxious stimuli. Br J Anaesth 2002; 88: 679–84     

Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle

The aim of this study is to evaluate the potency of piboserod (SB 207266), a selective 5-HT₄ receptor antagonist, at inhibiting the 5-HT₄-mediated potentiating effect of serotonin (5-HT) on the neurally-mediated contractile responses of human detrusor strips to electrical field stimulations (EFS). Strips of human detrusor muscle were mounted in Krebs-HEPES buffer under a resting tension of 500 mg and EFS (20 Hz, 1 ms duration at 300 mA for 5 s) was applied continuously at 1 min intervals. After stabilization of the EFS-induced contractions, concentration-response curves to 5-HT (0.1 nM–100 M) were constructed in the absence or presence of 1 or 100 nM of piboserod. The experiments were performed in the presence of methysergide (1 M) and ondansetron (3 M) to block 5HT₁/5HT₂ and 5-HT₃ receptors, respectively. 5-HT potentiated the contractile responses to EFS of human bladder strips in a concentration-dependent manner, with a maximum mean of 60.0±19.9% of the basal EFS-evoked contractions. Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0±7.9 and 38.7±8.7%, respectively. A mean apparent antagonist dissociation constant value (K_B) of 0.56±0.09 nM was determined. These data show the ability of piboserod to antagonize with high potency the enhancing properties of 5-HT on neurally-mediated contractions of isolated human bladder strips. Therefore, the 5-HT₄ receptor might represent an attractive pharmacological target for the treatment of overactive bladder.     

Postoperative neuroleptic malignant syndrome-like symptoms improved with intravenous diazepam: a case report

A 75-year-old man who had undergone left upper lobectomy of the lung exhibited fever and insomnia on postoperative day (POD) 1 and muscle rigidity, autonomic instability, and somnolence on POD2 after epidural administration of droperidol and withdrawal of oral etizolam. He had not been known to have any neuromuscular diseases or psychiatric diseases, with the exception of anxiety disorder. Brain computed tomography did not show cerebrovascular disorders. Consultation with a neurologist led to a suspicion of neuroleptic malignant syndrome (NMS). Epidural droperidol was stopped and administration of dantrolene was initiated. These measures, in addition to supportive care, only partially ameliorated the symptoms of the patient, and consciousness disturbance developed; the patient finally became comatose on POD3. However, intravenous diazepam (10 mg) improved his symptoms abruptly. Subsequently, oral administration of lorazepam (1 mg/day) was started, and his symptoms disappeared within 2 days (POD5). Although NMS-like symptoms are rarely seen in clinical practice, some factors may induce it during the perioperative period, such as the administration of dopamine antagonists and the cessation of benzodiazepines. Intravenous diazepam is an effective treatment in cases with suspected gamma-aminobutyric acid (GABA) hypoactivity at the GABA_A receptor induced by the cessation of benzodiazepines.     

Pharmacological and nonpharmacological prevention of fentanyl-induced cough: a meta-analysis

Fentanyl-induced cough (FIC) is often observed after intravenous bolus administration of fentanyl during anesthesia induction. This meta-analysis assessed the efficacy of pharmacological and nonpharmacological interventions to reduce the incidence of FIC. We searched for randomized controlled trials comparing pharmacological or nonpharmacological interventions with controls to prevent FIC; we included 28 studies retrieved from PubMed, Embase, and Cochrane Library. Overall incidence of FIC was approximately 31 %. Lidocaine [odds ratio (OR)  = 0.29, 95 % confidence interval (CI) 0.21–0.39], N-methyl-D-aspartate (NMDA) receptor antagonists (OR 0.09, 95 % CI 0.02–0.42), propofol (OR 0.07, 95 % CI 0.01–0.36), α₂ agonists (OR 0.32, 95 % CI 0.21–0.48), β₂ agonists (OR 0.10, 95 % CI 0.03–0.30), fentanyl priming (OR 0.33, 95 % CI 0.19–0.56), and slow injection of fentanyl (OR 0.25, 95 % CI 0.11–0.58)] were effective in decreasing the incidence of FIC, whereas atropine (OR 1.10, 95 % CI 0.58–2.11) and benzodiazepines (OR 2.04, 95 % CI 1.33–3.13) were not effective. This meta-analysis found that lidocaine, NMDA receptor antagonists, propofol, α₂ agonists, β₂ agonists, and priming dose of fentanyl were effective in preventing FIC, but atropine and benzodiazepines were not. Slow injection of fentanyl was effective in preventing FIC, but results depend on the speed of administration.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist, and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist and nabilone, a synthetic cannabinoid.