H2 Antagonists Research Articles

Association of use of proton pump inhibitors and H2 antagonists with stomach wall uptake in 99mTc-methoxy-isobutyl-isonitrile (MIBI) myocardial perfusion imaging

BackgroundStomach wall uptake (SWU) of tracer in 99mTc-MIBI myocardial perfusion imaging (MPI) occasionally leads to imaging artifacts, thereby lowering the diagnostic accuracy. It is less-studied phenomenon for possible link with proton pump inhibitors (PPIs) intake. This prospective work looked for association of SWU with PPI intake and compared its incidence with H2 antagonists (H2A) users and patients not on either gastroprotective medication. MethodsOne hundred fifty-six patients undergoing one day stress/rest 99mTc-MIBI SPECT-MPI were distributed into four groups: control group (n = 48, not on any gastroprotective medication), PPI group (n = 47, on PPI treatment), H2A group (n = 19, on H2A therapy), and intervention group (N = 42, PPI discontinued for 3 days before MPI). Poststress planar images were analyzed for clinically relevant SWU. ResultsClinically relevant SWU was seen in 36% of PPI group patients compared to 8% in the control group, 10.5% in the H2A group, and 9.5% in the intervention group, respectively, with statistically significant difference. Only 1/40 patients undergoing exercise stress showed clinically relevant SWU compared to 26/116 patients undergoing adenosine stress (P = .020). ConclusionPatients on PPIs scheduled for vasodilator stress MPI may discontinue PPIs for 3 days, or replace with H2A to reduce the incidence of clinically relevant SWU associated with PPI therapy.

Design and Synthesis of Novel Anti-inflammatory/Anti-ulcer Hybrid Molecules with Antioxidant Activity.

NSAIDs are the most widely prescribed medications worldwide for their anti-inflammatory, antipyretic, and analgesic effects. However, their chronic use can lead to several adverse drug events including GI toxicity. The selective COX-2 inhibitors developed as gastrosparing NSAIDs also suffer from serious adverse effects which limit their efficacy. Local generation of reactive oxygen species is implicated in NSAID-mediated gastric ulceration and their combination with H2 antagonists like famotidine reduces the risk of ulcers. The objective of this work was to design and synthesize novel methanesulphonamido isoxazole derivatives by hybridizing the structural features of NSAIDs with those of antiulcer drugs (ranitidine, famotidine, etc.) to utilize a dual combination of anti-inflammatory activity and reducing (antioxidant) potential. The designing process utilized three dimensional similarity studies and utilized an isoxazole core having a potential for anti-inflammatory as well as radical scavenging antioxidant activity. The compounds were assayed for their anti-inflammatory activity in established in vivo models. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Compounds 5, 6, 9 and 10 showed antiinflammatory activity comparable to the standard drugs and were also found to be non-ulcerogenic at the test doses. Compounds 6-10 exhibited good antioxidant effect in the concentration range of 1.0- 50.0 μmol/ml. The test compounds were also found to comply with the Lipinski rule suggesting good oral absorption. A new series of isoxazole based compounds is being reported with good antiinflammatory activity coupled with antioxidant potential as gastro-sparing anti-inflammatory agents.

A case report of sleep terrors exacerbated by cetirizine

Sleep terrors are a type of sleep disorder that is classified as parasomnias and is more common in children than in adults. Cetirizine is a histamine H1 antagonist that is US Food and Drug Administration approved for the treatment of allergic rhinitis and urticaria and has common adverse effects of drowsiness and headaches. We present a case of an adult man with a history of chronic sleep terror disorder and allergic rhinitis who developed worsening of his sleep terrors after initiation of cetirizine that subsequently resolved after discontinuing cetirizine and starting paroxetine.

Cutaneous manifestations due to histamine H1 antagonist

Cutaneous manifestations due to histamine H1 antagonist

Infant acid suppression use is associated with the development of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an esophageal allergic inflammatory disorder often presenting with infant/toddler gastroesophageal reflux symptoms refractory to treatment, including acid suppression trials with histamine H2 antagonists and proton pump inhibitors. We propose to evaluate the impact of infant acid suppressant exposure in EoE. Geisinger's pediatric EoE cases were matched to controls (1:5 EoE case control ratio) using age, race, sex, and ages at other diagnoses of asthma, eczema, and environmental allergies, totaling 526 EoE cases and 2,630 controls. Comparisons between EoE cases and matched controls were tested with regard to rates of acid suppression use with H2 antagonists and PPIs during infancy. Our analyses found the use of acid suppression in infancy was positively associated with EoE: PPI (5.7% EoE cases vs. 1.6% controls; P < 0.0001), H2 antagonists (8.8% EoE cases vs. 4.5% controls; P < 0.0001). Additionally, analysis of EoE cases using acid suppression during infancy indicated a likelihood for the diagnosis with EoE at an earlier age. Early acid suppression use in infants is significantly associated with the diagnosis of EoE in childhood in this well-matched retrospective cohort study. The potential link warrants additional investigation. Our study further reinforces the evidence-based stewardship of acid suppressant use, especially in our most vulnerable populations.

Envenomations by coral snakes in an Amazonian metropolis: Ecological, epidemiological and clinical aspects

Envenomation by coral snakes represents a little known burden in Brazilian Amazonia. So far, details on clinical and epidemiological aspects remain obscure in the region. We gathered data from medical charts and from the scientific collection of snakes from Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, finding 26 cases of envenomation by five species of Micrurus in Manaus region, between 1987 and 2018. They represent 0.7% of the snakebites treated in the hospital since the records began, in 1979. Micrurus lemniscatus was responsible for most of the bites (10), followed by M. hemprichii (five), M. spixii (three), M. surinamensis (three) and M. averyi (one). There was no difference between the sexes of the snakes that caused bites. Patients were mostly males, and most of the cases were reported in urban areas. Bites predominated in dry season, and there was a clear geographical segregation among species. We describe seven cases of envenomation, three mild and four severe, all of which evolved to cure. Paresthesia (six), pain (five) and edema (four) were the most common local symptoms. Systemic features such as dyspnea/shallow breath (four), palpebral ptosis (four), blurred vision (three), dysarthria (three) and difficulty to walk (three) were also detected. Two patients bitten by Micrurus sp. and M. hemprichii, showed slight increased serum levels of creatine kinase (reference level <190 U/L), 1184 U/L and 1229 U/L, respectively, indicative of mild systemic myotoxicity. This is the first report of myotoxic manifestation in the envenomation by M. hemprichii. No patient developed respiratory failure, though one bitten by an adult M. spixii required intubation and mechanical ventilation due to decreased level of consciousness during evolution, probably related to induced sedation caused by concurrent alcohol intoxication. All patients were treated with Brazilian Micrurus antivenom (soro antielapídico, median = 10 vials). Six patients were pretreated intravenously with H1 and H2 antagonists and steroids, with two patients developing early adverse reactions. The median length of hospital stay was four days. Envenomations by coral snakes in Manaus region are clinically severe, but rare and sparsely distributed over time, making the detection of epidemiological and clinical patterns a challenge for public health.

An Herbal H2 Blocker in Melasma Treatment.

Melasma is a skin pigmentation disorder that remains resistant to available therapies. The exact cause of melasma is unknown. Histamine is an inflammatory factor. Its involvement in pigmentation is obscure. The aim of this study is to introduce an herbal antihistamine H2 receptor which is effective in these disorders. This is a review study by searching the electronic databases and also Persian Medicine books, from 2000 to 2018 by the keywords such as H2 antagonist, H2 blocker and melasma. According to the researched studies, histamine can induce melanogenesis and melasma after a series of stages in the body. Also, Histamine, through receptors 2, triggers melasma. Therefore, it can be said that antihistamine H2 receptor can be effective in melasma. Considering chemical antihistamine, H2 receptors have side effects, such as digestive problems, H2 antagonists can be used in the treatment of diseases such as dyspepsia but they have multiple complications. On the other hand, there is an herbal H2 antagonist that can be useful for melasma due to having some special properties. Herbal H2 blockers should be noted in melasma treatment along with the topical drugs.

Synthesis and Screening of Some Novel Thieno[2,3-d][1,2,3] triazine Derivatives as Non-sedative H1 Antihistaminics

Histamine receptor H1 antagonists are widely used as antihistamines for allergy conditions. The brain-penetrating antihistamines can cause sedation and some with poor-penetration do not cause sedation potential. In the present study, a new series of thieno[2,3-d][1,2,3]triazine derivatives 7a-e have been synthesized and screened for their H1 antihistaminic activity and sedation potential. Among all the screened compounds, compound 7b, 7c and 7d, show high H1 antihistaminic activity with IC50 value of 0.1 - 0.8 µM, which are comparable with that of the standard drug cetirizine. The sedative potential of the compounds was tested on albino mice using the photoactometer method. All the three compounds show less sedation potential than that of the standard drug diphenhydramine. In conclusion, the novel compounds appear with promising potential as non-sedating antihistamine agents. &#x0D;

Azelastine a potent antihistamine agent, as hypolipidemic and modulator for aortic calcification in diabetic hyperlipidemic rats model

Aim Our study aimed to illustrate the effect of the antihistaminic drug azelastine on aortic calcification in diabetic hyperlipidemic (DH) rats along with the underlying molecular mechanism. Methods Twenty-four male albino Wistar rats were categorised into four groups. One group received normal rodent chow (normal group), while the other groups were rendered diabetic and hyperlipidemic; one received no drugs and served as a positive control while the other two groups received either azelastine (4 mg/kg) or 10-dehydrogingerdione (10 mg/kg) orally and daily for 8 weeks. Results Azelastine significantly reduced blood glucose, HbA1c and serum ALP, OCN, downregulated apo B, improved the lipid profile (LDL-c decrease and HDL-c increase), attenuated calcium deposition and aortic calcification as compared to control group. 10-DHGD showed comparatively lower effect. Conclusion Anti-calcifying effect of azelastine might be related to upregulation of apo A (HDL-c) and downregulation of apo B mRNA expression indeed good modulator of aortic calcification. Impact Statement Many studies have indicated that high-density lipoprotein-cholesterol (HDL-c) is inversely correlated with atherosclerotic plaque progression and could reduce cardiovascular disease risk. An anti-calcifying effect of HDL-c has been reported and targeting this lipoprotein may therefore be a valuable approach to vascular calcification control. Azelastine is a selective H1 antagonist that was identified to increase mRNA expression of apolipoprotein A. This encouraged us to investigate the effect of azelastine on lipid profile and markers of aortic calcification in DH rats. Our findings showed that azelastine ameliorated aortic calcification and increased apoA expression along with a decline in apo B. This may represent the underlying mechanism while the histopathological findings offered a significant support to the collected biochemical data.

QSAR and Molecular Docking Studies on Non-Imidazole-Based Histamine H3 Receptor Antagonists

Background: In the recent years, histamine H3 receptor (H3R) has been receiving increasing attention in pharmacotherapy of neurological disorders. The aim of the current study was to investigate structural requirements for the prediction of H3 antagonistic activity using quantitative structure-activity relationship (QSAR) and molecular docking techniques. Methods: To this end, genetic algorithm coupled partial least square and stepwise multiple linear regression methods were employed for developing a QSAR model. The obtained QSAR model was stringently assessed using different validation criteria. Results: The generated model indicated that connectivity information and mean absolute charge are two important descriptors for the prediction of H3 antagonistic activity of the studied compounds. To gain insight into the mechanism of interaction between studied molecules and H3R, molecular docking was performed. The most important residues involved in the ligand-receptor interactions were identified. Conclusion: The result of current study can be used for designing of new H3 antagonist and proposing structural modifications to improve H3 inhibitory potency.

Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis.

Fragility hip fractures and their associated morbidity and mortality pose a global healthcare problem. Several pharmaceutical products have been postulated to alter bone architecture and contribute to fragility hip fractures. We searched four electronic databases from inception to September 2017. Inclusion criteria were the following: (1) adult patients with fragility hip fractures, (2) full text in English, (3) minimum one-year follow-up, and (4) reporting of at least one risk factor. To minimize heterogeneity among the studies, we performed subgroup analyses. Whenever heterogeneity remained significant, we employed random effect meta-analysis for data pooling. Thirty-eight studies were included, containing 1,244,155 subjects and 188,966 cases of fragility hip fractures. Following medications were significantly associated with fragility hip fractures: Antidepressants (OR 2.07, 95% CI 1.98-2.17), antiparkinsonian drugs (OR 2.21, 95% CI 1.15-4.24), antipsychotic drugs (OR 2.0, 95% CI 1.50-2.66), anxiolytic drugs (OR 1.44, 95% CI 1.19-1.75), benzodiazepines (OR 1.84, 95% CI 1.26-2.69), sedatives (OR 1.33, 95% CI 1.14-1.54), systemic corticosteroids (OR 1.65, 95% CI 1.37-1.99), H2 antagonists (OR 1.21, 95% CI 1.18-1.24), proton pump inhibitors (OR 1.41, 95% CI 1.16-1.71), and thyroid hormone (OR 1.29, 95% CI 1.13-1.47). Hormone replacement therapy with estrogen (HRT) was associated with decreased risk of hip fracture (OR 0.80, 95% CI 0.65-0.98). There are several medications associated with sustaining a fragility hip fracture. Medical interventions should be considered for patients on these medications, including information about osteoporosis and fracture prevention.

CLINICAL CHARACTERISTIC OF ADULT PATIENTS WITH DENGUE HEMORRHAGIC FEVER AT PROF. DR. SULIANTI SAROSO SUNTER INFECTIOUS HOSPITAL 2018

Background: Dengue is a viral disease transmitted by mosquito to humans and becomes a problem for the health of Indonesian people. Dengue Hemorrhagic Fever occurs due to several epidemiological factors. The purpose of this study is to determine the clinical characteristics of adult patients with Dengue Hemorrhagic Fever at Prof. dr. Sulianti Saroso Sunter Infectious Hospital 2018. Method: This Study was an observational descriptive study by taking medical record samples in 49 adult patients Dengue Hemorrhagic Fever in 2018. Results: From the 49 cases of Dengue Haemorrhagic Fever, the highest fender category was male (65,3%), occurred in the 18-25 year age category (38,8%), and the average patient worked as a Private Employee (55,1%). Most patients were hospitalized for the less than 7 days (83,7%). Clinical manifestations were fever (95,9%), nausea (85,7%) and headache (71,4%). Physical examination found was fever (100%) and hepatomegaly (12,2%). Laboratory tests showed normal hematocrit values (71,4%), thrombocytopenia values (87,8%), normal leukocyte values (49%), positive IgG serology tests (83,7%), IgM serology tests (71,4%), Positive IgM and IgG Serology test (69,3%), and NS1 Serology test (2%). Management provided is the administration of intravenous infus fluid drops (100%), PPI (87,8%), H2 Antagonist (4,1%), and Antipiretik (83,7%). The outcome patient is recovered and no complications were found. Conclusion: Dengue Hemorrhagic fever occurs in the age range of 18-25 years with dominant clinical characteristic of fever and thrombocytopenia. And, the most given treatment is Intravena Fluid therapy.

Vasomotor effects of 5-hydroxytryptamine, histamine, angiotensin II, acetylcholine, noradrenaline, and bradykinin on the cerebral artery of bottlenose dolphin (Tursiops truncatus).

From an evolutionary aspect, dolphins share a very close phylogenetic relationship with pigs. Previously, we characterized porcine cerebral artery responsiveness to intrinsic vasoactive substances. Therefore, here, we investigated dolphin (Tursiops truncatus) cerebral artery responsiveness to 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, acetylcholine (ACh), noradrenaline (NA), and bradykinin (BK) to characterize their related receptor subtypes. We also compared dolphin cerebral artery responsiveness with porcine cerebral artery responsiveness. We found that 5-HT and His induced concentration-dependent contraction of the dolphin cerebral artery. Ketanserin (a 5-HT2 antagonist) and methiothepin (a 5-HT1 and 5-HT2 antagonist) shifted the concentration-response curve for 5-HT to the right. Although diphenhydramine (an H1 antagonist) shifted the concentration-response curve for His to the right, cimetidine (an H2 antagonist) had no such effect. Ang II and ACh did not produce any vasomotor actions. NA induced concentration-dependent relaxation. Propranolol (a β antagonist) shifted the concentration-response curve for NA to the right, whereas phentolamine (an α antagonist) had no significant effect. BK induced relaxation followed by contraction in pre-contracted arteries with intact endothelium. HOE140 (a B2 antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg9-[Leu8]-BK (a B1 antagonist) had no significant effect. These results suggest that 5-HT1, 5-HT2, and H1 receptor subtypes are important in arterial contraction and that β and B2 receptor subtypes modify these contractions to relaxations. The responsiveness of the dolphin cerebral artery is very similar to that of porcine cerebral artery, supporting their evolutionary linkage.

Cinnamaldehyde elicits itch behavior via TRPV1 and TRPV4 but not TRPA1.

Introduction:Cinnamaldehyde (CA) elicits itch sensation in humans. We investigated if CA elicits scratching behavior in mice and determined the roles for TRPV1, TRPA1, and TRPV4.Materials and Methods:Scratching behavior elicited by intradermal injection of CA was assessed in wildtype (WT) mice and knockout (KO) mice lacking TRPV1, TRPA1, TRPV4, or deficient in mast cells. We also assessed scratching and wet dog shakes elicited by low-threshold mechanical stimulation of skin treated topically with CA or vehicle. Using calcium imaging we tested if CA activates dorsal root ganglion (DRG) neurons of each genotype.Results:Intradermal cheek injection of CA elicited dose-dependent hindlimb scratch bouts, with fewer forelimb wipes and facial groom bouts that were not dose-dependent. CA elicited significantly fewer scratch bouts in TRPV1 and TRPV4 KO mice, but not TRPA1KOs, compared with WTs. There were no sex differences across genotypes. The histamine H1 antagonist cetirizine did not affect CA-evoked scratching, which was normal in mast cell deficient mice, indicating lack of histamine involvement. Scores for alloknesis were significantly greater following topical application of CA compared with vehicle. Post-CA alloknesis scores were significantly higher in TRPV4KOs of both sexes and in female TRPV1 and TRPA1KOs, compared with WTs. Low threshold mechanical stimuli also elicited significantly more wet dog shakes in mice treated topically with 20% CA, with significantly fewer in TRPV1, TRPA1, and TRPV4KOs compared with WTs. In calcium imaging studies, CA excited 24% of WT DRG cells, significantly fewer (11.5%) in cells from TRPV4KOs, and none in TRPA1KOs. Responses of cells of all genotypes exhibited significant sensitization to repeated CA stimulation. Sensitization was significantly enhanced by IL-4, which itself excited 16% of WT DRG cells and none from TRPA1KOs.Discussion:The results indicate that TRPA1 is dispensable for CA-evoked scratching, which depends partly on TRPV1 and TRPV4.

Evaluation of target attainment of oral posaconazole suspension in immunocompromised children.

Posaconazole is a broad-spectrum antifungal that is not licensed for use in children <13 years of age. Despite this and by necessity, it is used extensively in paediatric hospitals for prophylaxis of invasive fungal disease. To determine whether initial prophylactic dosing recommendations attain a posaconazole plasma concentration of ≥700 ng/mL in immunocompromised children <13 years of age. We performed a retrospective study of immunocompromised children <13 years of age receiving posaconazole suspension prophylaxis at a starting dose of 5 mg/kg every 8 h for ≥7 days and who had a posaconazole concentration measured after ≥7 days. Posaconazole plasma concentrations and rate of breakthrough infection were recorded. A total of 70 patients were included with a median age of 5 years (range 3 months to 12 years). The mean posaconazole plasma concentration was 783.4 ng/mL (IQR 428.3-980 ng/mL) and the percentage of patients with a posaconazole plasma concentration ≥700ng/mL was 47.9%. Patients who were on a proton pump inhibitor, a histamine H2 antagonist or metoclopramide, had mucositis or were enterally fed had a lower posaconazole plasma concentration compared with patients without these co-administered drugs/mucositis/enteral feeding (542.3 versus 1069.8 ng/mL; P<0.001). The breakthrough invasive fungal infection rate was 4.3% (3/70). The studied 5 mg/kg posaconazole suspension every 8 h resulted in target concentrations in only 47.9% of patients and further studies looking at newer posaconazole formulations are needed.

Histamine H4 receptor stimulation in the locus coeruleus attenuates neuropathic pain by promoting the coeruleospinal noradrenergic inhibitory pathway

The locus coeruleus (LC) adrenergic nuclei constitute a pain-control inhibitory system nucleus implicated in descending modulation of pain through the action on spinal α2-adrenoceptors. Histaminergic innervation from the tuberomammillary nucleus of the LC increases firing of noradrenergic neurons and might contribute to pain control. Here we evaluated the contribution of LC histaminergic innervation in descending modulation of neuropathic hypersensitivity, by investigating the role of the histamine H4 receptor subtype in a mouse model of neuropathic pain. Intra LC administration of the H4 agonist VUF 8430 attenuated mechanical and thermal allodynia of mice that underwent spared nerve injury (SNI). Similarly, histamine in the LC showed mechanical and thermal anti-hypersensitivity. Pretreatment of LC with JNJ 10191584 (H4 antagonist) prevented the beneficial effect of VUF 8430 and histamine on nociceptive behaviour. Comparable results were obtained after intrathecal administration of drugs. The intrathecal administration of the α2-adrenoceptor agonist clonidine ameliorated mechanical and thermal allodynia in SNI mice. The clonidine-induced anti-hypersensitivity effect was prevented by intra LC pretreatment with JNJ 10191584. In addition, clonidine failed to suppress neuropathic pain in H4 deficient mice. LC H4 receptors showed a ubiquitous distribution within LC, a neuronal localization and H4 immunostaining was detected on noradrenergic neurons expressing phosphorylated cAMP response element-binding protein (CREB), a marker of neuronal activation. Under pain pathological conditions H4 stimulation might promote the activation of the coeruleospinal noradrenergic neurons that exert an inhibitory control over spinal dorsal horn neuronal excitability. Thus, histamine H4 receptor stimulation may represent a perspective for neuropathic pain management.

Unexpected Ca2+-mobilization of oxaliplatin via H1 histamine receptors

Oxaliplatin is a widely used chemotherapeutic drug and represents the cornerstone of colorectal cancer therapy, in combination with 5-fluorouracil and folinic acid. As with many chemotherapeutic agents, its use is associated with a number of side effects, ranging from hypersensitivity reactions to haematological dyscrasias. Oxaliplatin also induces acute and chronic peripheral neuropathy.While it is likely that the haematological side effects are associated with its anti-proliferative effects and with the ability to form DNA adducts, the molecular mechanisms underlying peripheral neuropathy and hypersensitivity reactions are poorly understood, and therefore the choice of adequate supportive therapies is largely empirical.Here we show that an acute low dose oxaliplatin application on DRG neurons is able to induce an increase in intracellular calcium that is dependent on the Histamine 1 receptor (H1). Oxaliplatin-induced intracellular calcium rises are blocked by two selective H1 antagonist, as well as by U73122, a PLC inhibitor, and by 2-APB, a non-specific IP3 receptor blocker. Moreover, expression of the H1 receptor on HEK293 t cells unmasks an oxaliplatin-induced Ca2+-rise. Last, activation of H1 via either histamine or oxaliplatin activates TRPV1 receptors, a mechanism that has been associated with itch. These data, together with literature data that has shown that anti-histamine agents reduce the incidence of oxaliplatin-induced hypersensitivity, may provide a molecular mechanism of this side effect in oncological patients.

Blockade of multiple monoamines receptors reduce insulin secretion from pancreatic \u03b2-cells

Clinical use of olanzapine frequently causes severe hyperglycemia as an adverse effect. In this study, we elucidated mechanisms by which olanzapine reduced insulin secretion using the hamster pancreatic β-cell line HIT-T15. Reverse transcriptional-PCR analysis revealed expression of dopamine (D2, D3 and D4), serotonin (5-HT2A, 5-HT2B, 5-HT2C, and 5-HT6), and histamine (H1 and H2) receptors in HIT-T15 cells. Olanzapine decreased insulin secretion from HIT-T15 cells at clinically relevant concentrations (64–160 nM). A dopamine D2 agonist, D3 antagonist, and D4 antagonist suppressed insulin secretion, whereas a D2 antagonist and D3 agonist increased it. A serotonin 5-HT2B agonist slightly increased insulin secretion, while a 5-HT2C antagonist slightly decreased it. Other agonists and antagonists for serotonin receptors did not affect insulin secretion. A histamine H1 agonist increased insulin secretion, whereas an H1 antagonist and H2 agonist suppressed it. Our results suggest that dopamine (D2, D3 and D4), serotonin (5-HT2B and 5-HT2C), and histamine (H1 and H2) receptors, which are expressed on pancreatic β-cells, directly modulate insulin secretion from pancreatic β-cells. Thus, olanzapine may induce hyperglycemia in clinical settings by suppressing insulin secretion from pancreatic β-cells through inhibition of dopamine D3, serotonin 5-HT2B and 5-HT2C, and histamine H1 receptors.

PGI56 EVALUATION OF MORTALITY ASSOCIATED WITH PROTON PUMP INHIBITORS AND H2 BLOCKERS: A REAL WORLD EVIDENCE STUDY

The aim of this analysis was to estimate all-cause mortality among patients taking proton pump inhibitors (PPIs) and histamine H2 antagonists (H2 blockers). Patients identified through a federated network of electronic medical records were required to have taken PPIs or H2 blockers. Among these two cohorts, patients were required to have two records of these treatments recorded in their medical history at least three months apart. Patients treated with PPIs were matched 1-to-1 with patients treated with H2 blockers, using a greedy-nearest-neighbor algorithm. The risk of mortality was measured in the one year, five years, and ten years following the index treatment. All criteria were defined using ICD9/10, CPT, and RxNorm terminology. Kaplan-Meier curves and risk ratios (95% CI) were used to compare groups. The mean age was 54.4 ± 18.8 (N=1,455,638) and 46.6 ± 22.7 (N=496,538) among PPI- and H2 blocker-treated patients. In the matched analysis (N=448,446), H2 blocker patients were 0.089 (0.778,0.841), 0.8 (0.785,0.815), and 0.799 (0.786,0.812) more likely to die than PPI patients in the one year, five years, and ten years following treatment. The survival probability was 0.25%, 1.34%, and 2.35% higher in PPI-treated patients than in H2-treated patients in the one year, five years, and ten years following treatment (all with p<0.05). Taking H2 blockers is associated with a small increased risk of mortality. This burden is observed in patients with and without an indication for PPI or H2 blocker use. PPIs were not associated with an increased risk of death, in contrast to other studies. This difference may be due to a broader and less selective patient population, or use of different controls.

Histamine H2 antagonists for functional dyspepsia: A protocol for a systematic review and meta-analysis.

Functional dyspepsia (FD) is a prevalent gastrointestinal disorder. Histamine H2 antagonists (H2RAs) are the pharmacological treatment option for FD, but no potent evidence has been found for the efficacy of these drugs in the condition. Therefore, this systematic review protocol aims to examine the efficacy and safety of H2RAs in the treatment of FD. We will perform a systematic search in the following electronic databases: the Cochrane Central Register of Controlled Trials (to October 2019), MEDLINE (OvidSP; to October 2019), EMBASE (OvidSP; to October 2019). Only randomized clinical trials (RCTs) comparing any H2RA with placebo for the treatment of FD will be included. The primary outcome will be an improvement in global symptoms of dyspepsia. Study selection, data extraction, and study quality will be performed by 2 independent reviewers. Dichotomous data will be presented as a risk ratio (RR) with 95% confidence intervals (CI), and continuous data as mean difference (MD) or standardized MD (SMD) with 95% CI. RevMan v.5.3 software will be used for all statistical analyses. This study will provide a high-quality synthesis to examine the role of H2RAs in FD as reflected by the improvement of global symptoms of dyspepsia, quality of life scores, and adverse events. This systematic review will provide updated evidence to judge whether H2RAs are of benefit in FD.