The renin-angiotensin system plays a major role in voiding dysfunction of ovariectomized rats.
Multiple drug use is common among old, frail nursing home residents who are, as a consequence, susceptible to adverse effects and drug interactions. This study uses the updated Beers criteria for potentially inappropriate drug (PID) use in older adults to determine the extent and nature of PIDs in older nursing home residents in Helsinki, Finland. The study also uses the Swedish, Finnish, INteraction X-referencing (SFINX) interaction database to assess the possibility of clinically significant class D ("clinically significant interaction, and the combination should be avoided") drug-drug interactions (DDIs) in the same population.
Known agonists of the orphan receptor GPR35 are kynurenic acid, zaprinast, 5-nitro-2-(3-phenylproplyamino) benzoic acid, and lysophosphatidic acids. Their relatively low affinities for GPR35 and prominent off-target effects at other pathways, however, diminish their utility for understanding GPR35 signaling and for identifying potential therapeutic uses of GPR35. In a screen of the Prestwick Library of drugs and drug-like compounds, we have found that pamoic acid is a potent GPR35 agonist. Pamoic acid is considered by the Food and Drug Administration as an inactive compound that enables long-acting formulations of numerous drugs, such as the antihelminthics oxantel pamoate and pyrantel pamoate; the psychoactive compounds hydroxyzine pamoate (Vistaril) and imipramine pamoate (Tofranil-PM); and the peptide hormones triptorelin pamoate (Trelstar) and octreotide pamoate (OncoLar). We have found that pamoic acid induces a G(i/o)-linked, GPR35-mediated increase in the phosphorylation of extracellular signal-regulated kinase 1/2, recruitment of β-arrestin2 to GPR35, and internalization of GPR35. In mice, it attenuates visceral pain perception, indicating an antinociceptive effect, possibly through GPR35 receptors. We have also identified in collaboration with the Sanford-Burnham Institute Molecular Libraries Probe Production Center new classes of GPR35 antagonist compounds, including the nanomolar potency antagonist methyl-5-[(tert-butylcarbamothioylhydrazinylidene)methyl]-1-(2,4-difluorophenyl)pyrazole-4-carboxylate (CID2745687). Pamoic acid and potent antagonists such as CID2745687 present novel opportunities for expanding the chemical space of GPR35, elucidating GPR35 pharmacology, and stimulating GPR35-associated drug development. Our results indicate that the unexpected biological functions of pamoic acid may yield potential new uses for a common drug constituent.
Cetirizine concentrations in the skin could be monitored by the microdialysis technique. The results indicate no simple linear correlation between cetirizine skin levels and inhibition of skin reactions.
Since 2012, Matsudo City Hospital has increased the number of pharmacists stationed in the ward on weekday mornings at the emergency care center, the intensive care unit (ICU) and the high care unit (HCU). Multidisciplinary joint meetings and joint conferences are conducted in the emergency care center, and patient and drug information is shared. A 20-year-old man was transferred to our hospital after a traffic accident. He was diagnosed with subarachnoid hemorrhage and brain contusion. He exhibited violent movement and intense restlessness. He was sedated with a continuous intravenous infusion of 5 mg/h midazolam and 20 μg/h fentanyl, with intubation. Propofol was also used intermittently. The midazolam infusion was concluded on day 5 of hospitalization. However, his restlessness recurred so an intravenous drip infusion of 150 mg/h haloperidol was administered. On the 7th day, he developed a high-grade fever, muscle rigidity, perspiration, and leukocytosis, and malignant syndrome or malignant hyperthermia was suspected. For malignant syndrome treatment, he received an intravenous drip infusion of 60 mg dantrolene, followed by the combined oral administration of 100 mg/d dantrolene and 7.5 mg/d bromocriptine. Considering various pharmacological effects, we selected an intravenous drip infusion of 25 mg hydroxyzine hydrochloride as the drug to alleviate restlessness. The patient's course continued without recurrence of malignant syndrome; his symptoms improved because of pharmaceutical care with an awareness of patient benefits through clinical and laboratory findings, consultation with the attending physician, presentation of information on causative and therapeutic drugs, and coordinated planning of a prescription design.
This study was intended to confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU using an identical protocol design (randomized, double-blind, parallel-group comparison having the same symptom scoring system, endpoints, and statistical analyses), thus demonstrating reproducibility of studies conducted in the EEU.
An increased dose of the prescribed drug or a change of the drug is recommended in the treatment for the patients with urticaria refractory to the standard dose of antihistamines. Efficacy and safety of doubling the dose of cetirizine were compared with olopatadine in the patients with symptoms like wheal or itching, despite the treatment with the standard dose of cetirizine.