Paroxetine Markedly Increases Plasma Concentrations of Ophthalmic Timolol; CYP2D6 Inhibitors May Increase the Risk of Cardiovascular Adverse Effects of 0.5% Timolol Eye Drops

Objective This study was aimed to determine mydriatic regimen(s) used in neonatal units in Aotearoa New Zealand (NZ) and Australia and to estimate the frequency of adverse drug events following mydriatic administration in preterm neonates. Study Design A cross-sectional survey was sent to neonatal nursing staff listed in the Australian and New Zealand Neonatal Network contact list. Participants were asked to state what mydriatic regimen they use, and to estimate the frequency of adverse drug events when eye drops were administered for retinopathy of prematurity eye examinations (ROPEE). Results Thirteen different mydriatic regimens were identified; phenylephrine 2.5% and cyclopentolate 0.5% (1 standard drop of each) was the most commonly used regimen. Two of the regimens exceeded adult doses and five regimens included a mydriatic that is equivalent to an adult dose. Following mydriatic instillation, the three most common adverse effects were apnea, tachycardia, and periorbital pallor. Conclusion Low-concentration single-microdrop regimens are currently in use and resulting in successful ROPEE, yet doses exceeding adult doses are in use throughout Aotearoa NZ and Australian units. We know from this dataset that neonates are experiencing unwanted and potentially preventable, adverse effects associated with mydriatics, and every effort should be made to minimize this risk. Key Points

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Overview of lithium's use: a nationwide survey

International Journal of Bipolar Disorders ◽

10.1186/s40345-020-00215-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Xabier Pérez de Mendiola ◽

Diego Hidalgo-Mazzei ◽

Eduard Vieta ◽

Ana González-Pinto

Keyword(s):

Adverse Effects ◽

Clinical Guidelines ◽

Lithium Treatment ◽

Scientific Evidence ◽

Plasma Concentrations ◽

Maintenance Phase ◽

Nationwide Survey ◽

Developed Countries ◽

Lithium Salts ◽

National Society

Abstract Background Lithium is considered the gold standard treatment for bipolar disorder (BD). Current clinical guidelines and scientific evidence support its use as a first-line treatment in BD. However, over the last two decades, there has been a downward tendency in lithium's use in several developed countries. Based on a nationwide survey, this study's objective is to analyze in a large sample of psychiatrists relevant issues of the use of lithium salts in BD. Methods Data were collected through an anonymous survey sent by email among 500 psychiatrists who belong to a National Society of Psychiatry (Spanish Society of Biological Psychiatry). The survey is a self-administered questionnaire consisting of 21 items on the most key aspects of lithium's use (indication, dosage, monitoring, and information for patients). Results 212 psychiatrists completed the survey. 70% of psychiatrists prescribe lithium to more than 50% of patients diagnosed with BD. Adverse effects are the main reason not to use lithium salts. Over 75% of the participants consider lithium salts the treatment of choice for the maintenance phase of BD, both in women and men. Most of the participants (> 50%) start lithium after the first affective episode, use conservative plasma concentrations (0.6–0.8 mmol/L), and generally prescribe it twice a day. 57% of psychiatrists who treat patients under 18 do not use lithium in this population. About 70% of the survey respondents use official protocols to inform and monitor patients on lithium treatment. Conclusions From the results of the present study, it can be concluded that the use of lithium in Spain is in line with the recommendations of the main international clinical guidelines and current scientific literature. The first reason not to prescribe lithium in our country is the perception of its adverse effects and not the aspects related to its practical use or its effectiveness. Considering that BD is a chronic disease with a typical onset in adolescence, the low rate of prescription of lithium salts in patients under 18 must be thoroughly studied.

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E

Neonatal Formulary ◽

10.1093/med/9780198840787.003.0018 ◽

2020 ◽

pp. 275-307

Author(s):

Sean Ainsworth

Keyword(s):

Adverse Effects ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Recombinant Human Erythropoietin ◽

Eye Drops ◽

Enzyme Replacement ◽

Maternal Treatment ◽

Human Erythropoietin

This chapter presents information on neonatal drugs that begin with E, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Enemas, laxatives, and suppositories, Enoxaparin, Enzyme replacement therapy, Epoetin (recombinant human erythropoietin = rEPO), Epoprostenol and other prostanoids (iloprost and teoprostinil), Erythromycin, Esomeprazole, Ethambutol, and Eye drops (and ointments)

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Restarting antidepressant and antipsychotic medication after intentional overdoses: need for evidence-based guidance

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125319836889 ◽

2019 ◽

Vol 9 ◽

pp. 204512531983688

Author(s):

Emma Tay ◽

Andreas Sotiriou ◽

Garry G. Graham ◽

Kay Wilhelm ◽

Leone Snowden ◽

...

Keyword(s):

Cytochrome P450 ◽

Adverse Effects ◽

Antipsychotic Drugs ◽

Plasma Concentrations ◽

Pharmacokinetic Data ◽

Psychoactive Drugs ◽

Cytochrome P450 Enzymes ◽

Psychoactive Medication ◽

Drug Overdoses ◽

P450 Inhibitors

Intentional drug overdoses with antidepressant and antipsychotic medications are an increasingly common problem. Currently, there is little guidance with regard to reintroduction of these medications after intentional overdoses. We have used published toxicological and pharmacokinetic data to obtain factors which control the recovery from overdoses. From such data, we have proposed guidance regarding their reintroduction, provided there are no adverse effects or contraindications. Tentatively, we suggest that when adverse effects from the overdose are lost, treatment could recommence after a further mean half-life of elimination. Most antidepressant and antipsychotic drugs are metabolized by cytochrome P450 enzymes and, where cytochrome P450 inhibitors are co-ingested, serial plasma concentrations should optimally be obtained in order to assess a suitable time for reintroduction of the psychoactive drugs. We hope the proposals presented will stimulate research and discussion that lead to better guidance for clinicians concerning reintroduction of psychoactive medication after intentional overdose.

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Effect of Thunbergia laurifolia Herbal Tea on Glucose Homeostasis in Healthy Volunteers: A Single-Arm Phase I Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/3212546 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Lukana Preechasuk ◽

Pravit Akarasereenont ◽

Ranida Boonrak ◽

Onusa Thamsermsang ◽

Busadee Pratumvinit ◽

...

Keyword(s):

Adverse Effects ◽

Healthy Volunteers ◽

Glucose Homeostasis ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Plasma Concentrations ◽

Herbal Tea ◽

Serious Adverse Events ◽

Fasting Plasma ◽

Thunbergia Laurifolia

Background. Thunbergia laurifolia (TL) is a commonly used herbal medicine in Thailand and in other Asian countries. TL has been approved as a Thai traditional medicine for detoxifying poisons, and the list of possible adverse effects includes hypoglycemia. TL showed hypoglycemic effect in animals possibly due to antioxidant effect and beta-cell preservation. However, the safety of TL herbal tea and its effects on glucose homeostasis have never been investigated in humans. Methods. Twenty healthy volunteers (10 men and 10 women) drank TL herbal tea 3 times/day for 2 weeks. Ten subjects took TL herbal tea 9 grams daily. After the safety of TL herbal tea was established, 10 more subjects took TL 12 grams daily. Clinical and biochemical tests were assessed at baseline and at 2 weeks. Results. Mean age was 34.9 ± 10.2 years, and mean body mass index was 27.5 ± 5.8 kg/m2. Baseline and posttreatment plasma concentrations were as follows: fasting plasma glucose (89 ± 6 vs. 89 ± 7 mg/dL), fructosamine (213 ± 32 vs. 212 ± 33 μmol/L), fasting insulin (8.8 [IQR: 5.9–18.4] vs. 10.4 [IQR: 7.4–15.2] μU/mL), HOMA-B (101.6 [IQR: 82.3–189.8] vs. 120.4 [IQR: 93.2–153.2]), and HOMA-IR (1.1 [IQR: 0.8–2.3] vs. 1.4 [IQR: 0.9–2.0]), all respectively. There were no significant changes in these parameters, including body weight, blood pressure, lipid profile, and C-reactive protein. No serious adverse events were observed during the study period. Conclusions. TL herbal tea at doses of 9 and 12 grams daily had good tolerability without any significant adverse effects on fasting plasma glucose level or other glucose homeostasis parameters measured.

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Efficacy, plasma concentrations and adverse effects of a new sustained release procainamide preparation

The American Journal of Cardiology ◽

10.1016/0002-9149(80)90440-3 ◽

1980 ◽

Vol 46 (5) ◽

pp. 855-862 ◽

Cited By ~ 36

Author(s):

Elsa-Grace V. Glardina ◽

Paul E. Fenster ◽

J. Thomas Bigger ◽

Michael Mayersohn ◽

Donald Perrier ◽

...

Keyword(s):

Adverse Effects ◽

Sustained Release ◽

Plasma Concentrations

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Managing Primary Open-angle Glaucoma – Ocular Tolerability, Compliance, Persistence and Patient Outcomes

European Ophthalmic Review ◽

10.17925/eor.2009.03.01.19 ◽

2009 ◽

Vol 03 (01) ◽

pp. 19 ◽

Cited By ~ 2

Author(s):

Anton Hommer ◽

Keyword(s):

Adverse Effects ◽

Patient Compliance ◽

Vision Loss ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Tolerability Profile ◽

Eye Drops ◽

Open Angle ◽

The Individual ◽

Ocular Tolerability

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy that, left untreated, can lead to irreversible damage to the optic nerve and permanent vision loss. To date, intraocular pressure (IOP) is the only modifiable risk factor for disease progression, and topical eye-drops are currently used as the leading non-surgical glaucoma therapy. Despite the efficacy of pharmacotherapy in lowering IOP, success is ultimately defined by patient compliance and patient persistence. Ocular tolerability is a crucial factor in patient compliance and persistence; non-adherence owing to adverse effects can lead to poor control of IOP and treatment failure. Prostaglandin analogues are currently the first-line antiglaucoma agents, with a good tolerability profile and a better IOP-lowering effect compared with β-blockers. Combination therapies have also shown greater efficacy in lowering IOP compared with the individual constituents, with fewer adverse effects. Treatment should be tailored to the individual patient, with a focus on ocular tolerability and its role in adherence, compliance and vision preservation.

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Pharmacogenomics of Tamoxifen Therapy

Clinical Chemistry ◽

10.1373/clinchem.2008.121756 ◽

2009 ◽

Vol 55 (10) ◽

pp. 1770-1782 ◽

Cited By ~ 96

Author(s):

Hiltrud Brauch ◽

Thomas E Mürdter ◽

Michel Eichelbaum ◽

Matthias Schwab

Keyword(s):

Cytochrome P450 ◽

Selective Serotonin Reuptake Inhibitors ◽

Plasma Concentrations ◽

Hot Flashes ◽

Parent Drug ◽

Endocrine Treatment ◽

Active Metabolites ◽

Recurrence Rates ◽

Hormone Receptor Positive ◽

Cyp2d6 Inhibitors

Abstract Background: Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor–positive breast cancer. Content: Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for the estrogen receptor and the ability to inhibit cell proliferation. The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In particular, nonfunctional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 alleles are associated with higher recurrence rates. Summary: Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) genotyping before treatment to predict metabolizer status may open new avenues for individualizing endocrine treatment, with the maximum benefit being expected for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.

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Effects of Exposure to Aflatoxin G1 on the Plasma Biochemical Factors and Histopathological Properties of Renal Tissue in Mice

Iranian Jornal of Toxicology ◽

10.32598/ijt.15.2.787.1 ◽

2021 ◽

Vol 15 (2) ◽

pp. 127-134

Author(s):

Touraj Zamir-Nasta ◽

◽

Arash Ahmadi ◽

Moein Yazdkhasti ◽

Mona Pazhouhi ◽

...

Keyword(s):

Adverse Effects ◽

Biochemical Analysis ◽

Plasma Concentrations ◽

Renal Tissue ◽

Control Group ◽

Male Mice ◽

Blood Samples ◽

Aquaporin 1 ◽

Histopathological Studies ◽

Sodium And Potassium

Background: Among aflatoxins, the subtype aflatoxin G1 is one of the most toxic, commonly found in cereals, legumes, dairy and non-alcoholic beers. Aflatoxins have been known as nephrotoxic compounds. In this study, changes in the expression of aquaporin-1, the histopathology of renal tissue and plasma biochemical factors after exposure to aflatoxin G1 were investigated in mice. Methods: Twenty-four adult male mice (weighing 20±2 g) were divided into four groups of six. The control group received the vehicle (0.2 ml) and the three experimental groups were injected intraperitoneally with aflatoxin G1 at 20 μg/kg for 7, 15 or 35 days, respectively. On days 7, 15 and 35, blood samples were drawn from the mice for biochemical analysis of plasma and the kidney tissues were sampled for real-time PCR and histopathological studies. Results: The real PCR results showed a reduction in aquaporin-1 expression in the experimental groups compared to those in the controls (P<0.05). Also, the plasma concentrations of urea and creatinine were significantly increased in the experimental groups compared to those in the controls (P<0.05). Also, the serum sodium and potassium levels had decreased significantly compared to the controls (P<0.05). Various damages were observed in the ureters and glomeruli among the experimental groups compared to those in the controls. Conclusion: Aflatoxin G1 had adverse effects on the renal tissue by reducing the expression of aquaporin-1. Subsequently, there were biochemical manifestations in the serum, consisting of changes in the concentrations of urea, creatinine, sodium and potassium, confirming the histopathological toxicity of aflatoxin G1.

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Pharmacokinetics of Buprenorphine and Sustained-release Buprenorphine in Common Marmosets (Callithrix jacchus)

Journal of the American Association for Laboratory Animal Science ◽

10.30802/aalas-jaalas-20-000082 ◽

2020 ◽

Author(s):

Casey B Fitz ◽

Anna E Goodroe ◽

David E Moody ◽

Wenfang B Fang ◽

Saverio V Capuano III

Keyword(s):

Adverse Effects ◽

Sustained Release ◽

Peak Plasma ◽

Plasma Concentrations ◽

Callithrix Jacchus ◽

Terminal Phase ◽

Pharmacokinetic Parameters ◽

Common Marmosets ◽

Adult Age ◽

Concentration Time

Buprenorphine is an essential component of analgesic protocols in common marmosets (Callithrix jacchus). The use of buprenorphine HCl (BUP) and sustained-release buprenorphine (BSR) formulations has become commonplace in this species, but the pharmacokinetics have not been evaluated. Healthy adult (age, 2.4 to 6.8 y; 6 female and 6 male) common marmosets were enrolled in this study to determine the pharmacokinetic parameters, plasma concentration–time curves, and any apparent adverse effects of these compounds. Equal numbers of each sex were randomly assigned to receive BUP (0.02 mg/kg IM) orBSR (0.2 mg/kg SC), resulting in peak plasma concentrations (mean ± 1 SD) of 15.2 ± 8.1 and 2.8 ± 1.2 ng/mL, terminal phase t1/2 of 2.2 ± 1.0 and 32.6 ± 9.6 h, and AUC0-last of 16.1 ± 3.7 and 98.6 ± 42.7 ng×h/mL. The plasma concentrations of buprenorphine exceeded the proposed minimal therapeutic threshold (0.1 ng/mL) at 5 and 15 min after BUP and BSR administration,showing that both compounds are rapid-acting, and remained above that threshold through the final time points of 8 and 72h. Extrapolation of the terminal elimination phase of the mean concentration–time curves was used to develop the clinical dosing frequencies of 6 to 8 h for BUP and 3.0 to 3.5 d for BSR. Some adverse effects were observed after the administration of BUP to common marmosets in this study, thus mandating judicious use in clinical practice. BSR provided a safe, long-acting option for analgesia and therefore can be used to refine analgesic protocols in this species.

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