Manage drug-induced dry mouth with drug regimen changes, lifestyle interventions and topical or oral symptom-relieving products

2019 ◽  
Vol 35 (5) ◽  
pp. 226-229
Author(s):  
Keyword(s):  
Drug Regimen ◽  
Dry Mouth ◽  
Lifestyle Interventions ◽  
Drug Induced ◽  
Oral Symptom

scholarly journals Pyrazinamide triggers degradation of its target aspartate decarboxylase

2019 ◽  
Author(s):  
Pooja Gopal ◽  
Jickky Sarathy ◽  
Michelle Yee ◽  
Priya Ragunathan ◽  
Joon Shin ◽  
...  
Keyword(s):  
Protein Function ◽  
Enzyme Inhibitor ◽  
Drug Regimen ◽  
Growth Media ◽  
Antibacterial Drug ◽  
Missense Mutations ◽  
Binding Studies ◽  
Drug Induced

AbstractThe introduction of pyrazinamide (PZA) in the tuberculosis drug regimen shortened treatment from 12 to 6 months 1. PZA is a prodrug that is activated by a Mycobacterium tuberculosis (Mtb) amidase to release its bioactive component pyrazinoic acid (POA) 2. Aspartate decarboxylase PanD, a proenzyme activated by autocatalytic cleavage (Supplementary Fig. 1A, 3) and required for Coenzyme A (CoA) biosynthesis, emerged as a target of POA 4-7. In vitro and in vivo screening to isolate spontaneous POA-resistant Mtb mutants identified missense mutations in either panD or the unfoldase clpC1, encoding a component of the caseinolytic protease ClpC1-ClpP 4,6-9. Overexpression and binding studies of PanD or ClpC1 pointed to PanD as the direct target of POA whereas clpC1 mutations appeared to indirectly cause resistance 4,5,7,9,10. Indeed, supplementing growth media with CoA precursors downstream of the PanD catalyzed step conferred POA resistance 4,7,11. Metabolomic analyses and biophysical studies using recombinant proteins confirmed targeting of PanD by POA 5. However, the exact molecular mechanism of PanD inhibition by POA remained unknown. While most drugs act by inhibiting protein function upon target binding, we show here that POA is not a bona fide enzyme inhibitor. Rather, POA binding to PanD triggers degradation of the protein by ClpC1-ClpP. Thus, the old tuberculosis drug PZA promotes degradation of its target. While novel for an antibacterial, drug-induced target degradation has recently emerged as a strategy in drug discovery across disease indications. Our findings provide the basis for the rational discovery of next generation PZA.

scholarly journals Comparative Study of the Anti-Human Cytomegalovirus Activities and Toxicities of a Tetrahydrofuran Phosphonate Analogue of Guanosine and Cidofovir

1999 ◽  
Vol 43 (3) ◽  
pp. 557-567 ◽  
Author(s):  
Jean Bedard ◽  
Suzanne May ◽  
Martin Lis ◽  
Leander Tryphonas ◽  
John Drach ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Guinea Pigs ◽  
Laboratory Strain ◽  
Drug Regimen ◽  
New Drugs ◽  
Murine Cytomegalovirus ◽  
Mcmv Infection ◽  
Drug Induced ◽  
Nuclear Modifications

ABSTRACT Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (−)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9′-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 μg/ml for cidofovir and <0.05 to 0.09 μg/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.

scholarly journals Weight loss during tuberculosis treatment is an important risk factor for drug-induced hepatotoxicity

2010 ◽  
Vol 105 (3) ◽  
pp. 400-408 ◽  
Author(s):  
Ina Warmelink ◽  
Nick H. ten Hacken ◽  
Tjip S. van der Werf ◽  
Richard van Altena
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Risk Factor ◽  
Multivariate Logistic Regression Analysis ◽  
Liver Function Tests ◽  
Drug Regimen ◽  
Important Risk Factor ◽  
Drug Induced ◽  
Tb Treatment ◽  
Independent Risk Factors

The objective of this study was to determine the association between weight loss and drug-induced hepatotoxicity (DIH). A retrospective observational study of 192 active tuberculosis (TB) patients consecutively admitted in a tertiary referral TB centre in the Netherlands was conducted. The outcome measure for DIH was defined as hepatotoxicity necessitating interruption of anti-TB drugs. Multivariate logistic regression analysis on interruption of anti-TB drugs was performed, with age, sex, nutritional status, TB disease severity, drug resistance, comorbidity including baseline liver function tests, anti-TB drug regimen, co-medication and addictions as independent risk factors. Anti-TB drugs were interrupted in thirty-one patients (16·1 %). The most important risk factor was weight loss of 2 kg or more within 4 weeks during TB treatment (OR 211, 95 % CI 36·0, 1232). Other independent risk factors were infection with hepatitis C (OR 19·6, 95 % CI 2·4, 164), age over 60 years (OR 18·5, 95 % CI 2·3, 151) and multi-drug-resistant TB (OR 8·2, 95 % CI 1·3, 53·6). This study shows that weight loss during TB treatment was the most important risk factor for DIH necessitating interruption of anti-TB drugs. Causes of weight loss during TB treatment and the association between weight change and hepatotoxicity need further investigation.

Possible Hypothyroidism Associated with Quetiapine

2000 ◽  
Vol 34 (4) ◽  
pp. 483-486 ◽  
Author(s):  
Brett M Feret ◽  
Charles F Caley
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
African American Woman ◽  
American Woman ◽  
Drug Regimen ◽  
Thyroid Stimulating Hormone ◽  
Subsequent Treatment ◽  
Drug Induced ◽  
Bipolar Type ◽  
Receive Treatment

OBJECTIVE: To report a case of hypothyroidism occurring after the addition of quetiapine to an existing drug regimen. CASE SUMMARY: A 46-year-old African-American woman diagnosed with schizoaffective disorder, bipolar type, and a four-year history of successfully treated hyperthyroidism, was suboptimally responsive to olanzapine treatment. Transition from olanzapine to quetiapine was initiated and, approximately two months after adding quetiapine to a standing pharmacotherapeutic regimen, the patient developed an elevated thyroid-stimulating hormone (TSH) concentration of 8.45 μU/L. A diagnosis of hypothyroidism was subsequently made, treatment with levothyroxine was initiated, and the patient's thyroid function became stable. DISCUSSION: Drug-induced hypothyroidism is known to occur with several medications. Quetiapine is an atypical antipsychotic with the potential to decrease thyroid hormone concentrations in some patients; this effect may be dose related. Despite this known adverse effect, the manufacturer of quetiapine reports that elevated TSH concentrations and subsequent treatment with thyroid hormone supplementation have occurred only rarely. We report the development of hypothyroidism in a patient who had previously received successful radioactive iodine treatment for hyperthyroidism in 1994, but who had no detected thyroid abnormalities until treatment with quetiapine was started four years later. CONCLUSIONS: Patients with compromised thyroid function who receive treatment with quetiapine may develop hypothyroidism. Appropriate care for these patients may include an increased awareness of possible hypothyroidism and consideration of thyroid function monitoring.

Adverse Reaction to a Dietary Supplement in an Elderly Patient

2003 ◽  
Vol 37 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Rebecca B Sleeper ◽  
Shalyn M Kennedy
Keyword(s):  
Elderly Patient ◽  
Acute Hepatitis ◽  
Dietary Supplement ◽  
Abdominal Ultrasound ◽  
Drug Regimen ◽  
Drug Event ◽  
Hepatic Enzymes ◽  
Drug Induced ◽  
History Of ◽  
Antibody Screen

OBJECTIVE To describe the case of an elderly patient who experienced hepatic enzyme elevations and symptoms of hepatitis associated with the administration of a dietary supplement. CASE SUMMARY A 92-year-old white woman with no history of hepatic disease developed jaundice and increased confusion associated with increased hepatic enzymes. The hepatitis panel, abdominal ultrasound, and antinuclear antibody screen indicated no abnormalities. A drug regimen review revealed that the patient was receiving a dietary supplement, Nutrilite Double X Multivitamin–Multimineral. Following discontinuation of the supplement, the patient's symptoms resolved and the hepatic enzymes decreased or returned to the reference range at evaluations occurring 1 week and 1 month after intervention. An objective causality assessment revealed this to be a probable adverse drug event. DISCUSSION While the association of certain herbal preparations with hepatotoxicity has been demonstrated, the potential for this adverse effect is easily overlooked. In this patient, infectious or autoimmune causes of acute hepatitis were ruled out, and drug-induced causes were considered. The resolution of symptoms and laboratory values following discontinuation of the supplement support a relationship between the dietary supplement and this episode of hepatitis. CONCLUSIONS Our case indicates that there was a probable relationship between the dietary supplement Nutrilite Double X Multivitamin–Multimineral and the development of acute hepatitis. Due to the multiingredient formulation of the product, as well as lack of data describing manufacturing procedures, it is difficult to determine which component may be associated with this effect. Over-the-counter supplements should be considered as a part of the differential diagnosis in patients presenting with increased liver enzymes and related symptoms.

Case Report on Mild Anemia and Gastritis due to Zidovudine, Lamivudine and Nevirapine (ZLN) Regimen

2021 ◽  
pp. 5911-5912
Author(s):  
Deepalakshmi M ◽  
Ajay Samraj P ◽  
Diya C ◽  
Jonna Venkatesh ◽  
Kamalrathinam R S ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Causality Assessment ◽  
Gastrointestinal Symptoms ◽  
Drug Regimen ◽  
Drug Induced ◽  
Mild Anemia ◽  
Highly Active ◽  
Blood Haemoglobin ◽  
The Relationship

AIDS is a deadly syndrome in which Highly Active Anti-retroviral therapy is used to reduce the viral load. However these anti-retroviral drugs are supposed to cause several adverse drug reaction. There are several studies that report anemia with Zidovudine and gastrointestinal symptoms with Lamivudine. In this report, We present a case of a 38 year old female patient suffering from HIV infection who is suspected to drug induced anemia and gastritis due to Zidovudine, Lamivudine and Nevirapine combination (ZLN) regimen. The relationship between the administered drug regimen and the suspected ADR’s was found using causality assessment. Severity, predictability and probability was also found for the suspected ADR’s. We need to monitor the HIV patients who are under ZLN regimen for their blood haemoglobin and gastrointestinal symptoms.

Oral Complications in Patients with Advanced Cancer

1989 ◽  
Vol 5 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Franco De Conno ◽  
Carla Ripamonti ◽  
Alberto Sbanotto ◽  
Vittorio Ventafridda
Keyword(s):  
Oral Cavity ◽  
Cancer Patient ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Advanced Disease ◽  
Dry Mouth ◽  
Drug Induced ◽  
Oral Complications ◽  
Advanced Phase ◽  
Taste Alteration

Disturbances caused by lesions of the oral cavity play an important part in the alteration of the qualtity of life of cancer patients. The main complications affecting the oral cavity are infections (fungal, viral, bacterial), neutropenic ulcers, drug-induced stomatitis, dry mouth, and taste alteration. Most of the information available about these entities has been acquired in the cancer patient without advanced disease. The little known about the epidemiology and physiopathology of such lesions in the advanced phase of cancer is presented and approaches to management are suggested.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

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