Effect of CYP2C9 *11/*11 genotype on initial and long-term warfarin dose requirement and therapeutic response

2020 ◽  
Vol 21 (18) ◽  
pp. 1271-1277
Author(s):  
Alison LH Quinn ◽  
Shubha Bhat ◽  
James C Lee
Keyword(s):  
Therapeutic Response ◽  
Warfarin Dose ◽  
International Normalized Ratio ◽  
Term Treatment ◽  
Dose Requirement ◽  
Long Term Treatment ◽  
Warfarin Dose Requirement ◽  
Short And Long Term ◽  
Load Dose

The warfarin dose requirement and therapeutic response of a 42-year-old African–American male with genotype CYP2C9 *11/*11, VKORC1 -1639GG and CYP4F2 433Val/Val anticoagulated for ischemic stroke is described herein. Warfarin was dosed according to the institution’s personalized medicine program recommendations of a 10 mg mini-load dose, followed by dose decreases to 4–6 mg/day through discharge. Stable international normalized ratio was achieved after eight doses, with good overall long-term maintenance of therapeutic international normalized ratio over several years with warfarin doses of 3.1–4.3 mg/day. This case report sheds further light on the clinical impact of CYP2C9 *11/*11 on warfarin dose requirements, short- and long-term treatment response and practical considerations for warfarin management in suspected carriers of rare variant CYP2C9 alleles.

scholarly journals The international normalized ratio (INR) as seen in a population of patients with atrial fibrillation and cerebral infarction undergoing long-term treatment with vitamin K antagonists

2015 ◽  
Vol 28 (4) ◽  
pp. 269-272
Author(s):  
Anna Szczepańska-Szerej ◽  
Magdalena Wojtan ◽  
Beata Szajnoga
Keyword(s):  
Atrial Fibrillation ◽  
Cerebral Infarction ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Blood Parameters ◽  
Term Treatment ◽  
Adequate Treatment ◽  
Long Term Treatment

Abstract It is estimated that nearly 20% of all cerebral infarctions in the total population are the result of a complication of atrial fibrillation (AF). While oral anticoagulation with vitamin K antagonists (AVKs) substantially reduces this risk, this requires regular monitoring of the international normalized ratio (INR) in order to achieve therapeutic levels (2,0-3,0). The aim of this study was to evaluate a group at high risk of cerebral infarction, among patients with AF undergoing long-term treatment with VKAs, taking into account the significance of therapeutic INR values. The analysed group consisted of 90 acute ischaemic stroke patients with paroxysmal or chronic “non-valvular” AF, receiving treatment with VKAs. As a result of the study, therapeutic INR values (≥ 2) were seen in thirty-five of these individuals (38,8%), while 55 (61,2%) showed non-therapeutic INR values. Moreover, there were no differences in demographics, vascular risk factors, biochemical and morphological blood parameters, mean CHA2DS2-VASc score and TOAST classification between either of the two groups. Furthermore, no additional factor that would increase their risk of cerebral infarction during the adequate treatment with VKAs was found. However, patients with non-therapeutic INR values had a statistically significantly higher frequency of concomitant moderate pathology of the bicuspid valve, p<0.05. Hence, a lack of proper control of INR can proved to be particularly dangerous for this subgroup of patients. Hence, this is a group with an elevated risk of cerebral infarction and therefore requires special oversight of VKA treatment or NOA treatment.

Candida Overgrowth in Gastric Juice of Peptic Ulcer Subjects on Short- and Long-Term Treatment with H2-Receptor Antagonists

Digestion ◽  
1983 ◽  
Vol 28 (3) ◽  
pp. 158-163 ◽  
Author(s):  
M. Boero ◽  
A. Pera ◽  
A. Andriulli ◽  
V. Ponti ◽  
G. Canepa ◽  
...  
Keyword(s):  
Peptic Ulcer ◽  
Gastric Juice ◽  
Term Treatment ◽  
Receptor Antagonists ◽  
Long Term Treatment ◽  
Short And Long Term

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

scholarly journals Protein Metabolism in Acromegaly: Differential Effects of Short- and Long-Term Treatment

2007 ◽  
Vol 92 (4) ◽  
pp. 1479-1484 ◽  
Author(s):  
James Gibney ◽  
Troels Wolthers ◽  
Morton G. Burt ◽  
Kin-Chuen Leung ◽  
A. Margot Umpleby ◽  
...  
Keyword(s):  
Protein Oxidation ◽  
Protein Metabolism ◽  
Normal Subjects ◽  
Term Treatment ◽  
Protein Breakdown ◽  
Short Term ◽  
Leucine Oxidation ◽  
Long Term Treatment ◽  
Short And Long Term

Abstract Context: GH acutely increases body protein by stimulating protein synthesis and reducing protein oxidation. Objective: The objective of the study was to determine whether these changes in protein metabolism are sustained in long-term GH excess and reversed by correction. Design: We conducted a cross-sectional study in 16 acromegalic and 18 normal subjects and a longitudinal study in which acromegalic subjects were studied before and after short-term (n = 8) or long-term (n = 10) treatment. Setting: The study was conducted at a clinical research center. Main Outcome Measures: Whole-body rates of leucine appearance (leucine Ra; an index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine were measured. Results: Leucine Ra and NOLD were greater (P &lt; 0.01) in acromegalic compared with normal subjects, whereas leucine oxidation did not differ. Leucine oxidation increased significantly (P &lt; 0.05) after short-term treatment but returned to baseline after long-term treatment. Both leucine Ra and NOLD decreased significantly (P &lt; 0.05) after short- and long-term treatment. Adjustment for body composition did not affect results. Conclusions: In acromegalic subjects, protein breakdown and synthesis are increased, whereas protein oxidation does not differ from normal subjects. Protein oxidation increases transiently, whereas protein breakdown and synthesis are stably reduced after treatment. Because protein oxidation represents irreversible loss, we conclude that the normal state of protein oxidation found in acromegaly and after long-term treatment represents metabolic adaptation, which maintains protein mass at a steady state after stable changes in GH status.

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