The aim of this study was to evaluate the association between OPRM1 and ABCB1 polymorphisms on pain relief with epidural sufentanil in 69 patients after rectosigma resection for cancer. The median number of injections (SD) 2.31 (1.36), IQR=1, required by 118AA subjects was significantly lower in comparison with 118AG group 5.25 (3.13), IQR=6.5, (chi(2)=9.75, p=0.001); correspondingly median drug consumption of 1.16 (0.79), IQR=1.083, defined daily doses (DDD) was significantly less in the 118AA group in comparison with 2.14 (1.17), IQR=2.23, DDD in 118AG subjects, (chi(2)=7.00, p=0.008). Opioid-induced adverse effects were observed in 15 % and 33 % of patients in 118AA and 118AG groups, respectively (chi(2)=8.16, p=0.004). The median number of injections (SD) required by women and men was 3.30 (2.16), IQR=2, and 2.80 (1.59), IQR=1, respectively (chi(2)=6.25, p=0.012). Opioid-induced adverse effects were observed in 26 % and 12 % of women and men, respectively (chi(2)=5.49, p=0.011). Heterozygotes of OPRM1 polymorphism and women were more difficult to treat subpopulations that required higher doses of rescue analgesic medication and suffered more adverse effects.

• MeSH
• epidurální analgezie metody   MeSH
• kolorektální nádory chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• management bolesti metody   MeSH
• opioidní analgetika aplikace a dávkování   MeSH
• P-glykoproteiny genetika   MeSH
• polymorfismus genetický fyziologie   MeSH
• pooperační bolest farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory opiátové mu genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sufentanil aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABCB1 protein, human MeSH Prohlížeč
• opioidní analgetika MeSH
• OPRM1 protein, human MeSH Prohlížeč
• P-glykoproteiny MeSH
• receptory opiátové mu MeSH
• sufentanil MeSH

Unfortunately, original article has been published without acknowledgement section.

• Publikační typ
• tisková chyba MeSH

Dopamine was shown to induce mydriasis by excitation of alpha-adrenergic receptors at the dilator pupillae muscle. Pupilla diameter may thus serve as an indirect measure of peripheral pharmacokinetics of L-DOPA and dopamine. The aim of this study is to evaluate the effect of L-DOPA dosage on pupillometric parameters in Parkinson's disease (PD) patients. Sixteen PD patients and 14 healthy control subjects (CS) were studied. The statistical analysis revealed significant differences between CS and PD patients for the mean maximum and minimum pupil diameters (p = 0.017, p = 0.028, respectively), with higher values found in PD. Moreover, a significant dose-response relationship was found between the maximum pupil diameter and both the morning L-DOPA dose (R 2 = 0.78) and the total daily L-DOPA dose (R 2 = 0.93). A sigmoid-shaped curve best describes the dose-response relationship, with a ceiling effect at about 400 mg L-DOPA daily dose. In conclusion, measuring pupillometric parameters represents a sensitive tool for non-invasive evaluation of the peripheral effect of L-DOPA, especially with daily doses below 400 mg L-DOPA.

• Klíčová slova
• Dose–response relationship, L-DOPA, Maximum pupil diameter, Parkinson’s disease, Pupil parameters, Pupillometry,
• MeSH
• antiparkinsonika aplikace a dávkování   MeSH
• dospělí MeSH
• levodopa aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc farmakoterapie   MeSH
• pupila účinky léků   MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antiparkinsonika MeSH
• levodopa MeSH

Genetic factors may contribute to the differential response to opioids. The aim of this study was to evaluate the association between polymorphisms of µ1-opioid receptor gene OPRM1 (rs1799971), and P-glycoprotein transporter gene ABCB1 (rs1045642, rs2032582), and piritramide efficacy under postoperative patient-controlled analgesia (PCA). In 51 patients, OPRM1 variant was associated with decreased efficacy in early postoperative period evidenced by sum of pain intensity difference in the 0-6 h postoperative period (SPID(0-6)), (F=3.27, p=0.029). Mean (SD) SPID(0-6) was observed in the 118AA genotype 22.9 (6.1) mm, which was significantly higher from the 118GG genotype 10.0 (4.4) mm, p=0.006. The lowest cumulative dose was recorded in 118AA genotype 19.1 (9.8) mg, which was significantly less than in the 118GG genotype group 36.6 (6.1) mg, p=0.017. Opioid-induced adverse effects were observed in 11, 30, and 100 % of patients in 118AA, 118AG, and 118GG genotype groups, respectively (p<0.05). Piritramide efficacy and safety was not significantly affected by ABCB1 (rs1045642, rs2032582) polymorphisms. Variant OPRM1 118G allele is associated with decreased acute postoperative pain relief after piritramide. Decreased efficacy leads to higher drug consumption under PCA settings, which however, does not fully compensate insufficient pain relief, but increases incidence of adverse effects.

• MeSH
• dospělí MeSH
• jednoduchá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti účinky léků   metody   MeSH
• opioidní analgetika farmakologie   terapeutické užití   MeSH
• P-glykoproteiny genetika   MeSH
• pirinitramid farmakologie   terapeutické užití   MeSH
• polymorfismus genetický genetika   MeSH
• pooperační bolest diagnóza   farmakoterapie   genetika   MeSH
• prospektivní studie MeSH
• receptory opiátové mu genetika   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABCB1 protein, human MeSH Prohlížeč
• opioidní analgetika MeSH
• OPRM1 protein, human MeSH Prohlížeč
• P-glykoproteiny MeSH
• pirinitramid MeSH
• receptory opiátové mu MeSH

OBJECTIVES: The aim of prospective study was to evaluate the therapeutic efficacy of piritramide in patients after removal of parathyroid glands in relation to MDR1 genotype. In the treatment of moderate acute postoperative pain, piritramide plays a major role. It is difficult to predict its optimal therapeutic efficacy and tolerability in individual patients. METHODS: We compared the effect of piritramide in 56 patients after surgical removal of parathyroid glands in a prospective study. We evaluated pain intensity, pain difference and sum of pain difference (SPID) using visual analogue scale (VAS in mm) and adverse effects in the relationship with the MDR1 - polymorphism of G2677T/A. RESULTS: In the wild-type group (2677GG), there was maximal pain difference of 30.6 ± 24.9 and SPID of 209.33 ± 95.80 while in genotype 2677TT and 2677GT, the corresponding values were 19.5 ± 25.5 and 147.07 ± 91.38, respectively. In group of patients with wild type of 2677GG genotype, there was 80 % of responders with more than 50 % reduction in VAS as compared to baseline while in group with carriers of 2677T allele, there are only 39 % of responders present (χ² = 5. 83; p = 0.016). Furthermore, the total consumption of piritramide was lower in comparison with the variant-allele carrying group (p = 0.008). The total incidence of adverse drug reactions was observed in 40 % of patients with wild type of 2677GG genotype when compared to 83% in the group carrying the variant allele (χ² = 7.92; p = 0.005). Significantly more patients in the wild-type group were satisfied with postoperative pain treatment in comparison to the variant allele group (χ² = 6. 49; p = 0.0109). CONCLUSION: We observed a better analgesic effect of piritramide and a decreased incidence of side effects in the wild-type genotype (2677GG) group, when compared with variant-allele carrying patients (Tab. 2, Fig. 1, Ref. 7).

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti * MeSH
• opioidní analgetika terapeutické užití   MeSH
• P-glykoprotein genetika   MeSH
• paratyreoidektomie MeSH
• pirinitramid terapeutické užití   MeSH
• polymorfismus genetický * MeSH
• pooperační bolest farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• opioidní analgetika MeSH
• P-glykoprotein MeSH
• pirinitramid MeSH

Metabolic liver functions are significantly involved in the total clearance of a number of drugs. In liver cirrhosis the reduced drug elimination is a result of the blood flow through the liver, hepatocytes function and volume of hepatic tissue. Pharmacokinetic and pharmacodynamic changes depend on the nature and degree of hepatic impairment and on the characteristics of the dosed drug. Hepatocytes have a different extraction ability with respect to the individual drugs. The following are examples of drugs with high hepatic extraction: anodyne, propranolol, metoprolol, verapamil and lidocaine. These drugs are significantly dependent on the first passage through the liver. Intrahepatic and extrahepatic collateral blood flows significantly increase their bio-logical availability and reduce the clearance. The reduction in hepatic clearance of drugs with low extraction coefficient, such as chlordiazepoxide, diazepam or furosemide, is a result of its own limited functional capacity to eliminate the drug. Predicting a hepatic metabolic disorder based on a common bio-chemical assessment of enzyme activities is not sufficient. In advanced liver cirrhosis a higher risk is demonstrated for drugs with a narrow therapeutic width. It is always necessary to take into account whether the pharmacotherapy is necessary, use small doses and cautiously monitor the patient.

• MeSH
• analgetika farmakokinetika   MeSH
• anestetika lokální farmakokinetika   MeSH
• antiarytmika farmakokinetika   MeSH
• antihypertenziva farmakokinetika   MeSH
• jaterní cirhóza metabolismus   MeSH
• jaterní insuficience metabolismus   MeSH
• játra metabolismus   MeSH
• lidé MeSH
• lidokain farmakokinetika   MeSH
• metoprolol farmakokinetika   MeSH
• propranolol farmakokinetika   MeSH
• riziko MeSH
• verapamil farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• analgetika MeSH
• anestetika lokální MeSH
• antiarytmika MeSH
• antihypertenziva MeSH
• lidokain MeSH
• metoprolol MeSH
• propranolol MeSH
• verapamil MeSH

OBJECTIVES: The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy. BACKGROUND: Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population. Available data provide controversial results regarding the analgesic efficacy of tramadol in subjects with different CYP2D6 genotypes. METHODS: Pain intensity was assessed using visual analogue scale at 2 and 24 hours after the knee arthroscopy in 156 patients. Polymorphisms CYP2D6*3,*4,*5,*6, and gene duplication and C3435T in MDR1 gene were analyzed by PCR - RFLP. RESULTS: Mean VAS2h value in the whole study group was 44.0 ± 16.5 mm. Mean pain difference, was lowest in the UM group and highest in the PM group. The pain difference varied significantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with significant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no significant differences among MDR1 subgroups with regards of pain difference. Mean tramadol consumption was 2.47 ± 1.17 mg/kg during the 24 h period. There were no significant differences in the drug consumption, reporting of adverse reactions, need for rescue analgesic medication or verbal description of pain among the CYP2D6 or MDR1 genotype subgroups. CONCLUSION: CYP2D6 plays a significant role in tramadol analgesic efficacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18).

• MeSH
• artroskopie MeSH
• cytochrom P-450 CYP2D6 genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• heterozygot MeSH
• kolenní kloub chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti MeSH
• opioidní analgetika terapeutické užití   MeSH
• P-glykoprotein genetika   MeSH
• polymorfismus genetický * MeSH
• pooperační bolest farmakoterapie   MeSH
• tramadol terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytochrom P-450 CYP2D6 MeSH
• opioidní analgetika MeSH
• P-glykoprotein MeSH
• tramadol MeSH

WHAT IS KNOWN AND OBJECTIVE: The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers. METHODS: Sixty-nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed. RESULTS AND DISCUSSION: Large interindividual variability was observed in the tramadol-induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P < 0·05) except for the reflex amplitude and constriction velocity. WHAT IS NEW AND CONCLUSION: The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.

• MeSH
• aplikace orální MeSH
• biomarkery farmakologické metabolismus   MeSH
• cytochrom P-450 CYP2D6 genetika   metabolismus   MeSH
• dospělí MeSH
• lidé MeSH
• mióza chemicky indukované   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mydriáza chemicky indukované   MeSH
• opioidní analgetika aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• polymorfismus genetický MeSH
• pupila účinky léků   MeSH
• tramadol aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biomarkery farmakologické MeSH
• cytochrom P-450 CYP2D6 MeSH
• opioidní analgetika MeSH
• tramadol MeSH

OBJECTIVES: The aim of the study was to compare the effects of diclofenac and piritramide in acute postoperative pain after hernioplasty. BACKGROUND: In the treatment of moderate acute postoperative pain, non-steroidal anti-inflammatory drugs and opioids play the major role. The data on safety and effect of analgesia based on opioid and non-opioid drugs are still a controversial topic. METHODS: We compared the first-line treatment effects of diclofenac and piritramide in 105 patients after hernioplasty in a retrospective manner. The subsequent therapy combined piritramide with diclofenac. We evaluated the intensity of pain and its relief using a visual analogue scale (VAS). We also evaluated the necessity of application of other analgesics. RESULTS: One hour after the application of the first analgesic dose, we observed complete pain relief in 39.5% of patients treated with piritramide and in 19.4% of patients treated with diclofenac (chi2=5.17; p=0.02). After the use of piritramide, the pain relief (3.84 +/- 1.27 mm) was significantly higher than after diclofenac (3.34 +/- 0.77 mm). Another injection was needed in 76% and 54% of patients subjected to first-line treatment based on diclofenac and piritramide, respectively. CONCLUSION: We observed that the first-line analgesic treatment based on piritramide was more effective when compared to that based on diclofenac (Tab. 3, Ref. 3). Full Text in free PDF www.bmj.sk.

• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• diklofenak terapeutické užití   MeSH
• inguinální hernie chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti MeSH
• opioidní analgetika terapeutické užití   MeSH
• pirinitramid terapeutické užití   MeSH
• pooperační bolest farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• diklofenak MeSH
• opioidní analgetika MeSH
• pirinitramid MeSH

BACKGROUND: Polymorphisms in drug metabolizing enzymes are considered as a major factor influencing the incidence of adverse drug reactions or failure of pharmacotherapy. Our aim was to compare the distribution of functional polymorphisms in the genes CYP2D6 and CYP2C19 between healthy control group and of patients reffered to our department due to adverse drug reactions or insufficient efficacy of a treatment. METHODS AND RESULTS: The group of patients comprised of 60 subjects, 218 healthy unrelated subjects were included in the cotrol group. In both groups genotypes of CYP2D6 and CYP2C19 were analyzed. There were significantly fewer extensive metabolizers of CYP2D6 in the patient group comparison with healthy control subjects (25.0% vs. 49.8%) while the proportion of intermediate metabolizers was significantly higher than in helthy population (58.3% vs. 38.5%). We also observed more poor metabolizers than in control group (13.3% vs. 6.8%), but the difference did not reach level of statistical significance probably due to low number of subjects. The distribution of either ultrarapid metabolizers of CYP2D6 or deficient alleles of CYP2C19 was similar in both groups. CONCLUSIONS: Clinically apparent alteration of drug effects are often caused by partial or complete deficit of CYP2D6 activity. Our results confirm the importance of CYP2D6 polymorphisms on the efficycy and safety of pharmacotherapy.

• MeSH
• aromatické hydroxylasy genetika   MeSH
• cytochrom P-450 CYP2D6 genetika   MeSH
• cytochrom P450 CYP2C19 MeSH
• farmakogenetika MeSH
• farmakokinetika MeSH
• genotyp MeSH
• lidé MeSH
• oxygenasy se smíšenou funkcí genetika   MeSH
• polymorfismus genetický MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aromatické hydroxylasy MeSH
• CYP2C19 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP2D6 MeSH
• cytochrom P450 CYP2C19 MeSH
• oxygenasy se smíšenou funkcí MeSH