Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics...
-
Upload
hollie-jennings -
Category
Documents
-
view
224 -
download
1
Transcript of Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics...
![Page 1: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/1.jpg)
Prof. Flavia Franconi
University of Sassari
![Page 2: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/2.jpg)
![Page 3: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/3.jpg)
Pharmacogenetics chronopharlacology
Pharmacogenetics chronopharlacology
Drugs
Pharmacokinetics Modulators of pharmacological effects (sex hormones)
Pharmacodynamics
Efficacy and Safety
Modulators of pharmacological effects (sex hormones)
![Page 4: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/4.jpg)
The presence of critical periods
The wide use of oral anticonceptionals creates another population to be studied
![Page 5: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/5.jpg)
However, pharmacokinetic differences do not necessarily result in different pharmacological responses. For example, women in the luteal
phase are more sensitive to methylprednisolone (as measured by cortisol suppression test).
However, since they eliminate this drug more quickly than men, the final response of
methylprednisolone is similar in both sexes (Lew et al., 1993).
![Page 6: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/6.jpg)
Correlation between circulating levels of estradiol and amygdalamopioid receptor binding during the follicular phase during the follicular phase of 10 healthy women. Pearson correlation: r520.75;P , 0.01 (Smith AR et al J Clin Endocrinol Metab 83, 4498–4505, 1998
![Page 7: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/7.jpg)
Actually, it is not yet completely elucidated whether gender can influence specific organ metabolism. The topic is relevant,because in some tissues, including particular neuronal populations, CYP isoenzyme expression can be as high as, or higher than, in liver cells and can also display a higher sensitivity toward environmental inducers (Miksys and Tyndale, 2002).
Indeed, variations in the activity of brain CYP enzymes can contribute tothe inter-individual changes in drug responses,
![Page 8: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/8.jpg)
Several physiological parameters (plasma volume, sympathic and parasympathic systems) are varied in
pregnancy. The activity of some CYP is also changed, moreover, CYP enzymes are also localized in placenta
(Anderson, 2005).
![Page 9: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/9.jpg)
The time required to recovery the pre-pregnant status after the delivery regarding drug and physiological responses.
Lactation
![Page 10: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/10.jpg)
Programming is well established through experimental and epidemiological studies
[Hales C.N et al. Br Med J 303, 1019, 1991; Phillips DI Diabetlogia 39, 1119, 1996; Lithell HO et al Br Med J 312,
406, 1996; McCance et al DR Br Med J.308, 942, 1994; Phillips DI Diabetologia 37, 150, 1994; Phipps K et al
Diabetologia 36, 225–228].
![Page 11: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/11.jpg)
IVH Prevention Trial demonstrated that indomethacin significantly decreased the incidence of IVH, prevented parenchymal hemorrhage, and was associated with higher verbal test scores at ages 3 to 8 years, although this protective effect of indomethacin on cognitive outcome seemed to be specific only to male subjects
(Ment LR, Vohr B, Makuch RW, et al. Prevention of intraventricular hemorrhage by indomethacin in male preterm infants. J Pediatr. 2004;145:832–834)
![Page 12: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/12.jpg)
Neonatal treatment has different long lasting effect in males and females
![Page 13: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/13.jpg)
Psychosocial Nutrition Drug/
ChemicalsIllness Physical
INFANT
Event induced response
ADULTSCardiovascular diseases, DM, obesity, behaviour
![Page 14: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/14.jpg)
The question whether female and male have differently to placebo /nocebo effects hardly received any attention and at the moment, the issue is still controversial and largelyunderstudied. (Rickels , 1965; Wilcox et al., 1992; Compton et al, 2003; Saxon et al, 2001; Gear et al., 1999; Averbuch and Katzper, 2001; Mencke et al., 2004; Olofsen et al., 2005 ).
![Page 15: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/15.jpg)
It will be important to have standard values for single urine plasma and blood parameters referred to male and female, strains, age and hormonal cycle.
![Page 16: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/16.jpg)
it is important to know the transferability of results to humans
![Page 17: Prof. Flavia Franconi University of Sassari. Pharmacogenetics chronopharlacology Pharmacogenetics chronopharlacology Drugs Pharmacokinetics Modulators.](https://reader030.fdocuments.net/reader030/viewer/2022032313/56649e685503460f94b6405c/html5/thumbnails/17.jpg)
Gender Pharmacology
Individuate GD
Individuate them in the
single period of life
Use the biodiversity to improve the health