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Hello,
My name is Ravi Kanth.B. Just i am having one doubt. I have worked on
various stress models during my M.Pharm days in BITS,Pilani.It is a well
established fact that there will be elevation in Cartisol(Stress
Hormone)levels during stress. It is also a documented that as cartisol
receptors are densely peppered on the abdominal walls and due to release of
Cartisol there will be increase in fat absorption( One of the
pharmacological effect of Cartisol)which is cited as one of the reason why
people under stress are prone to become obese.
So keeping this backround in mind please clarify whether there
will be any change in the pharmacokinetic profile of highly lipophilic
drugs during stress. As there will be increase in fat absorption during
stress isn't there a chance of alteration in kinetic profile of lipophilic
drugs?
If you find any references in this regard please send to
bravikanth.-a-.hotmail.com
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Ravi,
Some references of interest to stress and gastric emptying/drug absorption
are below. From my lab we currently have a paper in press with J Vet Pharm
Therap in which digoxin absorption was 5 - 10 fold slower in dogs dosed on
admission to hospital versus those dosed at home then sampled as
outpatients - from TDM data using population approach.
Ted Whittem
===============================
Reference Type: Journal Article
Record Number: 1582
Author: Jamali, F.; Kunz-Dober, C. M.
Year: 1999
Title: Pain-mediated altered absorption and metabolism of ibuprofen: an
explanation for decreased serum enantiomer concentration after dental
surgery
Journal: British Journal of Clinical Pharmacology
Volume: 47
Issue: 4
Pages: 391-6
Label: 99249931
Keywords: Adult
Anti-Inflammatory Agents, Non-Steroidal/*pharmacokinetics
Epinephrine/pharmacology
Female
Gastric Emptying
Human
Ibuprofen/*pharmacokinetics
Male
Pain/*metabolism
Stereoisomerism
Support, Non-U.S. Gov't
Tooth Extraction
Abstract: AIMS: Rapid onset of analgesia is essential in the treatment of
acute pain. There is evidence that conditions of stress cause delayed and
decreased pain relief from oral analgesic products through impaired
absorption. The aim was to determine the effect of surgery for removal of
wisdom teeth on the plasma concentration-time profile of ibuprofen
enantiomers. METHODS: Racemic ibuprofen, 200 mg in one group (n=7) and 600
mg in another group (n=7) was administered 1 week before (control) and again
after (test) surgical removal of wisdom teeth. Serum concentrations of
ibuprofen enantiomers were measured for 6 h. RESULTS: During the control
phase, S- and R-ibuprofen concentrations were within the suggested
therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak
concentration, significant decreases in serum ibuprofen concentration
following both doses, and a fall to sub-optimal serum concentrations
following the 200 mg dose. During the first 2 h after the 200 mg dose,
dental extraction resulted in a significant reduction of the area under
serum drug concentration (AUC (0, 2 h) mg l- 1 h) from 5.6+/-2.9 to
1.6+/-1.8 (P0.01) and from 5.5+/-3.0 to 2.1+/- 2.0 (P0.05) for S and
R-ibuprofen, respectively. Similar observations were made following the 600
mg dose for AUC (0, 2 h) of S-ibuprofen (from 14.2+/-6.1 to 7.2+/-5.5 mg l-1
h, P0.05) with no significant difference for R-ibuprofen (from 14.4+/-9.5 to
5.8+/-7. 1). AUC (0, 6 h) was also significantly reduced by surgery. The
pattern of stereoselectivity in serum ibuprofen concentration was reversed
by surgery such that the S enantiomer was predominant in the control phase
but not in the post-surgery phase, which is suggestive of reduced metabolic
chiral inversion. CONCLUSIONS: Surgery for wisdom tooth removal resulted in
substantial decreases in the serum concentration of ibuprofen enantiomers
and a prolongation in the time to peak concentration. Reduced absorption and
altered metabolism are the likely cause of these changes. Thus, dental
patients may experience a delayed response and possible treatment failure
when taking ibuprofen for pain relief after surgery. Our observation may
have implications for the treatment of other diseases.
===================================
Reference Type: Journal Article
Record Number: 1583
Author: Lee, C.; Sarna, S. K.
Year: 1997
Title: Central regulation of gastric emptying of solid nutrient meals by
corticotropin releasing factor
Journal: Neurogastroenterology and Motilility
Volume: 9
Issue: 4
Pages: 221-9
Label: 98092598
Keywords: Animal
Cerebral Ventricles/drug effects/*physiology
Corticotropin-Releasing Hormone/administration & dosage/*pharmacology
Dogs
Duodenum/drug effects/physiology
Eating
Female
Gastric Emptying/*drug effects/physiology
Gastrointestinal Motility/*drug effects/physiology
Infusions, Parenteral
Male
Muscle Contraction/drug effects/physiology
Muscle, Smooth/drug effects/physiology
Pylorus/drug effects/physiology
Stomach/drug effects/physiology
Support, Non-U.S. Gov't
Support, U.S. Gov't, Non-P.H.S.
Support, U.S. Gov't, P.H.S.
Abstract: Central regulation of gastric emptying of a solid nutrient meal
and spatial and temporal parameters of gastro-pyloro-duodenal contractions
by corticotropin-releasing factor (CRF) were investigated in conscious dogs.
Intracerebroventricular (i.c.v.) infusion of CRF at 0.033 nmol kg- 1 min-1
for 15 min in a volume of 0.2 mL significantly delayed the total gastric
emptying time of the meal. I.c.v infusion of CRF also increased the mean
frequency of proximal duodenal contractions and decreased the percentage of
distally propagating contractions in the whole duodenum. The remaining
parameters of pyloric and duodenal contractions were not affected. A prior
i.c.v. infusion of I-helical CRF9-41 (0.166 nmol kg-1 min-1 for 15 min in a
volume of 0.2 mL) blocked the central effects of CRF on gastric emptying
time and the duodenal contractions. Central infusion of CRF had no
significant effect on the lag phase of gastric emptying. Bilateral truncal
vagotomy significantly delayed the gastric emptying time of the solid
nutrient meal. However, after vagotomy, i.c.v. infusion of CRF had no effect
on gastric emptying time or the spatial and temporal parameters of gastro-
pyloro-duodenal contractions. In conclusion, CRF, the mediator of stress
response, delays the total gastric emptying time of solid nutrient meals.
The delay in gastric emptying may not be due to a change in the spatial and
temporal parameters of gastric or pyloric contractions, but mainly due to
changes in the parameters of duodenal contractions. The central effects of
CRF on gastric emptying and duodenal contractions may be mediated by the
vagus nerves.
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It is probably not the pain per se but the stress response the pain elicits.
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Ravi and Ted,
Re: stress and gastric emptying (in humans)
Some years ago I had the job of finding references to delayed
gastric emptying during migraine attacks in order to justify
including metoclopramide in Paramax a mixture with paracetamol
(aminocetophen), the idea being that the metoclopramide improved
absorption of the analgesic. There wasn't much but I did find Flavell-
Matts SG 1974, Practitioner 212, 887-890. We had to do some of
our own experiments and Anna Rainbird et al 1987 ( Effect of
posture and cold stress on impedance measurements of gastric
emptying, Pharmaceut Med 2, 35-42.) tried to slow gastric
emptying by the cold stress method in a group of medical
students. They showed the postural effect but apparently,
experimental cold stress was not sufficiently severe. We later
measured gastric emptying during migraine attacks using a non-
invasive method and showed that the delay is proportional to the
pain of migraine (Boyle R, Behan PO and Sutton JA 1990. Br J Clin
Pharmacol 30, 405-409) and that the pain has to be rated at least
moderate before we found delayed emptying. I have often wondered
if the new antimigraine drugs achieve better gastric emptying, but I
have never found a reference to it.
There is the original standard work by Clements JA et al, on the
correlation between gastric emptying and acetominophen
absorption (Clin Pharmacol Therapeut 1978, 24, 420-431) and
several papers by Walter Nimmo on anaesthesia and gastric
emptying which I can give to anyone who might be interested.
The other side of the coin is that drugs that promote gastric motility
like erythromycin increase absorption which adds to the well
known metabolic interaction.
Kind regards
Andrew Sutton.
Andrew Sutton MD
Guildford Clinical Pharmacology
ASutton.-a-.gcpl.co.uk
+44 (0) 1483 406886
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Dear Dr. Sutton,
The idea of adding metoclopramide to an
anitmigraine preparation may be to offset the episodes of vomiting
associated with this condition
Dr Amit Taneja
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Dear Dr. Sutton,
The idea of adding metoclopramide to an
anitmigraine preparation may be to offset the episodes of vomiting
associated with this condition
Dr Amit Taneja
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