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Medicamentos que atuam na motilidade intestinal
Mechanism of action of laxatives
Bulk laxatives
osmotic laxatives
Mg 2+
lactulose
H2O
sterculia
salt
bran ispaghula
swells and
distends colon
H2O
cholecystokinin
stimulates motility
increases intestinal
fluid secretion
fecal softener
docusate
H2O
stimulates enteric
nervous system
stimulante (irritant) laxatives
senna danthron
area postrema
(chemoreceptor
trigger zone)
The major
soft palatene
visceral and
epiglottis
central
trachea
structures
involved in phrenoesophageal
ligament
diaphragm
the emetic
pylori sphincter
reflex
vomiting center
pharynx
esophagus
cardiac
spincter
fundus
duodenal bulb
body
cardia
duodenum
pyloric antrum
Causes and incidence of nausea
and vomiting
Alcohol
15%
food poisoning
9.5%
binge eating
7.4%
migraine
4%
induced vomiting
3.2%
food allergy
2.7%
stress
2%
travel
1.2%
Causes and incidence of nausea and
vomiting
nausea
vomiting
Percentage of respondants
80
60
40
20
0
18-30
31-60 >60
18-30
31-60 >60
The frequency of sickness in pregnancy
during the first trimester
Percentage of pregnant
women
50
nausea
40
 Daily
 Weekly
 Less often
30
20
10
0
4
6
8
12
Duration of pregnancy (weeks)
The frequency of sickness in pregnancy
during the first trimester
Percentage of pregnant
women
50
vomiting
40
 Daily
 Weekly
 Less often
30
20
10
0
4
6
8
12
Duration of pregnancy (weeks)
The major emetic stimuli, pathways, and structures mediating the
emetic reflex and nausea.
layrinth
endogenous or exogenous
toxins or drugs
VIII nerve
vestibular nucleous
in the blood stream
or cerebrospinal fluid
cerebellum
chemoreceptor trigger zone in area postrema
in the gut
vagus and/or sympathetic
nerves
mechanical stimuli
higher centers visual
olfactory emotional
anticipatory
pharynx
vomiting center: effector nuclei coordinating
the emetic reflex
salivary gastroinstestinal respiratory centers
pain
retching and vomiting
nausea
Cortex inferior frontal gyrus
cardiovascular system
H1
area
postrema
nucleus
tractus
5-HT3solitarius
DA
ACh
Chemical
transmitters
mediating
emetic
stimuli
vagal/splanchic
afferent nerves
NT
S
VC
circulation
gut
capillary
5-HT
afferent vagus
nerve
5-HT
EC
capillary
platelets
lumen
PGs
kinis
inflammation
GI irritation
chemotherapy, radiation,
Infection, drugs
Stimulus
Pain, repulsive
sights
and
smells, emotional
factors
Input
Integration
Sensory afferents
and CNS pathways
H1-receptor
antagonists,
muscarinic receptor
antagonists
Motion sickness
Dopamine antagonists,
5-HT3 antagonists
Nerves to
somatic and
visceral
receptors
CTZ
(D2 and 5-HT3
receptors)
Vomiting
centre
(mACh receptors)
Blood
Release of emetogenic
agents (5-HT, prostanoids,
free radicals)
Stimuli from
pharynx and
stomach
Higher centres
-
Labyrinth
Vestibular nuclei
(H1 and mACh receptors)
Endogenous
toxins, drugs
Output
Visceral afferents
(5-HT3 receptors?)
5-HT3
anatagonists
-
Nucleus of the
solitary tract (mACh
and H1 receptors
-
Muscarinic receptor
antagonists
-
H1-receptor
antagonists
Hyoscine
Antihistamines
Motion
Vestibular apparatus
(ear)(ACh, H1)
Metoclopramide,
Domperidone increase
gastric emptying rate
and oesophageal tone
5-HT3
anatagonists
Vomiting centre
(medullar)
(ACh, H1, 5-HT3)
Chemoreceptor
trigger zone
(4th ventricle)(D2)
Efferent
Afferent
Metoclopramide, 5HT3 antagonists
decrease sensitivity
Phenothiazines
Butyrophenones
Metoclopramide
Domperidone
Antihistamines
Receptors in pharynx
pylorus, bowel, and biliary
tree
Elevation of cardia, closure
of pylorus, contraction of
abdominal muscles
Vomiting
Vagus, sympathetic,
phrenic, and other nevers
Other stimuli,
e.g. emetics
Commonly used laxatives
1 - Bulk-forming agents
 Bran
 Ispaghula husk
 Methylcellulose
 Sterculia
3 - Gastrointestinal stimulants
 Senna
 Anthraquinones
 Danthron
 Sodium picosulfate
 Bisacodyl
 Castor oil
2 - Faecal Softeners and lubricants
 Arachis oil
 Dioctyl sodium sulfosuccinate
2 - Osmotic laxatives
 Lactulose
 Magnesium salts
 Sodium salts
Drugs used in the symptomatic treatment of diarrhoea
1 - Drugs that alter gastrointestinal molity
 Codeine
 Diphenoxylate (combined with
atropine in Lomotil®)
 Loperamide
 Morphine
2 – Fluid adsorbents
 Kaolin
3 – Fluid absorbents
 Bulk-forming agents
4 – Drugs used in specific circumstances
 Indomethacin (radiation-induced
enteritis)
 Cholestyramine (diarrhoea due to
excess bile acids
 Pancreatic enzymes (pancreatic
malabsorption)
Daily Secretion of Intestinal Juices
Daily Volume (ml)
pH
• Saliva
1000
6.0 – 7.0
• Gastric secretion
1500
1.0 – 3.5
• Pancreatic secretion
1000
8.0 – 8.3
• Bile
1000
7.8
• Small intestine secretion
1800
7.5 – 8.0
• Brunner’s gland secretion
200
8.0 – 8.9
• Large intestinal secretion
200
7.5 – 8.0
TOTAL
6700
Postulated mechanism for the secretion of hydrochlric acid
Extracellular fluid
Parietal cell
CO2
CO2
HCO3
HCO3-
K+
Lumen of canaliculus
H2 O
H+ (155 mEq/L)
CO2 + OH- + H+
P
K+
K+
K+ (15 mEq/L)
Na+
Na+
Na+ (3 mEq/L)
P
Na+
P
Cl-
H2 O
Cl-
Cl(Osmosis)
P
Cl- (173 mEq/L)
H2 O
Secretion of isosmotic sodium bicarbonate solution by the
pancreatic ductules and ducts
Bloo
d
Ductule cells
Na+
Na+
H+
H+
Lumen
Na+
HCO3
HCO3(Active transport)
(Active transport)
H2CO3
(Carbonic
anyhydrase)
H2O
CO2
H2 O
CO2
H2O
Vagus
nerve
Cholesresis
Cholecystokinin
Secretin
Stimulate
secretion
Stimulate
secretion
Hormones of the
Gastrointestinal
Tract
HCI
Inhibit
secretion
Stimulated
motility
Food
acid
Food
distention
Inhibit
motility
Secretin
Enzymes
Water, bicarbonate
Pancreas
GIP
Food fat
Food fat
Motilin
Neuroendocrine cel
Stimulates
smooth
muscle
Thick line indicates
primary action
Thin lin indicates
secondary action
Hormones of the Gastrointestinal Tract
Hormone
Neuroendocrine Cell
Type and Location
Gastrin
G cell
Stomach, duodenum
Vagus, destention,
amino acids
Stimulate HCl secretion
Inhibit gastric emptying
Secretin
S cell
Duodenum
Acid
Stimulate pancreatic
ductal cell H2O and
HCO3- secretion
Inhibit gastric secretion, inhibit
gastric motility, and stimulate bile
duct secretion of H2O and HCO3-
Cholecystokinin
I cell
Duodenum, jejunum
Fat, vagus
Stimulate enzyme
secretion by pancreatic
acinar cells and contract
the gallbladder
Inhibit gastric motility
GIP
K cell
Duodenum, jejunum
Fat
Inhibit gastric secretion
and motility
Stimulate insulin secretion
Motilin
M cell
Duodenum, jejunum
Stimuluis for Secretion Primary Action
Increase motility and
initiate the MMC
Other Action
Drugs used for the tratment of constipation
A variety of bulk-forming laxatives
including bran, ispaghula, sterculia,
methylcellulose
Senna
Minimal absorption: action takes up to 12
hours given orally and less than 2 hours
rectally
Bisacodyl
Administered orally or rectally
Minimal absorption but relatively quick action
after 6-8 hours orally but less than 60 minutes rectaly
Lactulose
Poorly absorbed orally and broken down to
active acids in the colon
Takes 1-2 days to act
Docusate
Surfactant action. Minimally absorbed. Acts in up to 3 days
Magnesium sulfate
Acts within 6 hours. Up to 30% absorbed. Renal elimination
Danthron
An animal carcionogen restricted for use in terminally ill
Liver damage
Sodium picosulfate
Used only as a preoperative bowel preparation
Int. Pharmacology – Chapter 21
Drugs and inflammatory bowel disease
● Aminosalicylates such as mesalamine and olsalazine maintain remission
● Glucocorticosteroids are effective for acute relapse of the disease
● Poorly absorbed glucocorticosteroids (e.g. budesonide) have little effect
on the hypothalamic-pituitary-adrenal axis
● Nonsteroidal anti-inflammatory drugs exarcerbate inflammatory
Int. Pharmacology – Chapter 21
Mechanism of action of some drugs
that cause jaundice
Mechanism
Hemolysis
bilirubin production)
Drug
Antimalarials
Sulfonamides
Aspirin
Phenacetin
Cephalosporins
Methyldopa
Commen
Occurs in people with glucose-6- (increased
phosphate dehydrogenase (G6PD)
Immunologic basis
Altered Hepatic bilirubin uptake
Rifampin
Hepatotoxicity
Caebon tetrachloride
Acetaminophen overdose
Tetracycline
Treat with N-acetylcysteine
Avoid in pregnancy
Diffuse hepatocellular damage
Tricyclic antidepressants
Isoniazid
Uncommon
Related to dose and patient’s age
Intrahepatic Cholestasis
Anbolic steroids
Phenothiazines
Erythromycin
Int. Pharmacology – Chapter 21
Incidence probably not related to
type of salt used (e.g. Estolate)
Causes and incidence of nausea and vomiting
9,5%
7,4%
Binge eating
Migraine
4%
3,2%
Induced vomiting
Food allergy
travel
2,7%
2%
1,2%
Percentage of respondants
Food poisoning
Stress
80
15%
Acohol
nausea
vomiting
18-30 31-60 >60
18-30 31-60 >60
60
40
20
0
Age (year)
Int. Pharmacology – Chapter 21
Pivotal events nausea and emesis
● Relaxantion of the esophagus, esophageal sphincter, cardiac
sphincter, and fundus and body of the stomach
● Contraction of the upper small intestine and pyloric stomach,
emptying their contents int the relaxed stomach
● Deep inspiration and closure of the glottis and raising of the soft
palate
● Rhythmic contraction of the diaphragm and abdominal muscles to
compress the stomach and evacuate its contents via the mouth
Int. Pharmacology – Chapter 21
The frequency of sickness in pregnancy during the
first trimester
50
50
nausea
vomiting
40
Percentage of pregnant women
Percentage of pregnant women
40
30
20
10
0
4
6
8
Duration of pregnancy (weeks)
Int. Pharmacology – Chapter 21
20
10
0
4
12
Daily
30
6
8
12
Duration of pregnancy (weeks)
Weekly
Less often
Emetic potential of chemotherapeutic drugs
Severely emetogenic in
almost all patients
Moderately
emetogenic
Cisplatin
Mitomycin C
5-Fluorouracil
Mustine
Procarbazine
Cytarabine
Cyclophosphamide
Nitrosoureas
6-Mercaptopurine
Least emetogenic
Dacarbazine
Bleomycin
Doxorubicin
Vinblastine
Doxorubicin
Vinsristine
Int. Pharmacology – Chapter 21
Major stimuli of nausea and vomiting
● Gastrointestinal irritation
● Motion sckness
● Hormone disturbance
● Intracranial pathology
● Metabolic disieders
● Psychogenic factors
● Pain
● Drugs and radiation
● Endogenous Toxins
Int. Pharmacology – Chapter 21
The number of women who reported sickness with
oral contraceptives, travel, or migraine and the
relationship to vomiting in pregnancy
Pregnancy
sickness
Oral
contraceptive
sickness
Travel
sickness
Migraine
sickness
Vomiting
30 (70%)
77 (63%)
45 (65%)
No vomiting
13 (30%)
46 (37%)
24 (35%)
Int. Pharmacology – Chapter 21
The major emetic stimuli, pathways, and structures mediating the emetic reflex and nausea
labyrinth
Endogenous or oxgenous toxins or drugs
VIII nerve
In the blood stream or cerebrospinal fluid
Vstibular nucleus
Chemoreceptor trigger zone in
area postrema
In the gut
Mechanical
stimuli
Vagus and/or
sympathetic nerves
cerebellum
Higher centers visual olfactory
emotional anticipatory
Vomiting center: effector nuclei
coordinating the emetic reflex
Salivary
gastrointestinal respiratory
centers
Pharynx
Pain
Int. Pharmacology – Chapter 21
Retching and vomiting
nausea
Cardiovascular system
Cortex inferior
frontal gyrus
Opioid-induced bowel dysfunction: prevalence, pathophysiology and burden
Journal compilation ª 2007 Blackwell Publishing Ltd Int J Clin Pract, July 2007, 61, 7, 1181–1187
Medications known to cause chronic constipation
Prescription
Over-the-Cou nter
Opiates
Antacids, especially those containing calcium
Anticholinergic agents
Calcium supplements
Tricyclic antidepressants
Iron supplements
Calcium channel blockers
Antidiarrheal agents
Antiparkinsonian agents
NSAIDs
Sympathomimetic agents
Antipsychotic agents
Diuretics
Antihistamines
Lubiprostone: Chloride Channel Activator for Chronic Constipation - Clinical Therapeutics/Volume 28, Number 12, 2006
Selected laxatives, their usual doses, and adverse effects
Lubiprostone: Chloride Channel Activator for Chronic Constipation - Clinical Therapeutics/Volume 28, Number 12, 2006
Selected laxatives, their usual doses, and adverse effects (cont)
Lubiprostone: Chloride Channel Activator for Chronic Constipation - Clinical Therapeutics/Volume 28, Number 12, 2006
Selected laxatives, their usual doses, and adverse effects (Cont)
Lubiprostone: Chloride Channel Activator for Chronic Constipation - Clinical Therapeutics/Volume 28, Number 12, 2006
Summary of efficacy data for various classes of laxatives
Lubiprostone: Chloride Channel Activator for Chronic Constipation - Clinical Therapeutics/Volume 28, Number 12, 2006
Probiotics for maintenance of remission in Crohn’s disease
Implications for practice
There is no evidence that probiotic preparations are
superior to placebo or aminosalicylates for the maintenance
of remission in patients with Crohn’s disease .
It should be noted that aminosalicylates are probably
not effective for maintenance of remission in Crohn’s disease
(Akobeng 2005). The use of probiotics as maintenance
therapy for medically or surgically induced remission in
Crohn’s disease cannot be recommended at this time.
Rolfe VE, Fortun PJ,Hawkey CJ, Bath-Hextall FJ. Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews
2006, Issue 4.
Probiotics for maintenance of remission in Crohn’s disease
Implications for research
Some probiotic agents may warrant further study. The
limitations of small-scale studies should be taken into
account, and larger scale studies are currently underway in
Europe and the US. Better designed studies of probiotic
treatment (dosage, duration and species) are required to
determine the role of probiotics in CD treatment.
Future trials should ensure consistent reporting of
safety results, the dosage of probiotic(s) administered and
levels of prebiotics and probiotics in the diet of the patient.
Studies should evaluate the viability of live probiotic
preparations, and gain an understanding of the levels already
within the gastrointestinal tract prior to the start of the trial.
Rolfe VE, Fortun PJ,Hawkey CJ, Bath-Hextall FJ. Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database of Systematic Reviews
2006, Issue 4.
Antiemetics for reducing vomiting related to acute gastroenteritis in
children and adolescents (Review)
Implications for practice
It appears that ondansetron may reduce the amount of acute vomiting as
well as reducing the number of children who required intravenous rehydration, and
admission for acute gastroenteritis.
However this conclusion is only based on four studies. In addition,
participants in the ondansetron group did have more diarrhoea than in the placebo
group, but the amount is likely not clinically significant.
Alhashimi D, Al-Hashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic
Reviews 2009, Issue 2.
Antiemetics for reducing vomiting related to acute gastroenteritis in
children and adolescents (Review)
Implications for practice
The four included trials reported on two possible routes of administration for
two
antiemetics;
either
oral
or
intravenous
ondansetron
or
intravenous
metoclopramide.
It is conceivable that in the presence of persistent vomiting the intravenous
single dose of ondansetron, if available,may offer some advantages over the oral
route particularly in that the intravenous route is most likely to obviate any further
irritation to the gastric mucosa.
Alhashimi D, Al-Hashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic
Reviews 2009, Issue 2.
Antiemetics for reducing vomiting related to acute gastroenteritis in
children and adolescents (Review)
Implications for research
In view of the likelihood of a higher incidence of gastroenteritis in
developing countries the importance of further research into the effectiveness and
cost effectiveness of antiemetics cannot be underestimated, particularly if this may
lead to a reduction in the frequency with which costly intravenous fluids and
hospitalisation are required.
Alhashimi D, Al-Hashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic
Reviews 2009, Issue 2.
Antiemetics for reducing vomiting related to acute gastroenteritis in
children and adolescents (Review)
Implications for research
Future research should also focus on outcomes that are of relevance to
patients and thus the time to cessation of vomiting rather than a reduction in the
number of episodes of vomiting as outcomes would appear to be more appropriate.
Alhashimi D, Al-Hashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic
Reviews 2009, Issue 2.
Classification of Laxative and Antidiarrheal Agentsileus: time
to first bowel movement
Site: http://www.numarklabs.com/images/evalable1.jpg
Molecular structure of domperidone
Savio C. Reddymasu, M.D., Irfan Soykan, M.D., and Richard W. McCallum, M.D.. Domperidone: Review of Pharmacology and Clinical Applications in Gastroenterology. Am J
Gastroenterol 2007;102:2036–2045
Mechanisms of action of domperidone
Savio C. Reddymasu, M.D., Irfan Soykan, M.D., and Richard W. McCallum, M.D.. Domperidone: Review of Pharmacology and Clinical Applications in Gastroenterology. Am J
Gastroenterol 2007;102:2036–2045
Probiotics for pediatric antibiotic-associated diarrhea: a
meta-analysis of randomized placebo-controlled trials
Six studies were included (total n = 707 patients).
The combined results, analyzed with a per-protocol method that reported
on the incidence of diarrhea during antibiotic treatment, showed significant benefit
for the use of probiotics over placebo (relative risk [RR] 0.43, 95% confidence
interval [CI] 0.25–0.75, I2 = 70.1%).
In contrast, results from intention-to-treat analysis were nonsignificant
overall (RR 1.01, 95% CI 0.64–1.61).
Bradley C. Johnston, Alison L. Supina, Sunita Vohra. Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ •
August 15, 2006 • 175(4) | 377.
Probiotics for pediatric antibiotic-associated diarrhea: a metaanalysis of randomized placebo-controlled trials
Subgroup analysis on 4 studies that provided at least 5 billion singlestrain colony-forming units (CFUs) daily (range 5.5–40 × 109
Lactobacillus
GG, L. sporogens or Saccharomyces boulardii ) showed strong evidence with
narrow CIs for the preventative effects of probiotics for antibiotic-associated
diarrhea (RR 0.36, 95% CI 0.25–0.53, I2 = 3.5%).
No serious adverse events were reported.
Bradley C. Johnston, Alison L. Supina, Sunita Vohra. Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ •
August 15, 2006 • 175(4) | 377.
Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of
randomized placebo-controlled trials
Interpretation: The potential protective effects of probiotics to prevent
antibiotic-associated diarrhea in children do not withstand intention-to-treat
analysis.
Before routine use is recommended, further studies (with limited losses
of subjects to follow-up) are merited.
Trials should involve those probiotic strains and doses with the most
promising evidence (i.e., Lactobacillus GG, L. sporogens or S. boulardii at 5–40
× 109 CFUs daily).
Bradley C. Johnston, Alison L. Supina, Sunita Vohra. Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ •
August 15, 2006 • 175(4) | 377.
Model for antidiarrheal action of zinc in intestinal cells
Angus G. Scrimgeoura and Henry C. Lukaskib. Zinc and diarrheal disease: current status and future perspectives. Curr Opin Clin Nutr Metab Care 11:711–717, 2008.
Opioid Action in the Intestinal Tract
Anthony De Luca*t and lan M. Coupart. Insights into Opioid Action in the Intestinal Tract. Pharmacol. Ther. Vol. 69, No. 2, pp. 103-115, 1996.
Pathogenic mechanism of acute infectious diarrhoea
R. Tormo, I. Polanco, E.Salazar-L, O. Goulet. Acute infectious diarrhoea in children: new insights in antisecretory treatment with racecadotril. Foundation Acta Pædiatrica/Acta
Pædiatrica 2008 97, pp. 1008–1015. 2008.
Mechanism of acute diarrhoeal illness caused by rotavirus
R. Tormo, I. Polanco, E.Salazar-L, O. Goulet. Acute infectious diarrhoea in children: new insights in antisecretory treatment with racecadotril. Foundation Acta Pædiatrica/Acta
Pædiatrica 2008 97, pp. 1008–1015. 2008.
Mechanism of action of racecadotril
R. Tormo, I. Polanco, E.Salazar-L, O. Goulet. Acute infectious diarrhoea in children: new insights in antisecretory treatment with racecadotril. Foundation Acta Pædiatrica/Acta
Pædiatrica 2008 97, pp. 1008–1015. 2008.
CFTR activators and inhibitors
Jay R Thiagarajah and AS Verkman. CFTR pharmacology and its role in intestinal fluid secretion. Current Opinion in Pharmacology 2003, 3:594–599.
Identification of CFTR inhibitors by high-throughput screening
Jay R Thiagarajah and AS Verkman. CFTR pharmacology and its role in intestinal fluid secretion. Current Opinion in Pharmacology 2003, 3:594–599.
Intestinal secretory pathways
Jay R Thiagarajah and AS Verkman. CFTR pharmacology and its role in intestinal fluid secretion. Current Opinion in Pharmacology 2003, 3:594–599.
Antidiarrheal properties of a CFTR inhibitor
Jay R Thiagarajah and AS Verkman. CFTR pharmacology and its role in intestinal fluid secretion. Current Opinion in Pharmacology 2003, 3:594–599.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Approved and investigational agents for the treatment of IBS
Michael J. Callahan. Irritable Bowel Syndrome Neuropharmacology. A Review of Approved and Investigational Compounds. J Clin Gn.\r~oerire,v/ 2002:35(Suppl.):S58-S67.
Structure of ADL 8-2698
(+)-[[2(S)-[[4(R)-(3-hydroxyphenyl)-3(R),4-dimethyl-1-piperidinyl]-methyl]-1-oxo-3-phenylpropyl]amino]acetic acid dihydrate.
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Whole-body autoradiographs (rat) with [14C]ADL 8-2698
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Early clinical study
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 prevents morphine delay in oral-cecal transit time
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 does not reverse morphine analgesia
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 clinical benefits in opioid bowel dysfunction
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 in long-term opioid-treated patients: time to first bowel movement
response
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Overall satisfaction with bowel movement
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 clinical benefits in 4-day progressive dose study
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 clinical benefits in postoperative ileus
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Postoperative ileus: time to first bowel movement
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Postoperative ileus: time to tolerability of solid food
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
Postoperative ileus: time to actual hospital discharge
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.
ADL 8-2698 reduced nausea and vomiting in postoperative ileus
William K. Schmidt, Ph.D. . Alvimopan (ADL 8-2698) Is a Novel Peripheral Opioid Antagonist. The American Journal of Surgery 182 (Suppl to November 2001) 27S–38S.