Transcript 01_Gastric emptying

Gastric emptying
Dr Mohammad Issa Saleh
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Gastric emptying
• After a meal, the digestible food will have
been processed to chyme and passed to
the small intestine leaving a residue of
mucus and undigested solids
• Undigested solids remain in the stomach
until the small intestine has finished
absorbing nutrients from the chyme i.e.
approximately 2 h after the last of the
digestible food has left the stomach
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Gastric emptying: Fasted state
• At this point the digestive phase of activity
ceases and is replaced by the
interdigestive phase, which is also the
normal resting condition of the stomach
and small intestine (i.e. under fasting)
• All gastric residues which the stomach has
failed to process to chyme are removed in
this phase, the migrating myoelectric
complex (MMC) or so called ‘housekeeper
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contractions’
Migrating Myoelectric Complex
(MMC)
• MMC is a propulsive movement that
empties the upper GI tract to the cecum
• Under fasting conditions, MMC occurs
every two hours until a meal is eaten
• Under fed conditions, MMC stops until 2
hours after the stomach has been cleared
of the digestible components of the meal
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Gastric emptying: Fed state
• Solids and liquids do not empty from the
stomach together as a homogeneous
mass (Figure)
• Liquids empty according to the pressure
gradient between the stomach and
duodenum, with isotonic liquid meals
emptying more rapidly than hypotonic or
hypertonic mixtures
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Gastric emptying: Fed state
• Larger particles require a longer period of
digestion to break them down into a size
suitable to exit through the pylorus
• Small indigestible solids of between 1 to 5
mm in diameter are progressively emptied
during the whole postprandial period even
before liquid emptying is completed
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Gastric emptying: liquid vs. solid
Which one is
faster?
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Gastric emptying of dosage
forms
• The gastric emptying of tablets, pellets and
liquids is highly dependent on the presence and
amount of food in the stomach
• Large disintegrating tablets disintegrate in the
stomach and empty with the digestible phase of
the meal
• Large non-disintegrating tablets will empty with
MMC. Large non-disintegrating tablet emptying
will appear erratic, occurring any time between a
few minutes and 3 hours after administration
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Gastric emptying of dosage
forms
• When a large unit is given after a light meal
(1500 kJ) the emptying becomes more
predictable at around 2 to 3 hours
• The meal serves to put the motility cycle into
phase by initiating the fed pattern until the small
calorific load has been passed to the duodenum
• The next MMC then removes the tablet
approximately 2 hours after the stomach has
been cleared of the digestible components of the
meal
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Gastric emptying of dosage
forms
• If a large single unit is given with a heavy meal
(3600 kJ) and the subject is fed at regular
intervals, the unit can remain in the stomach for
longer than 8 hours due to prolonged
suppression of the MMC
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Gastric emptying of dosage
forms
• Dosage forms are often administered to fasting
subjects during pharmacokinetic studies in an
attempt to reduce variability
• The effect of erratic emptying can affect the time
of appearance of the drug in the plasma.
• If the formulation is given with food to
synchronise motility, the absorption of the drug
can be influenced by the food
• A possible solution is to give the drug with apple
juice, which is a clear liquid, but has sufficient
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calories to synchronise gastric motility
Factors Influencing Gastric
Emptying
Factor
Influence on Gastric Emptying
1-Volume
The larger the starting volume, the greater the initial rate of emptying, after
this initial period, the larger the original volume, the slower the rate of
emptying.
2-Type of meal
A-Fatty acids
Reduction in rate of emptying is in direct proportion to their concentration
and carbon chain length; little difference is detected from acetic to octanoic
acids; major inhibitory influence is seen in chain lengths greater than 10
carbons (decanoic to stearic acids).
B-Triglycerides
Reduction in rate of emptying; unsaturated triglycerides are more effective
than saturated ones in reducing emptying rate
C-Carbohydrates Reduction in rate emptying, primarily as a result of osmotic pressure;
inhibition of emptying increases as concentration increases.
D-Amino acids
Reduction in rate of emptying to an extent directly dependent upon
concentration, probably as a result of osmotic pressure.
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Factors Influencing Gastric
Emptying
Factor
Influence on Gastric Emptying
3-Physical state of
gastric contents
Solutions or suspensions of small particles empty more rapidly than do
chunks of material that must be reduced in size prior to emptying.
4-Chemicals
A-Acids
B-Alkali (NaHCO3)
Reduction in rate of emptying dependent upon concentration and
molecular weight of the acid; lower molecular weight acids are more
effective than those of higher molecular weight (in order of decreasing
effectiveness: HCl, acetic, lactic, tartaric, citric acids).
Increased rate of emptying at low concentrations (1%), and decreased
rate at higher concentrations (5%).
5-Drugs
A-Anticholinergics
B-Narcotic
analgesics
Reduction in rate of emptying.
Reduction in rate of emptying.
C-Metoclopramide
D-Ethanol
Increase in rate of emptying.
Reduction in rate of emptying.
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Factors Influencing Gastric
Emptying
Factor
Influence on Gastric Emptying
6-Miscellaneous
A-Body position Rate of emptying is reduced in a patient laying on left side.
B-Viscosity
Rate of emptying is greater for less viscous solutions.
C-Emotional
Aggressive or stressful emotional states increase stomach contractions and
states
emptying rate; depression reduces stomach contraction and emptying.
D-Bile salts
Rate of emptying is reduced.
E-Disease states Rate of emptying is reduced in some diabetics and in patients with local
pyloric lesions (duodenal or pyloric ulcers; pyloric stenosis) and
hypothyroidism; gastric emptying rate is increased in hyperthyroidism.
F-Exercise
Vigorous exercise reduces emptying rate.
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