git physiology Flashcards
what is the only route without an absorption step
IV
Factors affecting absorption will depend on:
– The physiology of the administration site(s)
– The membrane barriers present at those
site(s) that the drug needs to cross in order to
reach the systemic circulation.
why is the oral rout popular
– It is natural and convenient for the patient
– It is relatively easy to manufacture oral
dosage forms.
• Oral dosage forms do not need to be
sterilized
• They are compact
• They can be produced in large quantities
by automated machines.
why is the oral rout popular
– It is natural and convenient for the patient
– It is relatively easy to manufacture oral
dosage forms.
• Oral dosage forms do not need to be
sterilized
• They are compact
• They can be produced in large quantities
by automated machines.
what are the different rate limiting steps
1.For a drug which has a very poor aqueous
solubility the rate at which it dissolves in the
gastrointestinal fluids is often the slowest step
• The bioavailability of that drug is said to be
dissolution-rate limited.
2.for a drug that has a high aqueous
solubility its dissolution will be rapid and the
rate at which the drug crosses the gastrointestinal
membrane may be the rate-limiting step
(permeability limited).
4– The rate of release of the drug from the dosage
form This can be by design in the case of
controlled- release dosage forms)
5– The rate at which the stomach empties the drug
into the small intestine
6– The rate at which the drug is metabolized by
enzymes in the intestinal mucosal cells during its
passage through them into the mesenteric blood
vessels
7– The rate of metabolism of drug during its initial
passage through the liver, often termed the ‘firstpass’ effect.
what is the GIT
The gastrointestinal tract is a muscular tube
approximately 6 m in length with varying diameters.
• It stretches from the mouth to the anus and consists of
four main anatomical areas:
– The oesophagus,
– The stomach
– The small intestine
– The large intestine or colon.
• The luminal surface of the tube is not smooth but very
rough thereby increasing the surface area for
absorption.
what is the GIT
The gastrointestinal tract is a muscular tube
approximately 6 m in length with varying diameters.
• It stretches from the mouth to the anus and consists of
four main anatomical areas:
– The oesophagus,
– The stomach
– The small intestine
– The large intestine or colon.
• The luminal surface of the tube is not smooth but very
rough thereby increasing the surface area for
absorption.
what are the different layers in the gait tract
– The serosa: which is an outer layer of epithelium
and supporting connective tissue;
– The muscularis externa: which contains two layers
of smooth muscle tissue
–A thinner outer layer: longitudinal in
orientation
–A thicker inner layer: whose fibers are
oriented in a circular pattern.
• Contractions of these muscles provide the forces
for movement of gastrointestinal contents;
– The submucosa,: which is a connective tissue layer
• It contains some secretory tissue
• It is richly supplied with blood and lymphatic
vessels.
• A network of nerve cells, known as the
submucous plexus, is also located in this layer;
– The mucosa: which is essentially composed of
three layers
• The muscularis mucosa
• A layer of connective tissue known as the lamina
propria
• The epithelium.
The majority of the gastrointestinal epithelium is
covered by a layer of mucus.
– It has a large water component (~95%).
– Its other primary components are large
glycoproteins called mucins.
what is the mucins
A protein backbone approximately 800 amino
acids long and
• Oligosaccharide side chains that are typically up
to 18 residues in length.
– The mucus layer ranges in thickness from 5 m to
500 m along the length of the gastrointestinal tract
(with average values of around 80 m).
how is the mucus replaced (turned over)
Mucus is constantly being removed from the luminal
surface of the gastrointestinal tract through abrasion
and acidic and enzymatic breakdown and is
continually replaced from beneath.
• Turnover time has been estimated at 4-5 hours, but
this may well be an underestimate and is liable to
vary along the length of the tract.
what is the oesophagus
The oesophagus Links the oral cavity with the
stomach
– It is composed of a thick muscular layer
approximately 250 mm long and 20 mm in
diameter.
– It joins the stomach at the gastrooesophageal
junction (or cardiac orifice).
The oesophagus contains a well differentiated
squamous epithelium of non-proliferative cells.
• The last 20 mm of oesophagus is similar to the
gastric mucosa.
Epithelial cell function is mainly protective.
• Simple mucous glands secrete mucus into the
narrow lumen to lubricate food and protect the lower
part of the oesophagus from gastric acid.
• The pH of the oesophageal lumen is usually
between 5 and 6.
Materials are moved down the oesophagus by the act of
swallowing.
Peroral administration: via the mouth.
• At this point contact with the oral mucosa is usually
brief.
what happens after swallowing
a single peristaltic wave of contraction
passes down the length of the oesophagus at the rate of
20-60 mm per second, speeding up as it progresses.
– Its amplitude linked to the size of the material being
swallowed.
• When swallowing is repeated in quick succession
– The subsequent swallows interrupt the initial
peristaltic wave
– Only the final wave proceeds down the length of the
oesophagus to the gastrointestinal junction, carrying
material within the lumen with it.
Secondary peristaltic waves occur involuntarily
in response to any distension of the oesophagus
and serve to move sticky lumps of material or
refluxed material to the stomach.
• In the upright position the transit of materials
through the oesophagus is assisted by gravity.
• The oesophageal transit of dosage forms is
extremely rapid, usually of the order of 10—14
seconds.
what is the stomach function
– To act as a temporary reservoir for ingested food and
to deliver it to the duodenum at a controlled rate.
– To reduce ingested solids to a uniform creamy
consistency, known as chyme, by the action of acid
and enzymatic digestion.
– This enables better contact of the ingested
material with the mucous membrane of the
intestines and thereby facilitates absorption.
• Another, perhaps less obvious, function of the stomach
is its role in reducing the risk of noxious agents reaching
the intestine.
what is the anatomy of the stomach
• The stomach is the most dilated part of the
gastrointestinal tract .
• It is situated between the lower end of the
oesophagus and the small intestine.
• Its opening to the duodenum is controlled by the
pyloric sphincter.
• The stomach can be divided into four anatomical
regions
– The fundus
– The body
– The antrum
– The pylorus.
what is the anatomy of the stomach
• The stomach is the most dilated part of the
gastrointestinal tract .
• It is situated between the lower end of the
oesophagus and the small intestine.
• Its opening to the duodenum is controlled by the
pyloric sphincter.
• The stomach can be divided into four anatomical
regions
– The fundus
– The body
– The antrum
– The pylorus.
The stomach under fasting conditions usually
contains no more than 50 mL of fluid, which is
mostly gastric secretions.
what are the stomach secretions
- Acid secreted by the parietal cells: which
maintains the pH of the stomach between 1
and 3.5 in the fasted state - The hormone gastrin: which itself is a potent
stimulator of gastric acid production. The
release of gastrin is stimulated by peptides,
amino acids and distension of the stomach - Pepsins:
• Secreted by the peptic cells in the form of its
precursor pepsinogen.
• They are peptidases which break down
proteins to peptides at low pH.
• Above pH 5 pepsin is denatured; - Mucus:
• Secreted by the surface mucosal cells
• It lines the gastric mucosa
• It protects the gastric mucosa from
autodigestion by the pepsin-acid
combination.
• Very little drug absorption occurs in the stomach
owing to its small surface area compared to the
small intestine.
• The rate of gastric emptying can be a controlling
factor in the onset of drug absorption from the
major absorptive site, the small intestine.
what is the small intestine function
– Digestion: the process of enzymatic digestion, which
began in the stomach, is completed in the small
intestine.
– Absorption: the small intestine is the region where
most nutrients and other materials are absorbed.
what is the small intestine anatomy
The small intestine is the longest (4-5 m) and most
convoluted part of the gastrointestinal tract
– It extends from the pyloric sphincter of the stomach to
the ileocaecal junction where it joins the large
intestine
The small intestine is divided into
– The duodenum: 200-300 mm in length
– The jejunum: approximately 2 m in length
– The ileum: approximately 3 m in length.
• The wall of the small intestine has a rich network of
both blood and lymphatic vessels.
• The gastrointestinal circulation is the largest systemic
regional vasculature and nearly a third of the cardiac
output flows through the gastrointestinal viscera.
• The blood vessels of the small intestine receive blood
from the superior mesenteric artery via branched
arterioles.
The blood leaving the small intestine flows into the
hepatic portal vein, which carries it via the liver to
the systemic circulation.
• Drugs that are metabolized by the liver are
degraded before they reach the systemic circulation:
this is termed hepatic presystemic clearance, or
first-pass metabolism.
• The wall of the small intestine also contains lacteals:
which contain lymph and are part of the lymphatic
system.
The lymphatic system is important in the
absorption of fats from the gastrointestinal tract.
• In the ileum, there are areas of lymphoid tissue
close to the epithelial surface which are known as
Peyer’s patches.
• These cells play a key role in the immune
response as they transport macromolecules and
are involved in antigen uptake
what are the adaptations that increases the small intestine size
- Folds of Kerckring:
• These are submucosal folds which extend
circularly most of the way around the intestine
• The are particularly well developed in the
duodenum and jejunum.
• They are several millimetres in depth.
2.
Villi:
–
These have been described as finger-like
projections into the lumen
–
Approximately 0.5-1.5 mm in length and 0.1 mm in
diameter.
–
They are well supplied with blood vessels.: Each
villus contains an arteriole, a venule and a
blindending lymphatic vessel (lacteal).
3.
Microvilli:
–
~ 1 m in length and 0.1 m in width.
–
Approximately 600-1000 of these brush-like
structures cover each villus
–
The provide the largest increase in surface area.
what are the secretions that increase the small intestine ph
1– Brunner’s glands
• They are located in the duodenum
• They are responsible for the secretion of
bicarbonate which neutralizes the acid emptied
from the stomach.
2– Intestinal cells
• They are present throughout the small intestine.
• They secrete mucus and enzymes.
• The enzymes, hydrolases and proteases, continue
the digestive process
3• Pancreatic secretions:
– The pancreas is a large gland which secretes about
1-2 L of pancreatic juice per day into the small
intestine via a duct.
– The components of pancreatic juice are sodium
bicarbonate and enzymes.
– The enzymes consist of proteases, principally trypsin,
chymotrypsin and carboxypeptidases, which are
secreted as inactive precursors or zymogens and
converted to their active forms in the lumen by the
enzyme enterokinase.
– Lipase and amylase are both secreted in their active
forms.
– The bicarbonate component is largely regulated by
the pH of chyme delivered into the small intestine
from the stomach.
4-bile
what are the secretions that increase the small intestine ph
1– Brunner’s glands
• They are located in the duodenum
• They are responsible for the secretion of
bicarbonate which neutralizes the acid emptied
from the stomach.
2– Intestinal cells
• They are present throughout the small intestine.
• They secrete mucus and enzymes.
• The enzymes, hydrolases and proteases, continue
the digestive process
3• Pancreatic secretions:
– The pancreas is a large gland which secretes about
1-2 L of pancreatic juice per day into the small
intestine via a duct.
– The components of pancreatic juice are sodium
bicarbonate and enzymes.
– The enzymes consist of proteases, principally trypsin,
chymotrypsin and carboxypeptidases, which are
secreted as inactive precursors or zymogens and
converted to their active forms in the lumen by the
enzyme enterokinase.
– Lipase and amylase are both secreted in their active
forms.
– The bicarbonate component is largely regulated by
the pH of chyme delivered into the small intestine
from the stomach.
4-bile