Gastrointestinal Drugs
Dr. Manoj Sharma
✓In addition to its main function of digestion and
absorption of food, the gastrointestinal tract is one of
the major endocrine systems in the body and has its
own integrative neuronal network, the enteric nervous
system.
✓which contains almost the same number of neurons
as the spinal cord.
THE INNERVATION AND HORMONES OF THE
GASTROINTESTINAL TRACT :-
•The blood vessels and the glands (exocrine, endocrine and paracrine) that comprise the
gastrointestinal tract are under both neuronal and hormonal control
1. NEURONAL CONTROL:-
There are two principal intramural plexuses in the tract:
• Myenteric plexus (Auerbach’s plexus): B/W outer, longitudinal and middle, circular
muscle layers, and
•Submucous plexus (Meissner’s plexus): on the lumenal side of the circular muscle layer.
✓These plexuses are interconnected, and their ganglion cells receive preganglionic
parasympathetic fibres from the vagus, which are mostly cholinergic and excitatory, although a
few are inhibitory.
✓Incoming sympathetic fibres are largely postganglionic, and these, in addition to innervating
blood vessels, smooth muscle and some glandular cells directly, may terminate in these plexuses,
where they inhibit acetylcholine secretion.
✓The neurons within the plexuses constitute the enteric nervous system and secrete not only
acetylcholine and noradrenaline (norepinephrine), but also 5-hydroxytryptamine, purines, nitric
oxide and a variety of pharmacologically active peptides.
✓The enteric plexus also contains sensory neurons, which respond to mechanical and chemical
stimuli.
2. HORMONAL CONTROL :-
•The hormones of GIT include both:-
1. Endocrine secretion and
2. Paracrine secretions.
•The endocrine secretions (i.e. substances released into the bloodstream) are mainly peptidic in
nature and are synthesised by endocrine cells in the mucosa. e.g. gastrin and cholecystokinin.
•The paracrine secretions include many regulatory peptides released from special cells found
throughout the wall of the tract.
•These hormones act on nearby cells, and in the stomach: mainly is histamine.
•Some of these paracrine factors also function as neurotransmitte.
✓Orally administered drugs are absorbed in the GIT .
✓The main functions of GIT that are important from the viewpoint of
pharmacological intervention are:
•Gastric Secretion
•Vomiting (emesis)
•Motility of the bowel and the expulsion of the faeces
•Formation and excretion of bile
GASTRIC SECRETION:-
• The stomach secretes about 2.5 litres of gastric juice daily.
• The principal exocrine secretions are proenzymes such as
• Prorennin and Pepsinogen from chief or peptic cells, and
•hydrochloric acid (HCl) and intrinsic factor secreted by the parietal or oxyntic cells.
•Mucus-secreting cells abound among the surface cells of the gastric mucosa.
•Bicarbonate ions are also secreted and are trapped in the mucus, creating a gel-like
protective barrier that maintains the mucosal surface at a pH of 6-7 in the face of a much
more acidic environment (pH 1-2) in the lumen.
• Alcohol and bile can disrupt this layer.
•Locally produced ‘cytoprotective’ prostaglandins stimulate the secretion of both mucus and
bicarbonate.
•Disturbances in these secretory and protective mechanisms are thought to be involved in
the pathogenesis of peptic ulcer, and the therapy of this condition includes drugs that
modify each of these factors.
THE REGULATION OF ACID SECRETION BY PARIETAL CELLS :-
•The regulation of acid secretion by parietal cells is especially important in the pathogenesis of peptic
ulcer, and constitutes a particular target for drug action.
• The secretion of the parietal cells is an isotonic solution of HCl (150 mmol/l) with a pH < 1,
•The concentration of hydrogen ions being more than a million times higher than that of the plasma.
•The Cl- is actively transported into canaliculi in the cells that communicate with the lumen of the
gastric glands and thus with the stomach itself.
• This Cl- secretion is accompanied by K+, which is then exchanged for H+ from within the cell by a
K+/H+ ATPase (+ and bicarbonate ions. The latter exchanges across the basal membrane of the
parietal cell for Cl-.
•The principal stimuli acting on the parietal cells are:
•Gastrin (a stimulatory hormone)
•Acetylcholine (a stimulatory neurotransmitter)
•Histamine (a stimulatory local hormone)
•Prostaglandins E2 and I2 (local hormones that inhibit acid secretion
Gastrin :-
Gastrin is a peptide hormone synthesised in endocrine cells of the mucosa of the
gastric antrum and duodenum, and secreted into the portal blood.
Its main action is stimulation of the secretion of acid by the parietal cells, but
there is controversy about the precise mechanism of stimulatory action.
Gastrin also indirectly increases pepsinogen secretion, stimulates blood flow
and increases gastric motility.
Release of this hormone is controlled both by neuronal transmitters and blood-
borne mediators, as well as the chemistry of the stomach contents.
Gastrin secreation is inhibited when PH of the gastric content falls to2.5 or
lower.
Acetylcholine:
It is released from (e.g. vagal) neurons and stimulates specific muscarinic receptors on the surface
of the parietal cells and on the surface of histamine-containing cells.
Histamine:
•Histamine play important role in gastric secretion.
•Within the stomach, mast cells (or histamine-containing cells similar to mast cells) lying close to
the parietal cell release a steady basal release of histamine, which is further increased by gastrin
and acetylcholine.
•The hormone acts on parietal cell H2 receptors, which are responsive to histamine concentrations
that are below the threshold required for vascular H2 receptor activation
The coordinated role of acetylcholine, histamine and gastrin in
regulating acid secretion :-
Secretion of gastric acid, mucus and bicarbonate
•The control of the gastrointestinal tract is through nervous and humoral mechanisms.
• Acid is secreted from gastric parietal cells by a proton pump (K+/H+ ATPase).
• The three endogenous secretagogues for acid are histamine, acetylcholine and
gastrin.
• Prostaglandins E2 and I2 inhibit acid, stimulate mucus and bicarbonate secretion,
and dilate mucosal blood vessels.
•The genesis of peptic ulcers involves:
• infection of the gastric mucosa with Helicobacter pylori.
• an imbalance between the mucosal-damaging (acid, pepsin) and the mucosal-
protecting agents (mucus, bicarbonate, prostaglandins E2 and I2, and nitric oxide
A Gastric Peptic Ulcer
Therapy of peptic ulcer and reflux oesophagitis:-
• Aims to decrease the secretion of gastric
Antacids are the simplest of all the therapies for treating the symptoms of excessive gastric acid
secretion. They directly neutralise acid, thus raising the gastric pH; this also has the effect of inhibiting
the activity of peptic enzymes, which practically ceases at pH 5. Given in sufficient quantity for long
enough, they can produce healing of duodenal ulcers but are less effective for gastric ulcers.
Most antacids in common use are salts of magnesium and aluminium. Magnesium salts cause diarrhoea
and aluminium salts constipation, so mixtures of these two can, happily, be used to preserve normal
bowel function. Some preparations of these substances (e.g. magnesium trisilicate mixture and some
proprietary aluminium preparations) contain high concentrations of sodium and should not be given to
patients on a sodium-restricted diet. Numerous antacid preparations are available; a few of the more
significant are given below.
Magnesium hydroxide is an insoluble powder that forms magnesium chloride in the stomach. It does
not produce systemic alkalosis, because Mg2+ is poorly absorbed from the gut. Another salt,
magnesium trisilicate, is an insoluble powder that reacts slowly with the gastric juice, forming
magnesium chloride and colloidal silica. This agent has a prolonged antacid effect, and it also adsorbs
pepsin
Aluminium hydroxide gel forms aluminium chloride in the stomach; when this reaches the intestine, the chloride is released and is
reabsorbed. Aluminium hydroxide raises the pH of the gastric juice to about 4, and also adsorbs pepsin. Its action is gradual, and its
effect continues for several hours.2 Colloidal aluminium hydroxide combines with phosphates in the gastrointestinal tract, and the
increased excretion of phosphate in the faeces that occurs results in decreased excretion of phosphate via the kidney. This effect has been
used in treating patients with chronic renal failure (see Ch. 24, p. 382).
•Sodium bicarbonate acts rapidly and is said to raise the pH of gastric juice to about 7.4. Carbon dioxide is liberated, and this causes
eructation (belching). The carbon dioxide stimulates gastrin secretion and can result in a secondary rise in acid secretion. Because some
sodium bicarbonate is absorbed in the intestine, large doses or frequent administration of this antacid can cause alkalosis, the onset of
which can be insidious. To avoid this possibility, sodium bicarbonate should not be prescribed for long-term treatment, nor should it be
given to patients who are on a sodium-restricted diet.
Alginates or simeticone are sometimes combined with antacids. The former are believed to increase the viscosity and adherence of
mucus to the oesophageal mucosa, forming a protective barrier (see also below), whereas the latter is a surface active compound that, by
preventing ‘foaming’, can relieve bloating and flatulence.
THE MOTILITY OF THE GASTROINTESTINAL TRACT:-
Drugs that alter the motility of the gastrointestinal tract include:
•Purgatives, which accelerate the passage of food through the intestine
•Agents that increase the motility of the gastrointestinal smooth muscle without causing
purgation
•Antidiarrhoeal drugs, which decrease motility
•Antispasmodic drugs, which decrease smooth muscle tone
PURGATIVES:-
•The transit of food through the intestine may be hastened by several different
types of drugs, including –
➢Laxatives,
➢Faecal softeners and
➢Stimulant Purgatives.
•These agents may be used to relieve constipation or to clear the bowel prior to
surgery or examination.
➢Bulk and osmotic laxatives
The bulk laxatives include
• Methylcellulose and
• Certain plant extracts such as Sterculia, Agar, Bran and Ispaghula husk.
• These agents are polysaccharide polymers that are not broken down by the normal
processes of digestion in the upper part of the GIT.
•They form a bulky hydrated mass in the gut lumen promoting peristalsis and
improving faecal consistency.
•They may take several days to work but have no serious unwanted effects.
•The osmotic laxatives consist of –
poorly absorbed solutes-the saline purgatives-and lactulose.
•The main salts in use are magnesium sulfate and magnesium hydroxide.
•By producing an osmotic load, these agents trap increased volumes of fluid in the lumen of the
bowel, accelerating the transfer of the gut contents through the small intestine.
• This results in an abnormally large volume entering the colon, causing distension and purgation
within about an hour. Abdominal cramps can occur..
Faecal softeners:-
•Docusate sodium is a surface-active compound that acts in the gastrointestinal tract in a manner
similar to a detergent and produces softer faeces.
•It is also a weak stimulant laxative.
• Other agents that achieve the same effect include arachis oil, which is given as an enema, and
liquid paraffin, although this is now seldom used.
Stimulant laxatives
The stimulant laxative drugs act mainly by increasing electrolyte and hence water secretion by
the mucosa, and also by increasing peristalsis-possibly by stimulating enteric nerves. Abdominal
cramping may be experienced as a side effect with almost any of these drugs.
•Bisacodyl may be given by mouth but is often given by suppository. In the latter case, it stimulates
the rectal mucosa, inducing defecation in 15-30 minutes.
• Glycerol suppositories act in the same manner.
• Sodium picosulfate and docusate sodium have similar actions. The former is given orally and is
often used in preparation for intestinal surgery or colonoscopy.
•Senna and dantron are anthroquinone laxatives. The active principle (after hydrolysis of glycosidic
linkages in the case of the plant extract, senna) directly stimulates the myenteric plexus, resulting in
increased peristalsis and thus defecation.
•Another member of the family is dantron. As this drug is a skin irritant and may be carcinogenic.
DRUGS THAT INCREASE GASTROINTESTINAL MOTILITY
Domperidone is primarily used as an antiemetic. but it also increases gastrointestinal motility
(although the mechanism is unknown).
Clinically, it increases lower oesophageal sphincter pressure (thus inhibiting gastro-
oesophageal reflux), increases gastric emptying and enhances duodenal peristalsis.
It is useful in disorders of gastric emptying and in chronic gastric reflux.
Metoclopramide (also an antiemetic) stimulates gastric motility, causing a marked
acceleration of gastric emptying.
It is useful in gastro-oesophageal reflux and in disorders of gastric emptying, but is
ineffective in paralytic ileus.
Cisapride stimulates acetylcholine release in the myenteric plexus in the upper
gastrointestinal tract through a 5-HT4 receptor-mediated effect.
This raises oesophageal sphincter pressure and increases gut motility.
The drug was used for treating reflux oesophagitis and in disorders of gastric emptying.
ANTIDIARRHOEAL AGENTS :-
•Diarrhoea is the frequent passage of liquid faeces, and this is generally accompanied by
abdominal cramps and sometimes nausea and vomiting.
•It may be viewed as a physiological mechanism for rapidly ridding the gut of poisonous or
irritating substances.
•There are numerous causes, including underlying disease, infection, toxins and even anxiety
•It may also arise as a side effect of drug or radiation therapy.
During an episode of diarrhoea, there is an increase in the motility of GIT, accompanied by
an increased secretion coupled with a decreased absorption of fluid, which leads to a loss of
electrolytes (particularly Na+) and water.
Cholera toxins and some other bacterial toxins produce a profound increase in electrolyte
and fluid secretion by irreversibly activating the guanine nucleotide regulatory proteins that
couple the surface receptors of the mucosal cells to adenylate cyclase
There are three approaches to the treatment of severe acute diarrhoea:
•maintenance of fluid and electrolyte balance
•use of anti-infective agents
•use of spasmolytic or other antidiarrhoeal agents.
The maintenance of fluid and electrolyte balance by means of oral rehydration is the first
priority, and wider application of this cheap and simple remedy could save the lives of many
infants in the developing world.
Many patients require no other treatment. In the ileum, as in parts of the nephron, there is
cotransport of Na+ and glucose across the epithelial cell. The presence of glucose (and some
amino acids) therefore enhances Na+ absorption and thus water uptake.
Preparations of sodium chloride and glucose for oral rehydration are available in powder
form, ready to be dissolved in water before use.
ANTIMOTILITY AND SPASMOLYTIC AGENTS
The main pharmacological agents that decrease motility are opiates and muscarinic receptor
antagonists.
Agents in this latter group are seldom employed as primary therapy for diarrhoea because of
their actions on other systems, but small doses of atropine are used, combined with
diphenoxylate.
The main opiates used for the symptomatic relief of diarrhoea are-
Codeine (a morphine congener),
Diphenoxylate and
Loperamide
(both pethidine congeners that do not readily penetrate the blood-brain barrier and are used
only for their actions in the gut).
All may have unwanted effects including constipation, abdominal cramps, drowsiness and
dizziness. Paralytic ileus can also occur. They should not be used in young (< 4 years of age)
children.
Loperamide is the drug of first choice for traveller’s diarrhoea and is a component of several
proprietary antidiarrhoeal medicines.
It has a relatively selective action on the gastrointestinal tract and undergoes significant
enterohepatic cycling. It reduces the frequency of abdominal cramps, decreases the passage of
faeces and shortens the duration of the illness.
•Muscarinic receptor antagonists decrease spasm by inhibiting parasympathetic
activity.
•Agents available include atropine, hyoscine, propantheline and dicycloverine. The
last named is thought to have some additional direct relaxant action on smooth
muscle.
•Mebeverine, a derivative of reserpine , has a direct relaxant action on gastrointestinal
smooth muscle. Unwanted effects are few
Adsorbents:-
Adsorbent agents are used extensively in the symptomatic treatment of diarrhoea,
The main preparations used contain
kaolin, pectin, chalk, charcoal, methyl cellulose and magnesium/ aluminium silicate).
It has been suggested that these agents may act by adsorbing micro-organisms or toxins,
by altering the intestinal flora or by coating and protecting the intestinal mucosa,
They are often given as mixtures with other drugs (e.g. kaolin and morphine mixture).
DRUGS AFFECTING THE BILIARY SYSTEM:-
•The commonest pathological condition of the biliary tract is cholesterol cholelithiasis,
• i.e. the formation of gallstones with high cholesterol content.
• Surgery is generally the preferred option, but there are orally active drugs that dissolve non-
calcified ‘radiolucent’ cholesterol gallstones.
•The principal agent is Ursodeoxycholic acid, a minor constituent of human bile (but the main
bile acid in the bear, hence urso).
•Diarrhoea is the main unwanted effect.
Drugs affecting biliary spasm :-
Biliarycolic, the pain produced by the passage of gallstones through the bile duct, can be very
intense, and immediate relief may be required.
Morphine relieves the pain effectively, but it may have an undesirable local effect because it
constricts the sphincter of Oddi and raises the pressure in the bile duct.
Buprenorphine may be preferable.
•Pethidine has similar actions, although it relaxes other smooth muscle, e.g. ureter.
•Atropine is commonly employed to relieve biliary spasm because it has antispasmodic action
and may be used in conjunction with morphine.
•The nitrates can produce a marked fall of intrabiliary pressure and may be used to relieve
biliary spasm
VOMITING :-
The act of vomiting is a physical event that results in the forceful evacuation of gastric
contents through the mouth.
It is often preceded by nausea (a feeling of ‘queaziness’ or of impending vomiting) and can
be accompanied by retching (repetitive contraction of the abdominal muscles with or
without actual discharge of vomit).
Vomiting can be a valuable (indeed life-saving) physiological response to the ingestion of a
toxic substance (e.g. alcohol),
but it is also an unwanted side-effect of many clinically used drugs, notably in patients
receiving cancer chemotherapy.
Vomiting also occurs in early pregnancy, in the form of motion sickness and accompanies
numerous disease states (e.g. migraine) and also bacterial and viral infections.
THE REFLEX MECHANISM OF VOMITING
The central neural regulation of vomiting is vested in two separate units in the medulla.
(1) vomiting centre and
(2) the chemoreceptor trigger zone (CTZ).
•Emetic stimuli include
•chemicals in blood
•neuronal input from gastrointestinal tract, labyrinth and CNS.
•Impulses from chemoreceptor trigger zone, and various CNS centres relay to the vomiting centre.
•
•Chemical transmitters include: histamine, acetylcholine, dopamine and 5-hydroxytryptamine,
acting on H1-, muscarinic, D2- and 5-HT3-receptors, respectively.
EMETIC DRUGS:
•In some circumstances, such as when a toxic substance has been swallowed, it may be necessary to
stimulate vomiting.
•This should never be attempted if the patient is not fully conscious or if the substance is corrosive
•The drug usually used to produce vomiting is ipecacuanha, which acts locally in the stomach.
•Its irritant action results from the presence of two alkaloids emetine and cephaeline.
•In cases of poisoning, activated charcoal can also be given to sequester the toxic drug.
•ANTIEMETIC DRUGS:
•Different antiemetic agents are used for different conditions, though there may be some overlap.
•Antiemetic drugs are of particular importance as an adjunct to cancer chemotherapy to combat
the nausea and vomiting produced by many cytotoxic drugs.
•These agents can cause almost unendurable nausea and vomiting.*
•In using drugs to treat the morning sickness of pregnancy, the problem of potential damage to the
fetus has to be borne in mind. In general, all drugs should be avoided, if possible, during the first 3
months of pregnancy.
1. H1-receptor antagonists : Meclizine, Cinnarizine, Cyclizine, Dimenhydrinate, Promethazine
and Diphenydramine
2. Muscarinic antagonists : (effective treatments for motion sickness and vomiting caused by the
presence of irritants in the stomach)
hyoscine (Scopolamine)
for prophylaxis and treatment of motion sickness and is often administered as a
transdermal patch.
3. 5-HT3-receptor antagonists :- Ondansetron, Granisetron, Tropisetron and Dolasetron
particular value in preventing and treating vomiting caused either by radiation therapy
in cancer patients or by administration of cytotoxic drugs
4. D2-receptor antagonists :- Thiethylperazine, Metoclopramide, Domperidone
Antipsychotic phenothiazines, such as chlorpromazine, prochlorperazine and trifluoperazine,
are effective antiemetics
5. Cannabinoids (e.g. nabilone & dronabinol)
6. Steroids : – High-dose glucocorticoids (particularly Dexamethasone & Methylpreednisolone
can have antiemetic action
7. neurokinin-1 antagonists.
•Main side-effects of principal antiemetics include:
•drowsiness and antiparasympathetic effects (hyoscine,
nabilone > cinnarizine)
•dystonic reactions (thiethylperazine > metoclopramide)
•general CNS disturbances (nabilone)
•headache, gastrointestinal tract upsets (ondansetron
Who Gets Peptic Ulcers
• Peptic Ulcer Disease Affects All Age Groups
–Can occur in children, although rare
–Duodenal ulcers tends to occur first at around the age 25 and
continue until the age of 75
–Gastric ulcers peak in people between the ages of 55 and 65
• Men Have Twice The Risk as Women Do
• Genetic Factors
–High levels of acid production, weakness in mucosal layer,
abnormal nonprotective mucus production
• Increase Acid Production and/or Decrease in Bicarbonate and PG
Production
–Caffeine, Cigarettes, Alcohol, Fruit Juices, Stress
What Causes Peptic Ulcer Disease
• Helicobacter Pylori (H. pylori)
–Most ulcers are the result of infection with H.
pylori
–Not all of those infected with H. pylori develop
ulcers
– H. pylori MAY result in a weakening of the
mucosal defense systems, allowing for
development of ulcer subsequent to acid/pepsin
aggression;
What Causes Peptic Ulcer Disease
•NSAIDs
Long term use of nonsteroidal anti-inflammatory
drugs. NSAIDs block COX enzymes and
decrease prostaglandins (PGs).
•Gastrinoma (Zollinger-Ellison Syndrome)
Tumors of the duodenum or pancreas and
secrete abnormally high amounts of gastrin
which stimulates gastric acid.
•Stress ulcers
Result of physical trauma (i.e., burn patients).
Helicobacter pylori
Spiral shaped, flagellated, Gram negative bacterium
Omeprazole (Prilosec)
• Prototype H+, K+-ATPase inhibitor; A prodrug that needs
a low pH to be active;
• Irreversible (forms a covalent bond with the proton pump)
– long lasting inhibition of acid production;
• Profound reduction of gastric acid – elevates gastric pH
significantly (20mg/day for 7days will decrease acid by
95%);
• Highly protein bound; Metabolized by CYP2C &
CYP3A; plasma half life of 1 to2 hours but long duration
of action; Should be taken just prior to a meal and should
NOT be taken with other acid-suppressing agents.
Esomeprazole (Nexium)
Simply the S-isomer of omeprazole;
H+, K+-ATPase inhibitor;
Given orally.
Rabeprazole (Aciphex)
Lansoprazole (Prevecid)
H+, K+-ATPase inhibitor;
Given orally.
Pantoprazole (Protonix)
H+, K+-ATPase inhibitor;
An acid-stable form and can be given by i.v.
Proton Pump Inhibitors (PPI)
Well Tolerated
Hypergastrinemia
(can lead to tumor growth in the GI)
Nausea
Headaches, skin rashes
Histamine Receptors
•H1 receptors
– Smooth muscle
– Nerves
•H2 receptors
– Parietal cells
Histamine H2 Antagonists
• Cimetidine (Tagamet)
• Ranitidine (Zantac)
• Famotidine (Pepcid)
• Nizatidine (Axid)
Drugs for Acid-Peptic Disorders
– Cimetidine (Tagamet)
• Competitive H2 receptor Antagonist;
• Markedly inhibits basal acid secretion including
nocturnal secretion;
• Readily absorbed after oral administration;
• Relatively brief duration of action (4-8 hr)
– Given on a multiple dosing schedule;
– (300-400 mg, 2-4 times daily);
– Typical therapy is for 4-8 weeks.
Drugs for Acid-Peptic Disorders – Cimetidine
(Tagamet)
• Side effects include inhibition of the microsomal
metabolism of other drugs
results in higher blood levels and enhancement of their effects
– Interactions have been shown with:
Diazepam Chlordiazepoxide
Theophylline Phenytoin
Warfarin Propranolol
Meperidine Pentobarbital
Lidocaine and many others…
Drugs for Acid-Peptic Disorders – Ranitidine
(Zantac), Famotidine (pepcid), Nizatidine
(Axid)
• Same mechanism of action as Cimetidine but a longer
duration of action (8 to 12 hrs);
• Can be given less frequently;
150 or 300 mg, 1-2 times daily
• Less interactions at P450 than Cimetidine.
Drugs for Acid-Peptic Disorders –
Anticholinergics
•Blockade of acetylcholine at muscarinic
(M3/M1) receptors
– Effectively blocks acid secretion (30 to 40%)
– Limited by side-effects
•Side-effects are typical of anticholinergics such
as atropine
– Dry mouth
– Tachycardia
– Blurred vision
– Bowel discomfort (constipation)
– Difficulty in urination
Drugs for Acid-Peptic Disorders –
Anticholinergics
• General muscarinic receptor antagonists
(block all types of muscarinic receptors)
– Atropine
– Propantheline (Pro-Banthine)
– Dicyclomine (Bentyl)
• Selective M1 receptor antagonists
– Pirenzepine
– Telenzepine
Strategies for Inhibiting Parietal Cell Acid
Secretion
Ca2+
Prostaglandin
(-)
Agonists
cAMP H+
Protein
PP
Kinase K+
ATP
Ca2+
M H2 CCK23
EP3
Drugs for Acid-Peptic Disorders –
Prostaglandins
Misoprostol (Cytotec):
• Synthetic Analog of Prostaglandin E1
• Anti-acid secretory
• 0.1 to 0.2 mg results in 85% to 95% acid reduction
• Prevention of NSAID gastric ulcers
Side Effects
• Diarrhea
• Abortion
• Exacerbate IBD and should not be given
Drugs for Acid-Peptic Disorders – Antacids
• Antacids are weak bases that neutralize HCl in the
stomach;
• They do not decrease the secretion of acid, and in some
cases increase secretion;
• They do not suppress nocturnal acid secretion
1. Neutralize acid
2. Decrease acid load to duodenum
3. Diminish pepsin activity
Drugs for Acid-Peptic Disorders –
Antacids
• Magnesium hydroxide
• Magnesium trisilicate
• Magnesium-aluminum
mixtures
• Calcium carbonate
• Sodium bicarbonate
Characteristics of Common Antacids
Feature Sodium Calcium Magnesium Aluminum
Bicarbonate Hydroxide
Onset of
rapid intermediate rapid slow
action
Duration of
short moderate moderate moderate
action
Systemic
yes ? no no
alkalosis
Effect on
— constipating laxative constipating
stool
Drugs for Acid-Peptic Disorders – Sucralfate
(Carafate)
• Sucralfate is a basic aluminum salt of sucrose
octasulfate;
• In the presence of acid (pH < 3-4) some of the aluminum
ions dissociate and the resulting negatively charged
molecule polymerizes to form a viscous paste-like
substance;
• This substance adheres strongly to gastric and duodenum
mucosa and adheres even more strongly to partially
denatured proteins such as those found at the base of the
ulcer.
Drugs for Acid-Peptic Disorders – Sucralfate
(Carafate)
•This compound does not decrease the concentration
or total amount of acid in the stomach;
•Sucralfate protects the gastric and duodenal mucosa
from acid/pepsin attack.
Side effects:
• The compound is not really absorbed and, therefore,
side-effects are minimal:
– constipation
– diarrhea
– nausea
Role of H. pylori in Peptic Ulcer Disease
•Treatment
–If H. pylori detected, eradication of the
bacteria, along with inhibition of acid.
–Eradication of H. pylori is a cure as
reinfection rates in Western countries is
less than 1%.
Role of H. pylori in Peptic Ulcer Disease
•Combination therapy with Omeprazole and
Amoxycillin
Eradication of H. pylori reduces the rate of
duodenal ulcer relapse
Study Year Follow up Ulcer relapse (%)
(months) H. pylori
Positive Negative
Coghlan et al. 1987 12 76 10
Lambert et al. 1987 6 76 0
Marshall et al. 1988 12 81 12
Smith et al. 1988 18 80 0
Borody et al. 1988 12-25 100 0
Rauws & Tyt gat 1990 12 81 0
Blum et al. 1990 6 41 0
George et al. 1990 12-48 0 0
H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999)
Treatment Pooled Eradication
Rate
Dual Therapy 72%
Triple Therapy 85%
Quad Therapy 90%
H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999)
GENERIC NAME DOSING DURATION CURE RATE (%)
Dual therapies
omeprazole 500 mg TID 14 days 70-80
amoxycillin 1,000 mg TID 14 days
ranitidine 400 mg BID 28 days 73-84
clarithromycin 500 mg TID 14 days
lansoprazole 30 mg TID 14 days 66-77
amoxycillin 1,000 mg TID 14 days
H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999) Cont.
GENERIC NAME DOSING DURATION CURE RATE (%)
Triple therapies
lansoprazole 30 mg BID 14 days 86-92
amoxycillin 1,000 mg BID 14 day
clarithromycin 500 mg BID 14 days
H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999) Cont.
GENERIC NAME DOSING DURATION CURE RATE (%)
Quad therapies
bismuth subsalicylate Two tablets 7 days 85-95
525 mg QID
metronidazole 250 mg QID 7 days
tetracycline 500 mg QID 7 days
omeprazole 20 mg BID 7 days
or
lansoprazole 30 mg BID 7 days
New Strains of H. pylori
• Recently a more virulent genetic strain of H.
Pylori known as cytotoxin-associated gene A
(cagA) has been found in some people with
peptic ulcers
Drugs for Acid-Peptic Disorders
Drugs Stage I Stage II Stage III Gastric & Major Side
GERD GERD GERD Duodenal Effects
(sporadic) (> 2-3 (Chronic) Ulcers
episode /wk)
Proton Pump + ++ ++ CYP450
Hypergastr.
Inhibitors
Antibiotics ++
H2 Antagonists + + + CYP450
Antiandrogen
Anticholinergics non- Parasym.
U.S.? ANS
Prostaglandins NSAID + diar rhea
Antacids + +? GI
+2
Ca
Sucralfate Stress + GI
Topics for Discussion
• Drugs for Acid-Peptic Disorders
– Eradication of Helicobacter pylori (Antibiotic/Inhibition of
Acid)
– Proton Pump Inhibitors (Omeprazole)
– Histamine (H2) Receptor Antagonists (Cimetidine,
Ranitidine)
– Anticholinergics
– Prostaglandins (Misoprostol)
– Antacids
– Mucoprotective Drugs (Sucralfate)
• Drugs for Motility Disorders
– Prokinetics (Metoclopramide)
– Laxatives (Bran)
– Antidiarrheals (Opioids)
Structure of the GI Tract
MU = Muscularis
Mucosa
Consists of:
– inner circular
layer
– outer
longitudinal layer
Functional Disorders of the GI
•Contractions may be propulsive – i.e., proximal to
distal contractions called “mass action”
contractions;
•Contractions may be non-propulsive – segmenting
or mixing contractions which increase luminal
fluid to mucosal surface to promote absorptive
action of the colon.
Peristalsis Produced by Coordinated Contraction
and Relaxation of Muscle Coats
Myenteric plexus
Longitudinal muscle
(Auerbach’s)
***** ***** *****
*****
Oral ***** Bolus Anal
***** ***** *****
Contracted
Relaxed Circular muscle Submucous plexus
(Meissner’s)
Colonic Transit and Stool Frequency in
Healthy Volunteers
80
60
40
20
0
2 4 6 8 10 12 14
No. stools/wk
Average mean colonic
transit time (hr)
Functional Disorders of the GI
• Pharmacotherapy (prescription and non-
prescription) amounts to $5 to $6 billion annually
for real or perceived disorders of colonic motility;
• Patients seek medical care because they are not
experiencing presumed “normal” pattern of
bowel movement (one per day) or stool
consistency;
• Complaints are highly subjective and personal,
and difficult to quantify and validate.
Functional Disorders of the GI
• Primary
– infection, inflammation, congenital defects (disorders
of the neuronal/muscular activity);
• Secondary
–metabolic disorders (hypo- or hyper-parathyroidism,
hypercalcemia), neurologic (diabetes mellitus –
damage to vagal and sympathetic extrinsic nerves,
intrinsic nerves; MS, heavy metal toxicity,
carcinoma);
• Examples of colonic dysfunction:
– IBS; chronic constipation; Hirschsprung’s disease
(agangliosis of myenteric plexus); sphincter
dysfunction, etc.
Prokinetic Drugs are Often Used for:
• Gastroesophageal reflux disease (GERD)
• Gastroparesis
• Nighttime heartburn
• Severe refractory constipation (sometimes caused
by irritable bowel syndrome (IBS))
Prokinetic Drugs
• Substances which enhance transit of
materials through the GI tract;
• Increase neuromuscular transmission
Prokinetic Drugs Act on Enteric Nerves to Increase
Cholinergic Stimulation
Muscarinic M2 (stimulated by Bethanechol)
Dopamine D2 (Blocked by Metoclopramide and Domperidone)
Dopaminergic
Neuron 5HT4 Stimulated by
Metoclopramide
Cisparide
Smooth (-) (+)
(+) (+)
Muscle
Cell (+) Cholinergic
Motilin Neuron
(+) Stimulated by Erythromycin
Motilin
• Indirect effects are mediated by M2 muscarinic receptors
• Metoclopramide crosses the blood-brain barrier
Ach
Ach
Prokinetic Drugs – Cholinomimetics
(Carbachol; Bethanechol)
• Actions
– Muscarinic receptor agonist
– Increase force of contraction
– Little effect on intestinal transit
• Adverse Side-effects
– Cardiovascular (hypotension, bradycardia)
– Urinary Bladder (increase voiding press., decrease capacity)
– Exocrine Glands (increase secretions)
– Eye (pupil constriction and loss of accommodation)
Prokinetic Drugs – Metoclopramide (Reglan)
• Metoclopramide is an antiemetic and improves
gastric emptying – indirectly releases acetylcholine
• Actions
– Dopamine D2 receptor antagonist
– 5-HT4 receptor agonist
– Ganglionic stimulant O
CH2 CH3
• Pharmacokinetics Cl C NH CH2 CH2 N
– Oral bioavailability CH2 CH3
– Crosses blood-brain barrier
• Adverse Side-effects NH2 OCH3
– Sedation
– Dystonic reactions
– Anxiety reactions
– Gynecomastia
– Galactorrhea
Prokinetic Drugs – Domperidone (Motilium)
• Domperidone is an antiemetic and improves
gastric emptying – Not very effective for GERD
• Actions
Dopamine receptor
antagonist
Ganglionic stimulant
• Pharmacokinetics
Low oral bioavailability
Does not cross blood-brain
barrier
• Adverse Side-effects
Headaches
Gynecomastia
Galactorrhea
Prokinetic Drugs – Cisapride
(Propulsid)
• Actions
5-HT4 agonist; other unknown actions.
• Adverse Side-effects
Serious cardiovascular problems including
arrhythmias (i.e., ventricular tachycardia,
ventricular fibrillation and QT prolongation
As of December 1999, 80 deaths
Janssen Pharmaceutical Inc. has stopped making
cisapride in the US as of 2000
Prokinetic Drugs – Additional
Compounds
• Erythromycin
–Motilin agonist
–Antibacterial
–Diarrhea
• Motilin (22 amino acid active peptide)
–Agonist for the Motilin receptor
–Stimulates gastric emptying
Comparison of Gastric Prokinetic Drugs
Pharmacological Specific Drugs Mechanism of
Class Action
Cholinergic ethanechol Muscarinic
Receptors M3
Dopamine Antagonist etoclopramide D2
Domperidone
Serotonin Agonist
etoclopramide 5-HT4
Motilin Agonist rythromycin Motilin Receptor
Laxatives
Three general mechanisms of action:
• Hydrophilic or osmotic properties promote retention of
water in the colon – increase bulk and softness and
facilitate transit;
• Act on colonic mucosa to decrease absorption of water;
• Increase intestinal propulsive motility, decreasing
absorption of fluid secondary to decreased transit time.
Laxatives
Secretory agents:
• Increase secretion of fluid in the intestine, probably by
opening chloride channels;
• Castor oil, cascara and senna (Senokot) are naturally
occurring substances. Phenolphthalein (Ex-Lax), and
bisacodyl (Dulcolax, Correctol) are popular OTC
substances.
• Active ingredient in Ex-Lax is now Senna.
Laxatives
Saline Agents:
• Contain a cation (magnesium) or anion (sulfate or
phosphate) that carries obligatory water of hydration and
is poorly absorbed from the intestinal lumen;
• Retain fluid in the bowel to promote flow. Examples
include magnesium hydroxide (Milk of Magnesia),
sodium phosphate and sodium sulfate;
• Disadvantage is rapid delivery of a large pressure head
to the distal colon and anal sphincter – difficult to time
and control.
Laxatives
Emollients:
• Nonabsorbed lubricants which enhance flow.
• Dioctyl sodium sulfosuccinate (Colace, Doxinate,
Surfak) – these are anionic surfactants. They produce
softening of the stool over a period of 1-3 days. Details
of pharmacology are uncertain.
• Mineral oil is also used – difficult to contain by the anal
sphincter – can be socially distressing (kind of like
Olestra).
Laxatives
Bulk-forming agents:
Bran, methylcellulose and psyllium (Metamucil).
Innocuous, inexpensive and recommended.
Diarrhea is Associated with Excessive Flow
Through the Lumen of the Bowel
Normal Diarrhea
Net fluid
Net fluid
absorption
accumulation
Increased
Normal mixing propulsive
and propulsive contractions
contractions
Decreased mixing
contractions
Normal Flow Increased Flow
The Goals of Antidiarrheal Therapy are to
Correct the Pathophysiology
Goals:
• Eliminate cause;
• Decrease fluid accumulation in lumen;
• Decrease propulsive contractions;
• Increase mixing contractions.
Opioids and Intestinal Motility
Segmenting Contractions
Normal
Normal Flow
Reduced Contractions
Increased
Flow
Diarrhea { Propulsive Contractions
Increased
Flow
Segmenting Contractions
Decreased
Opioids
Flow
Antidiarrheal Agents – Opioids
• Agonist at mu opioid receptors;
• Decreases fluid secretion;
• Increases fluid absorption;
• Decreases propulsive contractions;
• Increases segmenting contractions;
• Delays gastric emptying.
Adverse Side Effects:
– Constipation
– CNS effects
Opioids and Mucosal Transport of Salt and Water
Physiological
Normal
Balance
Net Fluid
Diarrhea Accumulation
Net Fluid
Opioids Absorption
Analgesics that can be used as Antidiarrheal
Agents
• Morphine
• Codeine
Antidiarrheal Agents – Loperamide
(Imodium)
Mu opioid agonist
Very little distribution into CNS
Low addiction liability
Side Effect
Constipating
Some Opioid Drugs Act Both in the CNS and on
Enteric Nerves, Others Act Only on Enteric Nerves
Drug Central Nervous Enteric Nerves
System
Morphine +++ +++
Codeine +++ +++
Diphenoxylate + +++
Loperamide 0 +++
Loperamide does not effectively cross the blood-brain barrier
after oral administration and exerts mainly peripheral effects
Antidiarrheal Agents – Anticholinergics
Muscarinic antagonists
Decrease propulsive contractions
Decrease cholinergic secretions
Side Effects
Produce typical antimuscarinic side-effects
Dry mouth
Tachycardia
Blurred vision
Bowel discomfort (constipation)
Difficulty in urination
Antidiarrheal Agents – Clonidine (Catapres)
Alpha2 agonist
Decreased release of secretagogues
Action on villus cells
increase fluid and electrolyte
absorption
Side Effect
Induces hypotension
Clonidine Acts at Alpha-2 Adrenergic Receptors to
Decrease Secretion and Increase Absorption
Mucosal
Epithelium Intestinal
Lumen
(+)
Villus
Clonidine
(+) a2
a2
Secretomotor Ach (+)
Crypt
Neuron VIP (+)
Clonidine acts at neural a2 receptors to inhibit release of secretory
neurotransmitters and at epithelial a2 receptors to stimulate absorption
Antidiarrheal Agents – Bismuth Subsalicylate
Bismuth Subsalicylate (Pepto-Bismol)
Binds bacterial toxins
Reduces formation of prostanoids
Antibacterial
Bismuth Subsalicylate
Blocks?
Bacterial
PGs cAMP Fluid
Toxins Accumulation
Antidiarrheal Agents – Gel Forming Agents
Attapulgite – natural clay
Kaolin – natural clay
Pectin – citrus pulp (Kaopectate)
ineffective
Excessive Reduce
Increase Viscosity
Fluid Flow
Bile Acid Catharsis
Cholestyramine (anion-exchange resin)
Lowers LDL cholesterol
Reduce
binds Bile Acids Flow
Side Effects
Not well absobed
Constipation
Antidiarrheal Drugs Act By a Variety of
Mechanisms
Drugs Inhibit Stimulate Decrease Enhance Bind
propulsive nonpropulsive fluid fluid luminal
contractions contractions secretion* absorption secretagogues
Opioids +++ +++ +++ ++
a2 agonists +++ +
Anticholinergics +++ ++
Somatostatin + +++
(Octreotide)
Bismuth +++
subsalicylate
+++
Cholestyramine
* Stimulated by secretagogues
What type of therapy is recommended
for a person diagnosed with peptic ulcer
disease and H. pylori positive?
1. Tagamet with Omeprazole
2. Antacid with Amoxicillin
3. Amoxicillin with Metronidazole
4. Omeprazole with Amoxicillin
5. Omeprazole
0%
1
2
3
4
5
The drug Misoprostol (Cytotek®) will:
1. Decrease the production of acid
2. Increase the mucosal barrier
3. Is “cyto-protective”
4. Is often used for NSAID induced gastric ulcers
5. All of the above
0%
6. 2 and 3 only 1
2
3
4
5
6
10
Propantheline works by what mechanism to
reduce gastric acid:
1. Directly blocks the proton pump
2. Act at the nicotinic receptors to stop Ach interactions
3. Block Ach activity at the M3/M1 receptors on parietal
cells
4. Act as an agonist at M3/M1 receptors to decrease acid
production from parietal cells
25% 25%
1
2
3
4
25% 25%
10
What type of antacid may result in a
laxative side effect?
1. Calcium based antacids
2. Sodium Bicarbonate
Antacids 25% 25% 25% 25%
3. Magnesium based antacids
4. Aluminum based antacids
1 2 3 410
Prokinetic drugs result in:
1. A decrease in propulsive
contractions
2. An increase in mixing 25% 25% 25% 25%
contractions
3. Increase fluidity within the
lumen of the GI tract
4. Improve antroduodenal
coordination
1 2 3 410
Metoclopramide acts as a prokinetic by:
1. Directly acting on the smooth
muscle to increase propulsive
contractions 25% 25% 25% 25%
2. By acting as an agonist at
5HT4 receptors to increase
the release of Acetylcholine
3. By acting as an agonist at D2
receptors to increase the
release of Acetylcholine
4. By releasing Motilin to
increase propulsive
contractions 1 2 3 410
Sucralfate (Carafate®) is a basic aluminum
salt of sucrose octasulfate. It is used for
peptic ulcers due to its ability to:
1. Complexes with proteins at
the ulcer site
2. Decreases back diffusion of
hydrogen ions
3. Binds to pepsin and bile
salts
4. None of the above
5. All of the above 0% 0% 0% 0% 0%
1 2 3 4 510
Laxatives work by decreasing secretions
into the lumen
1. True
2. False
1
50% 50% 2
10
The antidiarrheal drug that is best for
“bug”-induced diarrhea is bismuth
subsalicylate
1. True
2. False
1
50% 50% 2
10
An opioid such as Loperamide is useful as
an antidiarrheal drug since it can:
1. Increase segmenting
contractions of the GI
2. Decrease propulsive
contractions of the GI
3. Results in contents
remaining in the GI longer
for more fluid retention
4. 1 and 2 only
0% 0% 0% 0% 0%
5. All of the above
1 2 3 4 510
MedPharm, Fall 2004
GI CASE I John D. Palmer, Ph.D. M.D.
A 79 year old man
Chief Complaint: Chest Pain, ten episodes of bright red vomiting
and maroon and black colored stools.
PROBLEM LIST: MEDICATIONS:
Ischemic cardiomyopathy – CHF Allopurinol
Myocardial infarction Furosemide
Gout Metolazone
Hiatus hernia Spironolactone
Erosive esophagitis Omeprazole
Clopidogrel
Warfarin
Aspirin
Carvedilol
Laboratory:
Hemoglobin/Hematocrit 6.6/19.7 (normal = 14/44)
PT/INR 26.4/5.2
What is the most likely diagnosis?
1. NSAID induced ulcer
2. Food and Stress induced
ulcer
3. H. pylori induced ulcer
4. Acute Myocardial
Infarction
5. Gastric Cancer
0% 0% 0% 0% 0%
1 2 3 4 510
How would you Treat such a patient
1. Proton pump inhibitor
2. Antibiotic 20% 20% 20% 20% 20%
3. H2 receptor antagonist &
sucralfate
4. Proton pump inhibitor &
antibiotic
5. Prostaglandins
(Misoprostol)
1 2 3 4 510
GI – CASE II
A 55 year old man
Chief Complaint: Nausea, black tarry stools with diarrhea and vomiting
of blood
PROBLEM LIST: MEDICATIONS:
Psoriasis with arthritis Acetaminophen &
Obesity hydrocodone
Sleep apnea Folic acid
Chronic bronchitis Methotrexate
History of peptic ulcer disease Salsalate
No Alcohol used
Vital signs: BP 106/45 Pulse 106 Resp 20
Laboratory:
PT/INR 13.8/-
Hemoglobin/Hematocrit 13.6/38
What is the most likely diagnosis?
1. NSAID induced ulcer
2. Food and Stress induced
ulcer
3. H. pylori induced ulcer
4. Zollinger Ellison Syndrome
5. Gastric Cancer
0% 0% 0% 0% 0%
1 2 3 4 510
GI – CASE III
A 47 year old man
Chief Complaint: worsening abdominal pain and generalized weakness,
Complains of a 3 month history of stomach discomfort and
indigestion, little relationship to mealtime.
noted a recent black, tar-like bowel movement, which he
attributed to eating too many black beans.
PROBLEM LIST: occult blood (a small amount of blood not visible to the
naked eye) on a stool test (Hemoccult),
his red blood cell count was lower than normal (anemia).
MEDICATIONS: Antacids
Vital signs: BP 110/55 Pulse 90 Resp 20
Laboratory: Endoscopy exam revealed a large ulcer in the bottom of his
stomach with some evidence of recent bleeding,
Biopsy of the stomach demonstrated bacteria, Helicobacter pylori.
What is the most likely diagnosis?
1. NSAID induced ulcer
2. Food and Stress induced
ulcer
3. H. pylori induced ulcer
4. Zollinger Ellison Syndrome
5. Gastric Cancer
0% 0% 0% 0% 0%
1 2 3 4 510
How would you Treat such a patient
1. Proton pump inhibitor &
antacids
2. Antibiotic 20% 20% 20% 20% 20%
3. H2 receptor antagonist &
sucralfate
4. Proton pump inhibitor &
antibiotic
5. Prostaglandins
(Misoprostol)
1 2 3 4 510
GI – CASE IV
A 68 year old man
Chief Complaint: Chest pain with vomiting of bright red blood for
several days.
PROBLEM LIST: Chronic renal insufficiency and Osteoarthritis.
MEDICATIONS: Ibuprofen
Vital signs: BP 110/55 Pulse 80 Resp 20
Physical Exam: Tender in epigastrium
Laboratory: Hgb/Hct 15/44 PT/aPTT-WNL
Gastric aspiration- negative for blood
Stool negative for blood
What are the possible causes?
1. NSAID induced ulcer
2. Bleeding into bowel from
an aortic aneurysm
17% 17% 17% 17% 17% 17%
3. H. pylori induced ulcer
4. Cardiovascular event
5. Gastric Cancer
6. All of the above
1 2 3 4 5 610
Further laboratory evaluation, what
test(s) do you want?
1. Liver cell test
17% 17% 17% 17% 17% 17%
2. EGD
3. H. pylori induced breath test
4. EKG & Cardiac enzymes
5. Abdominal X-rays
6. All of the above
1 2 3 4 5 610
Hospital Course
• All Laboratory Tests Within Normal
Limits
• GI Consult
• Did Not Meet Criteria for EGD
• Discharged With Instructions to
Discontinue Use of NSAIDs
Return to ER
• 36 Hours later With History of vomiting
bright red blood and copious maroon
colored stools
• Physical Exam:
– Apperance- pale and sweaty
VS: BP 90/50 pulse 100 R 18
Epigastric tenderness
Lab Hgb/Hct 9/30
Hospital Course
• Admitted to ICU
• Stabilized with IV fluids
• GI Consult Requested
• GI agrees to perform EGD
• GI starts procedure with conscious sedation using
local anesthesia and midazolam
• Patient expels large volume of blood from the
mouth that can not be controlled with suction
What is going on?
Differential diagnosis would include all
of the following EXCEPT
1. Massive bleeding peptic ulcer 20% 20% 20% 20% 20%
2. Hemrroidal bleeding
3. Bleeding colon cancer
4. Communication between GI
tract and aorta
5. Hemorrhagic gastritis
1 2 3 4 510
Post-mortem
• Pathologist finds communication between
third portion of duodenum and abdominal
aortic aneurysm
• Microscopic exam: no evidence of
inflammation seen in duodenal wall
How does H. pylori contribute to
peptic ulcer disease?
1. Increases prostaglandin
synthesis
2. Decreases the mucosal barrier
3. Increases the synthesis of HCL
4. Increases pepsin production
0% 0% 0% 0%
1 2 3 410
The three major pathways regulating
parietal cell acid secretion include:
1. Vagal nerve stimulation
2. Endocrine stimulation via
gastrin
3. Paracrine stimulation via
histamine
4. 1 an 2
5. All of the above
0% 0% 0% 0% 0%
1 2 3 4 510
Cimetidine, an H2 antagonist, is effective
at reducing acid but has several side
effects EXCEPT:
1. Inhibition of drugs
25% 25% 25% 25%
metabolized by CYP450’s
2. An antiandrogen effect
3. Can result in
hypergastrinemia
4. Can cause confusion and
disorientation in the elderly
1 2 3 410
Therapeutic Strategy for Peptic Ulcer Disease
• Old Therapeutic Strategy:
–USED TO BE “no acid, no ulcer”.
–Accomplished by reduction of acid production OR
improvement of the integrity of the mucosal barrier,
or both.
• Current Therapeutic Strategy:
–Now “no NSAID damage, no Zollinger Ellison
syndrome, no H. pylori, no ulcer”.