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Drugs used in gastrointestinal Disorders

A. Remedies with influence on the appetite


I. Appetite stimulants (orexygens)
a) with reflex action
1. Bitters : bitter tincture from herba Absmthii, Herba Centaurii, Radix Taraxaci\
Species’ amarae
2. Condiments (garlic, onions, pepper )
3. Mineral waters
b) with indirect action
1. vitamins
2. steroid anabolics
3. insulin
4. carnitin
5. psychotropic remedies ( chlorpromazine, amitryptiline, lithium carbonas)
6. neurotropic antihypertensives (clonidine)
c) with central action
ciproheptadine (peritol)
II. Appetite suppressants (anorexygens)
a. remedies acting on cathecholinergic system :
Fenylachilamines: amphetamine, amphepramon
b. remedies acting on serotoninergic system
Fenylachilamines: phenfluramine
c) remedies with mixed action: sibutramine

B. Remedies that act digestive system secretion


I. Remedies used in hyposecretion of digestive glands
a) in hyposalivation
1. M- cholinomimetics and anticholinesterase

1
- pilocarpine - neostigmine
- carbachol - galantamine
-
b) hyposecretion of gastric glands
1. increase gastric secretion
M- cholinomimetics and anticholinesterase
2. with the diagnostic purpose
gastrin
caffeine
histamine
3. substitutes of gastric glands secretion
- natural gastric juice
- artificial gastric juice
- pepsin
4. substitutes of gastric secretion and other digestive glands ( pancreas, gall bl.)
- abomine - festal - pancurmen - pancreatin
- oraza - pansinorm - mexaza - digestal

2
II. Remedies that are used in hypersecretion of digestive glands
a. in hypersalivation
M- cholinoblockers : atropine, scopolamine, platyphylhne
b. in hypersecretion of gastric glands

1.1Remedies that inhibit NaCI secretion in the stomach


(Inhibitors of acid production)
M -non selective cholinoblockers
- atropine
- isopropamide
M- selective cholinoblockers
- pirenzepine (gastrozepine)
Ganglioblockers
- hexamethoniu
- pempidine
M-N-cholinoblockers
- gastrixoniu

1.2 Histaminoblockers
I generation Cimetidine
II generation Ranitidine
III generation Famotidine
IV generation Roxatidme, Nizatidine
1.3 Antigastrinics
Proglumide
1. 4 Prostaglandins and their
derivatives: Mizoprostol
1.5 Proton-Pump Inhibitors
I gen. Omeprazole
II gen. Pantoprozole
III gen. Lanzoprazole
IV gen. Rabeprazole
1.6 Antacids
Systemic
- sodium hydrocarbonate
- potassium hydrocarbonate
Non systemic
1. Magnesium compounds
- magnesii oxydum
- magnesii hydroxidum
- magnesii subcarbonas
- magnesii peroxydum
2. ; Aluminium compounds
- aluminium hydroxidum
- aluminium carbonas
- Almagel, Almagel A, Cast, jlugel. Phospholugel.
C. Gastroprotectors (cytoprotective) . (Protective Drugs)
I. Gastroprotectors:
- sucrafalte
- venter
Bismuth chelate
- Tab. "Vicalin"
- Tab. "Vicair"
- misoprostol
- colloidal bismuth subcitrate (De-nol)
- somatostatine

II. Remedies that enhance the regeneration of gastric mucosa


1) anabolic remedies
a) steroids
- Nandrolon phenylpropionate (Nerobolil)
- Nandrolon decameat (Retabolil)
- Nandrolon undecinate (Dinabolon)
b) non steroids
- Potassium orotate -Pentoxyl
- Methyluracil -Inozine (riboxine)
2) Vitamins U, P, E

- alanton
- underbrush oil
3) Vegetal origin remedies
- regesan (grapes seed oil)
- calephlon
- carbenoxolone
4) Synthetic remedies
- levodopa - sulpiride
- DOXA - solcoseril
5) Musculotropic spasmolytics
- papaverine
- drotaverine
6) Antifungal and antiprotozoal drugs
- metronidazole
7) Antibiotics (Eradication of Helicobacter pylori)
- erythromycin - tetracycline -amoxycillin
- oxacillin - penicillin - clarithromycin
D) remedies used in exocrine pancreatic deregulations
1. Remedies used in inadequate pancreatic secretion (excretory insufficiency)
abomine festal pancurmen pancreatin
oraza pansinorm mexaza pancitrat
festal plestal creon
2. Remedies used in pancreatic hypersecretion
a) M- cholinoblockers : atropine, scopolamine, platyphyiline
b) antienzymes : aprotinine (contrical, gordox, trasilol)

3. Pancreatic secretion stimulators: secretine, cholecystokinin


Orexygents
with reflex action: they excite oral cavity receptors and inhibit die center of
famine. Bitters don't increase gastric secretion.

With central action: mechanism of action:


- antiserotoninic action
- anti H1 histaminic action
- central cholinolitic action
- they stimulate hypothalamus centers , increasing the
appetite
Anorexigens: remedies acting cathecholinergic system : Fenylachilamines:
amphetamine enhances noradrenalin and dopamine release, inhibit their reuptake.
These mediators stimulate adrenoreceptors, inhibit famine center. Also the drugs
stimulate cortex and inhibit famine center. Effects: agitation, insomnia,
tachycardia, hypertension, dependence. Amphepramon has the same mechanism
of action and side effect. But has:
- more selective action
- less effects and it is less active than the first
Remedies that act serotoninergic system
Fenylachilamines: phenfluramine increase serotonin elimination from the brain
Inhibis its reuptake, and decrease serotonin amount in the brain.
Effects:
- sedative,
increasing glucose reutilization in peripheral tissue
-inhibition of lipid absorption and their synthesis and metabolism
-increasing of lipolys
-euphoria
-dependence
-dangerous effects like: pulmonary hypertention and valve's disease
( in USA it is prohibited))
Indication :
Severe obesity
Administration no more three months and obligatorily the patents must be
unformed
- remedies with mixed action
sibutramine increase elimination of noradrenalin, serotonin, dopamine, and inliibit
their reuptake. Side effects (see phenamine)
Mineral water : before alimentation with 15 minutes 3-4 times a day 200-300 ml
Gastrin - excites gastrinoreceptors, increases HCL secretion , stimulates pancreatic
and gall bladder secretion, and increases the synthesis of intrinsic factors.
Histamine: excite H2 histaminoreceptors and increase HCL elimination.
Substitutes of gastric glands secretion Indications: hyposecretion of gastric
glands, hypo and anacide gastritis , dyspepsia Remedies that are used in
hypersecretion of digestive glands Hypersalivation:
Indications: xerostomia, parkinsonism, helminthes, intoxication with heavy
metals. M- selective cholinoblockers pirenzepine (gastrozepine) acts only
Ml cholinoreceptors.
Indication: hyperacid gastritis
Drugs for Gastric and Duodenal Ulcers
Potential Causes of Peptic Ulcer
Common causes
Helicobacter pylori infection
Nonsteroidal anti-inflammatory drugs
Critical illness (stress-related mucosal damage)
Uncommon causes
Hypersecretion of gastric acid (e.g., Zollinger-Ellison syndrome)
Viral infections (e.g., cytomegalovirus)
Vascular insufficiency (crack cocaine–associated)
Radiation
Chemotherapy (e.g., hepatic artery infusions)
Rare genetic subtypes
Idiopathic
In the area of a gastric or duodenal peptic ulcer, the mucosa has been attacked by
digestive juices to such an extent as to expose the subjacent connective tissue layer
(submucosa). This self-digestion
occurs when the equilibrium between the corrosive hydrochloric acid and acid-
neutralizing mucus, which forms a protective cover on the mucosal surface, is shifted in favor
of hydrochloric acid. Mucosal damage can be promoted by Helicobacter pylori bacteria that
colonize the gastric mucus.
Drugs are employed with the following therapeutic aims: (1) to relieve pain; (2) to
accelerate healing; and (3) to prevent ulcer recurrence. Therapeutic approaches are threefold:
(a) to reduce aggressive forces by lowering H+output; (b) to increase protective forces by
means of mucoprotectants; and (c) to eradicate Helicobacter pylori.
I. Drugs for Lowering Acid Concentration
Ia. Acid neutralization. H+-binding groups such as CO3 2–, HCO3 – or OH–, together
with their counter ions, are contained in antacid drugs. Neutralization reactions occurring after
intake of CaCO3 and NaHCO3, respectively. With nonabsorbable antacids, the counter ion is
dissolved in the acidic gastric juice in the process of neutralization. Upon mixture with the
alkaline pancreatic secretion in the duodenum, it is largely precipitated again by basic groups,
e.g., as CaCO3 or AlPO4, and excreted in feces. Therefore, systemic absorption of counter ions
or basic residues is minor. In the presence of renal insufficiency, however, absorption of even
small amounts may cause
an increase in plasma levels of counter ions (e.g., magnesium intoxication with paralysis and
cardiac disturbances). Precipitation in the gut lumen is responsible for other side effects, such
as reduced absorption of other drugs due to their adsorption to the surface of precipitated
antacid or, phosphate depletion of the body with excessive intake of Al(OH)3. Na+ ions remain
in solution even in the presence of HCO3 –-rich pancreatic secretions and are subject to
absorption, like HCO3 –. Because of the uptake of Na+, use of NaHCO3 must be avoided in
conditions requiring restriction of NaCl intake, such as hypertension, cardiac failure, and
edema. Since food has a buffering effect, antacids are taken between meals (e.g.,1 and 3 h after
meals and at bedtime). Nonabsorbable antacids are preferred. Because Mg(OH)2 produces a
laxative effect (cause: osmotic action, release of cholecystokinin by Mg2+, or both) and
Al(OH)3 produces constipation (cause: astringent action of Al3+), these two antacids are
frequently used in combination.
Antacid or antacid combination products may cause gastrointestinal adverse effects (diarrhea or
constipation, depending on the product), alterations in mineral metabolism, and acid-base
disturbances. Aluminum-containing antacids may bind to phosphate in the gut and lead to bone
demineralization. In addition, antacids interact with a variety of drugs by altering gastric pH,
increasing urinary pH, adsorbing medications to their surfaces, providing a physical barrier to
absorption, or forming insoluble complexes with other medications.44 Antacids have clinically
significant drug interactions with tetracycline, ferrous sulfate, isoniazid, quinidine,
sulfonylureas, and quinolone antibiotics. Antacid-drug interactions are influenced by
composition, dose, and dosage schedule of the antacid, as well as by the formulation.

Ib. Inhibitors of acid production. Acting on their respective receptors, the transmitter
acetylcholine, the hormone gastrin, and histamine released intramucosally stimulate the parietal
cells of the gastric mucosa to increase output of HCl. Histamine comes from enterochromaffin-
like (ECL) cells; its release is stimulated by the vagus nerve (via M1receptors) and hormonally
by gastrin. The effects of acetylcholine and histamine can be abolished by orally applied
antagonists that reach parietal cells via the blood.
The cholinoceptor antagonist pirenzepine, unlike atropine, prefers cholinoceptors of the
M1 type, does not penetrate into the CNS, and thus produces fewer atropine-like side effects.
The cholinoceptors on parietal cells probably belong to the M3 subtype. Hence, pirenzepine
may act by blocking M1 receptors on ECL cells or submucosal neurons.
Histamine receptors on parietal cells belong to the H2 type and are blocked by H2-
antihistamines. Because histamine plays a pivotal role in the activation of parietal cells, H2-
antihistamines also diminish responsivity to other stimulants, e.g., gastrin (in gastrin-producing
pancreatic tumors, Zollinger-Ellison syndrome). ZES is characterized by gastric acid
hypersecretion and recurrent
peptic ulceration that results from a gastrin-producing tumor (gastrinoma).

Cimetidine,the first H2-antihistamine used therapeutically, only rarely produces side effects
(CNS disturbances such as confusion; endocrine effects in the male, such as gynecomastia,
decreased libido, impotence). Unlike cimetidine, its newer and more potent congeners,
ranitidine, nizatidine, and famotidine, do not interfere with the hepatic biotransformation of
other drugs. The most common adverse effects are headache, somnolence, fatigue, dizziness,
and either constipation or diarrhea. Patients should be monitored for the presence of adverse
effects as well as potential drug interactions, especially when on cimetidine. Cimetidine may
inhibit the metabolism of theophylline, warfarin, phenytoin, nifedipine, or propranolol, among
others.AnalternateH2-receptor antagonist should be selected if the patient is on any of these
medications.
Omeprazole can cause maximal inhibition of HCl secretion. Given orally in gastric juice-
resistant capsules, it reaches parietal cells via the blood. In the acidic milieu of the mucosa, an
active metabolite is formed and binds covalently to the ATP-driven proton pump (H+/K+
ATPase) that transports H+ in exchange for K+ into the gastric juice. Lansoprazole and
pantoprazole produce analogous effects. Proton pump inhibitors block gastric acid secretion by
inhibiting gastricH+/K+-adenosine triphosphatase in gastric parietal cells.
This produces a profound, long-lasting antisecretory effect capable of maintaining the gastric
pH above 4, even during acid surges seen postprandially.2,9 While the proton pump inhibitors
have the same mechanism of action, there are slight differences in their actual binding to the
cysteine residues in the proton pump. A correlation appears to exist between the percentage
The proton pump inhibitors are first-line drugs for the treatment of gastroesophageal
reflux disease. Comparable doses of proton pump inhibitors are omeprazole 20 mg =
esomeprazole 20 mg = lansoprazole 30 mg = rabeprazole 20 mg = pantoprazole 40 mg per day.
Symptomatic relief is seen in approximately 83% of patients treated with a proton pump
inhibitor, while the endoscopic healing rate at 8 weeks is 78%.All of the proton pump inhibitors
are generally well tolerated, while the newer agents, esomeprazole, pantoprazole, and
rabeprazole, appear less likely to cause significant drug interactions. In general, all of these
agents are safe and effective and the choice of a particular agent will most likely be based on
cost.
The proton pump inhibitors are usually well tolerated; however, potential adverse effects
include headache, dizziness, somnolence, diarrhea, constipation, and nausea. The frequency of
adverse events appears to be similar to that seen with the H2-receptor antagonists.
II. Protective Drugs
Sucralfate (A) contains numerous aluminum hydroxide residues. However, it is not an
antacid because it fails to lower the overall acidity of gastric juice. After oral intake, sucralfate
molecules undergo cross-linking in gastric juice, forming a paste that adheres to mucosal
defects and exposed deeper layers. Here sucralfate intercepts H+. Protected from acid, and also
from pepsin, trypsin, and bile acids, the mucosal defect can heal more rapidly. Sucralfate is
taken on an empty stomach (1 h before meals and at bedtime). It is well tolerated; however,
released Al3+ ions can cause constipation. Misoprostol (B) is a semisynthetic prostaglandin
derivative with greater stability than natural prostaglandin, permitting absorption after oral
administration. Like locally released prostaglandins, it promotes mucus production and inhibits
acid secretion. Additional systemic effects (frequent diarrhea; risk of precipitating contractions
of the gravid uterus) significantly restrict its therapeutic utility. Carbenoxolone (B) is a
derivative of glycyrrhetinic acid, which occurs in the sap of licorice root (succus liquiritiae).
Carbenoxolone stimulates mucus production. At the same time, it has a mineralocorticoid-like
action (due to inhibition of 11-hydroxysteroid dehydrogenase) that promotes renal reabsorption
of NaCl and water. It may, therefore, exacerbate hypertension, congestive heart failure, or
edemas. It is obsolete.
III. Eradication of Helicobacter pylori
Approximately 50% of the world’s population is colonized by HP.
Helicobacter pylori infection causes chronic gastritis in all infected individuals and is causally
linked to PUD, gastric cancer, and mucosaassociated lymphoid tissue (MALT) lymphoma.
However, only a small number of infected individuals will develop symptomatic Peptic ulcer
disease
PUD (about 20%) or gastric cancer (less than 1%). The pattern and distribution of gastritis
correlates strongly with the risk of a specific gastrointestinal disorder. The development of
atrophic gastritis and gastric cancer is a slow process that occurs over 20 to 40 years. Serologic
studies confirm an association between HP and gastric cancer. Supportive evidence for PUD is
based on the fact that most non-NSAID ulcers are infected with HP, and that HP eradication
markedly decreases ulcer recurrence. Host-specific cofactors and HP strain variability play an
important role in the pathogenesis of PUD and gastric cancer. Although an association between
HP and PUD bleeding is less clear, eradication of HP decreases recurrent bleeding. No specific
link has been established between HP and dyspepsia, nonulcer dyspepsia (NUD), or
gastroesophageal reflux disease.

C. This microorganism plays an important role in the pathogenesis of chronic gastritis and
peptic ulcer disease. The combination of antibacterial drugs and omeprazole has proven
effective. In case of intolerance to amoxicillin or clarithromycin , metronidazole can be used as
a substitute. Colloidal bismuth compounds are also effective; however, the problem of heavy-
metal exposure compromises their long-term use.
Drug Regimens to Eradicate Helicobacter Pylori