DRUGS INFLUENCING DIGESTIVE SYSTEM

Drugs Influecing Appetite

Appetite is an emotional feeling about man's desire to eat certain
foods. Appetite is realized by neurohumoral way. Nervous system
has the predominant role in this regulation. Appetite is under controle
of hunger center (lateral nuclei of the hypothalamus) and saturation
center (ventromedial nuclei of the hypothalamus). These centers re-
ceive impulses from the gustatory, visual, and olfactory systems. An
appetite largely depends on the state of cortex and limbic system.
The primary importance in the regulation of appetite belongs to
such mediators as noradrenaline, serotonin, and dopamene influecing
the appropriate receptors (β1- and β2-adrenergic receptors, α1-adrener-
gic receptors, 5-HT1B and 5-HT2C-serotoninergic receptors, D1-
dopaminergic receptors). Besides, specific neuropeptides regulating
appetite and energetic balans there are in hypothalamus. Appetite-in-
creasing substances (orexigens) are neuropeptide Y, orexigens A and
B, ghrelin (stomach peptide which after absorption in the blood stim-
ulates growth hormone production by hypothalamus), hormone stim-
ulating the growth hormone secretion, GABA etc.
There are substances which reduce appetite (anorexigenous sub-
stances). They are leptin (hormone of fatty cells which penetrates
into the brain and stimulates production of anorectic substances by
hypothalamus and simultaneously inhibits the secretion of orexigenic
substances), α-melanocyte-stimulating hormone, hormones stimulat-
ing release of thyrotropin, neurotensin, serotonin, cholecystokinin,
glucagon-like compounds, etc.

Drugs Increasing Appetite

Appetite is stimulated by means of taste and extractive sub-
stances of pepper, cinnamon, cloves, bay leaf, garlic, onion, horse-
radish, dill, mustard etc. Broth, vegetable broths, juices, mineral wa-
ter, dry wine also have stimulating influence upon appetite.
 Medicines used for stimulation of appetite include bitters: tinc-
tures of wormwood, centaury ordinary, water shamrock, rhizome of
calamus, etc. These drugs are taken 15 minutes before eating.
Mechanism of drugs action is following. Betters stimulate recep-
tors of oral cavity that results in increase of reflex excitability of
hunger center. Owing to this, first (complex-reflex) phase of gastric
setsretion is enhanced.
Drugs increasing appetite also include insulin, aminazinum,
amitriptyline, lithium carbonate, clophelinum, and anabolic steroids.

Drugs Decreasing Appetite

(Anorexic or Anorexigenic Drugs)
Anorexigenic drugs are used for treatment of alimentary obesity.
This disease is accompanied by disturbances of metabolism, which
result in increased hazard of diabetus mellitus, cardio-vascular dis-
eases, etc.
Main method of obesity treatment is the decrease of amount of
food with high energy value and the increase of physical activity.
Drugs which decrease the appetite and used for treatment of obe-
sity are called anorexigenic drugs or appetite suppressants. Accord-
ing to mechanism of action these drugs are classified into following
groups:
1. Drugs stimulating catecholaminergic system of brain: am-
phetamine , phepranone, desopimone, mazindole .
2. Drugs stimulating cerotoninergic system of brain: fenflu -
ramine, dexfenfluramine .
3. Drug stimulating both catecholaminergic and serotoninergic
systems of brain: sibutramine .
4. Inhibitor of gastrointestinal lipases: orlistat.

Active anorexigenic drug is amphetamine (phenaminum). It

is derivative of phenylalkylamine. Drug has central and peripheral
adrenomimetic action. Phenaminum increases the release of nora-
drenaline and dopamine by nervous endings and supresses reuptake
of these neurotransmitters. It is results in excitation of central adren-
ergic and dopaminergic nervous and reduction of feeling of hunger.
Simultaneously drug excitates other central and peripheral neurines
which results in number of undesirable effects: insomnia, agitation,
tachycardia, increase of blood pressure. The use of phenaminum can
result in physical and psychical dependence. In connection with the
above, phenaminum is not used as anorexigenic drug.
Phepranone is derivative of phenylalkylamine. Drug has iden-
tical mechanism of action with phenaminum. But phepranone less
stimulates central and peripheral nervous systems. Phepranone is pre-
scribed 30-60 minutes before meal. Because drug can cause insom-
nia, it is should be taken in the first half of the day. Possible side ef-
fects are agitation, insomnia, tachycardia, increase of blood pressure.
In case of chronical use of phepranone, the tolerance and drug depen-
dence can develop.
.

Fenfluramine selectively acts in area of serotoninergic recep-

tors and inhibits neuronal reuptake of serotonin. Drug inhibits central
nervous system and increases the blood pressure.
Sibutramine simultaneously inhibits neuronal reuptake of
adrenaline, serotonin, and dopamine. Drug decreases the level of uric
acid and lipid in the blood. During treatment with sibutramine such
side effects can be observed as tachycardia, sleep disturbances,
headache, and increased excitability of central nervous system.
One of the ways of treating obesity is decrease of intestinal ab-
sorption of lipids. It is achieved by inhibition of lipase activity (en-
zyme which is necessary for lipid absorption). This mechanism of ac-
tion is tipical for orlistat. Drug inhibits lipase in stomach and intes-
tine that results in reduction of hydrolisis of dietary triglycerides. In
result, the absorption of lipids is decreased on 30%. Orlistat also in-
hibits the absorption of lipid-soluble vitamins. Approximately 83%
of absorbed drug dose is excreted through intestine in unchanged
state. Full elimination of orlistat occurs during 3-5 days. Side effects
depend of triglycerides level in food. The urging to stool, abdominal
pain, diarrhea, nausea, and vomiting are possible.
 Restriction use of sugar or use of sweetener (saccharin, etc.) is
also recomemded for decrease of calorie food.
Recently, hormon of fat cells leptin is recommended for reduc-
tion of appetite. Its administration promotes the lowering of body
weight in patient with obesity. But drug is effective only in patients
with deficiency of endogenous leptin.
Melanocortin also inhibits an appetite in result of interaction
with specific MC4-receptors. Other agonists of these receptors also
have anorexigenic effect.
Cholecystokinin is also noteworthy. Besides the regulation of
functions of digestive system this hormon also acts as saturation fac-
tor. Series of compounds which activating the cholecystokinin sys-
tem are now being studied.
But nacessary to undestend, that pharmacotherapy of obesity has
auxiliary character and the base of obesity treatment is combination
of low-calorie diet with additional physical activity.

Drugs Influecing Function of Salivary Glands

Salivary glands secretion is under control of both parasympa-
thetic and sympathetic nervous system. The tone of parasympathetic
is predominante; therefore activation of stimulation of M-cholinocep-
tors which located in salivary glands determines the degree of saliva-
tion.
Drugs with M-cholinomimetic activity (proserinum, carba-
choline, pilocarpine , aceclidine , etc.) increase the salivation.
Cholinoblocking drugs (atropine, scopolamine, etc.) inhibit the
salivation. Drugs with blocking activity are used practically more
commonly for reduction of hypersalivation in patients with Parkin-
son disease, helminth infestation, and poisoning with heavy metals.

Drugs Which Used in Hyposecretion of Stomach

 Mucosa of stomach secretes several enzymes, main of which is
pepsinogen. The acidic environment is necessary for transformation
of it to active pepsin. Necessary acidity is achieved owing to secre-
tory activity of parietal cell producing hydrochloric acid (precisely,
ions of hydrogen).
Hypofunction of gastric glands occurs in 10-15% of practically
healthy people. Simetimes, it is only insufficient secretion of hy-
drochloric acid, but quite often it combines with hyposecretion of
pepsinogen. Hyposecretion can cause inflammation with develop-
ment of hypoacid gastritis.
Vagus nerve and several gastrointestinal hormones regulate the
stomach secretion. It is known, that the increase of vagal tone and the
release of gastrin and histamine result in the raise of gastric secre-
tion. In turn, reduction of cholinergic influence and supression of
gastrin and histamine release cause the decrease of gastric juice se-
cretion. Endogenous substances supressing gastric secretion are se-
cretin, cholecystokinin, prostaglandins, vasoactive intestinal peptide,
peptide inhibiting gastric secretion, atc.
Administration of gastrin, histamine or extractive substances
can significantly increase gastric secretion in patients with hypoacid
gastritis which caused by functional disorders. But administration of
these substances does not result in secretion increase in patients with
organic lesions of the gastric mucosa. Thereby, aforementioned sub-
stances may be used for diagnostic aim.
Pentagastrin is synthetic analogue of histamine. Drug stimu-
lates gastric secretion. Pharmaceutical industry produces 0.025% am-
pular solution of pentagastrin. Drug administered subcutaneously for
diagnosis of secretory activity of the stomach. Its administration
gives possibility to estimate the secretory ability of stomach and to
determinate the character of damages of stomach. In the patients with
functional insufficiencyof gastric mucosa pentagastrin increases the
secretion. But in patietns with organic diseases of the stomach the se-
cretion is not increased.
Attempts to increase secretion have low efficiency or are com-
plitly ineffective in patients with hypoacid gastritis which accompa-
nied by atrophic process. Therefore, treatment of patients with such
patoligical states needs the drugs of substitutive therapy. For this
aim, such drugs as natural gastric juice , pepsin, diluted hy-
drochloric acid , acidin-pepsin, and abomin are used.
Most physiological drug is natural gastric juice , which ob-
tained from animals. It is taken during meal in dose 1 table spoon.
Artificial gastric juice (obtained by insisting of stomach mucosa
of pigs in 0.2-0.5% solution of hydrochloric acid) has little less activ-
ity. It is taken also during meal in dose 1-2 table spoon.
Abomin is tableted drug obtained from gastric mucosa of calfs
and lambs. It is taken during meal in dose 1-2 tablets. Course of
treatment is 1-3 months. Abomin contains sum of proteolitic gastric
enzymes. The treatment with this drug needs simultaneous intake of
hydrochloric acid.
Pepsin is obtained from gastric mucosa of pigs. Mixture of
pepsin and hydrochloric acid is used during meal in dose 1 table
spoon.
Hydrochloric acid is used in hypoacid gastritis without defi-
ciency of pepsin. Diluted standard solution of hydrochloric acid is
taken during meal in dose 10-15 drops with ½ glass of water. This
solution in recommended to take through tubule for prevention of
tooth enamel destruction. Organic acids (malic, citric, or acetic) are
also used in hypoacid gastritis. These acid realease hydrogen ions in
stomach and undergo absorption and energy metabolism in body.
The use of acidic foods, such as sauerkraut, fruits, etc. also is recom-
mended.
Acidin-pepsin is also used in patients with hypoacid gastritis.
1 tablet of drug is dissilved in ½ glass of watet and is taken during or
immediately after eating.

Drugs Which Used in Hypersecretion of Gastric

Glands and in Disturbances of Trophism or
 Regeneration of Gastric Mucosa
These drugs are used in patients with hyperacid gastritis, ulcer
disease of stomach and duodenum. According to studies, approxi-
mately 10% of 30-55-year-old males and 6% of females under 55
years suffer from ulcer disease. Ulcer disease lasts for years and
characterized by periods of exacerbation and remission.
According with modern ideas, ulcer disease is result of imbal-
ance between protective and agressive factors influecing upon the
mucouse of stomach.
Acid-peptide (predominant role of hydrochloric acid) and bacte-
rial (Helicobacter pylori) factors play a key role between agressive
factors. Other agressive factors are bile components, such drugs as
non-steroid antiinflammatory agents and glucocorticoids, thermal
and mechanical lesions of the mucouse membrane, frequent stressful
situations, etc.
Protective factors include such factors as mucosal barrier, micro-
circulation, regenerative ability of mucous membrane of stomach and
duodenum, bicarbonate secretion, etc.
Considering the above factors, the main aims of ulcer disease
therapy are:
- a decrease of acid-peptide aggression;
- antibacterial therapy against Helicobacter pylori;
- an increase of protective abolity of mucous membrane of stom-
ach and duodenum;
- stimulation of regeneration on the ulcer surface.

Drugs Decreasing the Secretory Activity of Gastric Glands

This group occupies a central position in treatment of ulcer dis-
ease of stomach and duodenum, hyperacid gastritis, esophagitis, and
Zollinger-Ellison syndrome. It is necessary to consider the mecha-
nisms of secretion regulation at the cellular level to understand the
mechanisms of drugs action.
Secretion of gastric juice occurs continuously throughout the day
(nearly 2-3 L a day) and sharply increases during digestion. Mucous
membrane of stomach contains 3 types of cells: сhief cells which se-
crete pepsinogen, parietal cells secreting hydrogen ions, and mucous
cells secreting mucin and bicarbonate. In membranes of parietal cells
such receptors are located as M2-cholinergic, H2-histaminergic, and
gastrinergic. Stimulation of these receptors causes an increase of pro-
ton pump activity. In turn, proton pump secretes hydrogen ions into
the stomach. An increase of acidity of gastric juice promotes trans-
formation of pepsinogen to pepsin. Acetylcholine, gastrin, and his-
tamine also increase the secretion of сhief cells. M-cholinolytics,
blockers of H2-histamine receptors, and proton pump inhibitors are
used for decrease of secretion of these cells. Especially pronounced
therapeutic effect of these drugs is observed in patients with ulcer
disease of duodenum, in which acid-peptic factor is greater.
Drugs which decrease the gastric secretion are devided into fol-
lowing groups:
1. M-cholinoceptor antagonists:
- drugs of nonselective action: atropine, platyphyllin ,
methacin ;
- drugs which inhibit predominantly M1-cholinoceptors: piren-
zepine, telenzepine .
2. H2-histaminergic receptor antagonists: cimetidine , raniti-
dine, famotidine , nizatidine , roksatidine .
3. Proton pump inhibitors: omeprazole, pantoprazole , lan-
soprazole, rabeprozole, esomeprazole .
4. Prostaglandins and their synthetic analogues: misoprostol.
5. Gastrin receptor antagonists: proglumide .

M-Cholinoceptor Antagonists
This group includes atropine, platyphyllin , methacin ,
pirenzepine , and telenzepine . Depending on the affinity of the
different types of M-cholinoceptors these drug are devided into se-
lective (which block only M1-cholinoceptors) and non-selective
(which block all types of M-cholinoceptors) M-cholinergic antago-
nists. Non-selective drugs (atropine, platyphyllin,
methacinium ) are the first agents which were used for treatment of
ulcer disease and hyperacid gastritis. Mechanism of these drugs ac-
tion is associated with blockage of M2-cholinergic receptors which
located in membranes of the cells of mucous membrane of stomach
and in the cells of smooth muscles of gastrointestinal tract. Drugs
eliminate vagal influence predominantly upon basal and nocturnal
secretion. These drugs have less influence upon stimulated secretion.
Drugs influence results in the decrease as volume of gastric juice as
well as concentration of hydrochloric acid in it. However, drugs at
the same time reduce the tone of stomach and intestine and increase
the time of gastric emptying. These effects result in activation of gas-
tric secretion owing to gastric distension.
Clinically significant antisecretory effect of M-cholinergic an-
tagonists develops in case of high degree of blockage of M-choliner-
gic receptors. As a rule, such degree of blockage is accompanied by
side effects (constipation, dry mouth, disturbances of accomodation,
tachycardia, etc.). Therapeutic effect of M-cholinergic antagonists
quickly reduces owing to tolerance.
Practically, such nonselective drugs are used as tincture and ex-
tract of Belladonna; tablents and injections of atropine, platyphilin,
and methacinium and other. Combination drugs are used: “Bekar-
bon”, “Bellastezin ”, “Bellalgin ”, etc. Non-selective drugs are
used for reduction of hypertonus of pyloric section with delayed food
evacuation and cramping (spasmodic pains).
Pirenzepine and telenzepine , selective M1-cholinergic antag-
onists, are mainly used presently. These drugs are characterised by
higher affinity to M1-cholinergic receptors of parasympathetic gan-
glia of stomach. It is results in less possibility of side effects. More-
over, there is evidence that selective M-cholinergic antagonists in-
crease the mucosal resistance to damaging factors.
Pirenzepine is administered parenterally and prescribed orally.
Drug bioavailability in gastrointestinal tract is 20-30%. Maximal
concentration in the blood is achived in 2 hours after drug intake. In
blood, pirenzepine binds in insignificant degree with plasma pro-
teins. Drug is excreted predominantly with bile in unmodified form.
Pirenzepine is prescribed two times a day for 15-20 minutes prior to
meal. Prolonged drug use can causes side effects which is typical for
non-selective M-cholinergic antagonists: dry mouth, tachycardia, etc.
Telenzepine has activity in 25 tymes more than pirenzepine.
Drug significantly suppresses secretion of not only the gastric glands,
but also salivary. It is restricts use of telenzepine.

H2-Histaminergic Antagonists
H2-histaminergic antagonists are divided into 5 generations:
I generation: cimetidine ;
II generation: ranitidine (Zantac);
III generation: famotidine (Quamatel);
IV generation: nizatidine (Axid);
V generation: roxatidine (Roxane).

This classification is based on different pharmacological activity

of drugs, differences in pharmacokinetics, and side effects.
These drugs block H2-histaminergic receptors at competitive
type. Degree of drugs affinity to H2-receptors is significantly higher
in drugs of II-V generation. This makes it possible to prescribe drugs
in significantly less doses. H2-histaminergic antagonists inhibit basal
and nocturnal secretion, as well as secretion stimulated by food, gas-
tric distension, histamine, etc. Drugs increase the production of
prostaglandin E2 by the mucosal membrane of stomach and duode-
num. It results to gastroprotective effect, owing to which drugs pro-
mote the ulcer healing.
Must be borne in mind, that discontinuation of drug intake (ex-
cept for nizatidine and roxatidine) can results in rebound syndrome.
The causes of this phenomenon include hypergastrinemia which de-
veloped owing to decrease of gastric juice acidity, and increase of
density of H2-histaminergic receptors and its affinity to histamine.
Therefore, discontinuation of therapy with these drugs should be
gradual. Doctor should gradually decrease prescribed dose and pre-
scribes simultaneously other agents with antisecretory activity.
 H2-histaminergic antagonists are used intravenously and orally.
Their bioavailability from gastrointestinal tract varies from 50 to
90%. Degree of binding with plasma proteins is 15-20%. Drugs eas-
ily penetrate placenta and can be secreted with breast milk. Cimeti-
dine also easily penetrates through blood brain barrier. Duration of
cimetidine effect is 6 hours, ranitidine – 8-12 hours, famotidine – 12-
24 hours, nizatidine and roxatidine – more than 24 hours. Cimetidine
is prescribed 4 times a day (3 times after meal and once at night),
ranitidine – 2 times a day (in morning 30 minutes before meals and at
the night), famotidine and other drugs – 1 time a day at night. Course
of treatment lasts from 4 to 6 weeks.
50% of administered dose of cimetidine undergoes to biotrans-
formation. Ranitidine is metabolized in less degree. Famotidine and
other drugs are not metabolized practically. Main route of excretion
from the body is kidneys. Cimetidine is low-active, short-acting, and
rather toxic drug.
Combined drug ranitidine bismuth citrate (Pilorid) blocks
H2-histaminergic receptors and also has high bactericidal activity
against Helicobacter pylori.
Indications for clinical use of H2-histamenergic antagonists are
following:
1. Ulcer disease of stomach and duodenum.
2. Hyperacid gastritis.
3. Duodenitis, esophagitis and other diseases which accompa-
nied by increasing secretion of hydrochloric acid.
4. Prevention of ulcers and erosions in patients with craniocere-
bral traumas, sepsis significant burns, etc.
5. Emergency in bleeding ucers of stomach, duodenum, and
esophagus.
Side effects of H2-histaminergic drugs are diarrhea, constipation,
skin rash, headache, myalgia, and dizziness. These effects are more
common in case of cimetidine use. Besides, cimetidine blocks andro-
gen receptors that can results to impotetion and disturbances of sper-
matogenesis. If drug is prescribed to pregnant woman, adrenogenital
syndrome can develop in newborn. Cimetidine decreases secretion of
honadotropic hormones and increases the level prolactin. It can be
cause of gynecomastia, galactorrhea, and macromastia. II-V genera-
tions of drugs have not antiandrogenic activity.
In result of binding with H2-histaminergic receptors of blood
cells, drugs can cause leukopenia, thrombocytopenia, hemolytic ane-
mia. Aggrevations of bronchial asthma, cutaneous manifestations of
lupus erythematosus, etc. are possible owing to blockage of H 2-his-
taminergic receptors in the membranes of tissue basophils.
It is necessary to notice, that prolonged artificial decrease of gas-
tric acidity promotes cancerogenesis.

Proton Pump Inhibitors

Proton pump inhibitors include omeprazole, pantoprazole ,
lansoprazole , rabeprozole , and esomeprazole .
Independently of mode of stimulation (acetylcholine, histamine,
gastrin, etc.), the s ingle way of hydrochloric acid secretion exists. It
is reliased on the level of membranes of parietal cells by means of
energy-dependent exchange of potassium ions and hydrogen ions.
Specific H+,K+-ATPase exists in these membranes and provides pro-
duction of hydrochloric acid in stomach and entryof potassium ions
into the blood.
Based on these data, drugs blocking the activity of H+,K+-ATP-
ase were established. All of them are prodrugs. In acidic environment
near parietal cells, these drugs are transformed to active metabolites
– sulfenamides, which interact with sulfhydryl groups of H +,K+-ATP-
ase. Proton pump inhibitors markedly decrease basal, nocturnal, and
stimulated secretion of hydrochloric acid. These drugs are also effec-
tive in cases which resistive to the use of M-cholinergic and H2-his-
taminergic antagonists. Should be noted, that these drugs also sup-
press the activity of H+,K+-ATPase of Helicobacter pylori that results
in bacteriostatic effect.
A use of proton pump inhibitors causes the increase of gastrin
concentration in the blood. Therefore, sudden cessation of drug in-
take can cause the rebound-syndrome. In this regard, cessation of
proton pump inhibitor intake should be fulfiled in patients receiving
antacid drugs.
Proton pump inhibitors are administered intravenously or taken
orally prior breakfast. Drugs are poorly absorbed in acidic enviro-
ment; therefore its intake should be toogether with intake of sodium
hydrocarbonate. Enteric-soluble granules of drugs are protected by
means of gelatin capsules from hydrochloric acid. Therefore, they
can not chew. Bioavailability of drugs is 35-50%. The degree of
drugs binding with plasma proteins is nearly 95%. Proton pump in-
hibitors undergo the hepatic biotransformation. Maximum effect de-
velops in 1-2 hours after drugs intake. Because proton pump in-
hibitors are weak base, they fastly undergo absorption and accumula-
tion in acidic environment of parietal cells. Drugs of this group are
prescribed 1 time a day. Effect of drugs persists during 24 hours
(sometimes up to 3-4 days). Such long-time effect is due to irre-
versible inhibition of proton pump. Thereby, anew synthesized en-
zyme is needed for restoration of secretion.
The indications for use for proton pump inhibitors are identical
with indications for H2-histaminergic antagonists.
During treatment with proton pump inhibitors following side ef-
fects are possible: headache, drowsiness, dizziness, diarrhea or con-
stipation, and abdominal pain. These phenomena arise owing to first
drug intake and disappear in 1-2 days. Cases of vission loss and hear-
ing are discribed in case of intravenous drug administration. Long-
time administration of proton pump inhibitors is accompanied by risk
of mucous membrane hyperplasia with formation of carcinoids in
submucosal layer of stomach.

Prostaglandins and Their Synthetic Analogues

 Drugs of this group exhibit the two dose-dependent effects. Low
doses of drugs cause gastroprotective effect owing to the increase of
secretion of bicarbonates and mucus and improving of microcircula-
tion. Large doses of drugs cause blockage of hydrochloric acid secre-
tion. Representative of this group is misoprostol (synthetic analog
of prostaglandin E1). Drug blocks both basal and stimulated secretion
of hydrochloric acid and exhibits gastroprotective effect. Misoprostol
is used in treatment of erosions and ulcer disease of stomach and
duodenum. Drug is taken in tablets 3-4 times a day (during meal and
at night). Course of treatment lasts 3-8 weeks. Side effects of miso-
prostol are abdominal pain, meteorism, diarrhea, allergic reactions,
decrease of blood pressure, etc.

Blockers of Gastrin Receptors

Representative of this group is proglumide . Agent inhibits gas-
trointestinal motility and reduces gastric secretions.
Despite years of searching of inhibitors of gastrin receptors and
creation of several agents with this type of action, clinical use of
these drugs is not widely spreeded. Non-selective blocker of gastrin
receptors proglumide blocks both subtypes of gastrin receptors –
CCKA and CCKB. Antisecretory activity of proglumide is equivalent
to first generation of H2-histaminergic antagonists. But proglumide
has fewer side effects. Selective antagonists of gastrin receptors lorg-
lumide and devazipid are not used in clinical practice.

Gastroprotective Drugs
This group includes drugs with different chemical structure and
mechanisms of action, which provide protection of gastric mucosa
from aggressive influence. Also, gastroprotectors create conditions
for ulcers healing or stimulate it. Basically, gastroprotectors are used
for treatment of ulcer disease of stomach and duodenum.
Gastroprotectors are devided into two subgroups:
 1. Drugs creating mechanical protection of gastric mucosa: su-
cralfate, De-nol, bismuth subsalicylate .
2. Drugs increasing the protective properties of mucous barrier
and the stability of gastric mucosa: carbenoxolone , misoprostol.
Sucralfate (Venter) is sulfated disaccharide in complex with
aluminum hydroxide. Agent is polymerized in acid enviroment of
stomach. Polymerized molecules have significant negative charge,
owing to which drug bind with positively charged protein radicals of
the damaged surface. The sucralfate concentration within the ulcer
area is in 5-7 times more than on the healthy areas of mucosa. Pro-
tective pellicle is held on the ulcer surface of stomach up to 8 hours
and on the duodenal ulcer – up to 4 hours. Sucralfate is taken 4 times
a day: 3 times in 30 minutes prior the meal and 1 time at night. Dura-
tion of treatment is 4-6 weeks.
Sucralfate does not decrease the secretion of hydrochloric acid
and pepsin, but these sustances can be absorbed on the surface of
drug.
Sucralfate intake can result in following side effects: discomfort
in the epigastrium, dry mouth, itching and redness of the skin. Su-
cralfate can decrese the intestinal absorption of phosphate and fluo-
ride.
Drug is contraindicated in pregnant women, children up to 4
years of age, and nursing mothers.
De-nol is colloidal bismuth subcitrate, which forms complex
with proteins in acid environment. Most of the drug is concentrated
in erosive area. Furthermore, the gastroprotective activity of de-nol is
connected with its ability to increase the local synthesis of
prostaglandin E2 by mucosa of gastric antral and duodenum. De-nol
also improves the microcirculation and stimulates the secretion of
hydrocarbonate. Drug has bactericidal effect against Helicobacter
pylori. Bacteria disappear from the mucosal surface in 30-90 minutes
after de-nol intake. Pathogen completly is not detected after 3 weeks
of treatment, but cessation of de-nol can be accompanied by recolo-
nization of Helicobacter pylori. Therefore, combination of de-nol
with antibacterial drugs is most appropriate.
 De-nol is taken in 30 minutes prior meal and at night. Course of
treatment lasts 4-6 weeks.
Side effects of de-nol are nausea, vomiting, diarrhea, headache,
dizziness. Bismuth sulfide (which formed in the intestines) stains
tongue and feces in black color.
Carbenoxolone is glyceric acid of licorice root. Drug stimu-
lates mucus secretion and increases its viscosity. Furthermore, car-
benoxolone inhibits enzymes which participate in prostaglandin inac-
tivation. Carbenoxolone has some mineralocorticoid activity and an-
tiinflammatory properties. Drug inhibits the transformation of
pepsinogen to pepsin.
Absorbtion of carbenoxolone occurs in intestines. The degree of
binding with plasma proteins is 80-90%. Elimination of carbenox-
olone from the body is performed the kidneys (60%) and by the liver.
Should be noted, that drug undergoes enterohepatic recycling.
Carbenoxolone is taken in 30 minutes prior meal and at night.
Main indication is treatment of ulcer disease in patient with high se-
cretory rate. Sometimes drug is used in treatment of duldenal ulcers.
Side effects of carbenoxolone are result of its mineralocorticoid
activity. They are edemas, increase of body weight, hypertension,
muscular weakness, etc.
Misoprostol is synthetic analog of prostaglandin E1. It is
cknown, that gastric mucosa synthesizes prostaglandins, which stim-
ulate secretion of mucus and bicarbonate. Prostaglandins also inhibit
secretion of hydrogen ions by parietal cells, expand the vessels of
deep layers of mucosa, increase the resistance of vessels wall to ag-
gressive factors, and create the necessary conditions for healing of
erosions and ulcers.
Especially marked gastroprotective effect of misoprostol is ob-
served in treatment of ulcers, which developed owing to use steroid
and non-steroid antiinflammatory drugs (these agents inhibit the
prostaglandin synthesis). Misoprostol is taken during meal 3-4 times
a day. Effect develops in 30 minutes and lasts up to 3 hours. Duration
of treatment is 4-8 weeks. Misoprostol is not used as drug for
monotherapy in connection with frequent side effects which include
abdominal pain, nausea, vomiting, rash, uterine bleeding during men-
struation. Drug is predominantly recommended for prevention of ul-
cers in patient treated by antiinflammatory drugs.

Antacids
This group includes following drugs: sodium hydrocarbon -
ate, calcium carbonate , magnesium oxide , aluminium hy-
droxide, Almagel, Phosphalugel , Maalox, Gastal, etc.
These drigs are weak bases which inactivate the hydrochloric
acid in result of direct chemical interaction.
Depending on the ability to be absorbed from gastrointestinal
tract, antacids are divided into drugs of resorptive action and drugs of
pre-resorptive action.
Drugs of resorptive action are sodium hydrocarbonate and
calcium carbonate .
Sodium hydrocarbonate has high solubility in water. After
intake, drug is readily distributes in stomach. Sodium hydrocarbonate
shows almost lightning, but short antacid effect. Duration of effect is
15-20 minutes. Interaction of sodium hydrocarbonate with hy-
drochloric acid results in release of carbone dioxide which expands
the stomach. It is cause of belching gas and the feeling of heaviness
in epigastrium. Rebound syndrome is typical for sodium hydrocar-
bonate, in which gastric distension results in the secondary increase
of secretion of hydrochloric acid and pepsin. It is the cause of fast re-
sumption of pain.
Chronic intake of sodium hydrocarbonate can result in the sys-
temic alkalosis owing to absorption of bicarbonate ion. The risk of
this complication increases in patients with impaired renal function.
The symptoms of systemic alkalosis include poor appetite, nausea,
vomiting, weakness, abdominal pain, muscular spasms, and convul-
sions. Long-term use of sodium hydrocarbonate is accompanied by
accumulation of sodium ion, increase of blood pressure, development
of edemas.
 Calcium carbonate is poorly soluble in gastric contents. The
action is slow and absorption is less than absorption of sodium hy-
drocaronate. Drug neutralizes hydrochloric acid with the release of
carbone dioxide. Calcium carbonate causes strongest rebound syn-
drome. Chronic drug intake together with milk diet (typical diet for
patients with ulcer disease) is commonly accompanied by develop-
ment of “milk alkali syndrome”. Symptoms of this syndrome include
nausea, vomiting, hydruria, hypercalcemia, calcification of vessels
and kidneys, kidney stones, azotemia, psychical disorders.
Pre-resorptive antacids are magnesium oxide, aluminium hy-
droxide, Almagel and other drugs.
Magnesium oxide interacts with hydrochloric acid without the
release of carbone dioxide. Therefore, drug intake does not accompa-
nied by rebound syndrome. Synthesized in reaction of neutralization
magnesium chloride is poorly absorbed from intestines and has weak
laxative effect. Laxative effect is result of the increase of osmotic
pressure into the intestines and stimulation of cholecystokinin secre-
tion, which stimulates peristalsis. Magnesium oxide does not influ-
ence acid-base balance. Antacid effect of drug develops slowly.
Aluminium hydroxide is characterised by both antacid and
absorptive activity. Drug interacts with hydrochloric acid without the
release of carbone dioxide. Systemic alkalosis does not develop ow-
ing to chronic drug intake. Regular use of drug can be accompanied
by slowdown of intestinal motility which promotes constipation. Part
of administered dose, which does not interact with hydrochloric acid,
turns into phosphate and carbonate. These aluminium sults is poorly
absorbable in the intestines. Therefore, chronic aluminium hydroxide
intake reduces absorption of phosphates and can cause hypophos-
phatemia and hypophosphaturia. Deficiency of phosphates is mani-
fested by fatiguability, muscular weakness, thinking disturbances,
anorexia, etc. Prolonged phosphate deficiency is accompanied by
bone lesions (osteoporosis, osteomalacia), impaired healing of
wound, and increased risk of infections. Aluminium also binds fluo-
ride ions into intestines that result in damage to dental enamel.
 Combined antacid drugs are widely used in medicine for de-
crease of develompment of side effects and for increase of efficacy
of antacids. These drugs include Almagel, Posphalugel,
Maalox, Gastal, etc.
Almagel consists of aluminium hydroxide gel, magnesium ox-
ide, and sorbitol. Magnesium oxide has laxative effect and sorbitol –
cholagogic effect. Gel form promotes the uniform distribution of
drug over the surface of stomach.
Almagel A contains additionally anaesthsinum which causes
local anaesthesia and inhibits gastrin secretion.
Phosphalugel is drug containing aluminium phosphate in form
of hydrophilic colloidal micelles, pectin gel, and agar-agar. Drug has
antacid and absorptive activity. Micelles of aluminium hydroxide
bind bacteria, viruses, toxines, and gases and eliminate them from in-
testines. Drug does not influence upon acid-base balance and phos-
phates absorption. Pectin and agar-agar promote the formation of
mucoid protective layer in gastrointestinal tract.
As a rule, all antacids are prescribed in 1 hour after meal (in con-
nection with decrease of buffering effect of food in period of maxi-
mal secretion) or in 3 hours after meal (for restoration of antacid ac-
tion after food avacuation). Also, antacids are prescribed to hight for
protection of mucous membrane during nocturnal secretion. In acute
period of disease, the course of treatment with antacids lasts 2-4
weeks. In cases when pain arises during meals, antacids are pre-
scribed in 30-40 minutes prior meal.
Indications for antacids use are ulcer disease of stomach and
duodenum with hyperacid syndrome, hyperacid gastritis, esopha-
gatis, hiatal hernia, and reflux esophagitis.

Drugs which Used in Hypofunction of Pancreas

 During day, pancreas produces 1.5-2 L of juice which contains
more than 10 enzymes. Pancreatic juice also contains significant
amount of bicarbonate and has alkaline reaction. It is promotes the
neutralization of hydrochloric acid and the normal activity of pancre-
atic enzymes, which are involved in the digestion of peptides, lipids,
and carbohydrates.
Trypsin, chymotrypsin, carboxypeptidases A and B, and elastase
complete proteolysis of proteins which initiated by pepsin. Amylase
promotes the hydrolysis of polysaccharides. Lipase and phospholi-
pase hydrolyze fatty acids and phospholipids. Bile is also necessary
for hydrolysis of lipids, because promotes their emulsification. Addi-
tionally, bile participates in absorption of amino acids.
Pancreatic insufficiency is developed owing to transferred acute
and chronic pancreatitis; in patients with chronic gastritis, ulcer dis-
ease, cholangitis, etc.
Drugs of pancreatic enzymes often contain also pepsin or bile
components. Such combination increases functional integration of di-
gestive system and is the most effective in patients with chronic di-
gestive disturbances and in old patients.
Pancreatic enzymes are obtained from gland of livestock for
slaughter, sertain enzymes – from microorganisms and even plants.
Pancreatin (powder of the dry pancreas of livestock for
slaughter) contains predominantly two enzymes – trypsin and amy-
lase. It is used in patients with pancreatic insufficiency. Following
combined drugs are commonly used in medicine: Mezym Forte
(pancreatin contaning amylase, lipase, and protease), Panzinorm
(drug contains pancreatin, extract of gastric mucosa, bile ecstract,
aminoacids), Digestal (consists of pancreatin, bile extract, hemicel-
lulose), Festal, Enzystal, Licrease, Kreon, etc. All drugs act in
alkaline environment and are inactivated in acids. Therefore, drugs
are manufactured in intestinal-soluble dragee or capsules. Course of
treatment with pancreatic enzymes lasts from 2 up to 4-6 weeks.
Regular drug intake results in reduction of bloating, diarrhea, im-
proved the general condition of the patient.
 Indications for drugs use are chronic pancreatitis, ahiliya,
chronic hypoacid gastritis, hepatitis, cholecystitis, etc.
Drugs are well tolerated by patients. It is necessary to notice,
that these drugs contain significant amounts of purines and can cause
exacerbation of gout and formation of urate kidney stones.

Drugs Inhibiting Pancreatic Secretion

Drugs which inhibit pancreatic secretion are used for treatment
of acute pancreatitis.
Normally, inactive trypsinogen is synthesized in pancreas. In
duodenum by means of enterokinase, it is activated to trypsin. In
acute pancreatitis, transformation of trypsinogen to trypsin occurs di-
rectly in pancreas owing to action of cytokinase. In turn, trypsin acti-
vates other proteolytic enzymes in pancreas. These processes result
to autolysis and necrosis of pancreas. Simultaneously sinthesized
bradykinin causes vasodilation and hypotension.
The aim in treatment of acute pancreatitis is reduction of secre-
tion and activation of protelytic pancreatic enzymes – trypsin and
kallikrein. Following drugs are used for this aim:
1. M-choliceptor antagonists: atropine, platyphyllin , etc.;
2. Inhibitors of proteolytic enzymes: contrical, trasilol, gor-
dox, aminocapronic acid , etc.
Contrical is used most commonly. This drug obtained from lung
tissues of livestock for slaughter. Contrical inhibits the proteolytic
enzymes and prevents or reduces the autolysis and necrosis of pan-
creas. Contrical is dosed with units of action and administered intra-
venously drop by drop.
Treatment of acute pancreatitis also includes administration of
analgesics, antibiotics, antacids, plasma expanders, and electrolytes.
 Drugs Improving Functions of Liver
(Hepatotropic Drugs)
Hepatotropic drugs are devided into bile-expelling drugs,
gepatoprotectors, and drugs for dissolution of gallstones.
Hepatocytes produce bile continuously. Bile is deposited in large
bile-ducts and in gallbladder, in which bile is concentrated. Sphinc-
ters are located in the common bile duct, gallbladder, and in the out-
put in the duodenum. Parasympathetic nervous system plays an im-
portant role in the process of bile evacuation. Increase of tone of
parasympatheitc nervous system results to sphincters relaxation and
contraction of gallbladder.
Bile ejection occurs during digestion. It is stimulated by chole-
cystokinin, which is synthesized by duodenal epitelium owing to
food intake. Daily volume of produced bile is near 1 L.
Process of digestion requires the bile acids which participate in
emulsification of fats and activation of lipase. Bile acids also pro-
mote absorption of fat-soluble vitamins (A, D, E, K, F). Furthermore,
bile increases activity of pancreatic proteases and amylase, has bacte-
riostatic action against putrefactive intestinal microflora.
Bile-expelling drugs are devided into two groups:
1. Drugs stimulating bile production (cholosecretics).
2. Drugs promoting bile excretion (cholokinetics).

Drugs Stimulating Bile Secretion

These drugs are devided into 3 groups:
1. Drugs containing bile and bile acids: “Allohol”, “Cholen-
zymum”, lіobіlum , chenodeoxycholic acid .
2. Drugs of plant origin: “Cholaflux ”, holagol, flamіn,
berberine sulfate , holosas, syrup of wild rose , decoctions
from flowers of Helichrusum arenarium , oats seeds, Stig-
matum maydis .
3. Synthetic drugs: oxaphenamіdum , cycvalonum , nіkod-
inum, odeston.
 Bile-contaning drugs stimulate bile formation in hepatocytes and
simultaneously perform the function of drugs for substitutive the-
rapy.
“Allochol ” consists of bile, garlic and nettle extracts, and acti-
vated carbon. Drug is taken orally 3 times a day after meal. Dose is
1-2 tablets. Course of treatment is 3-4 weeks.
Tablets “Cholenzymum” consists of dry bile, chopped dried
pancreas, and dried mucous membrane of the small intestines of
slaughter cattle. Drug is taken orally, in dose 1 tablet three times a
day after meal.
Liobilum is manufactured in tablets containing 0, 2 g of freeze-
dried bovine bile. Drug is taken orally, in dose 1-3 tablets at the end
of meals 3 times a day. The course of treatment is 1-2 months.
Drugs of plant origin are widely used in form of infusions, de-
coctions, and extracts. Cholesecretory activity is typical for
flavonoids and essential oils of everlasting flower, corn silk, bar-
berry, dandelion root, fruits of mountain ash and wild rose, etc. Phar-
maceutical industry produces extracts of these plants in different
medicinal forms: drops for oral intake “Cholagol”, tablets
“Flaminum ”, tablets of berberine sulfate , sirup “Cholosas”.
“Cholagol” consists of pigments of turmeric root, frangulae-
modin, magnesium salicylate, peppermint oil, and eucalyptus oil.
Drug has choleretic, moderate antispasmodic, anti-inflammatory, dis-
infectant, and laxative effects. “Cholagol” is taken in dose 5-10 drops
on a piece of sugar 3 times a day in 30 minutes prior meals.
“Flaminum ” contains of dry extract Helichrysum arenarium.
Drug is taken in dose 1 tablet 3 times a day in 20 minutes priot meals
(tablet is dissolved in 1/2 cup warm water).
“Cholosas” contains extractum of wild rose. “Cholosas” has
choleretic and hepatoprotective effects. Druh restores and maintains
normal function of hepatocytes, restore the flow of bile, normalizes
the immune system. Also, “Cholosas” has anti-inflammatory and di-
uretic effects, increases intestinal motility. Due to the presence of vi-
tamin C and other bioactive natural products, drug improves immu-
nity. “Cholosas” is taken in dose 1 tea-spoon 2-3 times a day in 30
minutes prior meals.
Synthetic drugs (oxaphenamіdum , cycvalonum , nіkod-
inum, odeston) increase bile production and also promote its excre-
tion. These drugs have more prominent choleretic effect than bile-
containing drugs and drugs of plant origin.
Synthetic drugs (except nikodinum) increase the tone of gall-
bladder and relax the smooth muscles of bile ducts. In addition, some
of them (for example, nikodinum) have antimicrobial effect that is
clinicaly useful in treatment of inflammatory diseases of liver, bile
ducts, and gallbladder. These drugs are prescribed 3 times a day prior
meals.

Drugs Stimulating Bile Discharge

Cholokinetics cause the contraction of gallbladder and relaxation
of Oddi sphincter. It results in bile release into the duodenum. Mech-
anism of action of most of them is due to irritation of duodenal mu-
cosa owing to which cholecystokinin is released into the blood.
Namely cholecystokinin causes the release of bile.
Cholecystokinin is duodenal hormone, molecules of which
consist of 33 residues of aminoacids. This drug is derived from duo-
denal mucosa of pigs. Drug promotes the contraction of gallbladder
and activates hydrochloric acid secretion in stomach. Cholecys-
tokinin is used for diagnostics of gallbladder contractility and its con-
tent.
Magnesium sulfate is administered in a warm solution (25-
10% of 50-200 ml respectively by means of duodenal probe 1 time in
srveral days) or perorally (as 25% solution in dose 1 table-spoon 3-4
times a day during 2-3 weeks). Drug also may be used for tubage. In
this case, patient lying on his right side drinks during 30 minutes 100
ml of 10-20% solution of magnesium sulfate. After this, patient
should lie during 1.5-2 hours with hotty on the lives arrea.
 As cholokinetics also may be used following drugs: sorbitol
(50-70 ml of 10% solution, 2-3 times a day prior meal), sunflower
or olive oil (1-2 table-spoons, it is possible with lemon juice),
plants containing bitters (dandelion, yarrow, wormwood , etc.),
essential oils of coriander and cumin, extracts and fruit
juice of cranberries, cowberry , etc.
Indications for use of cholokinetics are dyskinesia, chronic hep-
atitis, hypoacid gastritis which is accompanied by gallbladder atony
with cholestasis. Druga are contraindicated in acute period of liver
diseases, in cholelithiasis, in exacerbation of hyperacid gastritis and
ulcer disease.
Myotropic antispasmodics, such as No-spa, papaverine , eu-
phillinum , atropine , platyphyllin , are used for reduction of
spasticity of bile ducts. These drugs reduce the pain which occurs in
pathology of bile ducts. Myotripic antispasmodics are effective in
moderate pain and well combined with other hepatotropic drugs.
These drugs should be administered parenterally together with anal-
gesics in case of intensive pain in attack of cholelithiasis.

Hepatoprotectors
Hepatoprotectors are drugs which increase the resistance of liver
to unfavorable factors and decrease the damage and destruction of
hepatocytes.
Hepatoprotective effect is due to the normalization of hepato-
cytes metabolism, the increase of microsomal enzymes activity, and
restoration of damaged cell membranes. Druga are used in acute and
chronic hepatitis, liver dystrophy, cirrhosis, and toxic liver damage
(including alcoholism and hepatic coma).
Hepatoprotectors derived from thistle (Silybum marianum) and
other plants richest on flavonoids are used most widely in medicine.
They are Legalon, Carsil, Hepabene, Hepatofalk Planta ,
LIV-52, etc.
Flavonoids are phenolic compounds – derivative of chromone.
Together with ascorbic acid, flavonoids paticipate in redox pro-
cesses. Flavonoids also belong to antioxidant system of cells.
Flavonoids have anti-inflammatory, bile-expelling, antiviral, anal-
gesic, and immunomodulatory effects. These agents stabilize the vas-
cular wall, imrove the hemophoresis, reduce vascular spasm, increase
level of calcium and hlucocorticoids into the blood, and reduce
cholesterol level. Flavonoids are widely used for prevention of stom-
ach, liver, and cardiovascular diseaes. Antioxidative activity of
flavonoids is higher than activity of vitamin E. Flavonoids are easily
absorbed in gastrointestinal tract and accumulated in the liver and
kidneys. Flavonoids of Silybum marianum have high hepatotropic
properties which are the base for their efficacy in liver diseases.
These drugs stimulate protein synthesis, normalize phospholipids
metabolism, and increase the glutathione reserve in liver.
Legalon is an extract of the fruit of Silybum marianum. It con-
tains of mixture of flavonoids with hepatoprotective activity – silibi-
nine, silimarine, etc. Mechanism of Legalon action is associated with
stabilization of hepatocytes membranes, antioxidative properties, and
ability to stimulate protein synthesis and increase the gluthatione re-
serve in the liver. Drug is used orally in capsules, dragee, and emul-
sion. Drug has low toxicity. Sometimes, diarrhea is possible.
Presently, monodrag of flavonoid silibinine is established –sili-
binine dihydrosuccinate sodium salt . This agent is adminis-
tered intravenously in poisoning by death cup.
Another group of hepatoprotectors is presented by drugs which
involved in the building of cellular membranes – unsaturated fatty
acids, choline, phospholipids, essential amino acids, etc. As a rule,
these drugs also contain vitamins which paticipate in detoxifying
function of liver and in restoration of cellular membranes. These
drugs are essentiale , thiotriazoline , ademethionine , lipoic
acid, etc.
Essentiale contains of fatty acids in the form of phospholipids,
vitamins of group B, and tocoferol. Drug is administered intra-
venously in emergency (hepatic coma, acute poisoning with hepatic
dysfunction, etc.). In other cases, essentiale is usually used orally in
dose 2-3 capsules 3 times a day prior meal. Essentiale is prescribed
in chronic hepatitis, liver cirrhosis, hepatic dysfunction in patients
with diabetes mellitus, for revention of reccurance of cholelithiasis,
in pre- and postoperative periods, etc.
Thiotriazoline is synthetic agent with antiischemic, antioxida-
tive, membrane stabilizing, and immunomodulatory effects. Drug
prevents the hepatocytes destruction, inhibits fatty infiltration and
necrosis of liver. Thiotriazoline normalizes peptide, carbohydrane,
and pigmentary metabolism is liver. Under influence of thiotriazo-
line, both synthesis and discharge of bile increase. Aditionally, thio-
triazoline reduces the ischemia of myocardium, reduces the necrotic
zones after myocardial infarction, activates fibrinolytic properties of
blood. Drug administered intravenously and intramuscularly in hep-
atitis, hepatic cirrhosis, ischemic heart disease, myocardial infarction,
cardiosclerosis, and arrhythmias.
Ademethionine (Heptral) contains the methyl groups which
involved in synthesis of membrane phospholipids. Also, methyl
groups are paticipate in synthesis of cysteine, glutathione, sulfate,
and taurine. All these substances are essential for detoxifying func-
tion of liver. Additionally, ademethionine has antidepressive, anal-
gesic, and anti-inflammatory activity. Drug is taken orally and ad-
ministered intravenously or intramuscularly. Indications for ademe-
thionine use are intrahepatic cholestasis; toxic, viral, alcoholic, and
drug-induced liver damage; cirrhosis, encephalopathy, including
those in hepatic failure, depressive and abstinence syndrome.
Lipoic acid stimilates the detoxifying function of liver, has an-
tioxidative activity, paticipates in lipid and carbohydrate metabolism.
Agent is prescribed in infective hepatitis, chronic hepatitis, cirrhosis,
intoxications, coronary atherosklerosis, and diabetic polyneuropathy.

Drugs Which are Used for Dissolution of Gallstones

 It is proved, that certain derivatives of deoxycholic acid, such as
ursodeoxycholic acid (ursofalk) and chenodeoxycholic
acid (chenofalk ) promote the dissolution of cholesterol stones in
gallbladder. These drugs use results in reduction of cholesterol con-
centration in bile. Chenodeoxycholic acid inhibits the synthesis of
cholesterol in hepatocytes. Ursodeoxycholic acid decreases the in-
testinal absorption of cholesterol and oppresses its synthesis. Reduc-
tion of cholesterol in bile results in the decrease of ability of stones
formation in gallbladder. The change in the ratio of cholesterol and
bile acids in favor of the latter promote gradual dissolution of choles-
terol-containing gallstones. These drugs are taken perorally during
long time (1 year and more). Side effects are diarrhea, itching, and
increase of aminotransferase level. Ursofalk also is used for treat-
ment of biliary cirrhosis.

Drugs Influencing Gastric Motility

These drugs are divided into agents which increase gastric motil-
ity (prokinetics) and agents which inhibit gastric motility.
Prokinetics are metoclopramide , cisapride, domperidone
(motilium ), etc. Prokinetics are used in case of delayed gastric emp-
tying and in reflux esophagitis. Metoclopramide blocks peripheral
and central D2-dopaminergic receptors and activates 5HT3-serotonin-
ergic receptors. Cisapride is agonist of 5HT3-serotoninergic receptors
and indirectly excites cholinergic receptors of intramural ganglia.
Domperidone blocks peripheral D2-dopaminergic receptors.
M-cholinoblocking drugs (atropine, platyphyllin ,
methacinium ), ganglion blocking drugs (benzohexonium , piri-
lene), agents which block both M-cholinoceptors and N-cholinoce-
pros of ganglia (buscopane, probanthine ), and myotropic spas-
molytics (papaverine , no-spa, etc.) are used for reduction of gas-
tric motility.

Emetic Drugs
 Emetic drugs are agents which cause vomiting. They are apo-
morphine, herb of thermopsis , root of ipecacuanha , cop-
per sulfate , and zinc sulfate .
Vomiting is complex reflex act with protective value which de-
velops due to activation of vomiting (emetic) centre. Stimulants of
vomiting cenre include impulsi from the mucous membrane of stom-
ach, intestines, and other hollow organs; impulsi from vestibular ap-
paratus and cortex (psychogenic vomiting), from visual, scents and
taste analyzers, etc. But chemorecepros of trigger zone have the main
value in stimulation of vomiting. Trigger zone is located on the floor
of the fourth ventricle. Its neuronal membranes contain D 2-dopamin-
ergic, 5-HT3-serotoninergic, and M1-cholinergic receptors. Excitation
of these receptors results in stimulation of vomiting centre.
Certain chemical substances which synthezied in disturbed me-
tabolism in renal and hepatic failure or in toxemia of pregnancy, as
well as number of drugs (opioid analgesics, digitalis, antitumoral
agents) also are stimulants of chemoreceptors of trigger zone.
Apomorphine is emetic drug with central action. It is specific
agonist of D2-receptors. Drug is used for elimination of gastric con-
tents caused poisoning in cases when gastric lavage is impossible
(for example, poisoning by mushrooms or by other foods which do
not pass through tube, in case of suicide, etc.). Apomorphine is ad-
ministered subcutaneously or intramuscularly. Emetic effect devel-
ops in 2-15 minutes.
Vomiting induction is contraindicated in unconscious patients, in
pregnants, in childhood and advanced age; as well as in poisoning by
gasoline, kerosene, turpentine, acids, alkalis, and other substances af-
fecting mucous membranes. In such cases, the gastric lavage with ab-
sorbents and following saline laxatives is preferable.
Thermopsis herb and ipecacuanha root are agents which
excite emetic centre by reflex way. If these drugs are taken orally in
high doses, they excite the stomach receptors and reflectory stimulate
vomiting. It is necessary to notice, that alkaloids of thermopsis and
ipecacuanha after absorption into the blood can directly stimulate the
chemoreceptors of trigger zone.
 Copper sulfate and zinc sulfate also have the peripheral
mechanism of emetic action which associated with irritation of mu-
cous membrane of stomach.
It is necessary to notice, that the use of emetic drugs in medical
practice is significantly restricted.

Antiemetic Drugs
Antiemetic drugs are devided into two main groups:
1. Agents which are effective in vomotinig of central origin:
- antagonists of D2-dopaminergic receptors: metoclopramide ,
thiethylperazine , aminazine (chlorpromazine), aethapera-
zine, triftazinum , etc.
- blockers of 5-HT3-serotoninergic receptors: ondansetron ,
tropisetron, granisetron.
2. Agetns which are effective in vomiting caused by irritation of
vestibular apparatus:
- M-cholinoblockering drugs: scopolamine, “Aeron”;
- antagonists of H1-histaminergic receptors: dimedrolum,
diprazinum.
In kinetoses (seasickness and airsickness), the case of vomiting
is overexcitation of vestibular apparatus. Vestibular apparatus carries
out impulses to the cerebellum, which in turn transmits impulses to
the vomiting centre. As M-cholinergic and H1-histaminergic recep-
tors of cerebellum paticipate in this transduction of impulses. The
following drugs are used for prevention of vestibular origin vomit-
ing: tablets “Aeron” (contains M-cholinoblockering agents scopo-
lamine and hyoscyamine), scopolamine in tablets or as patch
(Scopoderm TTS), and H1-histaminoblockering agents dime-
drolum and diprazinum. Efficacy of these drugs in kinetoses de-
velops due to blockage of M-cholinergic and H1-histaminergic recep-
tors in cerebellum. But it is possible, that direct inhibitory influence
upon vomiting centre also participates in antiemetic effect of these
agents. Side effects of these drugs include drowsiness, dry mouth,
and blurred vision.
Metoclopramide (cerucal, reglan ) is one of the most often
used antiemetic agents. Mechanism of its ection is associated with
blockage of D2-receptors in neurones of tregger zone. Agent used in
high doses can also block 5-HT3-serotoninergic receptors. Indications
for use of metoclapramide include ulcer disease of stomach and duo-
denum, meteorism, dyskinesia, oncological diseases of gastrointesti-
nal tract, radiation sickness, uraemia, delayed gastric emptying, and
reflux esophagitis. Drug is taken orally or administered parenterally
(intramuscularly or intravenously). Effect develops quickly and lasts
6-8 hours. Side effects of metoclapramide are drowsiness, sonitus,
dry mouth, and extrapyramidal diserders.
Sertain neurileptics – phenothiszine derivatives, such as
thiethylperazine , chlorpromazine (aminazine ), aethaper -
azine, and triftazinum are also used as antiemetic agents. Mecha-
nism of their action is associated with blockage of D 2-receptors of
tregger zone. Thiethylpirazine also directly oppresses vomiting cen-
tre. These drugs are also characterized by marked sedative and an-
tipsychotic effects. Neurileptics are effective in vomiting of central
origin.
Ondansetron (zofran), tropisetron, and granisetron are
antagonists of 5-HT3-serotoninergic receptors. Drugs are character-
ized by high efficacy in vomiting following chemotherapy of cancer,
in postoperative period, and in radiation sickness. Drugs are adminis-
tered 1 time a day orally or parenterally. Side effects are headache,
dizziness, and constipation.
Antiemetic drugs are not used in unconscious patients, in
patietns with gastrointestinal bleeding, with ulcer perforation, and
with ileus.

Drugs which Influence Intestinal Motility

 Drugs stimulating intestinal motility
This group includes drugs which elimanate the intestinal atony.
Agents are classified into following subgroups:
1. Drugs stimulating M-cholinergic receptors: aceclidine .
2. Cholinesterase inhibitors: proserinum, pyridostigmine ,
distigmine .
3. Agonists of 5-HT4-serotoninergic receptors: cisapride.
4. Agonists of motilin receptors: erythromycin, olean-
domycin.
Aceclidine interacts and excites M-cholinergic receptors of
smooth muscles of gastrointestinal tract. Whereas cholinesterase in-
hibitors suppress the activity of cholinesterase and increase the level
of acetylcholine in cholinergic synapses.
Motilin receptors are located in antrum of the stomach and in
duodenum. These receptors are excited by motilin. It is gastrointesti-
nal polypeptide hormone which stimulates smooth muscle contrac-
tions in the stomach and small intestine. Antibiotics erythromycin
and oleandomycin excite motilin receptors and stimulate intestinal
motility.
Moreover, such drugs as hormonal agent vasopressin and laxa-
tive drugs also stimulate intestinal smooth muscles.

Drugs Inhibiting Intastinal Motility and

Reducing Intestinal Spasms
Following groups of drugs are used in intestinal spasticity.
1. M-cholinoblockers: atropine, platyphyllin ,
methacinium .
2. Ganglion blockering drugs: benzohexonium (hexametho -
nium), pirilenum.
3. Myotropic spasmolytics: papaverine , drotaverine (No-
spa).
4. Agonist of peripheral opiod receptors: loperamide.
 Pharmacology of M-cholinoblockering and ganglion blockering
drugs is given in relevant sections. Myotropic spasmolytics or my-
otropic antispasmodic agents inhibit the enzyme phosphodiesterase
that leads to accumulation of cAMP and decrease of smooth muscles
tone and motility.
Loperamide (imodium ) is phenylpiperidine derivative which
stimulates μ-opioid receptors in the intestine and owing to this in-
hibits peristalsis.
Drugs which inhibit intestinal motility are used in spastic colitis
and for symptomatic treatment of acute and chronic diarrhea.

Laxative Drugs
Laxative agents are divided into following groups:
1. Saline laxatives: magnesium sulphate , sodium sul-
phate.
2. Organic laxatives.
2.1. Drugs of plant origin:
- vegetable oils: castor oil ;
- drugs contaning anthraquinone glycosides: extract of buck-
thorn (Rhamnus) cortex , rhubarb (Rheum) root , senna
leaves .
2.2. Synthetic drugs: isaphenine , phenolphthalein , gutta-
lax, bisacodyl .

Saline Laxatives
Magnesium sulphate and sodium sulphate are used for
purification both small and large intestine. These drugs create into in-
testine high osmotic pressure that causes the retention of water in lu-
men of intestine. An increase of intestinal content volume results in
distension of bowel and irritation of intestinal mechanoreceptors that
increases peristalsis. Drugs act throughout small and large intestine.
Saline laxatives are taken orally in dose 15-30 g with 1-2 glasses of
water. Effect develops in 2-3 hours and lasts up to 6 hours. Drugs are
used in acute poisoning and prevent the absorption of toxins into the
blood.

Vegetable Oils
Castor oil is obtained from castor seeds. In duodenum, castor
oil is hydrolysed under influence of pancreatic lipases with release of
glycerin and castor acid. Castor acid irritates receptors and stimulates
the peristalsis throughout small and large intestine. Moreover, castor
acid affects the absorption of ions and water from the intestine.
Agent is taken orally in dose 15-30 g during 30 minutes. Effect
develops in 2-6 hours.
Castor oil is used in acute constipations, in preparation of patient
to roentgenologic examinations or to surgery on the abdominal or-
gans. Castor oil stimulates the contractile activity of uterus.

Drugs Contaning Anthraquinone Glycosides

These drugs increase the peristalsis and facilitate the excretion
of feces. Extracts of buckthourn cortex, rhubarb root, and
senna leaves are drugs which used most commonly. Vegetable an-
thraquinone glycosides are lack laxative effect. Under the influence
of intestinal bacteries, these substances are hydrolysed to an-
thraquinone derivatives – emozin and chrysophanic acid which irri-
tate the intestinal receptors and stimulate peristalsis. These drugs act
only in large intestine.
Drugs are taken orally 1 time in 2-3 days, as a rule at night or in
the morning before breakfast. Laxative effect develops in 8-10 hours.
Anthraquinone glycosides are accumulated in the mucous mem-
brane and smooth muscles of bowels and can cause the atrophy of
smooth muscle layer. In this case constipation becomes chronic and
insensitive to therapy with laxative drugs. Prolonged drugs use also
can cause the disturbances in liver function.
 Synthetic Laxative Drugs
Phenolphthalein is absorbed into the small intestine and se-
creted into the large one, where drug irritates receptors and decreases
the absorption of ions and water. Laxative effect develops in 6-8
hours after drug intake. Phenolphthalein can cumulate in the body
and affect the kidneys function. Side effects of drug include the aller-
gic reactions, intestinal colics, tachycardia, and collaps.
Isaphenine is hydrolysed into the intestine with release of
dioxiphenylisatine. This substance irritates the receptors and in-
creases the peristalsis of large intestine. Laxative effect develops in
8-12 hours after isaphenine intake. Isaphenine has less than phe-
nolphtha-lein.
Guttalax and bisacodyl under the influence of intestinal bac-
teries release the active radicales stimulating intestinal receptors and
increasing peristalsis. Drugs are used in chronic constipations. Onset
of laxative effect is in 6-10 hours after drugs intake.

Table 1 – Drugs for prescription

Drug name Single doses and mode of Drug product
administration
Desopimonum Orally 0.025 g 2 times daily Tablets 0.025 g
Succus gastricus Orally 15-30 ml during meal Bottles 100 ml
naturalis
Pepsinum Orally 0.2-0.5 g during meal Powders
Acidum Orally 10-15 drops during meal Bottles 50 ml
chidrochloricum
dilutum
Pirenzepinum Orally 0.05 g 2 times per day; Tablets 0.025 or 0.05 g;
intravenously or intramuscularly ampoules 2 ml of
0.01 g 2 times per day 0.5% solution
Ranitidinum Orally 0.15 g 2-3 times daily Tablets 0.15 g
Omeprazolum Orally 0.02 g 1 time per day Capsules 0.02 g
Magnesii oxydum Orally 0.25-1.0 g 4 times per day Powders;
tablets 0.5 g
Almagelum Orally 1 tea-spoon 4 times per day Bottles 150 ml
De-nolum Orally 0.12 g 4 times per day Capsules 0.12 g
Sucralfat Orally 0.5-1.0 g 4 times per day Tablets 0.5 or 1.0 g
 Apomorphini hy- Subcutaneously 0.002-0.005 g Ampoules 1 ml of
drochloridum 1% solution
Metoclopramidum Orally 0.01-0.02 g 2-3 times per Tablets 0.01 g;
day; ampoules 2 ml of
intramuscularly or intravenously 0.5% solution
0.01 g 1-3 times daily
Aethaperazinum Orally 0.004-0.006 g 3-4 times Tablets 0.004 or 0.006
daily g
Tablets “Cholen- 1 tablets 1-3 times daily after meal Tablets
zymum”
Cholosasum Orally 1 tea-spoon 2-3 times per Bottles 50 or 300 ml
day after meal
Papaverini hy- Orally 0.04-0.06 g 3-4 times a Tablets 0.04 g;
drochloridum day; ampoules 2 ml of
subcutaneously, intramuscularly 2% solution
or intravenously 0.02-0.04 g
No-spanum Orally 0.04-0.08 g 2-3 times a Tablets 0.04 g;
day; ampoules 2 ml of
subcutaneously, intramuscularly 2% solution
or intravenously 0.04-0.08 g
Oxaphenamidum Orally 0.25-0.5 g 3 times daily af- Tablets 0.25 g
ter meal
Pancreatinum Orally 0.25 or 0.5 g tablets 3 times Tablets 0.25 or 0.5 g
daily during or after meal
Magnesii sulfas Orally 10-30 g in 1 glass of water Powders
Oleum Ricini Orally 15-30 g Capsules 1.0 g
Isapheninum Orally 0.005-0.01 g 1-2 times a Tablets 0.01 g
day
Contrical Drip intravenously 10000-50000 Bottles 10000,
IU per day 30000 or 50000 IU
of dry substance

DIURETIC AGENTS
Diuretic agents are drugs which increase the excretion of salts
and water from the organism. They are also called “saluretics” be-
cause the basis for mechanism of action of these drugs is increase of
sodium and chlorine ions excretion. Diuretics are widely used in
medicine, including the emergency treatment. Various diseases of
kidneys, cardiovascular system, lever patology, etc. are accompanied
by retention of salts and water that results to the increase of tissues
hydratation, development of edemas, and accumulation of fluids in
body cavities.
Mechanism of diuretics action can be understood on the basis of
modern ideas about process of diuresis. Nearly 150-200 L of fluid
and 25,000 milliequivalents of sodium are filtrated in human kidneys
during 24 hours. But up to 99% of initial urine undergoes reabsorp-
tion and only 2 L of fluid and 100 milliequivalents of sodium are ex-
creted from organism with urine. Initially, reasorption of sodium
from the renal tubules is occured through apical membrane. The
sodium transport through apical membrane occurs via special carrier
protein which is synthesized under control of aldosterone. After
moving through apical membrane into the cells of renal tubules,
sodium ions is absorbed through basal membrane into the intersti-
tium and capillaries. Sodium transport through basal membrane is ac-
tive process that occurs by means of special pumps against concen-
tration gradient with energy consumption. One pump transports the
sodium ions in exchange for potassium ions; another pump transports
sodium ions together with chlorine or hydrocarbonate ions indepen-
dently of potassium. Reabsorption of water is passive process which
depends of sodium reabsorption.
In proximal convoluted tubules reabsorption of sodium, chlorine,
potassium, calcium, magnesium and equivalent amount of water oc-
curs. Hydrocarbonate ions also undergo reabsorption under the con-
trol of carbonic anhydrase. Approximately 70-80% of initial urine is
reabsorbed in this segment of nephron. Isoosmotic urine remains af-
ter passing through proximal convoluted tubules.
Descending part of the Henle’s loop is easily permeable for wa-
ter, but isn’t permeable for ions. Owing to this, after passing through
this part of Henle’s loop urine becomes heperosmotic.
Thick ascending limb of the Henle’s loop is poorly permeable
for water. Ions of chlorine and sodium are reabsorbed by means of
active transport in this segment of nephron. In result of passing
through this segment, urine becomes hypoosmotic. But interstitial
fluid in the kidneys medulla becomes hyperosmotic. It is promotes
the reabsorption of water in descending part of Henle’s loop.
Reabsorption of sodium and chlorine ions continues in initial
part of distal convoluted tubules that increases the hyhoosmoticity of
urine. But water reabsorption occurs in finite part of distal convo-
luted tubules under control of vasopressin. Urine becomes isoos-
motic. The passive secretion of potassium ions occurs in distal con-
voluted tubules.
Uropoiesis is completed in collecting ducts. In this part of
nephron, the aldosterone-dependent reabsorption of sodium and se-
cretion of potassium ions occur. Water reabsorption controlled by va-
sopressin is also typical for collecting ducts.
Based on the characteristics of the process of urine formation, it
is evident that diuretics can or directly influence uropoiesis, or
change hormonal regulation of this process.
Numerous classifications of diuretics exist. Classification on the
base of mechanism of diuretics action and localization of action is
given below.
1. Diuretics acting on the level of epitelial cells of renal tubules.
1.1. Diuretics acting on the level of basal membrane:
a). derivatives of antranilic and benzoic acids: furosemide ,
torsemide, bumethanide (bufenox);
b). non-thiazide sulfonamides: oxodolinum , clopamide , in-
dopamide;
c). thiazides: dichlothiazidum (hydrochlorthiazide ), cy-
clomethiazide , polythiazide ;
d). derivatives of dichlorophenoxyacetic acid: ethacrynic
acid;
e). carbonic anhydrase inhibitors: diakarb.
1.2. Diuretics acting on the level of apical membrane – drugs in-
hibiting proteins which transfer sodium: triamterene , amiloride .
2. Aldosterone antagonists: spironolactone .
3. Osmotic diuretics: mannitol.
4. Drugs increasing kidneys blood flow: euphyllinum .
 5. Diuretics of plant origin: horsetail herb, bearberry
leaves , birch buds, etc.

Depending on the force of diuretic activity, all drugs may be

classified into following groups:
1. Most effective diuretics: furosemide, ethacrynic acid ,
clopamide , mannitol.
2. Diuretics with moderate activity: dichlothiazidum , cy-
clomethiazide , polythiazide , oxodolinum .
3. Diuretics with weak activity: spironolactone , tri-
amterene, amiloride , euphyllinum , drugs of plant origin .
Depending on speed of effect development, diuretics are classi-
fied into:
1. Diuretics with fast development of effect (in 30-40 minutes):
furosemide , ethacrynic acid , mannitol, bumethanide ,
torsemide.
2. Drugs with moderate speed of effect development (onset of
effect is in 1-4 hours after drug administration and duration of action
is 9-24 hours): dichlothiazidum , diakarb , euphyllinum , cy-
clomethiazide , clopamide , oxodolinum , triamterene , in-
dopamide.
3. Diuretics with clow development of effect (onset of effect is
in 2-5 days after drug intake, and duration of action is 5-7 days):
spironolactone .

Diuretics Acting on the Level of Epitelial Cells

of Renal Tubules
Loop Diuretics
Furosemide , torsemide , bumethanide (bufenox ) inhibit
hexokinase, malate dehydrogenase, succinate dehydrogenase, and
Na+,K+-ATPase. It results in worsening of activity of sodium pump.
Besides, these drugs disunite energy production and its input to the
pump. These changes cause the reduction of sodium current through
basal membrane into interstitium. Diuretics of this group increase the
synthesis of prostaglandins and kinines, which relax renal vessels
and increase the sodium excretion.
Main site of these drugs action is thick ascending limb of the
Henle’s loop, therefore these drugs are called “loop diuretics”. In ser-
tain degree antranilic acid derivatives inhibit sodium reabsorption in
proximal tubules.
All agents of this group increase potassium excretion that is un-
desirable moment. An elevation of potassium excretion is result of
the increase of permeability of luminal membrane of distal tubules
for sodium ions. It causes the the increase of potencial inside of
tubules and enhances passive potassium secretion into the tubules lu-
men.
Furosemide (lasix) was introduced in medical practice in
1963. Drug has marked diuretic effect in parenteral and in enteral ad-
ministration. In case of oral intake, effect develops in 30-60 minutes
and lasts 6-8 hours. In case of intravenous administration, effect de-
velops in 5-10 minutes and lasts 2-4 hours.
Furosemide is easily absorbed in gastrointestinal tract. After ab-
sorption, drug binds with plasma proteins. Furosemide undergoes he-
patic metabolism through hydrolysis and conjugation with glucuronic
acid. Metabolites are excreted by the kidneys.
Furosemide is low toxic agent and has breadth of therapeutic ac-
tion from 0.002 g to 2.0 g.
Indications for furosemide use are chronic oedemas of cardiac,
renal, and hepatic origin; acute heart failure, pulmonary oedema,
brain oedema, acute and chronic renal failure, forced diuresis, treat-
ment of hypertensive disease, and interruption of hypertensive crisis.
Hypotensive effect of furosemide is mainly result of the decrease
of sodium level in arterioles walls, and only partly – result of the de-
crease of blood volume. Reduction of sodium concentration in ves-
sels wall results in the decrease of vessels sensitivity to vasoconstric-
tive influence of catecholamines.
Side effects of furosemide are hypokalemia, hypokalemic meta-
bolic alkalosis, hyperglycemia (furosemide reduces the secretion of
insulin by pancreas), hyperuricemia, hypomagnesemia, increase of
renin activity, ototoxicity (in case of intravenous administration of
high doses of furosemide).
Torasemide acts longer than furosemide. It is presribed 1 time
a day.
Bumethanide (bufenox ) acts faster than furosemide. Diuretic
effect of bufenox is in 20-50 times more expressive than effect of
furosemide. Duration of action is 4-6 hours. Bumethanide is adminis-
tered parenterally or taken orally. Indications for use and side effects
are similar with furosemide. Bufenox causes hypokalemia less than
furosemide.
Pharmacological properties of clopamide are similar with
furosemide. Drug is taken orally. Onset of diuretic effect is 1-3
hours. Duration of action is 8-20 hours. Indications for use are oede-
mas in chronic heart failure, nephrosis, postthrombotic edema, cir-
rhosis, ascites, pregnancy, premenstrual syndrome, and hypertensive
disease. Side effects of clopamide are nausea, vomiting, arrhythmias,
decreased blood pressure, hypercalcemia, hypokalemia, hyper-
glycemia, hyperuricemia, male, flushing of the skin, and allergic re-
actions.
Indopamide has diuretic and hypotensive effects. Drug is taken
orally 1 time a day in morning. Indopamide is used predominantly
for treatment of hypertensive disease.

Thiazides
Hydrochlorthiazide (dichlothiazidum ) is drug with mod-
erate diuretic activity. Agent inhibits the reabsorption of sodium and
chlorine ions mainly in initial part of distal convoluted tubules and in
certain degree – in proximal convoluted tubules. Hydrochlorthiazide
is effective both in orall and parenteral administration, but practically
it is used mainly for orall drug intake. Onset of diuretic action is in
30-60 minutes after drug intake. Duration of action is 8-12 hours.
Nearly 60% of administered dose bind with plasma proteins. Hy-
drochlorthiazide is excreted through kidneys. Tolerance to dichloth-
iazidum practically does not develope. Indications for use are hyper-
tensive disease, oedemas of heart, hepatic and nephrotic origin, dia-
betes insipidus, and nephrolithiasis.
Mechanism of dichlothiazidum action in diabetes insipidus is
following. Drug inhibits phosphodiesterase in cells of kidneys
medulla that results in accumulation of intracellular cAMP. Owing to
this, the water reabsorption through epithelium of collecting ducts is
increased. Volume of urina is reduced. That is, dichlothiazidum po-
tentiates or restores the effect of vasopressin in patients with diabetes
insipidus.
Most common side effects of hydrochlorthiazide are hy-
pokalemia and alkalosis. Hypomagnesemia, hypercalcemia (due to
increase of parathyroid hormone activity in kidneys), hyperuricemia,
and hyperglycemia are also possible.
Polythiazide and cyclomethiazide have similar properties
and indications for use with dichlothiazidum. But diuretic activity of
these agents is higher than activity of dichlothiazidum: polythiazide –
in 50 times, cyclomethiazide – in 100 times.
Oxodolinum has similar properties with thiazides. This drug is
characterized by long duration of action. After oral intake, onset of
diuretic effect is in 2-4 hours, duration of effect is nearly 3 days.

Derivatives of Dichlorophenoxyacetic Acid

Ethacrynic acid is derivative of dichlorophenoxyacetic acid.
According to mechanism of action, this drug is loop diuretic. Agent
oppresses the reabsorption of sodium and chlorine ions on the level
of basal membrane of epithelial cells in the thick ascending limb of
the Henle’s loop. Diuretic effect of ethacrinic acid is high. Ethacrinic
acid is administered parenterally and orally. In case of oral use, effect
develops in 30-60 minutes after drug intake and lasts up 8 hours. In
intravenous administration, effect develops in 20-40 minutes after in-
jection and lasts 3-4 hours.
Indications for use of ethacrinic acid are chronic oedemas of car-
diac, renal, and hepatic origin; acute heart failure, pulmonary
oedema, brain oedema, acute and chronic renal failure, forced diure-
sis, treatment of hypertensive disease, and interruption of hyperten-
sive crisis.
Treatment with ethacrinic acid is accompanied by following side
effects: hypokalemia, hyponatriemia, hypomagnesemia, alkalosis,
hypocalcemia, hearing impairment, weakness, dizziness, diarrhea,
etc. Intravenous administration of ethacrinic acid is painful and can
causes phlebitis.

Carbonic Anhydrase Inhibitors

Diakarb is weak diuretic which inhibits carbonic anhydrase in
epithelial cells of proximal convoluted tubules. This enzyme catal-
izes the synthesis of carbonic acid from water and carbon dioxide.
Carbonic acid dissociates to hydrogen ions and hydrocarbonate ions.
Kidneys secrete the hydrogen ions into the urine with reabsorption of
the hydrocarbonate ions. This process provides support of acid-base
balance in organism. Owing to action of diacarb, the reabsorption of
hydrocarbonate ions is reduced and pH of urine increases. In this
case, alkaline reserve of blood is decreased. Retention of hydrogen
ions is accompanied by compensatory secretion of potassium ions.
Treatment with diacarb quickly results in acidosis owing to hyper-
chloremia.
Diacarb is diuretic for oral administration. Indications for use are
alkalosis, exacerbation of glaucoma, glaucomatous crisis, intracranial
hypertension, epilepsy, and poisoning by barbituric acid derivatives
(increase of pH of urine promote the excretion barbiturates by the
kidneys).
Main side effects of diacarb are acidosis and hypokalemia. In ad-
dition, such side effects as paresthesia, and allergic reactions (ery-
thema sulfa) can develop. Fever, leukopenia, hemolytic anemia, and
damage to the bone marrow also are possible.

Diuretics Acting on the Level of Apical Membrane

Drugs Inhibiting Proteins which Transfer Sodium
 Triamterene and amiloride are weak diuretics. These drugs
inhibit the passive transport of sodium ions through apical membrane
of epithelial cells in the distal convoluted tubules and collecting
ducts. Agents interact with both proteins transporting sodium and
sodium channels. Triamterene and amiloride inhibit the potassium
secretion in nephrons and are called “potassium-sparing diuretics”.
Both drugs are taken orally. Effect develops in 15-20 minutes after
drug intake and lasts up to 6-8 hours.
These drugs are used in long-term maintenance therapy of
chronic cardiovascular failure of various origins, in treatment of hep-
ertensive disease, and cirrhosis. Widely potassium-sparing diuretics
are used thogether with thiazides and loopp diuretics which cause hy-
pokalemia.
Side effects of potassium-sparing diuretics are hyperkalemia,
nausea, vomiting, headache, convulsions of muscles of the lower ex-
tremities.

Aldosterone Antagonists
Spironolactone (aldactone , verospiron) has similar
chemical structure to aldosterone. Spironolactone binds with intra-
cellular cytoplasmic receptors of aldosterone and prevents the aldos-
terone interaction with nuclear chromatin. It results in the decrease of
synthesis of the transporting sodium proteins – permeases. Owing to
such mechanism spironolactone decreases the aldosterone-dependent
sodium reabsorption and potassium secretion in collecting ducts of
nephron. Therefore, spironolactone is potassium-sparing diuretic.
Diuretic effect of spironolactone develops in 2-5 days after onset
of drug intake and lasts up to 2-3 days after stop of drug intake.
Indications for use of spironolactone are oedemas in patients
with chronic heart failure, liver cirrhosis, nephrotic syndrome, essen-
tial hypertension in adults, ascites, diagnosis and treatment of pri-
mary hyperaldosteronism (Conn's syndrome), prevention of hy-
pokalemia in the treatment with diuretics and in patients receiving
cardiac glycosides.
 Side effects of spironolactone include dizziness, drowsiness,
headache, ataxia, nausea, vomiting, diarrhea, abnormal liver func-
tion, gynecomastia, menstrual disorders, urticaria, hyperkalemia, etc.

Osmotic Diuretics
Mannitol has pronounced diuretic action and weak saluretic ef-
fect. Drug is easily filtered in renal glomerulus but is not reabsorbed
from the primery urine. Thereby mannitol creates high osmotic pres-
sure into tubular lumen and significantly decreases the water reab-
sorption. Reduction of sodium concentration into the tubular lumen
creates the concentration gradient of sodium between the intersticium
and tubular lumen. According to this concentration gradient, sodium
ions move through intercellular spaces into the tubular lumen.
Mannitol increases the osmotic pressure of blood that promotes
the water movement into the blood vessels and the increase of circu-
lating blood volume. Hypervolemia results to increase of release of
atrial natriuretic hormone which stimulates natriuresis.
Mannitol is used as dehydrating agent in acute oedemas of brain
and lungs, in glaucoma, for forced diuresis in poisined patients, in
acute renal failure, and in states of shock with decrease of blood
pressure.
Drug is administered slowly intravenously. Diuretic effect devel-
ops in 10-15 minutes and lasts 4-6 hours.
It must be remembered that the performance of dehydrating ther-
apy is dangerous in patients with heart failure. The raise of blood os-
motic pressure results in hypervolemia, particularly in patients with
concomitant renal failure. The increase of pressure in pulmonary cir-
culation and of systemic blood pressure can cause the overload of left
ventricle and development of pulmonary oedema.
Therapy with mannitol can be aggravated by dehydration, hy-
ponatremia, impaired consciousness, nausea, vomiting, dizziness,
and chest pain. Drug is not reccommended to treatment of children
under 1 year.
 Drugs Increasing the Renal Blood Supply
Aminophylline (euphillinum), theophylline , and theo-
bromine increase diuresis due to the increase of renal blood perfus-
ing and the raise of glomerular filtration. Simultaneously, drugs re-
duce to some extent the sodium reabsorbtion in proximal convoluted
tubules. It is due to the ability of methylxanthines to stimulate purine
(adenosine) receptors and to inhibit the phosphodiesterase activity. It
results to accumulation of cAMP and the decrease of vasopressin ac-
tivity.
Methylxanthines are weak diuretics. These drugs are prescribed
to elderly patients for reduction of insignifacant oedemas due to
chronic diseases.
It necessary to notice, that children are especially sensitive to
methylxanthines. Intravenous administration of drugs can cause them
serious poisoning. Therefore, methylxanthines are contraindicated to
children less than 2 years.

Diuretics of Vegetable Origin

Herbal diuretics occupy the special position among diuretics.
These agents are used as infusions and broth. Following herbal
agents are used as diuretics: leaves of bearberry, leaves of or -
thosiphon stamineus, leaves and buds of birch, horsetail
herb, flowers of cornflower , etc. These drugs have low diuretic
activity. Herbal diuretics are prescribed to children and elderly pa-
tients with oedemas due to cardiovascular, hepatic, and inflamatory
renal diseases. These drugs are taken 3-4 times a day. Therapy with
herbal diuretics does not result to disturbances of electrolyte balance.
Lespenefril is drug which derived from leaves and stems of
Lespedeza capitata and anise fruit. Drug increases diuresis, excretion
of nitrogenous compounds, and excretion of sodium and potassium
ions. Drug is used for reduction of azotemia. Indications for use of
lespenefril are acute and chronic nephritis with azotemia. Agent also
is used for reduction of extrarenal azotemia. Lespenefril is taken
orally in dose 1-2 tea-spoons a day. In severe cases dose may be in-
creased up to 6 tea-spoons a day.
Similar drug is lespeflan . Drug is taken in dose 1 tea-spoon or
1 table-spoon 3-4 times a day. Duration of course of treatment is 3-4
weeks. Lespeflan is contraindicated in pregnancy.

Principles of Combined Use of Diuretics

Diuretics are commonly combined with one another and also
with agents of other groups. Such combinations are used for treat-
ment of chronic heart failure, renal failure, hypertensive disease, etc.
To inchance the excretion of sodium and water from the organ-
ism, diuretics with different mechanisms of action are commonly
combined. For example, osmotic diuretic (mannitol) is combined
with loop diuretics (furosemide, ethacrynic acid). This combination
is used in emergencies: for forced diuresis in poisoning, in patients
with acute brain or lung oedema.
Combination of diuretics acting on the level of basal membrane
(furosemide, hydrochlorothiazide, etc.) with diuretics acting on the
level of apical membrane (spironolactone, triamterene, etc.) is often
used practically. Such combination increases the efficacy of diuretics
and also prevents the hypokalemia. Phrmaceutical industry manufac-
tures ready-made such combined drug as “Triampur Composi -
tum” (triamterene with hydrochlorothiazide), “Moduretic ”
(amiloride with hydrochlorothiazide), etc.
Combination of diuretics with hypotensive agents also widely
used in treatment of hypertensive disease. Following ready-made
drugs persist: “Tenoric” (β-adrenergic antagonist atenolol with di-
uretic oxodolinum), “Enap-H” (angiotensin-converting enzyme in-
hibitor enalapril with hydrochlorothiazide), “Adelphane ” (sympa-
tholytic reserpine with arterial vasodilator dihydralazine), “Crys-
tepin” (sympatholytic reserpine with clopamide and α-adrenoblock-
ering agent dihydroergocristine), etc.
Potassium-sparing diuretics (spironolactone, triamterene) are
used together with cardiac glycosides for prevention of hypokalemia.
 Diuretics can potentiate effects of many antitumoral agents.
But it is necessary to notice, that certain diuretics can enchance
the toxicity of other drugs. For example, furosemide and ethacrynic
acid increase ototoxicity of some antibiotics (gentamycin, etc.).

DRUGS INFLUENCING UPON THE

MYOMETRIUM
Uterus is smooth muscle organ which under control of certain
hymoral and nervous factors. Myometrium contains M-cholinergic,
α- and β-adrenergic receptors. M-cholinergic and α-adrenergic recep-
tors stimulate contractile activity of uterus, while as β2-adrenergic re-
ceptors inhibit its. Expressed stimulating influence upon uterus is
characteristic of estrogens, posterior pituitary hormone oxytocin, and
prostaglandins E2 and F2α. Progestins (progesterone) inhibits the con-
tractile activity of myometrium.
Drugs influencing uterus are classified into following groups:
1. Drugs stimulating contractile activity of uterus.
1.1. Drugs of oxytocin group: oxytocin, demoxytocin (san -
dopart), methyloxytocin (mesotocinum), pituitrinum .
1.2. Drugs of prostaglandin group: dinoprost
(prostaglandin F 2 α ), methyldinoprost, dinoprostone
(prostaglandin E 2 ).
1.3. Estrogens: estrone, estradiol , synoestrolum .
1.4. β-Adrenoblockering drugs: propranolol (anaprilinum) .
1.5. Miscellaneous drugs: proserinum, pachycarpine , cas-
tor oil, vitamins C and B 1 .
2. Drugs inhibiting uterus tone and contractile activity (tocolyt-
ics).
2.1. Drugs stimulating β2-adrenergic receptors: fenoterol
(partusisten ), salbutamol , terbutaline .
2.2. General anaesthetics: sodium oxybutirate .
2.3. Hormonal drugs: progesterone.
2.4. Miscellaneous drugs: magnesium sulfate , tocopherol .
3. Drugs increasing uterus tone.
 3.1. Ergot alkaloids: ergotal, ergotamine , ergometrine ,
methylergometrine , ergot extract .
3.2. Synthetic drugs: cotarnine .
4. Drugs decreasing the cervix tone: atropine, dinoprost ,
dinoprostone .

Drugs stimulating contractile activity of uterus

Drugs of Oxytocin Group
Oxytocin and prostaglandins are physiological stumulants of
uterus sontractions. The membranes of smooth muscle cell in uterus
contain the receptors which are sensitive to these substances. Excita-
tion of these receptors causes the sodium and calcium intrance into
the cells with depolarization and contraction of smooth muscles cells.

Oxytocin is polypeptide hormone of posterior pituitary which

consists of 8 amino acids. Drug in doses 3-5 UA causes the rhythmic
contraction of myometrium that promotes the labor. Sensitivity of
pregnant uterus to oxytocin is more than sensitivity of non-pregnant
uterus. High doses of hormone (up to 10 UA) cause more frequent
and strong uterus contractions and promote the increase of in-
trauterus pressure that can result to disturbances of blood supply to
placenta.
Oxytocin is destroyed in case of orall intake; therefore drug is
administered intravenously drop by drop. Effect of drug develops in
0.5-2 minutes. Oxytocin undergoes fast biotransformation in the liver
and kidneys. For cessation of uterus bleeding, oxytocin may be ad-
ministered intramuscularly.
Desaminooxytocin is synthetic analogue of oxytocin with
higher activity. Drug is used sublingually in form of buccal tablets.
Indications for use of desaminooxytocinum are acceleration of uter-
ine involution and stimulation of lactation.
Pituitrinum contains the mixture of hormones of posterior pi-
tuitary – oxytocin and vasopressin. Therefore, this drug not only
stimulates the uterus contraction, but also increases blood pressure.
Drug is administered subcutaneously or intramuscularly. Indications
for use are same as oxytocin.

Drugs of Prostaglandin Group

Small quantities of prostaglandins are permanently synthesized
in the uterus. Prostaglandins relax the uterus vessels, improve the
blood supply of placenta, and have cytoprotective effect. Concenrta-
tion of prostaglandins significantly increase in labor.
Prostaglandins E2 and F2α are used in medicine.
Dinoprost (prostaglandin F 2 α ) inhibits the function of cor-
pus luteum, blocks the synthesis of progesteron, and increases the
level of estrogens. Drug sensitizes myometrium to oxytocin. Dino-
prost causes rhythmical contraction, increases the tone both preg-
nancy and non-pregnancy uterus, and relaxes the uterus neck.
Prostaglandin F2α increases the bronchial tone, stimulates cardiac
rhithm and force of cardiac contraction, increases the motility of gas-
trointestinal tract, increases the tone of pulmonary vessels, and in-
creases the vessels permeability.
Methyldinoprost is more active and long acting analogue of
dinoprost.
Dinoproston (prostaglandin E 2 ) causes the rhythmic uterus
contraction and relaxes the uterus neck. Dinoproston causes the de-
generation of corpus luteum (luteolysis). Agent reduces peripheral
vascular resistance, relaxes pulmonary vessels and bronchi, increases
the capillar permeability, stimulates the motility of gastrointestinal
tract, and inhibits the gastric secretion.
Prostaglandins administration can cause excessive uterus con-
traction with disturbances of uterus and placenta blood supply.
Prostaglandins duration of action is more that duration of action of
osytocin. Common side effects include nausea, diarrhea, headache,
and elevation of body temperature. Intravenous administration of
prostaglandins can cause phlebitis. Due to such side effects,
prostaglandins are seldom used for stimulatin of labor. Drugs may be
used for abortions.
Administration of oxytocin and prostaglandins are admissible
only in clinic.

Estrogens
Such estrogens as estrone, estradiol, or synoestrolum are
commonly used for stimulation of labor. Drugs inhibit oxycitonase
patisipating in degradation of oxytocin and due to this stabilize the
level of oxytocin. In addition, estrogens sensitize the receptors to
oxytocin. For induction of labor, estrogens are administered parenter-
ally.

β-Adrenoblockers
Anaprilinum (propranolol ) decreases tocolytic effect of cat-
echolamines, which released through β2-adrenergic receptors. For in-
duction of labor, anaprilinum is administered intravenously drop-by-
drop. Agent is contraindicated in parturients with heart failure, hy-
potension, bronchial asthama, and blockage of conduction.

Miscellaneous Drugs
Following drugs also may be used for stimulation of labor:
proserinum, serotonin , pachycarpine , castor oil , calcium
chloride, ascorbic acid , and vitamin B 1 .
Proserinum inhibits the acetylcholinesterase activity and pro-
motes accumulation of acetylcholine near M-cholinergic receptors of
uterus. Excitation of M-cholinergic receptors increases the uterus
contraction.
Serotonin stimulates the intensivity of mytochondrial respira-
tory function in myofibrils, interacts with ATP, actomyosin, and cal-
cium. Drug improves membrane permeability for calcium ions that
results to increase of uterus contraction. Serotonin is administered in-
travenously drop-by-drop.
Pachycarpine is ganglion blockering drug. Drug inhibits Nn-
cholinergic receptors of mesenteric ganglion. In addition, pachy-
carpine stimulates the release of oxytocin by posterior pituitary and
sensitizes myometrium to action of estron and oxytocin.
Castor oil increases the cholinergic influence upon the uterus
and therefore stimulates contraction of myometrium.
Such vitamins as ascorbic acid and thiamin promote the la-
bor. Vitamin C stimulates the synthesis of estrogens which stimulate
the uterus contraction. Thiamin stimulates the synthesis of acetyl-
choline and inhibits the activity of acetylcholinesterase. These effects
result in stimulation of labor.

Drugs Decreasing Uterus Tone and

Contractile Activity (Tocolytics)
β2-adrenergic receptors inhibit the contractile activity and relax
the uterus. Quantity of β2-adrenergic receptors changes in different
periods of pregnancy. Highest density of β2-adrenergic receptors in
uterus is observed during last tremester that provides uterus rest and
childbearing. Before and during labor density of β2-adrenergic recep-
tors decreases that is accompanised by the increase of uterus senci-
tivity to oxytocin and estrogens.
β2-adrenergic agonists are reliable drugs for reduction of tone
and contractile activity of myometrium. These drugs are widely used
in obstetric practice. Drugs have few side effects, well tolerated by
the pregnant woman, and do not negatively influence the fetus and
newborn. Following β2-adrenergic agonists are used as tocolytics:
partusisten (fenoterol), salbutamol (salbupart), and terbu-
taline (brikanyl ). Drugs are prescribed orally, intramuscularly, and
intravenously drop-by-drop. Maximal tocolytic effect develops in 2
hours after drug intake orally, in 30 minutes after intramuscular ad-
ministration, and in 5-10 minutes after intravenous administration.
Administration of β2-adrenominetics can cause tachycardia (both in
mother and in fetus), constipations, nausea, anxiety, decrase of dias-
tolic blood pressure, and hyperglycemia.
Indicatons for use of β2-adrenomimetics are folliwng:
- prevention of premature labors;
- high tone of uterus neck at onset of labor;
- excecive fast delivery with strong and fast uterus contraction
which create threat of fracture of uterus;
- fetus hypoxia owing to delivery abnormalities, the need for in-
trauterine fetal resuscitation;
- performance of intrauterine fetal rotation, espetially in case of
twins;
- preparation to operation during delivery (cesarean).
Substitutive therapy by progesterone or synthetic progestin
turinal is used cases of threat of abortion in early period of preg-
nancy (under 4 months) and in recurrent abortions owing to insuffi-
ciency production of progesterone. Also, vitamin E (tocopherol )
is used in these cases.
Magnesium sulfate is antagonist of calcium. For relaxation of
uterus, this agent is administered intravenously in dose 5-10 ml of
25% solution.
Recently, calcium channel antagonist nifedipine is used as to-
colytic.
Sodium oxybutyrate is general anaesthetic. Agent sometimes
is used for decrease of excessive uterus contraction during delivery.

Drugs Increasing Tone of Myometrium and

Uterus Involution in the Postpartum Period
Postpartum uterine atony and delayed involution are accompa-
nied by bleeding which can cause the gemorrhagic anemia. Most ef-
fective agents for elimination of uterine atony are arugs containing
ergot alkaloids: ergotamine , ergometrine , methyler -
gometrine , ergotal, and ergot extract . Synthetic drug cotar-
nine is also used in this case. Oral intake or intramuscular adminis-
tration of these drugs is accompanied by stable contraction of my-
ometrium. It results to mechanical compression of vessels and bleed-
ing cessation. Similar effect is also typical for oxytocin in postpar-
tum period.
Indications for use of drugs increasing myometrium tone are fol-
lowing:
- postpartum bleeding, uterine atony, delayed involution of
uterus, bleeding after manual placenta separation;
- dysfunctional uterine bleeding in woman with fibroids;
- bleeding owing to inflammation;
- ergometrine is also used in migraine.
Treatment by ergot alkaloids can be accompanied by following
side effects: nausea, vomiting, diarrhea, and headache. Overdose of
ergot alkaloids causes the acute poisoning with following symptoms:
excitement, convulsions, nausea, vomiting, epigastric pain, tachycar-
dia, and disturbances of sensitivity. Prolonged drugs use can cause
chronic poisoning – ergotism which is persists in two clinical forms:
gangrenous and convulsive. Gangrenous form develops owing to
spasm of peripheral vessels and following necrosis of the extremities.
Convulsive form is due to drug influence upon central nervous sys-
tem.

Drugs Decreasing the Tone of Uterine Neck

This group includes atropine, nospa, dinoprost , and dino-
prostone. Drugs relax uterus neck and promote labor. Lidasum is
also used in case of cervix rigidity. Drug contains enzyme hyaluroni-
dise which destroys hyaluronic acid.

DRUGS USED FOR TREATMENT OF GOUT

Gout is disease which develops due to disorder of purine
metabolisim. In this disease, the concentration of urates is increased
that causes formation of urolithes and development of inflammation.
 Classification of drugs which are used for treatment of gout:
1. Drugs decreasing the uric acid concentration in the blood:
- drugs increasung the excretion of uric acid by kidnays:
aethamidum, probenecid , urodanum;
- drugs reducing the synthesis of uric acid: allopurinol .
2. Antiinflammatory drugs: colchicine , steroid antiinflamma-
tory drugs (prednisolone , dexamethazone ), nonsteroid antiin-
flammatory drugs (indomethacin , diclofenac sodium ,
phenylbutazone ).
Aethamidum and probenecid inhibit the reabsorbtion of uric
acid in proximal convoluted tubules of nephron. Drugs are used for
treatment of chronic gout. Urodanum increases the solubility of salt
of uric acid in the water that results in the increase of its excretion
with urine.
Allopurinol is inhibitor of xanthine oxidase (enzyme which
catalizes the transformation of hypoxantine and xanthine to the uric
acid). Drug suppresses the synthesis of uric acid. The effect of allop-
urinol develops slowly. The concentration of uric acid in the blood is
normalized in 7-10 days from start of treatment; the elimination of
urates from tissues is observed in several months.
Antiinflammatory drugs are used for interruption of acute at-
tacks of gout. Colchicine inhibits the proliferation of granulocytes
and its migration into the inflammatory arreas. Drug also reduces the
concentration of glycoprotein and lactate and suppresses the accumu-
lation of crystals of uric acid in the tissues. Colchicine stops the at-
tack of gout in several hours. Side effects of colchicine are inhibition
of hemopoiesis, nausea, vomiting, abdominal pain, etc. Pharmaco-
logical characteristic of steroid and nonsterois antiinflammatory
drugs are given in related topics.
Table 2 – Drugs for prescription
Drug name Single doses and mode of ad- Drug product
ministration
Dichlothiazidum Orally 0.025-0.05 g 1-2 times per Tablets 0.025 or 0.1 g
day
 Oxodolinum Orally 0.025-0.1 g 1time in 2 or 3 Tablets 0.05 g
days
Triamterenum Orally 0.05-0.1 g 2 times per day Capsules 0.05 g
Furosemidum Orally 0.04 g once a day in the Tablets 0.04 g;
morning; ampoules 2 ml of 1%
intramuscularly or intravenously solution
0.02 g 1-2 times per day
Acidum Orally 0.05-0.1 g 1 time a day or Tablets 0.05 g;
etacrinicum 1 time in 2 days; ampoules 0.05 g of dry
intravenously 0.05 g once a day substance dissolved be-
fore administration)
Spironolactonum Orally 0.025-0.05 g once a day Tablets 0.025 g
Mannitum Intravenously 0.5-1,5 g/kg Bottles 30.0 g of dry
substance (dissolved
and used as 10-15% so-
lution);
ampoules 200, 400 or
500 ml of 15% solution
Ergometrini Orally 0.0002-0.0004 g 2-3 times Tablets 0.0002 g;
maleas per day; ampoules 0.02% - 1 ml
intramuscularly or intravenously
0.0001-0.0002 g
Oxytocinum Intravenously drop-be-drop 5 UA Ampoules 1 ml (5 UA)
in 500 ml of 5% glucose solution;
intramuscularly 0.2-2 UA
Aethamidum Orally 0.35 g 4 times per day Tablets 0.35 g
Allopurinolum Orally 0.1-0.2 g 1 time per day Tablets 0.1 g
Fenoterolum Orally 0.005 g 4-6 times per day; Tablets 0.005 g;
intravenously drop-be-drop ampoules 10 ml of
0.0005 g in isotonic solution of 0.005% solution
NaCl or glucose

DRUGS INFLUENCING UPON HEMOPOIESIS

These drugs are devided into following groups:
I. Drugs influencing upon erythropoiesis.
1. Drugs stimulating erythropoiesis.
1.1. Drugs which used for treatment of hypochromic (iron-defi-
ciency) anemias:
 - iron-containing mono-drugs: ferrous sulfate , ferrous lac -
tate, Ferrum-Lek ;
- combined iron-containing drugs: Fercoven (iron and cobalt
sults with carbohydrate solution), Ferroplex (iron lactate with as-
rorbic acid), Ferramidum (complex compound of iron with nicoti-
namide), Tardyferon (iron lactate, ascorbic acid, and mucopro-
tease), Haemostimulinum (iron lactate and copper sulfate);
- cobalt-containing drugs: Coamidum;
- recombinant human erythropoietins: epoetin alfa , epoetin
beta.
1.2. Drugs which used for treatment of hyperchromic anemias:
cyanocobalamin , folic acid .
2. Drugs inhibiting erythropoiesis: sodium phosphate with
radioactive isotope 3 2 P.
II. Drugs influencing leukopoiesis.
1. Drugs stimulating leukopoiesis.
- non-specific drugs which stimulate the synthesis of nucleic
acid: sodium nucleinate , pentoxylum , methyluracilum ,
leukogenum ;
- myeloid growth factors: lenograstim, molgrastim, fil-
grastim.
2. Drugs inhibiting leukopoiesis:
2.1. Drugs inhibiting leukocytes in interphase:
- alkylating drugs: cyclophosphanum (cyclophos -
phamide), thiophosphamidum (thiotepa ), myelosanum ;
- antimetabolites: methotrexate , mercaptopurine ;
- cytotoxic antibiotics: rubomycinum;
- glucocorticoids: prednisolone , dexamethazone ;
- enzyme agents: L-asparaginase;
- cytokines: interferon α.
2.2. Drugs which inhibit mitosis of leukocytes:
- cytotoxic drugs of plant origin: vinblastine , vincristine .

Drugs Influencing Erythropoiesis

 Iron ions, cyanocobalamin, and folic acid are primarily neces-
sary for normal erythropoiesis. Their deficiency is accompanied by
development of anemia. Hormone erythropoietin stimulates erythro-
poiesis. This hormone is synthesized by peritubular intersticial renal
cells (nearly 90%) and in the liver (10%). Erythropoietin stimulates
proliferation and differentiation of erythrocytes.

Drugs Stimulating Erythropoiesis

Drugs which Used for Treatment of Hypochrmic Anemias
Main cause of hypochromic anemia is insufficient production of
hemoglobin by erythroblasts of bone marrow owing to iron defi-
ciency. Iron deficiency most common develops due to iron deficit in
food, disturbances of absorption, bleeding, during pregnancy, lacta-
tion, etc.
Iron-containing drugs are main agents for treatment of
hypochromic anemias. Daily demand of iron for adalts is nearly 0.2
mg/kg (with taking into account that only 10% of taken iron is ab-
sorbed into gastrointestinal tract). Distribution of iron in organism is
following: nearly 70% of iron (3-4 g) is included to hemoglobin, 10-
20% is deposited in forms of ferritin and hemosiderin, 10% is in-
cluded to muscular protein myoglobin, and nearly 10% is in structure
of respiratory enzymes and other enzymes.
Only ionized iron (better – in form of divalent ion) is absorbed
in gastrointestinal tract. Hydrochloric acid transforms molecular iron
to ionized form. Ascorbic acid restores trivalent iron to divalent one.
Therefore, hydrochloric acid and ascorbic acid are necessary for nor-
mal absorption of iron in gastrointestinal tract. Iron absorption is
mainly due to active transport. Apoferritin of intestinal mucosa is
binds with iron ions with formation of ferritin. After entering to
blood circulation, iron ions interact with β1-globulin transferrin. This
transport system delivers iron to various tissues, including bone mar-
row, where iron is released and included to structure of hemoglobin.
Excess of iron is deposited in forms of ferritin or hemosiderin. Iron is
eliminated from the body through intestine, kidneys, and sweat
glands.
 In case of hypochromic anemias, iron-containing drugs are pre-
scribed mainly orally. For prevention of contact of iron with mucous
membrane of oral cavity, iron-cntaining drugs are used in form of
tablets with special coating or in capsules. It is due to airon bility to
bind with hydrogen sulfide with formation of iron sulfide coloring
teeth black. Due to formation of iron sulfide, intake of iron-contain-
ing drugs also can cause constipation.
Iron-containing drugs are taken in 1.5 hours prior meal or in 2
hours after meal.
Recently, cobined iron- and vitamin-containing drugs are used in
medicine for treatment of hypochromic anemias. For example, such
drugs as Ferroplex, Sorbifer , Ascofer , Globiron, etc. Ferro-
gradumet is representative of combined drugs with prolonged ac-
tion.
Treatment of hypochromic anemia lasts 3-6 months. First im-
provement of hemopoiesis is obcerved in 5-7 days after start of drug
intake. In case when therapeutic effect is absence, parenteral admin-
istration of iron-containing drugs is beginning. Parenteral administra-
tion of iron-containing drugs is possible only for in-patients, because
it commonly is accompanied by side effects: redness of the face and
neck, lower back pain and joint pain, tightness in the chest, tachycar-
dia, nausea, vomiting, allergic reactions, etc. These side effects are
eliminated by administration of analgesics and atropine.
Coamide is cobalt-containing drug which is used for treatment
of hypochromic anemias. It is compound of cobalt with amide of
nicotinic acid. Cobalt stimulates erythropoiesis and promotes ab-
sorption of iron in gastrointestinal tract. Coamide is administered
subcutaneously.
Recently, recombinant human erythropoietins are used in
medicine. It is such drugs as epoetin alfa and epoetin beta .
Drugs are used for treatment of anemias in chronic renal deseases,
rheumatoid arthritis, aplastic anemia, malignant diseases of bone
marrow, AIDS, etc. Drugs are administered subcutaneously or intra-
muscularly 3 times a week. Side effects are headache, hyperkalemia,
arthralgias, etc. Therapeutic effect develops in 2 weeks, and normal-
ization on hemopoiesis is obcerved in 8-12 weeks.
 Drugs for Treatment of Hyperchromic Anemias
Megaloblastic anemia develops due to deficiency of vitamin B12
(cyanocobalamin). Lack of vitamin B12 results to disturbances of
DNA synthesis and patological changes in erythropoiesis. Erythro-
poiesis occurs by megaloblastic type. The large erythrocytes with
high RNA/DNA ratio are produced in megaloblastic anemia. Red
blood cells are over-saturated hemoglobin. Color index is usually
more than 1.1-1.3. However, the total hemoglobin in the blood is re-
duced significantly due to the significant decrease in the number of
red blood cells. Megaloblastic anemia occurs due to loss of intrinsic
Castle’s factor. This glycoprotein of gastric mucosa is necessary for
absorption of vitamin B12. Deficiency of Castle’s factor develops in
Addison Biermer anemia (primary loss of intrinsic Castle’s factor),
total gastrectomy, atrophy of mucous membrane of stomach and duo-
denum, invasion by broad tapeworm, and exclusively vegetable diet.
Deficiency of Castle’s factor results in reducrion of vitamin B12 ab-
sorption and disturbalces of neucleic acid synthesis. Except erythro-
poiesis, peripheral nervous system is also affected in megaloblastic
anemia. It is result of reduction of myelin synthesis in which
cyanocobalamine participates as cofactor. Therefore, along with
megaloblastic anemia observed damage to the nervous system.
In megaloblastic anemia, cyanocobalamin is administered in-
tramuscularly 1 time a day or every other day. Normalization of ery-
thropoiesis and functions of gastrointestinal tract and nervous system
is obcerved in 1-2 month.
Folic acid (vitamin B c ) participates in synthesis of proteins,
nucleic acids, and macroergic compounds. Deficiency of folic acid
results in disturbances of erythropoiesis with development of macro-
cytic anemia. In this case, erythroblast turns into hyperchromic
macronormoblast with following transformation into macrocyte.
 Folic acid is prescribed for treatment of alimentary and drug-in-
duced macrocytic anemia, sprue, and anemias of pregnancy. Drug-in-
duced anemia can develop owing to therapy with dipheninum, phe-
nobarbital, isoniazide, hormonal drugs, etc.
In patients with megaloblastic anemia, alone use of folic acid
normalizes erythropoiesis, but does not reduces pathological changes
of nervous system and gastrointestinal tract. Therefore, folic acid
may be used for treatment of megaloblastic anemia only with
cyanocobalamine.
Folic acid is taken orally. Simetimes, drug can causes allergic re-
actions.

Herbal Drugs which Used for Treatment of Anemias

Herbal drugs are widely used for treatment of anemias because
these drugs contain a variety of microelements, vitamins, antioxi-
dants, and other bioactive substances stimulating erythropoiesis.
These drugs increase the resistance to unfovarable factors, imrove
health, stimulate immunity and hemopoiesis.
Herbal drugs for treatment of anemia include strawberry
fruit, black currant, rowan, rose, etc.

Drugs Inhibiting Erythropoiesis

Drugs inhibiting erythropoiesis are used for treatment of poly-
cythemia (hyperglobulia). Solution of sodium phosphate with
radioactive isotope 3 2 P is one of these drugs. Use of this agent
reduces the number of erythrocytes and platelets. Drug is adminis-
tered intravenously or taken orally.

Drugs Influencing Leukopoiesis

Drugs Stimulating Leukopoiesis
Various poisons, radioactive radiation, certain medicines, etc.
can damage leukopoiesis. It results to leukopenia and agranulocyto-
sis. Following drugs are used for correction of these disturbances of
leukopoiesis: sodium nucleinate , pentoxylum , methylu -
racilum , leucogenum , molgramostim , filgrastim , etc.
Sodium nucleinate is sodium sult of nucleic acid which is ob-
tained from yeast. For stimulation of leukopoiesis, drug is adminis-
tered intramuscularly or taken orally.
Pentoxylum is synthetic agent – derivative of pyrimidine. Pen-
toxylum stimulates leukopoiesis, accelerates wounds healing, and has
antiinflammatory effect. Drug is taken orally 3-4 times a day.
Methyluracilum is synthetic agent stimulating synthesis of
pyrimidine nucleotides, increasing leukopoiesis, accelerating the
wound healing, and stimulating immunity (antibody synthesis and in-
terferon production). Also, drug has antiinflammatory action. Methy-
luracilum is taken orally and applied topically in ointments. Indica-
tions for use are leukopenia, agranulocytosis, gastro-duodenal ulcers,
wounds, burns, bone fractures, and chronic pancreatitis.
Leukogenum is prescribed for treatment of leukopenia and
agranulocytosis. Drug potentiates the effects of other leukopoiesis
stimulators. Leukogenum is taken orally.
Recently, growth factors which regulating leukopoiesis is intro-
duced in medical practice. Molgrastim and filgrastim are among
them.
Human recombinant granulocyte-macrophage colony stimulat-
ing factor is created by genetic engineering. Appropriate drug is
called molgramostim. This glycoprotein stimulates the prolifera-
tion, differentiation, and activity of granulocytes and monocytes.
These cells carry out phagocytosis, stimulate immunity, and produce
biologically active substances regulating cytokines production. Drug
increases the protective properties of the organism against bacteria,
fungi, and tumors. Molgramostim is administered intravenously in
cases of inhibition of leukopoiesis due to cancer chemotherapy, after
bone marrow transplantation, in aplastic anemia, and in AIDS. Side
effects of molgramostim are nausea, vomiting, diarrhea, hypertermia,
muscular pain, and allergic reactions.
 Filgrastim is recombinant human granulocyte colony stimulat-
ing factor. It is also glycoprotein. Agent stimulates proliferation and
differentiation of granulocytic progenitor cells and increases the ac-
tivity of mature granulocytes. Indications for use of filgrastim are
same with molgramostim. Filgrastim is administered intravenously
or subcutaneously. Side effects are seldom and include arthralgias,
allergic reactions, disturbances of hepatic function, etc.

Pharmacokinetics and pharmacodynamics of drugs inhibiting

leukopoiesis will be considered in the chapter “Antitumoral drugs”.

Table 3 – Drugs for prescription

Drug name Single doses and mode of Drug product

administration
Ferri lactas Orally 1.0 g 3-5 times daily Capsules 1.0 g
Fercovenum Intravenously 2-5 ml 1 time Ampoules 5 ml
daily
Coamidum Subcutaneously 0.01 g 1 Ampoules 1% -1 ml
once a day
Ferrum Lek Intramuscularly 2 ml 1-2 Ampoules 2 (for intra-
times per day; muscular introduction)
intravenously 2-5 ml once a or 5 ml (for intravenous
day introduction)
Cyanocobalaminum Subcutaneously, intramuscu- Ampoules 1 ml of
larly or intravenously 0.003%, 0.01%, 0.02%
0.0001-0.0005 g once a day or 0.05% solution
Acidum folicum Orally 0.005 g once a day Tablets 0.001 g
Penthoxylum Orally 0.2-0.3 g 3 times per Coated tablets 0.2 g
day
Filgrastimum Intravenously or subcuta- Bottles with 0.0003 g or
neously 0.000005 g/1 kg 0.00048 g of dry sub-
once a day stance
Cyclophosphanum Orally, intravenously or in- Coated tablets 0.05 g;
tramuscularly 0.2-0.4 g once ampoules with 0.1 g or
a day 0.2 g of dry substance
Chlorbutinum Orally 0.002-0.01 g once a Tablets 0.002 g or
day 0.005 g
Myelosanum Orally 0.002-0.006 g once a Tablets 0.002 g
day
 Methotrexatum Orally, intramuscularly or
intravenously 0.03 g 2 times
per a week or 0.05 g 1 time
per 5 days
Mercaptopurinum Orally 0.001-0.00125 g / 1
kg once a day
Vinblastinum (Ro- Intravenously 0.00015-
sevinum) 0.0003 g/kg 1 time per week
Coated tablets 0.0025 g;
ampoules with 0.005,
0.05 or 0.1 g of dry sub-
stance
Tablets 0.05 g
Ampoules with 0.005g
or 0.01 g of dry sub-
stance

DRUGS INFLUENCING BLOOD

COAGULATION

Two systems persist in organism in dynamic equilibrium: one of

them promotes blood clotting and another system prevents it. System
promoting blood coagulation consists of platelets and plastic clotting
factors which contained in them, as well as plasma proteins sinthe-
sized in liver (prothrombin, kappa factor, fibrinogen, etc.). System
preventing blood clotting consists of proteolytic enzyme fibrinolysin
(plasmin), its predecessor profibrinolysin (plasminogen), plasma
proreins inhibiting thrombin formation (antithrombin III, etc.), as
well as substances which produced or fixed on the vascular endothe-
lium (prostacyclin, heparin, etc.).
Disequilibrium between these two systems causes either an-
giostaxis or thrombosis. Sometimes, unification of both phenomena
develops – syndrom of disseminated intravascular coagulation. These
pathological states require the pharmacological correction.

Drugs influencing blood coagulation are classified into follow-

ing groups.
I. Drugs which are used for prevention and treatment of throm-
bosis.
1. Drugs decreasing blood coagulation (anticoagulants):
1.1. Directly-acting anticoagulants.
1.2. Indirectly-acting anticoagulants.
 2. Drugs which activate fibrinolysis (fibrinolytics).
3. Drugs decreasing platelets aggregation (antiaggregants).
II. Drugs which promote blood coagulation (hemostatics).
1. Drugs increasing blood clotting (procoagulants).
2. Drugs inhibiting fibrinolysis (antifibrinolytics).
3. Drugs promoting platelets agregation.

Drugs for Prevention and Treatment of Thrombosis

Drugs Decreasing Blood Coagulation (Anticoagulants)
Blood clotting is ordered system of enzymatic reactions with
partisipation of numerous factors of coagulation. Final result of these
reactions is formation of thrombin under influence of which fibrino-
gen is converted into insoluble fibers of fibrin.
In dependence of mechanism of action, drugs decreasing blood
coagulation are divided into following groups.
1. Directly-acting anticoagulants (agents which inactivate clot-
ting factors directly in the blood): heparin, fraxiparin , enoxa-
parin, dalteparin , nadroparin, hirudin , sodium hydroci -
trate.
2. Indirectly-acting anticoagulants (agents which inhibit the syn-
thesis of clotting factors in the liver): neodicumarinum , syn-
cumarum, warfarin, phenindione .

Directly-Acting Anticoagulants
Heparin is natural anticoagulant which synthesized by mast
cells and basophils. Especially high concentration of heparin is con-
tained in liver and lungs. Heparin is acidic mucopolysaccharide with
molecular weight 15,000-20,000 daltons. Molecules of heparin con-
tain residues of sulfuric acid owing to that have expressed acidity and
negativecharge. Heparin is obtained from lungs and liver of cattle.
Negatively charged sites of heparin interact with positively
charged amino groups of antithrombin III. Activated antithrombin III
neutralizes the IIa, IXa, Xa, XIa, XIIa, XIIIa clotting factors and sup-
presses the transformation of prothrombin to thrombin.
Moreover, heparin increases the activity of fibrinolytic system
owing to formation of complex with antifibrinolysin (factor VII, pro-
convertin, serum prothrombin conversion accelerator).
Also, heparin inhibits the adhesion and aggregation of platelets
because heparin molecules fix on the surface of endotheliocytes and
blood cells that creates negative charge endothelial surface and sur-
face of platelets. Thus, heparin is anticoagulant with antiaggregatory
and fibrinolytic activity. Heparin is active both in vivo and in vitro.
Heparin has also antiallergic effect. Agent suppresses coopera-
tion T- and B-lymphocytes and synthesis of immunoglobulines, and
activates histaminase.
Heparin increases pulmonary ventilation and coronary blood cir-
culation, inhibits complement system and excessive synthesis of al-
dosterone, activates lipoprotein lipase and decreases the blood level
of cholesterol and β-lipoproteins.
Heparin is administered intravenously, intramuscularly, subcuta-
neously, in inhalations, and by electrophoresis. Agent also may be
used topically in ointments and cremes. In intravenous administra-
tion, heparin effect develops immediately and last up to 4-6 hours. In
case of subcutaneous administration, onset of effect is in 40-60 min-
utes and duration is up to 12 hours. Maximal effect of inhaled hep-
arin develops in 18-20 hours and lasts up to 2 weeks. Average thera-
peutic dose of intravenously administered heparin in urgent cases
(for example, acute myocardial infarction) is 15,000-20,000 UA. In
critical case (pulmonary arterial thromboembolism) dose is increased
to 40,000-60,000 UA with following intramuscular or subcutaneous
administration of heparin (5,000-10,000 UA) every 4 hours. Discon-
tinuaton of heparin administration should be gradual because sudden
stop of heparin therapy can result to hypercoagulation.
Indications for use of heparin are following:
- thrmbosis of coronary vessels in myocardial infarction;
- thromboembolism of pulmonary and cerebral vessels;
- thrombophlebitis;
 - prevention of thromboembolism during surgery and in postser-
gical period in patients with embolism in anamnesis;
- lengthy orthopedic surgery and sugery of heart and vessels;
- prevention of blood clotting in heart-assist device;
- thrombophlebitis of superficial veins of lower extremities
(commonly in form of ointments and cremes);
- diseases with increased risk of thrombosis: atrial fibrillation,
endarteritis, acute nephritis);
- treatment of bronchial asthma and rheumatism.
High-molecular weight heparin does not cross through placenta
and not excreted in breast milk. Therefore, this heparin is drug of
choice in case of need to prescribe direct anticoagulant to pregnants
and breast-feeding mother.
Heparin therapy can cause the following complications:
1. Main complication of heparin therapy is bleeding due to over-
dose. In this case, antagonist of heparin is administered – protamine
sulfate. Agent is administered intravenously slowly. 1 mg of pro-
tamine neutralizes 85-100 UA of heparin. Duration of action of pro-
tamine sulfate is 2 hours.
2. Thrombocytopenia which can be of two different types. Mod-
erate thrombocytopenia which develops in 2-4 days from start of
heparin treatment is transient and is eliminated in following treat-
ment.
Life-threatening is thrombocytopenia which develops after 6-12
days of treatment. Its mechanism is related to antibodies formation
(immunoglobulins G and M) which causes platelets aggregation.
Owing to this, heparin-induced thrombosis (white clot syndrome) is
developed which can cause embolia.
3. Dispeptic disorders.
4. Allergic reactions.
5. Osteoporosis and calcification of soft tissues. This complica-
tion is developed in long-term use of heparin. A cause of it is binding
of calcium with heparin and fatty acids which are formed due to the
increase of activity of lipoprotein lipase and parathormone.
6. Alopecia.
 7. Re-thrombosis in case of sudden cessation of heparin therapy.
For prevention of re-thrombosis, cessation of heparin therapy should
be gradual and with use of indirect anticoagulants.
Recently, the new group of anticoagulants is introduced in
medicine – low-molecular weight heparins: logiparin, dal-
teparin, fraxiparin, nadroparin. Molecular weight of these
heparins is 2,500-8,000. These drugs are obtained by method of en-
zymatic depolymerization of heparin by bacterial heparinase. Low-
molecular weight heparins do not change the time of blood coagula-
tion, because these drugs do not inhibit IIa factor (thrombin). Mecha-
nism of these drugs action is associated with the increase of action of
antithrombin III upon Xa factor of blood clotting which is required
for transformation of prothrombin to thrombin. Main influence of
low-molecular weight heparins is directed to the decrease of adhe-
sion and aggregation of thrombocytes. Bioavailability of these drugs
is in three times more than bioavailability of heparin. Duration of ac-
tion of these drugs is more. Therefore, drugs are administered subcu-
taneously 1-2 times a day. Low-molecular weight heparins seldom
cause hemorrhages and thrombocytopenia. Antagonist of low-molec-
ular weight heparins is protamine sulfate.
Hirudin is anticoagulant contained in salivary glands of leech.
It is polypeptide which consists of 65 residues of amino acids.
Hirudin inactivates thrombin. Lepirudin is recombinant analog of
hirudin which used in medicine. Drug is administered intravenously.
Lepirudin has short duration of action; period of half-life is 1.3
hours. Agent can cause hemorrhages. Antagonist of lepirudin does
not exist.
Recently, derivatives of hirudin were synthesized: bivalirudin
and low molecular weight agents melagatran and ximelagatran .
Bivalirudin is administered intravenously for anticoagulant therapy
during percutaneous transluminal coronary angioplasty. Melagatran
is administered subcutaneously for prevention of venous thromboem-
bolism in patients undergoing elective surgery for hip or knee re-
placement. Ximelagatran is taken orally. Its indications for use are
same with melagatran.
 Sodium citrate is also directly-acting anticoagulant. Agent in-
teracts with calcium ions which participate in transformation of pro-
thrombin to thrombin. 4-5% solution of sodium citrate is used for
preservation of donor blood.

Indirectly-Acting Anticoagulants
Group of indirectly-acting anticoagulants consists of synthetic
agents which inhibit the biosynthesis of vitamin K-dependent clot-
ting factors in liver. This group includes neodicumarinum , syn-
cumarum, warfarin, and phenindione .
A chemical structure of neodicumarinum is similar to struc-
ture vitamin K that results to structural antagonism between neod-
icumarinum and vitamin K. Neodicumarinum inhibits enzyme epox-
ide reductase catalyzing transformation of epoxide form of vitamin K
to hydroquinone form. Namely hydroquinone form of vitamin K is
active and participates in synthesis of prothrombin (factor II), pro-
thrombin conversion factor (factor VII), antihemophilic globulin B
(factor IX), and thromboplastin (factor X). Because neodicumarinum
inhibits the synthesis of clotting factors in liver, agent is active only
in vivo.
Neodicumarinum also inhibits the activity of factor supporting
the elastisity of vessels wall. Therefore, prolonged intake of neod-
icumarinum increases the fragility and permeability of capillaries.
Neodicumarinum is taken orally 3-4 times a day. Drug is charac-
terized by high degree of gastrointestinal absorption. Anticoagulant
effect develops in 2-3 hours and reaches maximum in 12-24 hours.
This latent period in affect is due to presence in blood of previously
synthesized clotting factors. After cessation of drug intake, anticoag-
ulant effect exists during 1.5-2 days. Neodicumarinum can easily
penetrate through placenta. Drug is cumulated in the body.
Indications for use of neodicumarinum are following.
1. Prevention and treatment of venous thrombosis, throm-
bophlebitis, myocardial infarction, ischemic stroke.
2. Prevention of thrombosis in postoperative period.
 3. Prevention of thrombosis and thromboembolia in patients with
rheumatic heart damages.
4. Prevention of thrombosis after angioplasty, prosthetic heart
valves.
5. For prevention of thrombosis after cessation of therapy with
directly-acting anticoagulants.
Therapy with neodicumarinum can be aggravated by the follow-
ing side effects.
1. Hemorrhages due to excessive inhibition of blood clotting and
increase of vessels permeability. In this case necessary to stop neod-
icumarinum intake and to prescribe vitamin K or vicasolum (mena-
dione), vitamins C and P. Blood transfusion is also possible.
2. Coumarin-induced necrosis of soft tissues (buttocks, breasts,
cheeks, etc.) due to thrombosis of capillaries and small venules. This
complication develops in 4-10 days after start of drug intake.
Coumarin-induced thrombosis more frequently develops in woman.
A cause of coumarin necrosis is low levels of protein C, a serine
protease with anticoagulant and fibrinolytic activity. In the presence
of indirectly-acting anticoagulants, levels of protein C is decreased
more rapidly than level of procoagulant factors IX, X and prothrom-
bin. Therefore, when indirect anticoagulant is given to a patient with
low levels of protein C, a transient hypercoagulable state can develop
that result in local thrombosis.
3. Dispepsia.
4. Allergic reactions.
5. Toxic damage of liver and kidneys.
6. Drug intake by pregnant woman can cause malformations of
the skeleton in first part of pregnancy and hemorrhage in fetus in in
late pregnancy.
7. Sudden stop of neodicumarinum intake can cause thrombosis.
Warfarin, syncumarum, and phenindione after the mecha-
nism of action, effects, and indications for use are similar to neod-
icumarinum. Main differences of these drugs are longer duration of
latent period (anticoagulant effect develops in 24-72 hours) and
longer duration of action – up to 2-4 days.
 Antagonists of indirectly-acting anticoagulants are vitamin K
and its synthetic analog – vicasolum .

Drugs Activating Fibrinolysis (Fibrinolytic Drugs)

The fibrinolytic system is involved in restricting of clot propaga-
tion in the blood and in the removal of fibrin as wounds heal. Treat-
ment of patients with fibrinolytic drugs is not a substitute for the an-
ticoagulant drugs. Because the purpose of thrombolytic therapy is
rapid lysis of already formed clots, while the aim of anticoagulant
therapy is prevention of the formation of new clotting.
Fibrinolysis is initiated by the activation of profibrinolysin (plas-
minogen) of clots and plasma into fibrinolysin (plasmin). Fibri-
nolysin is proteolytic enzyme which normally is absent in blood. Fib-
rinolysin catalyzes the degradation of fibrin. Plasminogen activators
(tissue-type plasminogen activator and single-chain urokinase-type
plasminogen activator) are necessary for transformation of profibri-
nolysin to fibrinolysin. Plasminogen activators are synthesized in the
vascular endothelium and released into the blood.
Fibrinolytic drugs cause lysis of formed clots in both arteries and
veins and reestablish tissue perfusion.
Fibrinolytic drugs are devided into 2 groups.
1. Directly-acting fibrinolytics: fibrinolysin .
2. Indirectly-acting fibrinolytics: streptokinase , streptode -
case, anistreplase, urokinase, and alteplase .
Fibrinolysin is proteolytic enzyme which formed in result of
activation of profibrinolysin by trypsin. Fibrinolysin causes only su-
perficial lysis of thrombus (predominantly in veins) because fibri-
nolysin quickly is neutralized by antiplasmin. Fibrinolysin is active
both in vivo and in vitro. Drug is administered intravenoulsy drop-
by-drop. Immediately prior to administration, dry fibrinolysin is dis-
solved in sterile isotonic sodium chloride solution or isotonic glucose
solution at the rate of 100-160 UA of fibrinolysin in 1 ml of solution.
Heparin should be added to this solution at the rate 1 UA of heparin
for 2 UA of fibrinolysin. Course of treatment with fibrinolysin can
last 10-14 days.
Indications for use of fibrinolysin are thrombosis of peripheral
arteries, myocardial infarction, ischemic stroke, and thrombosis of
peripheral veins. It is necessary to notice, that in case of arterial
trombosis, fibrinolysin is effective during the first day (in initial 6
hours after the thrombosis); while in case of venous thrombosis, drug
is effective during 5-7 days.
Therapy with fibrinolysin can be accompanied by hemorrhages.
In this case, aminocapronic acid is given. Because fibrinolysin is
drug of peptide origin, its administration can be accompanied allergic
reactions.
Streptokinase is enzymatic agent which obtained from culture
of β-hemolytic streptococcus. This drug is fibrinolytic with indirect
action. Streptokinase forms a complex with plasminogen, which re-
sults in a conformational change and exposure of an active site that
can convert additional plasminogen into plasmin. Unlike fibrinolysin,
streptokinase is capable to penetrate inside of thrombus where acti-
vates fibrinolysis. Drug is administered intravenously or intraarteri-
ally drop-by drop during 16-18 hours. Onset of effect is in 30-60
minutes. Course of treatment lasts 4-6 weeks.
Indications for use of streptokinase are following.
1. Embolism of pulmonary artery and its branches.
2. Acute thrombosis and ambolism of peripheral arteries.
3. Acute thrombosis of superficial and deep veins.
4. Acute myocardial infarction (during first 8 hours).
5. Acute thrombosis of retinal thrombosis.
Side effects include hemorrhages, hemolysis, nephrotoxicity,
and allergic and anaphylactic reactions.
Streptodecase is prolonged form of streptokinase which ap-
plied to thewater-sluble polysaccharide matrix. Duration of strep-
todecase action is 48-72 hours. Drug is administered intravenously.
Recently, another drug containing strepkinase was created –
anistreplase. It is complex of streptokinase with modified plas-
minogen. Drug is administered intravenously in coronary thrombosis.
Elimination half-life is 70-120 minutes. Side effects of anistreplase
are hemorrhages, allergic reactions, bradycardia, transient hypoten-
sion, etc.

Urokinase is plasminogen activator which consists of two

polypeptide chains. The plasma half-life of urokinase is 10-20 min-
utes. Drug is administered intravenously in acute arterial and venous
thrombosis of different localization. Urokinase is not antigenic be-
cause is derived from human cells. Nowadays urokinase is derived
by genic engineering.
Alteplase (aktilyse ) is tissue-type plasminogen activator.
Agent is derived by genic engineering. Alteplase has a high affinity
for fibrin. Owing to this, alteplase causes the fibrin-selective activa-
tion of plasminogen. Drug causes insignificant activation of plas-
minogen in plasma. Alteplase is administered intravenously or in-
traarterialy. A plasma half-life of drug is 5 minutes. Fibrinolytic effi-
cacy of alteplase is higher than eficacy of streptokinase. Administra-
tion of alteplase can cause bleeding because its selectivity in activa-
tion of plasminogen of thrombus is not absolute.
Recently, tenecteplase (metalyse) was created. It is recombi-
nant genetically-modified activator of tissue plasminogen.
Tenecteplase binds to the fibrin component of the thrombus and se-
lectively catalyzes the transformation of associated with thrombus
plasminogen to plasmin, which breaks down fibrin of clot. A plasma
half-life of tenecteplase is nearly 20-25 minutes. Drug is adminis-
tered intravenously to patients with acute myocardial infarction.
Most common possible side effect is hemorrhage.

Drugs Inhibiting Thrombocyte Aggregation

(Antiaggregants)
Platelet aggregation is in significant degree regulated by ratio of
thromboxane A2 and prostacycline (PGI2). The release of ADP from
platelet granules causes the activation of platelet phospholipase A2.
This enzyme, cyclooxygenase-1, and thromboxane synthetase conse-
quentially convert arachidonic acid into cyclic endoperoxides and
thromboxane A2 (TXA2). In contrast to endothelial cells, platelets
lack PGI2 synthetase. Several endogenous substances promote the
platelet aggregation. These are such drugs, as serotonin, epinephrine,
thrombin, collagen of vessels wall, and platelet activating factor. But
certain substances which carried out opposite function are present in
organism. Prostacyclin is the most important among them. Prostacy-
clin is the result of metabolic transformation of arachidonic acid by
the endothelial cells of vessels. In these cells the prostacyclin syn-
thetase transforms the cyclic endoperoxides to prostacyclin. Besides
prostacyclin, such substances as PGE1, heparin, cAMP, adenosine,
and NO prevent the platelets aggregation. If the equilibrium between
these two groups of substances is broken for the benefit of TXA 2, the
platelet aggregation is increased. It can cause the myocardial infarc-
tion, ischemic stroke, etc.
Antiaggregants are drugs which used for prevention of formation
of platelet aggregates. According to mechanism of action these drugs
divided into following groups:
1. Agents which decrease the activity of thromboxane system:
acetylsalicylic acid (aspirin ), dasoxiben .
2. Drugs which increase the activity of prostacyclin system:
epoprostenol (prostacyclin ), carbacycline .
3. Drugs which inhibit the binding of fibrin with thrombocytes
receptors: ticlopidine , clopidogrel , and abciximab .
4. Miscellaneous agents: dipyridamole , trental.

Drugs Decreasing the Activity of Thromboxane System

Acetylsalicylic acid (aspirin) irreversibly inhibits cy-
clooxygenase by acetylation of it. This process develops both in
platelets, preventing the formation of TXA2; and in endothelial cells,
inhibiting the synthesis of PGI2. But endothelial cells can synthesize
anew cyclooxygenase; platelets can not, because platelets have not
the nucleus. Therefore, ratio between TXA 2 and PGI2 changes in fa-
vor of last. The aim of therapy with acetylsalicylic acid is the selec-
tive inhibition of TXA2 synthesis into the platelets that results to the
decrease of platelet aggregation. This is achieved by intake of drug in
dose from 75 mg to 325 mg per day. Effects of acetylsalicylic acid
are dose-depending: with increasing of drug concentration in the
blood, initially the antiaggregant effect appeares, followed by the ap-
pearance of antipyretic, analgetic, and antiinflammatory effects.
During last years the nitroaspirin has been synthesized. In the
human organism this drug releases the nitric oxide (NO), which de-
creases the tone of vessels and oppresses the platelets aggregation.
Dasoxiben is selective inhibitor of thromboxane synthase. But
monotherapy with dasoxiben is ineffective owing to the accumula-
tion of cyclic endoperoxides – substances with proaggregative activ-
ity. Therefore, dasoxiben is used in combination with acetylsalicylic
acid.

Drugs Increasing the Activity of Prostacyclin System

Epoprostenol (prostacyclin ) dilates the blood vessels and
inhibits the platelets aggregation. Because drug has very short dura-
tion of action, epoprostenol is administered intraarterially drop-by-
drop. Drug is used for treatment of patients with vascular diseases of
lower extremities. Epoprostenol improves the blood circulation in
skeletal muscules decreases the ischemic pain, and promotes the
healing of trophic ulcers. Agent is also used during hemodialysis and
hemosorption (for prevention of thrombocytes adhesion to dialysis
membrane), and in apparatus of extracorporeal circulation.
Carbacycline is the synthetic derivative of prostacyclin which
also has short duration of action. Drug acts up to 10 minutes. Indica-
tions for use of carbacycline are same.

Drugs inhibiting the Binding of Fibrin with

Thrombocytes Receptors
Abciximab (ReoPro) prevents the interaction of fibrinogen
with the platelet glicoprotein receptors (GP IIb/IIIa) in result of irre-
versible blockade of these receptors. This drug is administered intra-
venously. Abciximab are administered intravenously during angio-
plasty and in complex therapy of myocardial infarction and severe
angina pectoris. Duration of action is nearly 24 hours. Most common
side effect of abciximab is hemorrhages. Patients who received ab-
ciximab previously may produce the immune response after second
administration.
Ticlopidine (ticlid ) and clopidogrel (plavix) are drugs that
irreversibly inhibit platelet aggregation due to blockage of P2-
purinergic receptors for ADP on the platelet membrane. This action
inhibits ADP-induced binding of fibrinogen with glicoprotein recep-
tors of platelets. Antiaggregative effect develops gradually within
several days. Ticlopidine is taken orally with food 2 times a day. In-
dications for use are myocardial infarction, unstable angina pectoris,
ischemic stroke, and angioplasty. Drug is prescribed to patients who
cannot tolerate aspirin. Ticlopidine is well absorbed, binds to plasma
proteins, and is metabolized by the liver. Side effects are gastroin-
testinal disturbances, neutropenia, agranulocytosis, and allergic reac-
tions. Clopidogrel is taken orally 1 time a day. This agent produces
fewer side effects than ticlopidine.

Miscellaneous Agents
Dipyridamole is a coronary vasodilator with antiaggregative
activity. It is a phosphodiesterase inhibitor which increases platelet
cyclic adenosine monophosphate (cAMP) concentrations. Drug also
blocks enzyme adenosine deaminase and prevents the destruction of
adenosine. Adenosine inhibits the platelets aggregation and causes
vasodilation. Dipyridamole is also useful in combination with aspirin
(Aggrenox). Side effects of dipyridamole include headache, dis-
pepsy, hypotension, allergic reactions, and steal syndrome.
Pentoxifylline (trental) is derivative of xanthine. Agent in-
hibits phosphodiesterase and promotes accumulation of cAMP in
thrmocytes. It results in the decrease of platelets aggregation. Here-
with, the elastisity of erythrocytes is increased that creates the com-
fortable conditions for capillary blood flow. Pentoxifylline increases
the release of plasminogen activator, reduces the level of fibrinogen
in the blood, and decreases the blood viscosity. Agent has a moderate
vasodilative activity. Under the influence of trental, the reological
properties of blood are improved. Marked therapeutic effect of
trental develops in 2-4 weeks after stsrt of treatment. Indications for
use are Raynaud's disease, diabetic angiopathy, disturbances of cere-
bral and coronary blood circulation, and shock. Side effects of trental
include decrease of appetite, diarrhea, nausea, dizziness, hypoten-
sion, and facial flushing.

Drugs Promoting Blood Coagulation

(Hemostatics)
Drugs which promote hemostasis are used for prevention and
treatment of acute and chronic hemorrhages. Disorders of blood co-
agulation can develop due to genetically based deficiency of clotting
factors (haemophilia), sharp activation of fibrinolysis, inhibition of
adhesion and aggregation of thrombocytes, surgery (especially on the
lungs and pelvic organs), hepatic diseases, protein deficiency, radia-
tion sickness, intoxications, etc. For interruption of hemorrhages, fol-
lowing groups of drugs are used: drugs increasing blood clotting
(procoagulants), antifibrinolytics, and drugs promoting platelets
agregation.

Drugs Increasing Blood Clotting (Procoagulants)

Procaugulants promote the blood clotting. These drugs are di-
vided into two subgroups:
1. Drugs for the local use: thrombin, hemostatic sponge ,
and beriplast.
2. Drugs for systemic action: vicasolum , phytomenadione ,
fibrinogen , calcium chloride , calcium gluconate , gelatin,
etamsylate .
Thrombin is an active key factor (IIa) of blood coagulation
which converts the fibrinogen to fibrin. Drug is derived from donated
blood. This drug is used locally in surgery on parenchymatous organs
(most commonly on the liver), in hemorrhages from osteal tissues,
and gingiva. The parenteral introduction of thrombin is inadmissible,
because drug rapidly causes the generalized thrombosis.

Beriplast and hemostatic sponge are received from blood. Both

drugs contain thrombin. They are used only locally for arresting of
capillary bleeding.
Vitamin K exists in two forms: K1 (phytonadione ) and K2
(menaquinone). Phytonadione is vitamin of plant origin.
Menaquinone is synthesized by intestinal bacterial flora and is con-
tained in animal liver. Vitamin K participates in hepatic synthesis of
K-dependent factors of blood coagulation: prothrombin, VII (pro-
convertin), IX (Christmas factor), and X (Stuart-Prower factor).
Phytomenadione and vicasolum are synthetic analogues of
vitamin K. Phytomenadione is taken orally in 30 minutes prior meal
or administered parenterally – subcutaneously, intramuscularly, and
intravenously. Vicasolum is taken orally or administered intramuscu-
larly 2-3 times a day. In liver, vicasolum is transformed to vitamin
K1. The response to vitamin K drugs is slow, requiring about 24
hours. These drugs also have the antihypoxic activity. They are used
for treatment and prevention of hemorrhages before and after
surgery, in bleeding due to ulcer disease, radial illness, uterus bleed-
ing, hemorrhagic disease of newborn, in hypoprothrombinemia.
Fibrinogen is drug, which derived from donor blood. Drug is in-
troduced drip intravenously through the system with special filter
during 2-4 hours 1 time daily. The direct indication for its adminis-
tration is hypofibrinogenemia. This phenomenon develops in several
disease of liver, in case of overdosage of fibrinolitics, in proteins
starvation. Also fibrinogen is preventively used before surgery on or-
gans, which are rich on tissue activators of fibrinolysis (lung, pan-
creas, prostates, and thyroid glands).
Calcium-containing drugs (calcium chloride and calcium
gluconate ) stimulate the formation of thromboplastin, convertation
of prothrombin to thrombin, and polimerization of fibrin. Addition-
ally, calcium ions decrease the permeability of vessels wall. Drugs
are used in cases of internal bleeding due to thrombocytopenia and
increased permeability of vessels wall. Calciumc-containing drugs
are also administered to recipients during transfusion of citrated
blood.

Gelatin contains high quantity of calcium ions due to that in-

creases the blood coagulation. Also, gelatin increases blood viscosity
and thromboplastin release. 10% gelatin solution is administered in-
travenously.
Etamsylate stimulates the formation of thromboplastin. Also
drug inhibits hyaluronidase that results to stabilization of vessels
wall. Etamsylate is used for prevention and interruption of capillary
bleeding in patients with diabetic angiopathy and during various
surgery. Drug is taken orally or administered parenterally.

Drugs Inhibiting Fibrinolysis (Antifibrinolytic Drugs)

The activity of fibrinolytic system can increase due to overdose
of fibrinolytic drugs, sepsis, serious traumas of internal organs, etc.
in such cases, hemorrhages administration of procoagulants is inef-
fective and administration of antifibrinolytic drugs is necessary.
Antifibrinolytic drugs are divided into two groups:
1. Direct fibrinolysin inhibitors: сontrical, trasylol, gordox
(the active substance of these drugs is aprotinin ).
2. Inhibitors of factors, which promote profibrinolysin activa-
tion: aminocapronic acid (Amicar ), tranexamic acid (сy-
clokapron).
Aprotinin is inhibitor of proteases. Agent directly inhibits the
active fibrinolysin. This agent also oppresses other proteolytic en-
zymes. Aprotinin also inhibits the activity of trypsin, chemotripsin,
and kallikrein due to that agent is used in acute pancreatitis. Apro-
tinin-contained drugs are contrical, trasylol, and gordox. Drugs are
administered intravenously slowly or drop-by-drop.
 Aminocapronic acid is synthetic agent – derivative of amino
acid lysine. Drug interacts with activator of profibrinolysin and pre-
vents the transformation of profibrinolysin to fibrinolysin. Besides,
aminocapronic acid interacts with active centers of profibrinolysin
and fibrinolysin and oppresses theirs activity. Drug is introduced
orally or drips intravenously. The duration of action is 6 hours; there-
fore frequency of introduction is 4 time daily. Therapy with
aminocapronic acid may be accompanied by allergic reactions and
dispeptic disorders. Intravenous drug administration can result to de-
crease of blood pressure, thrombosis, embolism, etc.
Tranexamic acid (сyclokapron ) is drug with higher activ-
ity and longer duration of action than aminocapronic acid. Cyclo-
capron is taken orally or administered intravenously. Drug half-live
in intravenouls administration is 2 hours.
The indications for clinical application of fibrinolytic inhibitors
are:
- overdose of fibrinolytics;
- surgery and traumas of organs, which are rich by proteolytic
enzymes;
- hemorrhagic insult;
- intrauterine death of fetes.

Drugs Promoting Platelets Agregation

This group includes such drugs, as calcium chloride , cal-
cium gluconate , serotonin , adroxonum, and etamsylate .
Serotonin is endogenous amine. It activates S1- and S2-sero-
tinin receptors on the surface of platelets and thus promotes platelets
aggregation. Besides, serotonin causes the vasospasm. Drug is intro-
duced intravenously or intramuscularly in hemorrhages, hypo- and
aplastic anemias. Adverse effects are bronchospasm, spasms and
pain of intestine.
Adroxonum is derivative of adrenaline, which has not ability to
stimulate the adrenoceptors of smooth muscles and heart. Drug ex-
cites α-adrenoceptors on the platelet surface. This results in increase
of activity of phospholipase C and increase the aggregation of
platelets. Adroxonum is used orally, subcutaneously, intramuscularly
or as local agent in hemorrhages.
Calcium chloride and calcium gluconate increase the aggre-
gation of platelets, activate the formation of thrombin, and decrease
the permeability of vessels wall. Calcium gluconate is introduced
intramuscularly, intravenously or take orally before meal. Calcium
chloride is introduced only intravenously or take orally after meal.
The frequency of administration of calcium-containing drugs is 3-4
times daily. These drugs are used in hypocalcemia, thrombocytope-
nia, fragility of vessels, hemorrhages in ulcer diseases, lung diseases,
uterus hemorrhages and so on.
Etamsylate blocks the effects of prostacyclin. Presently it is
the most effective drug of this group. Etamsylate also increases the
polymerization of hyaluronic acid and thus increases the density of
basal membrane of capillaries. Etamsylate is used in parenchymatous
and capillary hemorrhages, in thrombocytopenia. Drug is introduced
intravenously, intramuscularly, or orally 3-4 times daily.

Table 4 – Drugs for prescription

Drug name Single doses and mode of Drug product
administration
Acidum acetylsali- Orally 0.075-0.325 g once a Tablets 0.075 or 0.325 g
cylicum day
Dipyridamolum Orally 0.025-0.05 g 3 times Tablets 0.025 or 0.075 g
per day
Heparinum Intravenously 5000-20000 Bottles 5 ml (1 ml –
UA 4 times per day 5000, 10000, or 20000
UA)
Calcii chloridum Intravenously slowly 0.5-1.0 Ampoules 5 or 10 ml of
g 1-2 times daily 10% solution
Neodicumarinum Orally 0.05-0.1 g 3 times per Tablets 0.05 or 0.1 g
day
Syncumarum Orally 0.001-0.006 g 1-2 Tablets 0.002 or 0.004 g
times per day
 Streptokinasum Drip intravenously 250000-
500000 AU (250000 AU is
dissolved in 50 ml of isotonic
NaCl)
Acidum Orally 2-3 g 4 times daily;
aminocapronicum intravenously drop-be-drop
5.0 g once a day
Contricalum Drip intravenously 10000-
50000 IU daily 4-6 times
daily
Fibrinogenum Intravenously drop-be-drop
1.0-2.0 g (1g is dissoled in
250 ml of water for injec-
tions)
Vikasolum Orally 0.015 g 2-3 times
daily;
intramuscularly 0.01 g once a
day
Ampoules 250000 or
500000 AU of dry sub-
stance
Powders for internal
use; bottles 100 ml of
5% solution
Bottles containing
10000, 30000 or 50000
IU of dry substance
Bottles containing 1.0
or 2.0 g of dry sub-
stances
Tablets 0.015 g;
ampoules 1ml of 1% so-
lution

A m i n a z i n e 33, 35
A m i n o c a p r o n i c a c i d 24, 82, 91, 92
INDEX A m i n o p h y l l i n e q.v. Euphillinum
A m p h e t a m i n e 2, 3
A n a p r i l i n u m 58
A A n i s t r e p l a s e 81, 83
A b c i x i m a b 85, 87 A p o m o r p h i n e 32
Abomin 6 A p r o t i n i n 91
A c e c l i d i ne 5, 35 Artificial gastric juice 6
A c e t y l s a l i c y l i c a c i d 85, 86 A s c o f e r 67
Acidin-pepsin 6 A s c o r b i c a c i d 28, 58, 59, 64, 66
A d e l p h a n e 53 A s p a r a g i n a se 65
A d e m e t h i o n i n e 29, 30 A s p i r i n q.v. Acetylsalicylic acid A t -
A d r o x o n u m 92, 93 r o p i n e 5, 9, 10, 24, 28, 31, 36, 55,
A e r o n 34 61, 67
A e t h a m i d u m 62 A x i d q.v. Nizatidine
A e t h a p e ra z i n e 33, 35
A k t i l y s e q.v. Alteplase B
A l d a c t o n e q.v. Spironolactone
A l l o c h o l 25 B e a r b e r r y l e a v e s 43
A l l o p u r i n o l 62
A l m a g e l 19-21
A l t e p l a s e 81, 83
A l u m i n i u m h y d r o x i d e 19-21
A m i c a r q.v. Aminocapronic acid B e k a r b o n 10
A m i l o r i d e 43, 44, 49, 53 B e l l a l g i n 10
B e l l a s t e z i n 10
B e n z o h e x o n i u m 31, 36
B e r b e r i n e s u l f a t e 25, 26
B e r i p l a s t 89
B i r c h b u d s 43
B i s a c o d y l 37, 39
B i s m u t h c i t r a t e 12
B i s m u t h s u b s a l i c y l a t e 16
B l a c k c u r r a n t 69
B u f e n o x q.v. Bumethanide
B u m e t h a n i d e 42, 44
B u s c o p a n e 32
C D i m e d r o l u m 34
C a l c i u m c a r b o n a t e 19, 20
C a l c i u m c h l o r i d e 58, 89, 90, 92
C a l c i u m g l u c o n a t e 89, 90, 92, 93
C a r b a c h o l i ne 4
C a r b a c yc l i n e 85, 86
C a r b e n o x o l o n e 16-18
C a r s i l 28
C a s t o r o i , 37, 38, 55, 58, 59
C h e n o d e o x y c h o l i c a c i d 25, 31
C h l o r p r o m a z i n e q.v. Aminazine
C h o l a f l u x 25
C h o l e c y s t o k i n i n 4, 27
C h o l e n z y m u m 25, 40
С i m e t i d i n e 9, 11-13
C i s a p r i d e 31, 36
C l o p a m i d e 42-44, 46, 53
C l o p i d o g r e l 85, 87
C o a m i d e 67
C o a m i d u m 64, 72
C o l c h i c i n e 62, 63
C o n t r i c a l 24, 91
C o p p e r s u l f a t e 32, 33
C o t a r n i n e 55, 61
C r y s t e p i n 53
C y a n o c o b a l a m i n 64, 66, 68, 69
C y c l o k a p r o n q.v. Tranexamic acid
C y c l o m e t h i a z i d e 43, 44, 47
C y c l o p h o s p h a m i d e q.v. Cyclophos-
phanum
C y c l o p h o s p h a n u m 65
C y c v a l o n u m 25, 26
D
D a l t e p a r i n 74, 77
D a s o x i b e n 85, 86
D e - n o l 16, 17
D e s a m i n o o x y t o c i n 56
Desopimone 2
D e x a m e t ha z o n e 62, 65
D e x f e n f l u r a m i ne 2
D i a k a r b 43, 44, 48
D i c h l o t h i a z i d u m 43, 44, 47
D i c l o f e n ac s o d i u m 62
D i g e s t a l 23
D i l u t e d h y d r o c h l o r i c ac i d 6
D i n o p r o s t 54, 55, 57, 61
D i n o p r o s t o n e 54, 55, 61
D i p r a z i n u m 34
D i p y r i d a m o l e 85, 87
D i s t i g m i n e 35
D o m p e r i d o n e 31
D r o t a v e r i n e q.v. No-spa
E
E n a p - H 53
E n o x a p a r i n 74
E n z y s t a l 23
E p o e t i n a l f a 64, 67
E p o e t i n b e t a 64, 68
E p o p r o s t e n o l 85, 86
E r g o m e t r i n e 55, 61
E r g o t e x t r a c t 55, 61
E r g o t a l 55, 61
E r g o t a m i n e 55, 60
E r y t h r o m y c i n 36
E s o m e p r a z o le 9, 13
E s s e n t i a l e 29
E s t r a d i o l 54, 57
E s t r o n e 54, 57
E t a m s y l a t e 89, 91-93
E t h a c r y n i c a c i d 43, 44, 48, 53, 54
E u p h i l l i n u m 28
E u p h y l l i n u m 43, 44
Extract of buckthorn (Rhamnus)
c o r t e x 37
 F H y d r o c h l o r t h i a z i de q.v. Dichloth-
iazidum
F a m o t i d i n e 9, 11, 12
Fenfluramine 2
F e n o t e r o l 55, 59
I
F e r c o v e n 64 I m o d i u m q.v. Loperamide
F e r r a m i d u m 64 I n d o m e t h a c i n 62
F e r r o g r a d u m e t 67 I n d o p a m i d e 42, 44
F e r r o p l e x 64, 67 I n t e r f e r o n α 65
F e r r o u s l a c t a t e 64 I p e c a c u a n h a r o o t q.v. Root of
F e r r o u s s u l f a t e 64 ipecacuanha
F e r r u m - L e k 64 I s a p h e n i n e 37, 39
F e s t a l 23
F i b r i n o g e n 73, 74, 86-90
F i b r i n o l y s i n 73, 81, 82, 91, 92 K
F i l g r a s t i m 65, 70, 71 K r e o n 23
F l a m і n 25
F o l i c a c i d 64, 66, 69
F r a x i p a r i n 74, 77 L
F u r o s e m i d e 42-46, 53, 54
L a n s o p r a z o le 9, 13
L e g a l o n 28, 29
G L e n o g r a s t i m 65
L e p t i n 1, 4
G a s t a l 19, 21 L e s p e f l a n 52
G a s t r i n 5, 8, 14, 16, 21 L e s p e n e f r i l 52
G e l a t i n 14, 89, 90 L e u c o g e n u m 70
G l o b i r o n 67 L e u k o g e n u m 65, 71
G o r d o x 24, 91 L i c r e a se 23
G r a n i s e t r o n 33, 35 L i o b i l u m 25
G u t t a l a x 37, 39 L i p o i c a c i d 29, 30
L I V - 5 2 28
H L o g i p a r i n 77
L o p e r a m i d e 36
H a e m o s t i m u l i n u m 64 L і o b і l u m 25
H e l i c h r u s u m a r e n a r i u m 25
H e m o s t a t i c s p o n g e 89
H e p a b e ne 28 M
H e p a r i n 73-77, 81, 84 M a a l o x 19, 21
H e p a t o f a l k P l a n t a 28 M a g n e s i u m o x i d e 19-21
H e p t r a l q.v. Ademethionine M a g n e s i u m s u l f a t e 27, 55, 60
H e r b o f t h e r m o p s i s 32 M a g n e s i u m s u l p h a t e 37
H e x a m e t h o n i u m q.v. Benzohexonium M a n n i t o l 43, 51, 53
H i r u d i n 74, 78 Mazindole 2
H i s t a m i n e 5, 6, 8, 11, 12, 14 Melanocortin 4
H o l a g o l 25 M e n a q u i n o n e q.v. Vitamin K
H o l o s a s 25 M e r c a p t o p u r i ne 65
H o r s e t a i l h e r b 43, 52 M e t a l y s e q.v. Tenecteplase
M e t h a c i n i u m 9, 10, 31, 36
M e t h o t r e x a t e 65
M e t h y l d i n o p r o s t 57
M e t h y l e r g o m e t r i ne 55, 61
M e t h y l u r a c i l u m 65, 70
M e t o c l o p r a m i de 31, 33
M e z y m F o r t e 23
M i s o p r o s t o l 9, 15, 16, 18
M o d u r e t i c 53
M o l g r a m o s t i m 70, 71
M o l g r a s t i m 65, 71
M o t i l i u m q.v. Domperidone
M y e l o s a n u m 65
N P o l y t h i a z i d e 43, 47
N a d r o p a r i n 74, 77
Natural gastric juice 6
N e o d i c u m a r i n u m 74, 78, 79, 80
N i t r o a s p i r i n 86
N i z a t i d i n e 9, 11, 12
N o - s p a 28, 32, 36
N і k o d i n u m 25, 26
O P r o s t a g l a n d i n F 2 α q.v. Dinoprost
O a t s s e e d s 25
O d e s t o n 25, 26
O l e a n d o m y c i n 36
O m e p r a z o l e 9, 13
O n d a n s e t r o n 33, 35
O r l i s t a t 2, 4
O x a p h e n a m і d u m 25, 26
O x o d o l i n u m 42-44, 48, 53, 63
O x y t o c i n 55, 56
P R h u b a r b ( R h e u m ) r o o t , 37
P a c h y c a r p i ne 55, 58
P a n c r e a t i n 22
P a n t o p r a z o l e 9, 13
P a n z i n o r m 23
P a p a v e r i n e 28, 32, 36
P a r t u s i s t e n . q.v. Fenoterol
Pentagastrin 6
P e n t o x i f y l l i n e 88
P e n t o x y l u m 65, 70
P e p s i n , 5-8, 17-19, 22
P h e n a m i n u m q.v. Фmphetamine
P h e n i n d i o n e 74, 78, 80
P h e n o l p h t h a l e i n 37, 39
P h e n y l b u t a z o n e 62
P h e p r a n o n e 2, 3
P h o s p h a l u g e l 19, 21
P h y t o m e n a d i o n e 89, 90
P h y t o n a d i o n e q.v. Vitamin K
Pilocarpine 5
P i l o r i d q.v. Bismuth citrate
P i r e n z e p i n e 9-11
P i r i l e n e 31, 36
P i t u i t r i n u m 56
P l a t y p h y l l i n 9, 24, 28, 31, 36
P r e d n i s o l o n e 62, 65
P r o b a n t h i n e 32
P r o b e n e c i d 62
P r o g e s t e r o n e 54, 55, 60
P r o g l u m i d e 9, 15, 16
P r o p r a n o l o l q.v. Anaprilinum
P r o s e r i n u m 4, 35, 55, 58
P r o s t a c y c l i n 73, 84, 85, 86, 93
P r o s t a g l a n d i n E 2 q.v. Dinoproston
P y r i d o s t i g m i n e 35
Q
Q u a m a t e l . q.v. Famotidine
R
R a b e p r o z o le , 9, 13
R a n i t i d i n e , 9, 11, 12
R e o P r o . q.v. Abciximab
Roksatidine, 9
R o o t o f i p e c ac u a n h a , 32
R o s e , 26, 69
R o w a n , 69
R o x a n e q.v. Roxatidine
R u b o m y c i n u m 65
 S T h i o t r i a z o l i n e 29, 30
S a l b u t a m o l 55, 59
S c o p o l a m i n e 5, 34
S e n n a l e a v e s 37, 38
S e r o t o n i n 1, 3, 58, 84, 92
S i b u t r a m i n e 2, 3
Silibinine dihydrosuccinate
s o d i u m s a l , 29
S o d i u m h y d r o c a r b o n a t e 14, 19, 20
S o d i u m h y d r o c i t r a t e 74
S o d i u m n u c l e i n a t e 65, 70
S o d i u m o x y b u t i r a t e 55
S o d i u m o x y b u t y r a t e 60
Sodium phosphate with radioac-
t i v e i s o t o p e 3 2 P 64, 70
S o d i u m s u l p h a t e 37
S o r b i f e r 67
S o r b i t o l 21, 27
S p i r o n o l a c t o n e 43, 44, 50, 53, 54
S t i g m a t u m m a y d i s 25
S t r a w b e r r y f r u i t 69
S t r e p t o d e c a se 81, 83
S t r e p t o k i n a s e 81, 82, 83
S u c r a l f a t e 16, 17
S y n c u m a r u m 74, 78, 80
S y n o e s t r o l u m 54, 57
S y r u p o f w i l d r o s e 25
T Vitamin B12 q.v. Cyanocobalamin
T a r d y f e r o n 64
T e l e n z e p i n e 9-11
T e n e c t e p l a s e 83, 84
T e n o r i c 53
T e r b u t a l i n e 55, 59
T h e o b r o m i n e 51
T h e o p h y l l i n e 51
T h e r m o p s i s h e r b q.v. Herb of ther-
mopsis
T h i a m i n q.v. Vitamin B1
T h i e t h y l p e r a z i n e 33, 35
T h i o p h o s p h a m i d u m 65
T h i o t e p a q.v. Thiophosphamidum
T h r o m b i n 73, 74, 77, 78, 84, 89, 90,
93
T i c l o p i d i n e 85, 87
T o c o p h e r o l 55, 60
T o r a s e m i d e 42, 44, 46
T r a n e x a m ic a c i d 91
T r a s y l o l 24, 91
T r e n t a l 85, 88
T r i a m p u r C o m p o s i t u m 53
T r i a m t e r e ne 43, 44, 49, 53, 54
T r i f t a z i n u m 33, 35
T r o p i s e t r o n 33, 35
U
U r o d a n u m 62
U r o k i n a s e 81, 83
U r s o d e o x y c h o l i c a c i d 31
U r s o f a l k q.v. Ursodeoxycholic acid
V
V e n t e r q.v. Sucralfate
V e r o s p i r o n q.v. Spironolactone
V i c a s o l u m 79, 80, 89, 90
V i n b l a s t i n e 65
V i n c r i s t i n e 65
V i t a m i n B 1 58
V i t a m i n B c q.v. Folic acid
V i t a m i n E q.v. Tocopherol
V i t a m i n K 89
W
W a r f a r i n 74, 78, 80
Z
Z a n t a c q.v. Ranitidine
Z i n c s u l f a t e 32, 33
Z o f r a n q.v. Ondansetron
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 CONTENTS
P.
DRUGS INFLUENCING DIGESTIVE SYSTEM…..............…........ .
…...3
Drugs Influencing Appetite...................................................................... ........
3
Drugs Increasing Appetite.................................................................... ........
3
Drugs Decreasing Appetite (Anorexic or Anorexigenic Drugs).......... ........
4
Drugs Influencing Function of Salivary Glands...................................... ........
6
Drugs which Used in Hyposecretion of Stomach.................................... ........
7
Drugs which Used in Hypersecretion of Gastric Glands and in
Disturbances of Trophism or Regeneration of Gastric Mucosa............... ........
9
Drugs Decreasing the Secretory Activity of Gastric Glands................ ........
9
M-cholinoceptor Antagonists................................................................ ......1
0
H2-Histaminergic Antagonists.............................................................. ......1
2
Proton Pump Inhibitors........................................................................ ......1
4
Prostaglandins and Their Synthetic Analogues.................................... ......1
6
Blockers of Gastrin Receptors.............................................................. ......1
6
Gastroprotective Drugs.......................................................................... ......1
6
Antacids................................................................................................ ......1
9
Drugs which Used in Hypofunction of Pancreas..................................... ......2
2
Drugs Inhibiting Pancreatic Secretion..................................................... ......2
3
Drugs Improving Functions of Liver (Hepatotropic Drugs).................... ......2
 4
Drugs Stimulating Bile Secretion.......................................................... ......2
4
Drugs Stimulating Bile Discharge......................................................... ......2
6
Hepatoprotectors.................................................................................... ......2
7
Drugs which Used for Dissolution of Gallstones.................................. ......3
0
Drugs Influencing Gastric Motility.......................................................... ......3
0
Emetic Drugs............................................................................................ ......3
1
Antiemetic Drugs..................................................................................... ......3
2
Drugs which Influence Intestinal Motility............................................... ......3
4
Drugs Stimulating Intestinal Motility.................................................... ......3
4
Drugs Inhibiting Intestinal Motility and Reducing Intestinal Spasms.. ......3
4
Laxative Drugs...................................................................................... ......3
5
Saline Laxatives..................................................................................... ......3
5
Vegetable Oils....................................................................................... ......3
6
Drugs Containing Anthraquinone Glucosides...................................... ......3
6
Sinthetic Laxative Drugs........................................................................ ......3
7
DIURETIC DRUGS............................................................................... ......3
8
Diuretics Acting on the Level of Epithelial Cells of Renal Tubules........ ......4
1
Loop Diuretics...................................................................................... ......4
1
Thiazides............................................................................................... ......4
3
 Derivatives of Dichlorphenoxyacetic Acid........................................... ......4
4
Carbonic Anhydrase Inhibitors............................................................. ......4
5
Diuretics Acting on the Level of Apical Membrane................................ ......4
5
Drugs Inhibiting Proteins which Transfer Sodium................................ ......4
5
Aldosterone Antagonists........................................................................ ......4
6
Osmotic Diuretics..................................................................................... ......4
7
Drugs Increasing the Renal Blood Supply................................................. ......4
7
Diuretics of Vegetable Origin................................................................... ......4
8
Principles of Combined Use of Diuretics................................................. ......4
9
DRUGS INFLUENCING UPON THE MYOMETRIUM.................. ......5
0
Drugs Stimulating Contractile Activity of Uterus.................................... ......5
1
Drugs of Oxytocin Group...................................................................... ......5
1
Drugs of Prostaglandin Group............................................................... ......5
2
Estrogens............................................................................................... ......5
3
β-Adrenoblockers.................................................................................. ......5
3
Miscellaneous Drugs.............................................................................. ......5
3
Drugs Decreasing Uterus Tone and Contractile Activity
(Tocolytics)............................................................................................... ......5
4
Drugs Increasing Tone of Myometrium and Uterus Involution in the
Postpartum Period..................................................................................... ......5
5
Drugs Decreasing the Tone of Uterus Neck............................................. ......5
 6
DRUGS USED FOR TREATMENT OF GOUT................................. ......5
6
DRUGS INFLUENCING UPON HEMOPOIESIS............................. ......5
8
Drugs Influencing Erythropoiesis............................................................. ......5
9
Drugs Stimulating Erythropoiesis.......................................................... ......6
0
Drugs which Used for Treatment of Hypochromic Anemias................. ......6
0
Drugs for Treatment of Hyperchromic Anemias................................... ......6
2
Herbal Drugs which Used for Treatment of Anemias........................... ......6
3
Drugs Inhibiting Erythropoiesis............................................................. ......6
3
Drugs Influencing Leukopoiesis............................................................... ......6
3
Drugs Stimulating Leukopoiesis............................................................ ......6
3
DRUGS INFLUENCING BLOOD COAGULATION......................... ......6
6
Drugs for Prevention and Treatment of Thrombosis................................ ......6
7
Drugs Decreasing Blood Coagulation (Anticiagulants)........................ ......6
7
Directly-Acting Anticoagulants............................................................. ......6
7
Indirectly-Acting Anticoagulants........................................................... ......7
1
Drugs Activating Fibrinolysis (Fibrinolytic Drugs)................................ ......7
3
Drugs Inhibiting Thrombocytes Aggregation (Antiaggregants)............. ......7
5
Drugs Decreasing the Activity of Thromoxane System......................... ......7
6
Drugs Increasing the Activity of Prostacyclin System........................... ......7
7
 Drugs Inhibiting the Binding of Fibrin with Thrombocytes Receptors.. ......7
7
Miscellaneous Agents............................................................................ ......7
8
Drugs Promoting Blood Coagulation (Hemostatics)................................ ......7
9
Drugs Increasing Blood Clotting (Procoagulants)................................. ......7
9
Drugs Inhibiting Fibrinolysis (Antifibrinolytic Drugs)........................... ......8
1
Drugs Promoting Platelets Agregation................................................... ......8
2
INDEX.................................................................................................. ......8
5
REFERENCES.................................................................................... ......9
0