Kharkov National Medical University
Department of Pharmacology and Medical Prescription
assistant Gordiychuk D.
MEDICINES AFFECTING THE
BLOOD SYSTEM
1
THE SYSTEM OF BLOOD
CONSISTS OF:
•Peripheral blood (circulating in vessels)
•Bloodforming (Hemopoietic) organs:
the red bone marrow,
lymphatic nodes, and
spleen
•Bloodbreaking organs (liver, spleen)
•Neurohumoral regulation system
2
BLOOD CONSTITUENTS
3
Drugs acting on
haemopoiesis
4
Red Blood Cells
Erythrocytes
• Place of formation – the red bone marrow
• Period of life ≈ 120 days
• Functions:
- Transport (respiratory, nutritional, excretory
function)
- Defense
- Regulation of blood рН
5
DISORDERS OF ERYTHROPOIESIS
ANEMIAS
Anaemia is a decrease of erythrocytes
and/or hemoglobin in blood
Anemia can be considered to be a syndrome, not a diagnosis
The main types of anaemias are as follows:
─ Iron deficiency,
─ B12-vitamin and folic acid deficiency,
─ Hypoplastic anaemia
─ Hemolytic anaemia
6
7
1. IRON DEFICIENCY ANEMIA
Hypochromic anemia
Rather wide-spread type of anemia
Decreased amount of iron in the organism makes it
not possible to synthesize nessisary amount of
hemoglobin
Iron deficiency is
especially for women
a
common
problem,
5% of women between the ages of 20 and 49
have iron deficiency with anemia
and 11% have iron deficiency without anemia
8
9
SYMPTOMS OF ANEMIA
10
IRON ABSORBTION
IN THE GASTROINTESTINAL TRACT
• Only ionized iron can be absorbed
Fe2+ is absorbed best of all
• HCl facilitates absorption
as it converts elemental iron into ionized form
• Ascorbic acid facilitates absorption
as it converts Fe3+ into Fe2+
• calcium, antacids, tetracycline and
chloramphenicol inhibit Fe2+ absorption
• Fe2+ binds to apoferritin and in the form of ferritin
(with Fe3+) crosses intestinal epithelium
11
IRON METABOLISM:
Step 2 in blood
only Fe2+
is included in
hemoglobin
but Fe3+
is transported by
transferrin !
12
PHARMACOLOGICAL CORRECTION
OF THE HYPOCHROMIC ANEMIA IRON SUPPLEMENTATION
What iron compounds should be used
as drugs for parenteral administration:
Fe2+ or Fe3+ ?
For parenteral – only Fe3+ !
and for peroral – Fe2+ and Fe3+ is possible
13
NB!
Iron-containing drugs for peroral
administration should never be administered
at one time with iron-containing drugs for
parenteral administration !
Why ?
Transferin is in a limited amount!
When transferrin is saturated by iron
coming from the GIT poisoning by iron
administered parentally is highly possible
because it would be present in blood in
free form that is toxic !
14
Desferal is an antidote for iron
Erythropoiesis stimulants (antianaemics)
1. IRON-CONTAINING MEDICINES
FOR ENTERAL ADMINISTRATION
Fe2+ compounds
Ferrous sulphate
Ferro-gradumet
Ferrous glucanate
Fe3+ compounds
Ferrous saccharate
Ferrous hydroxide
polymaltose complex
Ferrous protein-acetylaspartylate
Combined drugs:
Ferroplex
Feramide
Hemopheron
Sorbifer durules
FOR PARENTERAL
ADMINISTRATION
Fe3+ compounds
Ferrous hydroxide
polymaltose complex
Ferrous saccharate
Ferrum-lek (dextrane
containing complex)
15
IRON-CONTAINING MEDICINES
Iron-containing medicines are donors of an iron
ion and stimulate the synthesis of haemoglobin
Pharmacodynamics (effects)
→
Indications
Increases amount of the erythrocytes Prevention and
treatment
Increases saturation of erythrocytes
of iron
by haemoglobin
deficiency
Improvement of the tissues
in hypochromic
oxygenation
anaemias
The reduction of symptoms of anemia
(weakness, paleness, tachycardia etc.)
which begins in 5-7 days after the
start of treatment
16
IRON-CONTAINING MEDICINES
SIDE EFFECTS
Side effects
→ Contraindications
Dyspepsia, pain in the epigastric
area, intestinal colics, seldom ulceration of the GIT
Constipation
(resulting
from
binding of iron to H2S in the
intestine and bowels)
Teeth darkness (resulting from
binding of iron to H2S in the oral
cavity and forming of black
compound FeS)
Black colour of feces imitating
intestinal bleeding
Nausea, vomiting, hemosiderosis,
hypotension – in parenteral
administration
Diseases of the GIT,
anaemias that are not connected
with the deficiency of iron in the
organism
17
2. B12-DEFICIENCY
AND FOLIC ACID DEFICIENCY ANAEMIAS
• Hyperchromic anemias
• Characterized by presence of megaloblasts in
blood
• Lack of vitamin B12 or folic acid leads to
the disorder of erythropoisis due to the
supression of DNA synthesis
(megaloblasts – abnormally large cells are formed
because of disorder of cell division and imbalance
between nucleus and cytoplasm development)
Note that blood cells are one of the most
intensively renewed in the body
so they are one of the first to suffer
in DNA and protein synthesis suppression18
19
Possible symptoms of
hyperchromic anemia:
• Disorders of peripheral sensitivity
or tingling
• Glossitis
• CNS disorders (loss of balance,
personality changes)
20
B12 binds to
intrinsic Castle
factor in the
stomach and is
absorbed by
endocytosis in
the intestine
and
concentrates
in the liver,
storage supply
in the liver is
enough for
several years
21
Folic acid is
water-soluble
and is
absorbed in
small intestine
and
concentrates
in the liver,
but storage
supply in the
liver is enough
for several
months only
22
CYANOCOBALAMINE (VITAMIN B12)
PROPERTIES
 The mechanism of action
 promotes the synthesis of the DNA
 Intensifies the cells’ division
and the formation of erythrocytes
as well as other highly divisible cells
• transforms megaloblastic hemopoiesis
into normoblastic one,
normalizes the amount of erythrocytes,
leucocytes and thrombocytes in blood
• takes part in the synthesis of myelin and
acetylcholine, decreases neurological
disturbances connected with megaloblastic
anemia
• takes part in the function of the epithelium and 23
decreases disturbances in tongue mucosa
INDICATIONS
FOR CYANOCOBALAMINE
(VITAMIN B12)
Hyperchromic megaloblast anemia
Hypoplastic anemia
Radiation sickness
Neurological diseases
Liver diseases
Dystrophy in children
Glossitis
FOR FOLIC
ACID
(VITAMIN Bc)
Hyperchromic megaloblast
anemia
Chronic gastro-enteritis
In pregnancy for the prophylaxis
of neurological pathology of the
fetus and newborn
Side effects:
allergy, hypercoagulation,
tachycardia, pain in the heart, worsen
in angina pectoris
Note that folic acid in
hyperchromic anemias should be
used only in combination with B12!
24
ERYTHROPOIETIN
Erythropoietin is the glycopeptide hormone
that stimulates erythropoiesis
It is produced by kidneys as a response for hypoxia
The higher level of the renal hypoxia is,
the more erythropoietin is produced
Nowadays with the help
of the genetic engineering
human erythropoietins
α, β, ώ have been obtained
They are mainly used to
normalize erythropoiesis
in patients with
chronic kidney diseases
25
ERYTHROPOIETIN
The mechanism of action
Stimulation of proliferation and differentiation
of cells of the red bone marrow
because of activation of the specific erythropoietin’s
receptors
Pharmacodynamics (effects)
Increase in erythrocytes and
reticulocytes amount,
increase in the level of
hemoglobin
Side effects
Increase of BP
→
Indications
Anaemias caused by the chronic
renal insufficiency, HIV- infection,
after usage of cytostatics, in
preterm born infants, hypo- and
aplastic anaemias
→
Contraindications
Hypertension
26
ERYTHROPOIESIS INHIBITORS
-Sodium phosphate solution labeled by phosphorus-32 -Imiphos
The mechanism of action
suppresses the erythropoietic part of the bone
marrow
Indication:
Erythremia it is an increased amount of immatured, inferior erythrocytes
in blood because of their increased production by the red
bone marrow
Side effect: Anemia
Contraindications: Erythropenia, HIV-infection
27
WHITE BLOOD CELLS
•Place of formation – the red bone marrow,
thymus, lymph nodes
•Period of life – from few days to 10 years
•Function: defence
- Phagocytosis
- Immunity (cellular and humoral)
- Synthesis of antibodies
with antibacterial and antitoxic properties
- Synthesis of enzymes
that increase permeability of capillaries
28
FORMATION OF BLOOD CELLS
Leukopoiesis is the process of leukocytes formation and
maturation.
Leukopenia is the decreased amount of leukocytes in blood.
Lymphogranulomatosis is a malignant tumour of the lymphoid
29
tissue.
DISORDERS OF LEUKOPOIESIS AND
THEIR CORRECTION
The deficient production of
leukocytes and decrease of their
amount in blood (leukopenia,
agranulocytosis)
leukopoiesis stimulants
and colony-stimulating
factors that accelerate
the formation of
leukocytes in the bone
marrow are used
an increased production of
inferior leukocytes
(leukosis, leukemia)
leukopoiesis inhibitors
are needed
30
Leukopoiesis stimulants
–Nucleic acid derivatives
Sodium nucleinate
– Pyrimidine derivatives
Methyluracilum
Pentoxilum
– Colony-stimulating factors (CSF)
Lenograstim
Molgrastim
The mechanism of action
They bind to specific receptors of myeloid cell-precursors
of the neutrophilic group, which are necessary for the
matured leukocytes formation.
31
It leads to increase of the matured leukocytes synthesis.
Leukopoiesis stimulants
Pharmacodynamics (effects) →
Leukopoiesis stimulants: the
increase of the matured
leukocytes amount in blood
Side effects
Leukopoiesis stimulants:
dyspepsia
Indications
Leukopenia including those
caused by the therapy with
antitumour medicines, radiation
sickness, HIV-infection
→
Contraindications
Diseases of the GIT
32
Leukopoiesis inhibitors
that suppress the formation of leukocytes.
Leukopoiesis inhibitors
Methotrexate
Mercaptopurine
Prednisolone
Pharmacodynamics (effects) →
Leukopoiesis inhibitors:
decrease of the leukocytes
amount in blood
Side effects
Indications
Leukemias, lymphogranulomatosis
→
Contraindications
Leukopoiesis inhibitors:
inhibition of hemopoiesis,
dysfunction of liver and kidneys
Leukopenia, anaemia,
thrombocytopenia, diseases of
liver and kidneys
Teratogenecity and embryotoxicity
Pregnancy, lactation
33
Drugs acting on
haemostasis
34
THROMBOCYTES
• Place of formation –
the red bone marrow
• Period of life – 8-12 days
• Function:
The blood clotting
Physiological properties:
Adhesion – ability to stick to the foreign and damaged surface
Aggregation – ability to form a clump (cork)
Agglutination – pasting of thrombocytes one with another
35
THE BLOOD CLOTTING
damage of vessels
2 phase – formation
of thrombocytes cork
1 phase of blood clotting –
vasoconstriction
3 phase – thromb (clot)
formation from fibrin
(marked yellow)
and blood cells 36
COAGULATION HEMOSTASIS
37
FIBRINOLYSIS
It is the process of fibrin dissolution
I – formation of blood activator of plasminogen–
extrinsic and intrinsic pathways
II –conversion of plasminogen to plasmin
III – plasmin disunites fibrin to peptides and
amino acids (splits fibrin)
38
PATHOLOGY OF HEMOSTASIS
AND FIBRINOLYSIS
I – A decrease in blood coagulation
and/or increase in fibrinolysis
RESULT IN BLEEDING
II – An increase in blood coagulation
and/or decrease in fibrinolysis
RESULT IN THROMBOSIS, thromboembolism,
syndrome of disseminated intravasal blood
coagulation
39
Drugs acting on hemostasis
•
•
•
•
•
•
•
•
I.
Drugs promoting haemostasis
1. Procoagulants
2. Fibrinolysis inhibitors
3. Heparin antagonist
II. Drugs preventing clot formation
1. Anticoagulants
2. Antiplatelet drugs (Antiaggregants)
III. Thrombolytics
40
ANTICOAGULANTS
these are drugs decreasing blood
coagulation
1. Direct acting
- heparins (Heparin, LMW heparins: Enoxaparin, Fraxiparine,
Dalteparin sodium)
- factor Xa inhibitors (Rivaroxaban, Apixaban)
- thrombin inhibitors (Lepirudin, Desirudin, Bivalirudin)
2. Indirect acting
• coumarins
• indandiones
41
Direct-acting anticoagulants
Systemic-acting
Local-acting
HIGH MOLECULAR HEPARINS
Heparin ointment
Heparin
LOW MOLECULAR HEPARINS
Calcium adroparin
Fraxiparine
The mechanism of action
Direct-acting anticoagulants have highly negative charge,
which promote the formation of the complex with positively
charged coagulation proteins.
As a result, coagulation proteins are inhibited.
42
Pharmacodynamics (effects)
→
Indications
Direct-acting anticoagulants
Anticoagulant
(inhibition
phases)
of
blood
coagulation
at
Myocardial infarction, direct blood
all transfusion, surgery on the heart or
vessels. Prophylaxis and treatment of
embolism and vascular thrombosis
Fibrinolysis activation, improvement Prophylaxis of thrombosis after
coronary vessels shunting and
of blood rheological properties
prosthetics of the heart valves
Thrombophlebitis, hypercoagulation
aggregation of thrombocytes and erythrocytes, syndrome
Antiaggregant (inhibition of adhesion and
normalization of the blood rheological
properties, improvement of microcirculation of
the brain, myocardium, retina etc.)
Hypolipidemic
Prophylaxis and treatment of
atherosclerosis
(decrease of the lipid level in blood)
Coronarodilating (improvement of blood Myocardial infarction, stable angina of
tension
circulation in the coronary vessels)
Immunosuppressive
Direct blood transfusion, surgery on the
heart or vessels, rheumatism, bronchial
asthma, glomerulonephritis, hemolytic
43
anemia, renal transplantation,
endocarditis
Heparin
Mechanism of action
• Heparin binds to the enzyme inhibitor
antithrombin III (AT) causing a
conformational change that results in its
activation up to 1000-fold .
• The activated AT then inactivates thrombin
and other proteases involved in blood
clotting, most notably factor Xa.
44
HEPARINE PHARMACOKINETICS
Is administered intravenously (IV), intramuscularly (IM),
subcutaneously (SC), topically
begins to act immediately after IV administration
and acts during 4-6 hours
begins to act in 15-30 min after IM administration
and acts during 6-8 hours
begins to act in 30-60 after SC administration
and acts during 8-12 hours
Is metabolized in the liver by heparinase
and is excreted with urine
45
SIDE EFFECTS OF HEPARINE
Bleeding
Hematomes
Micro- and macrohematuria
Thrombocytopenia
Allergy
Osteoporosis
Hair silvering
Protamine sulfate is an antidote
for heparin
46
FRAXIPARINE
low molecular weight heparin
do not inhibit thrombin (acts through supression of Xa
factor), so the control of activated partly thromboplastin
time (laboratory analysis) is not needed
Is administered subcutaneously once a day
has higher bioavailability, longer duration of action,
less binding to plasma proteins (in comparison with heparin)
is used for the treatment of thromboflebitis, prevention of
thrombus formation after surgeries
47
Factor Xa ihibitors
• Rivaroxaban
• Apixaban
Mechanism: they act directly upon Factor X
in the coagulation cascade, without using
antithrombin as a mediator
Advantages over LMW heparins and indirect
acting anticoagulants:
1. Oral administration 2. Absence of
hypoprothrombinemia
48
INDIRECT-ACTING ANTICOAGULANTS
Warfarin
Ethyl bisoumacetate
Acenocumarol
Fenindion
Note that these
drugs are vitamin
K antagonists!
The mechanism of action
Indirect-acting anticoagulants have no influence on coagulation factors
directly in the blood
They supress the biosynthesis of coagulation proteins (proconvertin and
prothrombin) in the liver as a result of antagonism with vitamin K.
Pharmacological effects
─ a decrease in blood coagulation
─ an increase in fibrinolysis
─ a decrease in lipids concentration in blood
49
Oral Anticoagulants
Vitamin K Antagonists (Coumarins)
• Vitamin K is co-factor for the hepatic synthesis of
clotting factors II, VII, IX & X
warfarin
By Vit.k reductase
Vit. K
(active form)
Vit. K epoxide
Warfarin inhibits Vit. K reductase  no active
form of Vit. K  no synthesis of clotting factors
Vitamin K Antagonists
Warfarin
Warfarin has 100% oral bioavailability, high
plasma protein binding & long plasma t1/2 of 36
hours
A high loading dose followed by an adjusted
maintenance dose
Warfarin is contraindicated with pregnancy as it
crosses the placental barrier and is teratogenic
in the first trimester & and induce intracranial
hemorrhage in the baby during delivery
Warfarin is metabolized by hepatic Cytochrome
P450 enzymes with half-life of 40 hrs
Warfarin Drug Pharmacokinetic &
Pharmacodynamic Interactions





Potentiating warfarin
Inhibitors of hepatic P450
enzymes (cimetidine,
cotrimoxazole, imipramine,
amiodarone)
Platelet aggregation inhibitors
(NSAIDs e.g. aspirin)
3rd generation cephalosporins*
Drugs displacing warfarin from
binding sites (NSAIDs)
Drugs reducing the availability of
vitamin K





Inhibiting Warfarin
Vitamin K in some
parenteral feed
Inducers of hepatic P450
enzymes (rifampicin,
barbiturates, … etc)
Reduction of GIT absorption
(cholestyramine)
Diuretics
Hypothyroidism
 Hepatic disease(↓ clotting factors)&
hyperthyroidism (↑ basal metabolic
rate)
*Cephalosporins potentiate warfarin’s effect by
killing vit.k producing normal flora
INDICATIONS and SIDE EFFECTS
FOR INDIRECT-ACTING ANTICOAGULANTS
Prophylaxis and treatment of venous and arterial thrombosis,
thromboembolism, thrombophlebitis,
obliterating endarteritis, hypercoagulation syndrome,
coronary insufficiency, miocardial infarction, ischemic insult,
prevention of thrombosis after surgeries
Nb!
Side effects:
Bleeding
Forming of hematomes
Hematuria
Dyspepsia
Supression of the liver function
Allergy
Index of
prothrombin
(laboratory value)
should be
controlled for the
safety of the
therapy!
53
FIBRINOLYTIC DRUGS (THROMBOLYTIC DRUGS)
Direct-acting: Fibrinolysin
Note that these
Indirect-acting: Urokinase
drugs are able to
Streptokinase
produce the lysis
Alteplase
of the blood clot!
The mechanism of action
Fibrinolytics (fibrinolysis activators) transform profibrinolysine (plasminogen)
into its active form - fibrinolysine (plasmin),
decrease the level of fibrinogen in the blood plasma,
inhibit aggregation of thrombocytes and the activity of natural blood
procoagulants,
i.e. they activate the fibrinolytic system (fibrinolysis)
Pharmacodynamics - Indications
Fibrinolytic - dissolution of
Venous and arterial thrombosis,
fibrin filaments of the recent (up acute myocardial infarction,
to 3 days) thrombs
pulmonary embolism
54
FIBRINOLYSIN
Is the protein from the donor’s plasma,
the active factor of fibrinolysis
Is administered by intravenous infusion
has a direct action on fibrin
and dissolves fibrin clot in the first hours after its formation
Is used for the treatment of acute thrombosis, acute
miocardial infarction, thrombophlebitis
may cause bleeding resulting from an increase in
fibrinolysis, allergy, anaphylaxis, arrhytmia, hypotension
contraindicated in bleeding, a cerebral vascular accident,
recent trauma of the brain, surgery, noncontrolled hypertension
55
STREPTOKINASE
Is the proteolytic enzyme from hemolytic streptococcus
has a plasma half life of 23 min, is administered by
intravenous infusion (intracoronary infusion in myocardial infarction)
acts indirectly,
promotes the conversion of plasminogen to plasmin,
causes systemic activation of fibrinolysis
and degradation both of fibrin and fibrinogen
resulting in dissolving of the thrombus
is more potent than fibrinolysin
does not cause arrhytmia
56
ALTEPLASE (ACTILISE)
Is a tissue plasminogen activator,
product of biotechnology
has a half life of 5 min,
is administered by intravenous infusion
has a high affinity for fibrin
act selectively on plasminogen bound with thrombus
57
DRUGS THAT DECREASE PLATELET
AGGREGATION (ANTIAGGREGANTS)
–COX-inhibitors
Acetylsalicylic acid (aspirin)
–Inhibitors of phosphodiesterase
Dipyridamole
–Inhibitors of ADP-mediated aggregation
Ticlopidine (Ticlid)
Clopidogrel
58
Acetylsalicilic
acid blocks
synthesis of
thromboxane A2
by inhibiting
COX1
Dipiridamol
increases
cAMP
concentrations
in the platelets
that supresses
clotting
associated
with TXA2
Clopidogrel and
ticlopidine block
ADP-receptors in
the platelet
membrane
59
ANTI-PLATELET EFFECT OF ASPIRINE
Anti-platelet effect occurs in low doses
100-300 mg
The effect lasts more than 48 hrs (till 7 days)
Why?
The inhibition of COX-1 is irreversible
Platelets have no nucleus
and they can not synthesize new COX-1
So the platelet that has once contacted with
aspirin never would take part in blood clotting
60
And average period of platelet’s life is 7 days
ANTI-PLATELET EFFECT
OF DIPYRIDAMOLE
Dipyridamole inhibits adenosine desaminase and
phosphodiesterase in platelets,
increases cAMP concentrations in the platelets
and inhibits TXA2 synthesis
that leads to decrease in platelet aggregation
It also increases prostacycline level
Remember antianginal drugs!
Dipyridamole also increases myocardial oxygen
supply by dilating coronary vessels but causes
«stealing sydrome» - redistribution of coronary blood
flow in favour of the normal areas of myocardium with61 the
worsening of blood supply in the area of ischemia
ANTI-PLATELET EFFECT
OF TICLOPIDINE
Ticlopidine irreversibly blocks purinergic receptors
for ADP in platelet membranes
The inhibition of ADP-induced expression of
glycoprotein IIa/IIIa receptors in the platelet
membranes decreases platelet aggregation
62
Antiaggregants
• Dipyridamol
• Ticlopidine
• Acetylsalicylic acid
Pharmacodynamics - Indications
Antiaggregant
effect
Prophylaxis and
treatment of the
hypercoagulation
syndrome,
chronic coronary
insufficiency.
Prophylaxis of ischemic
stroke and
encephalopathies
Side effects
→
Contraindications
Bleedings,
Low blood coagulability, increased
thrombocytopenia permeability of vessels, peptic ulcer
63
THE PHARMACOLOGICAL “FACE” OF
ANTICOAGULANTS AND ANTIAGGREGANTS
Medicines
Heparin
Nadroparin*
Acenocumarol
Fenindion
Dipyridamol**
Ticlopidine**
Acetylsalicylic
acid
•
•
Route of
administration
i/v
i/m
s/c
s/c
per os
per os
per os, i/v
per os
per os
Onset of
effect
5 min
Duration of
effect
2-6 h
15-30 min
30-40 min
3-4 h
2-8 h
4-12 h
up to 6 h
24-48 h
10-24 h
2-4 days
24-72 h
1-2 days
20-30 min
8-10 days
up to 7 days
* - nadroparin is more safe than heparin;
** - dipyridamol`s activity is similar to aspirin, and ticlopidine is more active
than aspirin.
64
MEDICINES INCREASING BLOOD COAGULATION
(HEMOSTATICS, ANTIHEMORRHAGIC MEDICINES)
Medicines that increase blood coagulation
promote stopping bleedings
they may be used locally as well as for resorptive action
Classification of medicines
Antifibrinolytic
Hemostatics
agents (inhibitors
SystemicLocal-acting
of fibrinolysis)
acting
Aminocapronic
acid
Tranexaemic
acid
Trasylol
(Aprotinin)
Fibrinogen
Calcium
chloride
Menadion
Thrombin
Hemostatic
sponge
Coagulants of the
synthetic, animal,
plant origin
Vicasol
Gelatin medical
Water pepper herb
Nettle herb
65
MEDICINES INCREASING BLOOD COAGULATION
(HEMOSTATICS, ANTIHEMORRHAGIC MEDICINES)
The mechanism of action
Antifibrinolytic agents inhibit the action of plasminogen
and the action of plasmin;
suppress the kinins’ system and the activity of fibrinolysis
Hemostatics are the natural components of the blood
coagulation system.
Coagulants of the synthetic, animal and plant origin
decrease permeability of the vascular wall, increase the
blood viscosity, slow the blood flow, promote conditions
for forming thrombi
66
Pharmacodynamics (effects)
Hemostatic
effect:
stoppage or
decrease of
bleedings
→
Indications
Inhibitors of fibrinolysis: bleedings caused by the
increased fibrinolysis, thrombocytopenia, including
ones caused by peptic and duodenal ulcer, postnatal
bleedings
Hemostatics: bleedings in surgery, obstetrics,
traumatology caused by deficiency of blood
coagulation system factors: capillary, from
parenchymal organs, local bleedings
(nasal, extraction of teeth, etc.)
Coagulants of synthetic, animal and plant origin:
hemorrhagic diathesis, metrorrhagia, nasal, renal,
intestinal bleedings
Side effects
Increase of blood
coagulation
→
Contraindications
Predisposition to thrombosis, thromboembolism
67
THE PHARMACOLOGICAL “FACE” OF MEDICINES
INCREASING THE BLOOD COAGULATION
Medicines
The route of
administration
Other effects /
peculiarities
Aminocapronic acid
per os, i/v
Anti-inflammatory, anti-allergic
Fibrinogen
i/v, locally
Calcium chloride
Thrombin
Menadion
per os, i/v
It is a component of the blood
coagulation system
Hemostatic sponge
Carbazochrome
Nettle herb
locally
per os, i/m, i/v
locally
locally, s/c, i/v
per os
A synthetic water soluble vitamin
K analogue
A mixture of CaCl2 and thrombin
on the solid carrier
A synthetic solid
Anti-inflammatory,
capillary-stabilizing
68
PLASMA SUBSTITUTES
Classification
I. Salines:
- Isotonic NaCl (0,9%)
- Ringer-Loc sol.
- Acesol
- Trysol
II. Alkaline solutions:
- Sodium hydrocarbonate (NaHCO3)
III. Drug contains the components of human
blood:
- human albumin
- dry plasma
69
Classification
IV. Synthetic plasma expanders:
- Reopoliglukine
- Neogemodes
- Gekodes
V. Glucose:
- Isotonic Glucose sol. (5%)
- Hypertonic Glucose sol. (10-40%)
Indications for plasma expanders
• Salines: compensation for loss of fluid in burns,
diarrhea, vomiting; detoxification, drug
dissolution - antibiotics, analgesics, cardiac
glycosides; violations of water-salt state,
correction of hemodynamic.
Contraindications: threat of lung or brain
edema, closed head injury with intracranial
hypertension.
• Alkaline solutions: metabolic acidosis.
Indications for plasma expanders
- Drug contains the components of human blood:
hemodynamic instability in bleeding, burns, liver diseases, malnutrition in
children; protein deficiency, dystrophy, as an agents for detoxification and
substitutes in hemophilia B.
Side effects: allergic reactions, caused by individual hypersensetivity.
• Synthetic plasma expanders: blood loss, shock, burns,
microcirculation disturbances, peritonitis, sepsis, diseases of the liver,
intoxication in purulent and other diseases, prevention of thrombosis.
Side effects: allergic reactions, lowering of blood pressure.
• Glucose: (5% sol.) - replenishing the blood stream as plasma
substitute, normalization of blood osmotic pressure.
(10-40%) - dangerous swelling of tissues, brain, lungs;
hypoglycemia, infectious processes, degeneration and atrophy of the liver,
decompensated cardiac function, hemorrhagic diathesis, poisoning by
narcotic analgesics, hydrogen cyanide, carbon monoxide, aniline,
fosfogenom, shock and collapse.
Thank you!
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