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MEDICINES AFFECTING THE BLOOD SYSTEM

Kharkov National Medical UniversityDepartment of Pharmacology and Medical Prescription

assistant Gordiychuk D.

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•Peripheral blood (circulating in vessels)•Bloodforming (Hemopoietic) organs:

the red bone marrow,

lymphatic nodes, and

spleen•Bloodbreaking organs (liver, spleen)•Neurohumoral regulation system

THE SYSTEM OF BLOOD CONSISTS OF:

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BLOOD CONSTITUENTS

Drugs acting on haemopoiesis

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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

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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

DISORDERS OF ERYTHROPOIESISANEMIAS

Anaemia is a decrease of erythrocytes and/or hemoglobin in blood

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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 a common problem, especially for women

5% of women between the ages of 20 and 49 have iron deficiency with anemia and 11% have iron deficiency without anemia

1. IRON DEFICIENCY ANEMIA

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SYMPTOMS OF ANEMIA

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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

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Step 2 in blood

only Fe2+ is included in hemoglobin

but Fe3+ is transported by

transferrin !

IRON METABOLISM:

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For parenteral – only Fe3+ !

What iron compounds should be used as drugs for parenteral administration: Fe2+ or Fe3+ ?

PHARMACOLOGICAL CORRECTION OF THE HYPOCHROMIC ANEMIA -

IRON SUPPLEMENTATION

and for peroral – Fe2+ and Fe3+ is possible

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NB! Iron-containing drugs for peroral administration should never be administered at one time with iron-containing drugs for parenteral administration !

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 !

Why ?

Desferal is an antidote for iron

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Erythropoiesis stimulants (antianaemics)1. IRON-CONTAINING MEDICINES

FOR ENTERAL ADMINISTRATION

Fe2+ compoundsFerrous sulphate

Ferro-gradumet

Ferrous glucanate

Fe3+ compoundsFerrous saccharate

Ferrous hydroxide polymaltose complex

Ferrous protein-acetyl-aspartylate

Combined drugs:

Ferroplex

Feramide

Hemopheron

Sorbifer durules

FOR PARENTERAL ADMINISTRATION

Fe3+ compounds

Ferrous hydroxide polymaltose complex

Ferrous saccharate

Ferrum-lek (dextrane containing complex)

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Pharmacodynamics (effects) → IndicationsIncreases amount of the erythrocytesIncreases saturation of erythrocytes

by haemoglobin Improvement of the tissues

oxygenationThe reduction of symptoms of anemia

(weakness, paleness, tachycardia etc.) which begins in 5-7 days after the start of treatment

Prevention and treatment

of iron deficiency

in hypochromic anaemias

IRON-CONTAINING MEDICINES

Iron-containing medicines are donors of an iron ion and stimulate the synthesis of haemoglobin

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Side effects → ContraindicationsDyspepsia, 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

IRON-CONTAINING MEDICINES SIDE EFFECTS

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• 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 suppression

2. B12-DEFICIENCY AND FOLIC ACID DEFICIENCY ANAEMIAS

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Possible symptoms of hyperchromic anemia:

• Disorders of peripheral sensitivity or tingling

• Glossitis

• CNS disorders (loss of balance, personality changes)

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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

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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

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CYANOCOBALAMINE (VITAMIN B12) PROPERTIES

• 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 decreases disturbances in tongue mucosa

The mechanism of actionpromotes the synthesis of the DNA Intensifies the cells’ division

and the formation of erythrocytesas well as other highly divisible cells

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INDICATIONSFOR CYANOCOBALAMINE

(VITAMIN B12)

Hyperchromic megaloblast anemia

Hypoplastic anemia

Radiation sickness

Neurological diseases

Liver diseases

Dystrophy in children

Glossitis

Side effects: allergy, hypercoagulation, tachycardia, pain in the heart, worsen in angina pectoris

FOR FOLIC ACID (VITAMIN Bc)

Hyperchromic megaloblast anemia

Chronic gastro-enteritis

In pregnancy for the prophylaxis of neurological pathology of the fetus and newborn

Note that folic acid in hyperchromic anemias should be used only in combination with B12!

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Erythropoietin is the glycopeptide hormone that stimulates erythropoiesis

It is produced by kidneys as a response for hypoxiaThe 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

ERYTHROPOIETIN

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Pharmacodynamics (effects) → Indications Increase in erythrocytes and reticulocytes amount, increase in the level of hemoglobin

Anaemias caused by the chronic renal insufficiency, HIV- infection, after usage of cytostatics, in preterm born infants, hypo- and aplastic anaemias

Side effects → Contraindications Increase of BP Hypertension

The mechanism of actionStimulation of proliferation and differentiation of cells of the red bone marrow because of activation of the specific erythropoietin’s receptors

ERYTHROPOIETIN

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-Sodium phosphate solution labeled by phosphorus-32 --Imiphos

The mechanism of actionsuppresses the erythropoietic part of the bone marrow

Side effect: Anemia

Contraindications: Erythropenia, HIV-infection

ERYTHROPOIESIS INHIBITORS

Indication:Erythremia - it is an increased amount of immatured, inferior erythrocytes in blood because of their increased production by the red bone marrow

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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

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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 tissue.

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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

DISORDERS OF LEUKOPOIESIS AND THEIR CORRECTION

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Leukopoiesis stimulants –Nucleic acid derivatives Sodium nucleinate– Pyrimidine derivatives Methyluracilum Pentoxilum– Colony-stimulating factors (CSF) Lenograstim Molgrastim

The mechanism of actionThey bind to specific receptors of myeloid cell-precursors of the neutrophilic group, which are necessary for the matured leukocytes formation. It leads to increase of the matured leukocytes synthesis.

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Pharmacodynamics (effects) → Indications

Leukopoiesis stimulants: the increase of the matured leukocytes amount in blood

Leukopenia including those caused by the therapy with antitumour medicines, radiation sickness, HIV-infection

Side effects → Contraindications

Leukopoiesis stimulants: dyspepsia

Diseases of the GIT

Leukopoiesis stimulants

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Leukopoiesis inhibitors

Methotrexate

Mercaptopurine

Prednisolone

Leukopoiesis inhibitors that suppress the formation of leukocytes.

Pharmacodynamics (effects) → Indications Leukopoiesis inhibitors: decrease of the leukocytes amount in blood

Leukemias, lymphogranulomatosis

Side effects → Contraindications Leukopoiesis inhibitors: inhibition of hemopoiesis, dysfunction of liver and kidneys

Leukopenia, anaemia, thrombocytopenia, diseases of liver and kidneys

Teratogenecity and embryotoxicity Pregnancy, lactation

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Drugs acting on haemostasis

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• Place of formation – the red bone marrow

• Period of life – 8-12 days

• Function:

The blood clotting

THROMBOCYTES

Physiological propertiesPhysiological properties::AdhesionAdhesion – – ability to stick to the foreign and damaged surfaceability to stick to the foreign and damaged surface

AggregationAggregation – – ability to form a clump (cork)ability to form a clump (cork)

AgglutinationAgglutination – – pasting of thrombocytes one with anotherpasting of thrombocytes one with another

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damage of vessels 1 phase of blood clotting – vasoconstriction

2 phase – formation of thrombocytes cork

3 phase – thromb (clot) formation from fibrin

(marked yellow) and blood cells

THE BLOOD CLOTTING

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COAGULATION HEMOSTASIS

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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)

FIBRINOLYSISIt is the process of fibrin dissolution

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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

PATHOLOGY OF HEMOSTASIS AND FIBRINOLYSIS

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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

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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

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Direct-acting anticoagulants

Systemic-acting Local-acting

HIGH MOLECULAR HEPARINS HeparinLOW MOLECULAR HEPARINS

Calcium adroparin

Fraxiparine

Heparin ointment

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.

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Pharmacodynamics (effects) → Indications Direct-acting anticoagulants

Anticoagulant (inhibition of blood coagulation at all phases)

Myocardial infarction, direct blood transfusion, surgery on the heart or vessels. Prophylaxis and treatment of embolism and vascular thrombosis

Fibrinolysis activation, improvement of blood rheological properties

Prophylaxis of thrombosis after coronary vessels shunting and prosthetics of the heart valves

Antiaggregant (inhibition of adhesion and aggregation of thrombocytes and erythrocytes, normalization of the blood rheological properties, improvement of microcirculation of the brain, myocardium, retina etc.)

Thrombophlebitis, hypercoagulation syndrome

Hypolipidemic (decrease of the lipid level in blood)

Prophylaxis and treatment of atherosclerosis

Coronarodilating (improvement of blood circulation in the coronary vessels)

Myocardial infarction, stable angina of tension

Immunosuppressive Direct blood transfusion, surgery on the heart or vessels, rheumatism, bronchial asthma, glomerulonephritis, hemolytic anemia, renal transplantation, endocarditis

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HeparinMechanism 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.

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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

HEPARINE PHARMACOKINETICS

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SIDE EFFECTS OF HEPARINEBleeding

Hematomes

Micro- and macrohematuria

Thrombocytopenia

Allergy

Osteoporosis

Hair silvering

Protamine sulfate is an antidote for heparin

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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

FRAXIPARINE

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Factor Xa ihibitors

• Rivaroxaban• ApixabanMechanism: 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

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Warfarin

Ethyl bisoumacetate

Acenocumarol

Fenindion

Indirect-acting anticoagulants have no influence on coagulation factors directly in the bloodThey supress the biosynthesis of coagulation proteins (proconvertin and prothrombin) in the liver as a result of antagonism with vitamin K.

The mechanism of action

INDIRECT-ACTING ANTICOAGULANTSNote that these

drugs are vitamin K antagonists!

Pharmacological effects

─ a decrease in blood coagulation ─ an increase in fibrinolysis─ a decrease in lipids concentration in blood

Oral Anticoagulants Vitamin K Antagonists (Coumarins)Vitamin K Antagonists (Coumarins)

• Vitamin K is co-factor for the hepatic synthesis of clotting factors II, VII, IX & X

Vit. K Vit. K epoxide (active form)

By Vit.k reductase

warfarin

Warfarin inhibits Vit. K reductase no active form of Vit. K no synthesis of clotting factorsWarfarin inhibits Vit. K reductase no active

form of Vit. K no synthesis of clotting factors

Vitamin K AntagonistsWarfarin

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 Hepatic disease(↓ clotting factors)&

hyperthyroidism (↑ basal metabolic rate)

Inhibiting Warfarin Vitamin K in some

parenteral feed Inducers of hepatic P450

enzymes (rifampicin, barbiturates, … etc)

Reduction of GIT absorption (cholestyramine)

Diuretics Hypothyroidism

*Cephalosporins potentiate warfarin’s effect by killing vit.k producing normal flora

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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

Side effects:BleedingForming of hematomes

Hematuria

Dyspepsia

Supression of the liver function

Allergy

Nb!

Index of prothrombin

(laboratory value) should be

controlled for the safety of the

therapy!

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Pharmacodynamics - Indications

Fibrinolytic - dissolution of fibrin filaments of the recent (up to 3 days) thrombs

Venous and arterial thrombosis, acute myocardial infarction, pulmonary embolism

FIBRINOLYTIC DRUGS (THROMBOLYTIC DRUGS)Direct-acting: Fibrinolysin

Indirect-acting: Urokinase

Streptokinase

Alteplase

Note that these drugs are able to produce the lysis of the blood clot!

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)

The mechanism of action

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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

FIBRINOLYSIN

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Is the proteolytic enzyme from hemolytic streptococcushas 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 fibrinolysindoes not cause arrhytmia

STREPTOKINASE

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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

ALTEPLASE (ACTILISE)

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DRUGS THAT DECREASE PLATELET AGGREGATION (ANTIAGGREGANTS)

–COX-inhibitorsAcetylsalicylic acid (aspirin)

–Inhibitors of phosphodiesterase Dipyridamole

–Inhibitors of ADP-mediated aggregationTiclopidine (Ticlid)Clopidogrel

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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

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Anti-platelet effect occurs in low doses

100-300 mg

The effect lasts more than 48 hrs (till 7 days)

ANTI-PLATELET EFFECT OF ASPIRINE

The inhibition of COX-1 is irreversible Why?

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

And average period of platelet’s life is 7 days

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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 with the worsening of blood supply in the area of ischemia

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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

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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, thrombocytopenia

Low blood coagulability, increased permeability of vessels, peptic ulcer

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THE PHARMACOLOGICAL “FACE” OF ANTICOAGULANTS AND ANTIAGGREGANTS

• * - nadroparin is more safe than heparin;• ** - dipyridamol`s activity is similar to aspirin, and ticlopidine is more active

than aspirin.

Medicines Route of administration

Onset of effect

Duration of effect

Heparin i/v 5 min 2-6 h

i/m 15-30 min 2-8 h

s/c 30-40 min 4-12 h Nadroparin* s/c 3-4 h up to 6 h Acenocumarol per os 24-48 h 2-4 days Fenindion per os 10-24 h 24-72 h Dipyridamol** per os, i/v Ticlopidine** per os 1-2 days 8-10 days Acetylsalicylic acid

per os 20-30 min up to 7 days

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Medicines that increase blood coagulation promote stopping bleedings they may be used locally as well as for resorptive action

Antifibrinolytic agents (inhibitors

of fibrinolysis)

Hemostatics Coagulants of the synthetic, animal,

plant origin Systemic-acting

Local-acting

Aminocapronic acidTranexaemic acidTrasylol (Aprotinin)

Fibrinogen

Calcium chloride

Menadion

Thrombin

Hemostatic sponge

Vicasol

Gelatin medical

Water pepper herb

Nettle herb

MEDICINES INCREASING BLOOD COAGULATION(HEMOSTATICS, ANTIHEMORRHAGIC MEDICINES)

Classification of medicines

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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

MEDICINES INCREASING BLOOD COAGULATION(HEMOSTATICS, ANTIHEMORRHAGIC MEDICINES)

The mechanism of action

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Pharmacodynamics (effects) → Indications

Hemostatic effect: stoppage or decrease of bleedings

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 → Contraindications

Increase of blood coagulation

Predisposition to thrombosis, thromboembolism

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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 It is a component of the blood coagulation system

Calcium chloride per os, i/v

Thrombin locally

Menadion per os, i/m, i/v A synthetic water soluble vitamin K analogue

Hemostatic sponge locally A mixture of CaCl2 and thrombin on the solid carrier

Carbazochrome locally, s/c, i/v A synthetic solid

Nettle herb per os Anti-inflammatory,

capillary-stabilizing

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PLASMA SUBSTITUTESClassification

I. Salines:- Isotonic NaCl (0,9%)- Ringer-Loc sol.- Acesol- TrysolII. Alkaline solutions:- Sodium hydrocarbonate (NaHCO3)III. Drug contains the components of human

blood:- human albumin- dry plasma

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.

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Thank you!