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Antifibrinolytics
Plasma substitutes
Blood derrivatives
Haematopoietic growth factors
Veasoprotective drugs
Fibrinolysis
Starts simultaneously with coagulation (coagulum removal)
Plasmin plays major role, is present in inactive form in plasma, is
incorporated into coagulum bound on fibrin
So as to prevent decomposition of coagulum is α2-antiplazmin
(an bound on plasmin.
Plasmin is then (based on actual circumstances) activated by
means of activators: t-PA produced in endothelium
and u-PA (source: fibroblasts, epitelium,
pneumocytes, placentalcells etc.)
Fibrinolysis
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The role of t-PA is regulation of intravascular coagulation, u-PA
takes a part on proteolytic processes like tissue remodelation,
tumor invasion, oocyte nidation, embryogenesis…
u-PA is metabolized to form urokinase – enzyme present in urine
with the conserved ability to cleavage proteins
Activation of fibrinolysis is under the control of inhibitors of
plasmin activators PAI 1-3 and nexin.
Fibrinolysis
on the surface of fibrin is bound complex t-PA + plasminogen +
fibrin; activated fibrin is immediately inhibited by α2-
antiplasmine
coagulum is cleavaged after tPA is released due to hemostasis
- this leads to release of small amount of plasmin, which
disrupts fibrin structure and increase its surface and another
plasminogen may be bound
- this prevails the activatory processes and coagulolysis is
accelerated
Fibrinolysis
Fibrinolysis is balanced on the basis of ratio PA/PAI, which may
be influenced by numerous exogenous factors:
physical activity, stress, fear, anger, smoking
↑↑ levels if PAI is in the morning with simultaneous ↓↓ t-
PA
=> Most myocardial infarction occurs in the morning
Fibrinolysis
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Antifibrinolytics
Are preventing plasmin to bind on fibrin
Are used as adjuvants in coagulation factors supplementation
in bleeding after surgery (e.g. tonsilectomy); or in
stomatology surgery in haemophilic patients
AE: nausea
CI: DIC
ε-aminocapronic acid (EACA) ↓ plasminogen activation,
p.o., i.v.
tranexamic acid, RMP Exacyl
p-aminometylbenzoic acid; RMP Pamba)
aprotinin – protease inhibitor – in bleeding due to defective
fibrinolysis (antidote in fibrinolytics overdose ) CVS surgery,
pancreatitis
Plasma substitutes
= „plasma expanders“
Used for temporaray fluid substitution (to incr. volume)
(after bleeding, shock, hypovolaemia)
NOT in hypoxia, lack of ERYS (concentrate of ERYS,
transfusion)
Requirements: physiologically iniferent
AB ballance – neutral
sufficiently long lasting
effect
physiologically eliminated /excreted
colloid-osmotic pressure
prevent trans -infection
price
Volume efficacy of plasma
substitutes
Glucose
Saline
Coloid
ICT
30 l
Intersticial
9 l
i.v. approx
3 L
ECT 12 Lt
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• volume substitution→ intravascular liquid
substitution for haemodynamics normalization
(mostly sol. of colloids)
• liquid substitution → extracelular liquid
defficiency based on the negative water
balance (crystalloids)
• electrolytes substitutions → so as to compense
changes in ECF and ICF composition
(balanced crystalloids solution)
„Fluid management“
Plasma substitutes
crystalloids
hypertonic crystalloids
colloids a) non-human gelatine
dextran
starch
b) human albumin
plasma
blood derrivatives
Plasma substitutes
crystalloids
hypertonic crystalloids
colloids gelatine
dextran
albumin
starch
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Colloids
- influence coagulation
- risk of allergy and renal insufficiency
- More effective than crystalloids
- Shelf stable, affordable, cheap
- ↓ risk of transmission of infection
- Improve (or at least do not change) the rheological
properties of blood
- Improves microcirculation and thus tissue perfusion
- Reduces swelling
Plasma substitutes
GELATINE
- first used 1915
- derrived from hydrolyzed beef collagen
- GLY-PRO-hydroxyPRO
- 12 to 15 kDa fragments, cross links (polymers to 35 kDa)
- Circulation half-life about 4 hours
↑ Ca content (patients on digoxin!)
FDA banned 1978 (due allergic reaction)
Ethical issues: vegetarianism, muslims, hindu
risk of BSE not confirmed
Plasma substitutes
DEXTRAN
- Polysaccharide (Leuconostoc mesenteroides)
- Approximately 200,000 glucose units (1 → 6) = 1 molecule
dextran
- Formed by the hydrolysis of about 60 kDa fragments
- The efficiency of approx 6 -8 h, excreted in urine
low molecular weight fragments improve rheological properties
(reduced platelet aggregation ERYS +trombocytes)
Antigenic properties - can be resolved by use of low molecular
weight dextran (1kDa)
Increases coagulation, ↑sedimentation
Plasma substitutes
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Albumin (Human)
- 5%, 20%
- Less antigenic than plasma
- M.v. 66500 Da
- Binds water: 18 ml / g
- Areas of application: ascites puncture, neonatology,
plasmapheresis
Plasma substitutes
HES - hydroxyethyl starch
• 1 → 4 glycosidic bond
• M.W. 70/200/450 kDa
• origin: amylopectin component in corn starch
• affinity to endogenous glycogen, good biocompatibility
• hydroxyetylation: exchange of H for hydroxyethylic group
(CH3CH2OH) → prolonged halflife of volume effect + increased
solubility
Plasma substitutes
HES
- fragments excreted in the urine after splitting of
amylase
- together with albumin lowest risk of anaphylaxis
- profile of effect
improve blood flow
side effects: pruritus (accumulation RES), bleeding
complications
Plasma substitutes
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Blood derivatives
= ready made medicinal products derived from plasma
collected from donors at transfusion dept.
plasma is processed to the final form of blood products by
fractionation in specialized centers.
a) albumin
b) immunoglobulins
c) concentrates of coagulation factor
d) concentrates of inhibitors
• Fractionation - a special method of plasma cutting into
individual components
Raw material - fresh frozen plasma
Product - individual products
Testing of plasma - HBsAg, anti HCV, HIV
Testing of final product - PCR for HCV
Antiviral treatment - solvent detergent and heat treatment
Blood derivatives
Albumin
• Sterile solution containing 5% (250 ml, 100 ml, 50 ml)
or 20% (100 ml, 50 ml) protein
• Name: Human Albumin 20%
• Human Albumin 5%
• Indications
- treatment of circulating blood volume loss or
insufficient production of albumin
dosage:
100 ml 20% albumin increases the circulating blood
volume of 400 ml
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Imunoglobulins
• monomeric and dimeric immunoglobulin G
• packing: 2.5 g, 5.0 g, 10.0 g
• Tradename: Flebogamma IV liquid, Kiovig
• Indications: primary and secondary antibody
deficiency, prevention and supportive treatment of
infections, treatment response
in autoimmune diseases (ITP ...)
Prothrombin complex
• The concentrate of coagulation factors II, VII, IX, X,
admixture AT III, PC, PS
• Packaging: 200 I.U.; 600 I.U.; 1200 I.U.
• tradename: Prothromplex
• Indications: prophylaxis and treatment of diseases
accompanied by deficiency of coagulation factors
(hepatopathy, DIC, need of antagonizing
anticoagulant therapy ...)
Fibrinogen
• The concentrate of coagulation factor I
• Packaging: 1000 mg, 2000 mg
• tradename: Fibrinogen Immuno, Haemocompletan
• Indications: prophylaxis and treatment of congenital and
acquired deficiencies of coagulation factor I,
below 1.0 g / l - substituting for sepsis, invasive
procedures ...
below 0.6 g / l - substituting in the absence of
hemorrhage
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Antithrombin III
• The main inhibitor of thrombin and other activated
coagulation factors
• Packaging: 500 I.U., 1000 I.U.
• name: Antithrombin III
• indications: congenital deficiency of AT III (prevention
and treatment of TEN during high-risk situations surgery,
trauma, immobilization ...)
• acquired AT III deficiency (hepatopathy, sepsis, DIC,
drug deficit ...)
• substituting the AT III decrease below 70 %
Factor VIII
• Highly purified factor VIII concentrate
• Packaging: 250 I.U., 500 I.U., 1000 I.U.
• tradename: Fanhdi, Immunate Stim Plus
• Indications: prophylaxis and treatment of bleeding in
hemophilia A
• Dosage: 1 I.U. / kg increased levels of 1.5-2 % f.VIII
Factor IX
• Highly purified coagulation factor IX concentrate
• Packaging: 200 I.U.; 600 I.U.; 1200 I.U.
• tradename: Immunine
• Indications: prophylaxis and treatment of bleeding in
hemophilia B
• Dosage: 1 IU / kg f IX levels increase by 0.8 %
• Dose calculation: the desired value x weight
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Factor VII
• Concentrate of Coagulation Factor VII
• Packaging: 500 I.U.
• tradename: Factor VII Baxter
• Indications: prophylaxis and treatment of
bleeding, deficiency of f. VII
• Cave ! due to the short half-life required more
frequent application
von Willebrand factor
• Von Willebrand factor concentrate
• Packaging: 500 I.U., 1000 I.U.
• tradename: Haemate P
• Indications: von Willebrand's disease,
hemophilia A
Factor VIIa
• Recombinant activated factor VII
• Packaging: 60 kI.U. (1.2 mg)
120 kI.U. (2.4 mg)
240 kI.U. (4.8 mg)
• tradename: NovoSeven
• Indications: bleeding in hemophilia with
inhibitors, impaired thrombin generation from
different causes of bleeding
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DRUGS USED IN HAEMATOPOIESIS DISORDERS
Anaemia - different classification approaches
• Due to iron deficiency
• Due to lack of vitamin B12
• Due to lack of folic acid or. both
• Due to lack of pyridoxine
Anaema concerning changes of MCV (mean
corpuscular volume)
Microcytic MCV ≤ 80 fL
Normocytic MCV = 80-100 fL
Macrocytic (megaloblastic) MCV ≥ 100 fL
Physiological values
Men Women
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Megaloblastic anaemia
Anemia pernicious
(approx 80 % of megaloblastic
anaemias)
• It may also be induced by drug admin.! (e.g. azathioprin,
trimethoprim, PPI)
• The most important treatment goal: adjustment of
missing inventory vitamin
• Two forms of vitamin B12
cyanocobalamin
hydroxocobalamin
easily utilized for the cells
initial vitamin retention is better
Vitamins of megaloblastic anaemia
treatment
folic acid B12
Daily requirements 200 ug 5 ug
Reserves in the body 5-10.000 ug 3.000 ug
Total Reserve (days) 25-50 600
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Vitamin B12 in pernicious anaemia
• Dose of 1 ug/day parenterally induce
haematological remission
• Parenteral regime (2000 ug/6 weeks)
Oral treatment of pernicious anaemia
with vitaminm B12
 patients refusing injections
 patients with hypersensitivity
 impairment of haemostasis
• 1% B12 absorbed independently of the intrinsic factor
• single dose of 300-1000 ug
• need for more rigorous monitoring of patients
Treatment with folic acid
• Folic acid tablets 10 mg
• 1 mg tablets would be sufficient
• minimal toxicity
• Contraindications: untreated vitamin B12
deficiency
• B12 deficiency may develop during treatment
with folate
• neurological symptoms
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Anemie sideropenic
= a consequence of negative Fe
balance
Oral treatment with ferrous or
ferric preparations
• simpler, safer than parenteral treatment
• is safer than parenteral
• lower risk of overdose
• no risk of anaphylactic reactions
• potential for poisoning if abused
• long-term need substitution
Oral preparations with Fe
• divalent Fe + +
Fe-sulphate
Fe-fumarate
Fe-gluconate
Fe-chloride
• trivalent Fe + + +
ferric hydroxide
complex of Fe + + + hydroxide
polymaltose
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Bioavailability of Fe in oral treatment
• In the deficit, there is absorbed up to 15% of the
administered Fe
• Proportion absorbed is reduced after adjustment
deficit
• overdose risk only in hemochromatosis, (even in
asymptomatic heterozygotes)
• capsules, syrups, suspensions, drops, chewable
tablets
• Vit. C increases the bioavailability of orally
administered Fe
• Fiber, milk, coffee, tannins reduce the availability!
Oral preparations with Fe
Influencing Fe oral bioavailability
• Increased resorption
fasting
together with ascorbic acid (commonlyOrg.
acids)
with orange (citrus, fruits) juice
• Reduction of resorption
Food reduces absorption by up to 50%
especially with tea, milk or cereal
together with antacids -hydroxides of Al, Mg
and Ca salts
with cholestyramine
with tetracyclines
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Adverse effects of oral Fe
preparations
• GIT: heartburn (pyrosis), nausea, abdominal
pain, cramps up, diarrhea
(in the elderly rather constipation)
problems have approximately ¼ of patients
Dosing of Fe preparations
• Optimal initial dose of 200 mg Fe / day
leads to the maximum recovery of Hb
resorption up to 15% in a patient with
sideropaenia
• resorption decreases after treatment of Fe deficiency
• resorption is increased in formulations with modified
release
• The maintenance dose is lower (individual)
• In case of intolerance to try to form tablets, suspensions
or other salt of Fe
Toxicity of Fe
• Accidentally ingested Fe
• lethal dose in children 3-10 g
• mucosal ulceration, bleeding in the gastrointestinal tract
• The course of intoxication Fe
First stage: vomiting, diarrhea, melena, shock
2nd: transient improvement for 6-24 h
3rd: metabolic acidosis
4th: bowel obstruction
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Treatment of Fe intoxication
• always lavage 1% bicarbonate
• deferoxamine 3-5 g / 50 ml of water into the
stomach via gastric probe
• Systemically deferoxamine 1 g i.v. / i.m.
repeated after 4-6 hours
• or sc. / iv. infusion into max. dose 6 g / day
Treatment with parenteral Fe+++
Indications: failure of oral therapy
patient does not tolerate iron orally
inflammation / ulceration of the stomach
rapid loss of Fe (unidentified cause)
disorder of resorption in the GIT
• Local
pain at i.m. injection
sensitivity of the regional lymph nodes after
i.m. administration
painful veins after i.v. application, metallic taste
in mouth
• Systemic: early
anaphylactic reactions, hypotension, weakness,
headache, nausea
• Systemic: late
lymphadenopatia, myalgia, arthralgia, fever
AE of parenteral Fe administration
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Hematopoietic growth factors - erythropoietin
is produced by kidney cells in the juxtatubular apparatus
recombinant human erythropoietin - epoetin α
- epoetin β
difference is not clinically relevant
stimulates the formation of erythrocytes
Pharmacokinetics: given i.v., s.c. i.p.
effect even fastest after the i.v., greatest after s.c.
Side effects: flu-like syndrome
hypertension - encephalopathy, headache, disorientation,
convulsions
Fe deficiency
Increased viscosity, hematocrit (↑ thrombosis)
Main indications:
Anemia associated with chronic disease (e.g., renal insufficiency)
anemia associated with cancer chemotherapy
prevention of anemia of premature delivered newborns
chronic inflammatory conditions
Anemia in AIDS patients
Increasing the amount ERYS before autologous donation
Hematopoietic growth factors - erythropoietin
CSF = Colony-stimulating factors
factor stimulating granulocyte-macrophage colony (GM-CSF)
granulocyte colony stimulating factor (G-CSF)
platelet-stimulating factor (in development)
recombinant derrivates:
- Filgrastim (G-CSF)
- Lenograstim (G-CSF)
- Molgrasmostim (GM-CSF) (+ monocytes neutrophilic
granulocytes)
Hematopoietic growth factors - CSF
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CSF used in cancer centers during chemotherapy or after as
imunostimulans
- to stimulate stem cell release into circulation
- conventional anticancer therapy
- Intensive chemotherapy chemotherapy damaging
haematopoiesis
- therapy after bone marrow transplant
Neutropenia in HIV infection
Induction of progenitor cells ex vivo
aplastic anemia
Hematopoietic growth factors - CSF
Administration: s.c., i.v.
Generally well tolerated, though:
Side effects: fever, bone pain, muscle
lethargy, pain at the injection site
hypotension, tachycardia, nausea, vomiting, lack of O2
saturation, thromboembolism
Hematopoietic growth factors - CSF
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Vasoprotectives and drugs influencing
rheology of blood
Vasoprotectives (ATC C05) =
Drugs for the treatment of venous diseases,
especially chronic venous insufficiency.
Substances used for sclerotherapy of varicose
veins
Vasoprotectives
Drugs for the treatment of venous diseases
Indications: primary and secondary venous
insufficiency
local swelling of the limbs and of lymphatic origin
posttraumatic oedema
microangiopathy (e.g. diabetic angiopathy)
states with increased capillary fragility hemorrhoids
Contraindications: pregnancy and lactation?
Side effects: allergic skin reactions, dyspepsia,
headache
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Vasoprotectives
Drugs for the treatment of venous diseases:
varicose veins, vein inflammation, atherosclerosis,
venous ulcers
increase venous tone → lumen reduction in affected
veins, accelerating outflow (slow blood flow is one of
the main mechanisms of thrombosis).
improve microcirculation, reduce permeability and
fragility of capillaries and improve lymphatic
drainage.
Prevent swelling and improve trophics in tissue.
Drugs of the treatment of venous diseases
anti-inflammatory effect (tribenoside, calcium
dobesilate)
improve metabolism
Occasionaly are combined with dihydrogenated
ergot alkaloids (DH-ergocristin) arteriolodilating,
venotonic and capillarotonic
effect
Very often: flavonoids / flavonoid fraction
Vasoprotectives
Flavonoids
Currently over 2.000 flavonoids known
2 - fenylbenzopyren ring
normalize metabolism between blood and tissue
inhibit hyaluronate lyase = slow down
degradation of hyaluronidase - cleaves
proteoglycans extracellular space = accelerate
the absorption of edema, hematoma
most of flavonoids have antioxidant properties
(scavenger activity)
O
O
Vasoprotectives
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Vasoprotectives
- Drugs for the treatment of venous diseases
Rutin (rutoside) – Ruta graveolens (Herb-of-grace),
Sophora Japonica (Pagoda Tree) ,
Fagopyrum vulg., F. esculentum (common
buckwheat)
= glukorhamnoside of quercetin
O
O
OH
OH
OH
OH
O-Glc-Rha
Vasoprotectives
- Drugs for the treatment of venous diseases
Rutin (rutosid) – Ruta graveolens, Sophora Japonica,
Fagopyrum vulg., F. esculentum
= glukorhamnosid of quercetine
O
O
OH
OH
OH
OH
O-Glc-Rha
Vasoprotectives
- Drugs for the treatment of venous diseases
Rutin (rutosid) – Ruta graveolens, Sophora Japonica,
Fagopyrum vulg., F. esculentum
= glukorhamnosid of quercetine
O
O
OH
OH
OH
OH
O-Glc-Rha
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Troxerutine
MA:
Reduction of capillary filtration,
decr. microvascular permeability for proteins
reduce the gaps between endothelial cells, interendotelial matrix
modification
Increase adhesion of endothelial cells to the microvascular wall
Inhibit erythrocyte aggregation and increase their deformability
Improve microvascular perfusion and oxygen content in the skin.
reduce oedema
I: chronic venous insufficiency, idiopathic edema, liver cirrhosis,
diabetic retinopathy.
O
O
HO-CH2-CH2-O
OH
O-CH2-CH2-OH
O-CH2-CH2-OH
O-Glc-Rha
troxerutin
Vasoprotectives
- Drugs for the treatment of venous diseases
Quercetin – aglycone of Rutoside
Ruta graveolens, Sophora Japonica, Fagopyrum
Vulgate., F. esculentum
antioxidant, ROS scavenger
CVS smooth muscle relaxation
stimulation of adenosine release
O
O
OH
OH
OH
OH
OH
Vasoprotectives
- Drugs for the treatment of venous diseases
Hesperidin – pericarpium spp. Citrus
O
O
Rha-Glc-O
OH
OMe
OH
Vasoprotectives
- Drugs for the treatment of venous diseases
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Diosmine
flavonoid with anti-inflammatory and vasoprotective
effect
Hesperidin + diosmine
Improve the venous return in CVS
- at veins decreases venous stasis and reduces distenzibility
- normalize capillary permeability and increases capillary
resistance,
- increase the level of lymphatic flow
- incr. venous tone
O
O
Rha-Glc-O
OMe
OH
Vasoprotectives
- Drugs for the treatment of venous diseases
Diosmine
flavonoid with anti-inflammatory effect and
venoprotektivním
Hesperidin + diosmine
Improve the venous return in CVS
- At veins decreases venous stasis and reduces distenzibility
- Normalize capillary permeability and increases capillary
resistance,
- increase the level of lymphatic flow
- Enhances venous tone
O
O
Rha-Glc-O
OMe
OH
Vasoprotectives
- Drugs for the treatment of venous diseases
Esculin
Coumarin derivatives contained in the seeds
hippocastani (chestnut, horse-chestnut)
decreases the permeability of capillaries
reduces capillary fragility
anti-inflammatory effect
O OOH
O
Glc
Vasoprotectives
- Drugs for the treatment of venous diseases
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Esculin
Coumarin derivatives contained in the seeds
hippocastani (chestnut, horse-chestnut)
decreases the permeability of capillaries
reduces capillary fragility
anti-inflammatory effect
O OOH
O
Glc
Vasoprotectives
- Drugs for the treatment of venous diseases
Aescin
amorphous, water-soluble mixture of triterpene saponins,
sapogenin glycosides
Effects: antiedematous, anti-inflammatory,
vasoprotective
seals capillaries, normalizes the permeability, reduces
transcapillary transudation.
reduces the inflammatory response
decr. exsudative phase of inflammation
accelerates the absorption of traumatic hematoma
improves venous-lymphatic circulation
facilitates emptying of varicose veins in patients with
flebopathy
Vasoprotectives
- Drugs for the treatment of venous diseases
Aescin
O
CH2OHCH3
OH
CH2OH
O C
O
CH3
O C
O
CH3
H
CH3
Glc-Glc-Glukur. kyselinaGlc- Glc- Glucur. Ac.
Vasoprotectives
- Drugs for the treatment of venous diseases
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Astaxanthin
carotenoid
orange-red natural pigment
antioxidant, potentially venoprotective action
improves blood rheology
Vasoprotectives
- Drugs for the treatment of venous diseases
http://en.wikipedia.org/wiki/
Ginkgo bilobae extractum siccum normatum
Active ingredients: flavonoid glycosides, ginkoflavon
glucosides, ginkgolides, bilobalid
MA: different mechanisms,
are not yet cmpletely understood
Vasoregulatory, improve blood rheology,
antioedematous
effects and positive effect on the intracellular
metabolism (neurons).
↑ synthesis of ACh and release + ↑ number of
cholinergic rcp.
http://www.growsundews.com
Vasoprotectives
- Drugs for the treatment of venous diseases
Ginkgo bilobae extractum siccum normatum
Vasodilating effect in the arterioles (EDRF, eventually. PgI2),
experimentally reduces arterial spasm and increases venous
tone wall.
Increases capillary resistance and reduces capillary
hyperpermeability
Antioedematous effect.
Effect on intracellular metabolism: ↑ ATP and lactate
at the cortical level, utilization of oxygen and glucose,
inh. lipoperoxidation of cell
membranes and the production and the presence of free
oxygen and hydroxyl radicals.
Interactions !!
http://www.growsundews.com
http://da.wikipedia.org
Vasoprotectives
- Drugs for the treatment of venous diseases
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DH ergocrystin - semi-synthetic ergot alkaloid
partial agonist 1, antagonist of 5-HT receptors, no effect on
uterus
Improving the distribution of oxygen, weak vasodilatory effect
(arterioles)
Extends arterioles and precapillary sphincters,
increases venous tone by acting on the smooth muscle of blood
vessels and thus improves the supply of oxygen to the tissues.
Side effects: nasal congestion, headache, metrorrhagia
(Combination with Rutoside, esculine)
Vasoprotectives
- Drugs for the treatment of venous diseases
Tribenoside - a semisynthetic derivative of glycide,
glucofuranosid
decreases the permeability of capillaries =
antioedematous effect
antagonizes the effects of various
endogenous substances that play
important role as mediators of inflammation
and in the pathophysiology of pain.
O
O
O
OH
O
O
Vasoprotectives
- Drugs for the treatment of venous diseases
Calcium dobesilate
regulates impaired
the capillary walls,
reduces its permeability and increases its resistance.
reduces the degradation of collagen, reduces blood
viscosity and increases blood circulation,
improves lymphatic drainage and reduces swelling
S
OH
OH
O
O O S
OH
OH
O
OO
Ca2+
Vasoprotectives
- Drugs for the treatment of venous diseases
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Pentoxyfylin - semi-synthetic derivative of
methylxanthine
Directly relaxes arteriolar smooth muscle, or through inhibition of
PDE
reducing blood viscosity mainly in the microcirculation
improve blood flow and tissue oxygen saturation
Inhibits platelet aggregation and adhesivity
↑ ATP in erythrocytes, improves elasticity
anti-inflammatory and cytoprotective effect, the inhibition of
cytokine production (mainly tumor necrosis factor – TNF)
Vasoprotectives
- Drugs for the treatment of venous diseases
Naftidrofuryl - synthetic substance
musculotropic spasmolytic effect on the smooth
muscles of arteries, arterioles
reduces the tone and peripheral vascular resistance
improvement of blood circulation in the peripheral tissues (especially
CNS) reduces ischemic pain.
nicotine and bradykinin antagonist
stimulates energy metabolism and decreases the production of
neuron algogenic substances (lactic acid)
activates succinyldehydrogenase, increasing the supply of oxygen to
tissues, improves glucose utilization, increases the production of
ATP
O
NO
O
Vasoprotectives
- Drugs for the treatment of venous diseases
Sulodexide – medium- MW - glycosaminoglycan composed
of heparin (80%) and dermatan component (20%).
Antithrombotic effect (inhibition of factor Xa - activation of
antithrombin III)
Weak fibrinolytic effect (stimulation of tPA, PAI inhibition)
Lipolytic effects (activation of lipoprotein lipase)
Vasoprotectives
- Drugs for the treatment of venous diseases
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Sulodexide – medium- MW - glycosaminoglycan composed
of heparin (80%) and dermatan component (20%).
• reduction of plasma viscosity
• protective and reparative effects on the endothelium, prevents
adhesion of platelets, lymphocytes, monocytes and neutrophils to
the vascular wall
• supports neoangiogenesis and enhances the natural
antithrombotic properties of endothelium
Vasoprotectives
- Drugs for the treatment of venous diseases
A number of products registered for more than 30 years ago
Venoprotective effects are sometimes considered controversial in
recent years; there has been a revision of medicinal products
containing venoprotective drugs concerning payment from
general health insuarance system
Evaluation of the quality of evidence on the effectiveness
A – Calcium dobesylate, micronised purified flavonoid fraction
(hesperidine, diosmine), hydroxyethylruotsides
B – escin, ruscucs extr.
C - troxerutin, extr. Ginkgo bilobae
Vasoprotectives
- Drugs for the treatment of venous diseases
LIMITATIONS
Drugs for sclerotherapy
- Injected into the varicose distended vein
- subsequent proliferation of fibrous tissue occurs and this cause
obliteration of varices.
CI: intraarterial administration; oral contraception,
in pregnancy and lactation.
Side effects: allergic skin reactions, pain at the injection site,
necrosis after extravasal administration and pain.
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30
Drugs for sclerotherapy
Polidokanol v 0,5-3% conc. (lauromacrogol 400)
- administration-compression-physical activity
- may be repeated after 7 days
Tetradecylsulphate sodium
LITERATURE:
• Lincová, Farghalli: Základní a aplikovaná farmakologie, Galén,
• Lullman, Mohr, Wehling: Farmakologie a Toxikologie, Avicenum
• Rang & Dale´s Pharmacology, 7th ed.
• Farmakoterapeutické informace 6/2009, SÚKL
• Martínková, Mičuda, Cermanová Vybrané kapitoly z klinické farmakologie
pro bakalářské studium : Kardiovaskulární systém
• Miroslav Tomíška: Léčba Anemie Interní hematoonkologická klinika FN
Brno
• Igor Sas: Možnosti objemové náhrady v intenzivní péči, KARIM, FN Brno
• Roman Gál: Využití želatiny v anesteziologii a intenzivní péči, evropská
doporučení. KARIM, FN Brno
• Pavel Těšínský: Charakteristiky, indikace a použití substrátů pro objemovou
terapii, II. interní klinika FNKV a 3. LF UK Praha
• www.sukl.cz
• Infopharm, AISLP