Cardiovascular agents

1
Cardiovascular agents

• anticoagulants

2
Platelet aggregation is affected by two factors
(1) In platelets thromboxan A2 is synthesized to
induce platelet aggregation, while (2) In blood
vessels prostacyclin PGI2 is synthesized to
inhibit platelet aggregation.
VIT.K is required in the liver biosynthesis of
prothrombin (factor II), thromboplastin (factor
III) is released from the injured cells and
tissues. Thromboplastin in presence of Ca2
(factor IV) convert Prothrombin to Thrombin which
consequently convert Fibrinogen (factor I) to
fibrin The main uses
of anti coagulants is to prevent blood
coagulation in myocardial infarction, venous
thrombosis, peripheral arterial emboli, pulmonary
emboli and atrial fibrillation. .
3
Heparin is a mucopolysaccharide, acidic in
nature ( Heparinic ) and used as sodium
salt. Heparin combines with coagulant factor (
antithrombin III ) forming Heparin-antithrombin
III complex which inactivate factor Xa and
consequently inhibit the generation of
Thrombin. The antidote of Heparin is protamine
sulfate Heparin is the best anticoagulant during
pregnancy, so it doesn't cross the placental
membrane. Heparin is also used with the patients
suffering from renal failure and used only during
the hemodialysis on artificial kidney units.
4
Classes of oral anticoagulants 4-Hydroxycoumarin
derivatives Warfarin sodium, Dicumarol and
Ethylbiscoumacetate.
1,3-Indandiones phenindione and ansindione
competitive inhibitors of vit.k in the
biosynthesis of prothrombin in the liver and
produce abnormal prothrombin. This attributed to
the structural similarity between the hemiketal
form of vit.k and the cyclic hemiketal of
4-hydroxycoumarin e.g. Warfarin.
5
Warfarin sodium
3-( acetonylbenzyl)-4-hydroxycoumarin sodium
salt.
Warfarin contains chiral benzylic carbon, and the
more potent isomer is the S isomer ,but it is
marketed as sodium salt of racemic mixture.
6
Dicumarol
3,3-Methylene bis (4-hydroxycoumarin)
7
Ethylbiscoumacetate
Ethyl bis (4-hydroxy-2-oxo-1(2H)-benzopyran-3-yl)a
cetate
8
(No Transcript)
9
1,3-indandione
This group of anticoagulants includes Phenindione
and Anisidione which are appears of the same
potency, substitution of methoxy group of
Anisindion with bromine increase the activity,
while nitro-group decrease the activity.
10
Phenindione
2-Phenyl-1,3-indandione
Ansindione
2-(p-Methoxyphenyl)-1,3-indandione
11
synthesis of phenindione
12
The enol-form of 1,3-indandione is a highly
conjugated compound and may be responsible for
the red colour of urine with patients who take
this drugs, this color is removed by urine
acidification to be distinguished from hematuria.
1,3-indandione inhibits the synthesis of
prothrombin and other coagulating factors.
13
assay of indandione derivatives
14
Antiplatelet agents
This group includes Aspirin, Dipyridamole,Sulfinp
yrazone and Ticlopidine.
15
Sulfinpyrazone
is related to phenylbutazone, but is used as
uricosuric and antiplatelet. It is a
cyclooxygenase inhibitor.
1,2-diphenyl-4-(2-(phenylsulphinyl)ethyl)-3,5-pyra
zolidindione
16
Ticlopidine
is a newer oral antiplatelet drug that is not a
NSAID. It works by inhibiting the aggregation
effect of ADP on the platelets.
17
Clot Busting Drugs
Blood clots are designed to be temporary. After
the vessel is healed and the blood clot is no
longer needed, the clot is removed by the
following way the clot itself stimulates the
secretion of tissue plasminogen activator (TPA),
which catalizes the activation of plasminogen to
plasmin which is an enzyme that dissolves clots.
18
Drugs used clinically to remove clots
include Tissue plasminogen activator (TPA), it
was recently cloned and is now produced as
Alteplase or Reteplase. It is used clinically to
dissolve clots in coronary arteries following a
heart attack. It is also used to dissolve clots
in the brain following stroke. Streptokinase, it
is an enzyme that directly dissolves blood clots.
It is produced by streptococcus bacteria. The
bacteria use streptokinase to dissolve clots that
negatively affects their growth in the human
host. However, streptokinase is not a human
enzyme and might initiate immune response.