Pharmacology of drugs acting on blood and
blood forming organs
Dr Urmila M. Aswar,
Sinhgad Institute of Pharmacy,
Narhe, Pune -41
Hemostasis: is a process which causes
bleeding to stop, meaning to keep blood
within a damaged blood vessel (the
opposite of hemostasis is hemorrhage)
Clotting disorders is a term used to
describe a group of conditions in which
there is an increased tendency, often
repeated and over an extended period of
time, for excessive clotting.
hypercoagibility. It affects a large number
of people around the world. It affects
approximately 5% to 7% of the European
Intrinsic pathway : all factors needed for
Blood coagulation are in plasma. Slow
process as lot many factors are needed to
Extrinsic pathway: also needs tissue
factor-thromboplastin. Occurs with in
Can be in artery or vein.
Symptoms depend on
Where it has formed
Is it a emboli
There are different terms used to further
define these thrombotic episodes, such as
deep vein thrombosis (DVT) or peripheral
vascular disease, when the clots are in the
arterial system (usually in the extremities).
Women are more sensitive
Pregnancy, oral contraceptives and postmenopausal hormone replacement
therapy are all triggering events for DVT
in women with thrombophilia.
Factor V Leiden: hypercoagulation
factor V Leiden
Discovered in Leiden city of Neitherland
Factor V is responsible for activation of
factor X and XII which further stimulates
There is mutation in the gene responsible.
So that PK C couldn’t degrade factor V. so
it is over activity of factor V.
Used in vitro
Ca complexing agents
Used in vivo
Heparin: LMW heparin
Oral anticoagulants: 1. Coumarin
2. Indandione derivatives: Phenindione
Isolated from liver
Present in mast cells
Present in lung, liver
Activating antithrombin III
Binds to intrinsic clotting factors: Xa, IIa,
IXa, XIa, XIIa, XIIIa and blocks their
No effect on VIIa of extrinsic pathway.
It inhibits conversion prothrombin to
thrombin by Xa.
Also it inhibits conversion of fibrinogen to
fibrin, Inactivates IIa.
Low concentration interfere with intrinsic
High affect both.
It inhibits platelet aggregation
It releases lipoprotein lipase from liver
and clears VLDL, chylomicrons and
triglycerides from plasma.
As it large inonized molecule, Not
Does not cross BBB or placenta
T1/2: 1 hr
Units: 1U : the amt of heparin that will
prevent 1 ml of citrated sheep plasma
from clotting for 1 hr after addition of 1%
Heparin sod: 1 mg has 120-140U of
Given IV 5,000-10,000U adults every 4-6
Infusion given (750-1000U) till bleeding
Children: 50-100 U/kg
Ocular and neurosurgery
Aspirin and other antiplatelet drugs
LMWHs, in contrast, consist of only short
chains of polysaccharide. LMWHs are
defined as heparin salts having an average
molecular weight of less than 8000 Da.
These are obtained by various methods of
fractionation or depolymerisation of
LMWHs have a potency for factor Xa
activity and for anti-thrombin activity (ATIII).
More specific in action
Less effects on platelets
Less hemorrhagic complications.
Good p’kinetic profile
Dose is given in mg and not in unit
LAB MONITORING NOT NEEDED.
Deep vein thrombosis
Eg Nadoparin, Enoxaparin, Dalteparin,
It is a synthetic pentasacchride. It is an
antithrombin III mediated selective inhibition
of factor Xa. Which further inhibits thrombin
Administered s.c daily.
Dose: 2.5 mg
T1/2: 17-21 hrs
Excreted unchanged in urine
Lesser antiplatlet action chances of
thrombocytopenia is less.
Bishydroxycoumarin was made in 1941
Warfarin was used as anti-cogulant In vivo only.
They act by interfering with synthesis of vit K
dependent clotting factors.
They behave as competitive inhibitors of vit K.
They interfere with regeneration of active form of
vitamin K, which is essential for carboxylation of
clotting factors- VII, IX, X.
Vitamin K is involved in the carboxylation of
certain glutamate residues in proteins to form
Caroboxylation enhances binding of clotting
factors to Ca2+ leading to coagulation.
Reduced Vitamin K
Oxidised Vitamin K
Synthesis of clotting factors diminishes within 2-4
hrs of warferin administration the anticoagulant
effects develops gradually over next 1-3 days.
Therapeutic effect occurs when synthesis of
clotting factors is reduced by 40-50%.
Pharmacokinetics: Racemic warferin sodium:
the most popular oral anticoagulant.
R+S, S is more potent, metabolized by oxidation.
Completely absorbed from stomach.
99% is plasma bound.
It crosses placenta and secreted in milk.
Metabolism is dose dependent
T1/2 is prolonged at higher doses
Has poor GI tolerance
Available as 50 mg tab
T1/2 of 8 hrs. produces an active
T1/2: 24 hrs.
Factors enhancing effect of oral
Prolonged antibiotic use
Liver disease : low synthesis of CF
Newborns: low CF
Hyperthyroidism: Fast degradation of CF
Factors decreasing the effect of oral
Nephrotic syndrome: drug bound to
plasma protein is lost in urine.
Pregnancy: skeletal abnormalities, foetal
warfarin syndrome– hypoplasia of nose,
eye socket, hand bones and growth
If given in later stage of pregnancy, it can
cause CNS defects, foetal death.
Enhanced anticoagulant action
1. Braod spectrum antibiotics
2. Newer cephalosporins eg moxalactam,
hypoprothrombinemia by the same
mech. as warfarin.
3. Aspirin: inhibits platelet aggregation, also
displaces warfarin from PBS.
4. Phenylbutazone: Decreases PB of
Long acting sulfonamides, indomethacin,
phenytoin, probenicids: competitor for
Chloramphinicol, erthromycin, cimetidine,
allopurinol, amidarone, metronidazole:
inhibits warferin metabolism
Tolbutamide and phenytoin: inhibits
Phenformin, anabolic steroids, quinidine,
clofiberate, potentiate warferin action
Liq paraffin: reduces vit K absorption.
Reduced anticoagulant action
Barbiturates and other hypnotics (not
BZD), rifampin, grisofulvin induce
metabolism of oral anticoagulant
Oral contraceptives increases level of
Deep vein thrombosis and pulmonary
embolism: venous thrombi are fibrin
thrombi- 3 month therapy
Post stroke required prophyllaxis.
Myocardial infarction: arterial thrombi are
platelet thrombi. Not very beneficial.
Aspirin+heparin followed by warfarin.
Rheumatic heart disease, auricular flutter:
Warfarin/ low dose heparin/ low does
Cerebrovascular disease: little value
Preferred in ischaemic attacks due to
Vascular surgery, prosthetic heart valves,
retinal vessel thrombosis: anticoagulants
are given along with antiplatelet drugs for
prevention of thromboembolism.
These drugs are used to lyse the clot.
Fibrin is formed
Fibrinolytic system get activated
t-PA activates Plasminogen---Plasmin is
the serine protease which digest fibrin
Plasminogen is present in bound (fibrin)
and free form.
Obtained from Streptococci C
T1/2: 30-80 m
Isolated from human urine
Prepared from human kidney cells
Activates plasminogen directly
T1/2: 10-15 m
Side effects: Less allergic
Produced by recombinant DNA tech.
Activates plasminogen bound to fibrin.
T1/2: 4-8 m
Therapy to be initiated 12 h of symptoms
Can be given IV
Heparin or aspirin is started thereoff
Deep vein thrombosis
Peripheral arterial occlusion
To be treated with in 72 hrs advised if
throbectomy is not possible
Aspirin is indicated as prophylaxis against
transient ischemic attacks, myocardial
infarction and thromboembolic disorders.
It is also used for the treatment of acute
coronary syndromes and in the
prevention of reoclusion in coronary
Dose: 75 mg to 325 mg
Ticlopidine is the oldest thienopyridine
currently available. It is approved for
secondary prevention of thrombotic
strokes in patients intolerant of aspirin
and for prevention of stent thrombosis in
combination with aspirin.
Clopidogrel is approved for prevention
of atherosclerotic events following recent
established peripheral arterial disease. It
has a better safety profile than ticlopidine.
Dipyridamole acts as vasodilator and
phosphodiesterase in platelet leading to
increase in cAMP in platelet. Adenosine
decreases platelet aggregability.
It is used in combination with aspirin or
Platelet membrane GPIIb-IIIa receptors
constitute the final common pathway of
platelet aggregation, the integrin
GPIIb/IIIa antagonists prevent crosslinking of platelets.
Abciximab is a human-murine monoclonal
antibody directed against GPIIb/IIIa,