Coagulation Disorders and Dyslipidemias

1. Dr.M.Usman Khalid
DPT,MS-NMPT

2.  The drugs used in clotting and
bleeding disorders fall into 2 major
groups: (1) drugs used to decrease
clotting or dissolve clots already
present in patients at risk for
vascular occlusion and (2) drugs
used to increase clotting in
patients with clotting deficiencies.

4.  Heparin is a large sulfated
polysaccharide polymer obtained
from animal sources. Each batch
contains molecules of varying size,
with an average molecular weight
of 15,000–20,000.
 Heparin is highly acidic and can be
neutralized by basic molecules (eg,
protamine). Heparin is given
intravenously or subcutaneously to
avoid the risk of hematoma
associated with intramuscular
injection.

5.  Complexes with antithrombin III
 • irreversibly inactivates the
coagulationmfactors thrombin and
factor Xa

6.  Venous thrombosis,
 pulmonary embolism,
 myocardial infarction,
 unstable angina, adjuvant to
percutaneous coronary
intervention (PCI) and
thrombolytics

7.  Bleeding (monitor with aPTT,
protamine is reversal agent)
• thrombocytopenia
• osteoporosis with chronic use

8.  Rivaroxaban:
 Binds to the active site of factor Xa
and inhibits its enzymatic action.
 USES: Venous thrombosis,
pulmonary embolism, prevention
of stroke in patients with
nonvalvular atrial fibrillation.
 TOXICITY: Bleeding • no specific
reversal agent

9.  Buvalirudin, argatroban,and
dabigatran
 Bind to thrombin’s active site and
inhibit its enzymatic action.
 USES: Anticoagulation in patients
with heparininduced
thrombocytopenia (HIT).
 Pharmacokinetic: Bivalirudin and
argatroban: IV administration
 Dabigatran: oral administration

10.  Warfarin: Inhibits vitamin K
epoxide reductase and thereby
interferes with production of
functional vitamin K-dependent
clotting and anticlotting factors.
 Uses: Venous thrombosis,
pulmonary embolism, prevention
of thromboembolic complications
of atrial fibrillation.

11.  Oral administration
• delayed onset and offset of
anticoagulant activity
• many drug interactions

12.  Bleeding (monitor with PT, vitamin
K1 is a reversal agent)
• Thrombosis early in therapy due to
protein C deficiency
• Teratogen

13.  Alteplase, recombinant human
tissue plasminogen activator (t-PA)
 Converts plasminogen to plasmin,
which degrades the fibrin in
thrombi.
 USES: Coronary artery thrombosis,
ischemic stroke, pulmonary
embolism
 TOXICITY: Bleeding, especially
cerebral hemorrhage

14.  Antiplatelet drugs include aspirin
and other nonsteroidal anti-
inflammatory drugs (NSAIDs),
glycoprotein IIb/IIIa receptor
inhibitors (abciximab, tirofiban,
and eptifibatide), antagonists of
ADP receptors (clopidogrel,
prasugrel, and ticlopidine), and
inhibitors of phosphodiesterase
(dipyridamole and cilostazol).

16.  Myocardial infarction
 Transient ischemic stroke
 Thrombotic events

17.  Bleeding
 Thrombocytopenia

18.  Vitamin K
 Clotting factors and desmopressin
 Antiplasmin agents

20.  The rate-limiting step in hepatic
cholesterol synthesis is conversion
of hydroxymethylglutaryl
coenzyme A (HMG-CoA) to
mevalonate by HMG-CoA
reductase. The statins are
structural analogs of HMG-CoA
that competitively inhibit the
enzyme.

21.  Statins can reduce LDL cholesterol
levels dramatically, especially when
used in combination with other
cholesterol- lowering drugs.
 Heart disease
 Ischemic stroke

22.  Bile acid-binding resins
(cholestyramine, colestipol, and
colesevelam) are large
nonabsorbable polymers that bind
bile acids and similar steroids in
the intestine and prevent their
absorption.
 The resins cause a modest
reduction in LDL cholesterol but
have little effect on HDL
cholesterol or triglycerides.

23.  Adverse effects from resins include
bloating, constipation, and an
unpleasant gritty taste. Absorption
of vitamins (eg, vitamin K, dietary
folates) and drugs (eg, thiazide
diuretics, warfarin, pravastatin,
fluvastatin) is impaired by the
resins.
 Uses: hypercholesterolemia

24.  Decreases VLDL synthesis and LDL
cholesterol concentrations •
increases HDL cholesterol
 Uses: Elevate HDL cholesterol,
Decrease VLDL and LDL
 Toxicity: Gastrointestinal irritation,
flushing, hepatic toxicity,
hyperuricemia, may reduce glucose
tolerance