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1. Blood Pharmacology
By
Berhan Begashaw [ Bpharm, MSc in Pharmacology]
E-mail: berhan.uog1912@gmail.com
Department of Pharmacy
ASWHSC, DBU
Berhan B. [ Pharmacology Dep't] 1

2. Learning Objectives
After reading and studying this chapter the students will be
able to
 Describe how heparin and oral anticoagulants produce
their effect.
 Discuss the indication of heparin and oral anticoagulants
 Identify major adverse reactions associated with heparin
and oral anticoagulants
 Discuss the pharmacokinetics of iron,Vit B12 and folic acid.
 Explain the mechanisms of action of major anti anemic
drugs
 Discuss the use of iron to treat iron deficiency anemia, the
use ofVit B12 and folic acid to treat megaloblastic anemia.
Berhan B. [ Pharmacology Dep't] 2

3. Drugs that are useful in treating three important
dysfunctions of blood:
 anemia
 thrombosis
 bleeding
Thrombosis-formation of an unwanted clot within a
blood vessel, most common abnormality of
hemostasis.
Thrombotic disorders include acute MI, DVT,
pulmonary embolism, and acute ischemic stroke.
Rx with drugs such as anticoagulants & fibrinolytics.
Berhan B. [ Pharmacology Dep't] 3

4.  Bleeding disorders involving failure of hemostasis
are less common than thromboembolic diseases.
Include
Hemophilia,
which is treated with transfusion of Factor
VIII prepared by recombinant DNA techniques,
and
Vitamin K deficiency,
which is treated with dietary supplements of
vit-K.
Berhan B. [ Pharmacology Dep't] 4

5. BLOOD COAGULATION
Coagulation:
 is a cascade of proteolytic reaction
 Each protease factor activates the next
clotting factor in the sequence
Several of protease factors are targets for drug
therapy
Coagulants:
Are agents which promote coagulation and are
indicated in hemorrhagic states.
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Berhan B. [ Pharmacology Dep't]

6. Drugs for hemostasis /drugs facilitate clotting:
Vitamin K: K1 [phytonadione]- fat soluble)
Action:
 Vitamin K is a cofactor in post translational
modification of clotting factors II,VII, IX and X
Berhan B. [ Pharmacology Dep't] 6

7. Pharmacokinetics:
 Vitamins K1 and K2 require bile salts for absorption
from the intestinal tract
 Vit K is only temporarily concentrated in liver
 Metabolized in liver and excreted in bile and urine
 Onset of effect is delayed for 6 hours but the
effect is complete by 24 hours when treating
depression of prothrombin activity by excess
warfarin or vitamin K deficiency
Berhan B. [ Pharmacology Dep't] 7

8. Use:
 Only in prophylaxis & treatment of bleeding due to
deficiency of clotting factors
 And in newborns, who are at risk of vit.K deficiency :
bleeding.
Adverse effects:
 Intravenous administration of vitamin K1 should be
slow,
- because rapid infusion can produce dyspnea,
chest and back pain, and even death
Berhan B. [ Pharmacology Dep't] 8

9. Anticoagulants
 Are drugs used to reduce the coagulability of
blood
A. Heparin [ Fast and direct acting]
B. Oral anticoagulants [ Slow and indirect acting]
 Warfarin
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Berhan B. [ Pharmacology Dep't]

10. ◦ Heparin
 Mechanism of anticoagulant action—Helps
antithrombimn III to inactivate coagulation -factor
(II,VII, IX, X)
 Pharmacokinetics—Cannot be given PO since can’t
cross CM & ineffective because it is inactivated by
gastric acids
Administration of heparin Iv, sc
Not administered im because of hematoma
formation at injection site
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Berhan B. [ Pharmacology Dep't]

11. Heparin is often initiated as an intravenous bolus
to achieve immediate anticoagulation
Renal insufficiency prolongs the half-life of
LMWHs.
Therefore, the dose of LMWHs should be reduced
in patients with renal impairment
 Therapeutic uses
 Preferred during pregnancy & for situations
requiring rapid onset
 For pulmonary embolism, evolving stroke and
massive deep vein thrombosis (DVT)
 as well as patients undergoing open heart
surgery & renal dialysis
Berhan B. [ Pharmacology Dep't] 11

12.  Adverse effects —Hemorrhage, thrombocytopenia,
hypersensitivity reactions; local irritation &
hematoma from subcutaneous administration;
vasospastic reactions; long-term use with high
doses may cause osteoporosis.
 Anti-dote: Protamine sulfate
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Berhan B. [ Pharmacology Dep't]

13.  Oral Anticoagulants—To prevent thrombosis;
delayed onset of action; not for emergency use;
carry significant risk of hemorrhage; risk amplified
by many drug interactions;
A. Warfarin —the oldest oral anticoagulant
 Mechanism of action—Antagonist of vitamin K
(factorsVII, IX, X and prothrombin).
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Berhan B. [ Pharmacology Dep't]

14. Pharmacokinetics
 Readily absorbed after oral administration
 Hepatic metabolism & excretion in urine &feces
 Doesn’t affect clotting factors already present,
only those being synthesized (may be delayed 6
hours to 2.5 days)
 After discontinuing drug, effects still present for
2–5 days
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Berhan B. [ Pharmacology Dep't]

15.  Therapeutic uses—Long-term prophylaxis of
thrombosis for those needing prevention of
pulmonary embolism, patients with prosthetic heart
valves, and those with atrial fibrillation
 Dose: 2.5 -7.5mg/day
 Adverse effects—Hemorrhage; fetal hemorrhage and
teratogenesis with use during pregnancy; not for
use during breast feeding;
—others (skin necrosis, alopecia, urticaria,
dermatitis, fever, GI disturbances, & red-
orange urine)
Anti-dote: Vitamin K1(phytonadione)
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Berhan B. [ Pharmacology Dep't]

16. Drug interactions
—More interactions than probably any other drug;
 three major categories
- drugs that increase anticoagulant effects,
- drugs that promote bleeding, and
- drugs that decrease anticoagulant effects
 especially of concern are heparin, aspirin,
acetaminophen now thought to inhibit warfarin
degradation
Berhan B. [ Pharmacology Dep't] 16

17. Aspirin and phenylbutazone inhibit platelet
aggregation and hence
- potentiate warfarin action
Acute alcohol intoxication, Cimetidine,
cotrimoxazole , chloramphenicole and
metronidazole block metabolism of warfarin
-potentiate its effects.
Chronic alcohol consumption, barbiturates
,griseofulvin and rifampicin stimulate metabolism of
warfarin and
- decreases its effect.
Berhan B. [ Pharmacology Dep't] 17

18. Antiplatelet Drugs:
 Interfere with platelet function and may be useful
in the prophylaxis of thromboembolic disorders
Drugs interfering with platelet function:
 Aspirin
 Clopidogrol
 Others
 ASA: used as a long-term, at low doses, to help
prevent heart attacks, strokes, and blood clot
formation in people at high risk for developing
blood clots.
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Berhan B. [ Pharmacology Dep't]

19. Aspirin
 Has an antiplatelet effect by inhibiting production
of thromboxane A2 which promotes platelet
aggregation.
 Low dose ( 80 mg po coated tablets) should be
used b/c at high dose, it also inhibits prostacycline
(PGI2 which prevents platelet aggregation)
 Also used long-term, at low doses, to help prevent
heart attacks, strokes, and blood clot formation in
people at high risk for developing blood clots.
 low doses of aspirin may be given immediately
after a heart attack to reduce the risk of another
heart attack or of the death.
Berhan B. [ Pharmacology Dep't] 19

20. Lipid Lowering Agents
Why Should we lower Lipids?
 To lower risk of
1. Coronary heart disease
 ed LDL associated with atherogenesis
 ed HDL associated with ed coronary vascular
diseases
2. Pancreatitis
 Associated with ed levels
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Berhan B. [ Pharmacology Dep't]

21. Treatment of Hyperlipidemia
1. Treat underlying cause
2. Dietary treatment:
 Limit;- cholesterol intake
Saturated fat intake
 Limit total fat intake
 Limit simple sugar intake
3. Pharmacological;
 Dietary treatment should continue
 Statins: Atorvastatine, levostatin, etc.
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Berhan B. [ Pharmacology Dep't]

22. Agents Used toTreat Anemia
◦ Anemia
 Defined as a below-normal plasma hemoglobin
concentration.
 Results from:
a decreased number of circulating RBCs
or
an abnormally low total hemoglobin
content per unit of blood volume.
Berhan B. [ Pharmacology Dep't] 22

23.  Anaemia occurs when balance b/n production
and destruction of RBCs is disturbed/caused by:
◦ Blood loss (acute or chronic)
◦ Impaired red cell formation:
due to deficiency of essential factors i.e. iron,
vitamin B12, folic acid
◦ bone marrow abnormalities
◦ infections, malignancy
◦ increased destruction of RBCs (haemolytic anaemia)
◦ drugs
Berhan B. [ Pharmacology Dep't] 23

24.  It can be at least temporarily corrected by
transfusion of whole blood.
A large number of drugs cause toxic effects on
blood cells, hemoglobin production, erythropoietic
organs, which in turn may cause anemia.
Nutritional anemias are caused by dietary
deficiencies such as iron, folic acid, or vitamin B12
(cyanocobalamin)
Anemia's caused by nutritional deficiencies, such as
the commonly encountered iron deficiency
anemia, can be treated with either dietary or
pharmaceutical supplementation.
Berhan B. [ Pharmacology Dep't] 24

25. Iron Deficiency Anemia (IDA)
 Most common cause of anemia
 Is manifestation of an underlying disease condition.
Common causes of IDA include:
 increased iron requirements ( pregnancy & lactation)
 blood loss (chronic bleeding, blood donation)
 worm infestation (hookworm), inadequate Fe supply
(malnutrition, malabsorption)
 The symptoms of IDA include;
fatigue,
headache,
tinnitus, palpitations,
sore tongue and dysphagia.
Berhan B. [ Pharmacology Dep't] 25

26. Drug therapy of IDA
 Ferrous sulfate, ferrous gluconate, ferrous fumarate
 S/Es: Nausea, abdominal cramps & dyspeptic
symptoms, constipation or diarrhea.
 Patients who do not tolerate ferrous sulfate tablets
may be advised to take it with meals, or to start a
smaller dose, or to change the brand to ferrous
gluconate or fumarate tablets.
 D/Is: Antacids, tetracyclines, etc. interfere with the
absorption & metabolism of iron.
Berhan B. [ Pharmacology Dep't] 26

27. Alternative
Iron dextran injection.
S/Es: Pain, swelling, staining at site of injection; nausea,
vomiting, taste disturbances; hypersensitivity
reactions.
C/Is: History of allergic reactions (including asthma);
severe hepatic or renal impairment; pregnancy.
Berhan B. [ Pharmacology Dep't] 27

28. N.B.
 Iron parenteral therapy is rarely indicated.
 indications include;
 Oral iron intolerance,
Mal-absorption, presence of an inflammatory
bowl
active peptic ulcer disease,
inability or unwillingness by the patient to take
oral Fe.
A dose of 25mg (0.5ml) IV is given first to test
for hypersensitivity reactions and the patient is
observed closely for possible complications.
Berhan B. [ Pharmacology Dep't] 28

29. Megaloblastic Anemia (MA)
 >95% of MA is due to deficiency or unbalanced
metabolism of either cobalamin (vitamin B12) or
folate, cofactors required for the normal maturation
of red blood cells.
 Folate deficiency MA is more common in Ethiopians.
 Folate deficient patients are usually malnourished.
 Poor absorption of Vit B12
Berhan B. [ Pharmacology Dep't] 29

30.  Folate deficiency may be caused by
1. increased demand ( pregnancy and lactation)
2. poor absorption caused by pathology of the
small intestine,
3. alcoholism
4. Rx with drugs that are dihydrofolate reductase
inhibitors(methotrexate, pyrimethamine, and
trimethoprim).
folinic acid—also known as leucovorin calcium
Berhan B. [ Pharmacology Dep't] 30

31.  Neuropsychiatric manifestations /neurologic defects
are encountered in cobalamin deficiency, but not in
folate deficiency states.
 may become irreversible if not treated promptly
 Neuropsychiatric manifestations include;
confusion; memory changes; delirium, hallucinations
and/or delusions;
 depression; acute psychotic states; and (more
rarely) reversible manic and schizophreniform states.
Berhan B. [ Pharmacology Dep't] 31

32. Treatment of MA
 Vitamin B12(Cyanocobalamine)
 Because vitamin B12 deficiency anemia is almost
always caused by inadequate absorption, therapy
should be by replacement of vitamin B12
 S/Es: Itching, fever chills, hot flushes, nausea and
dizziness.
Berhan B. [ Pharmacology Dep't] 32

33. Folic acid (Folate deficiency MA)
 Because maternal folic acid deficiency is associated
with increased risk of neural tube defects in the
fetus,
folic acid supplementation is recommended before
and during pregnancy.
 Folic acid supplements correct the anemia but not
the neurologic deficits of vitamin B12 deficiency.
 Therefore, vitamin B12 deficiency must be ruled out
before one selects folic acid as the sole therapeutic
agent in the treatment of a patient with MA.
Berhan B. [ Pharmacology Dep't] 33

34. N.B.
 The hematologic picture normalizes in about 2 months
in both cobalamine and folate replacement therapy.
 Large doses of folate may produce hematologic
response in cobalamine deficiency states.
 This masks the cobalamine deficiency state and allows
the neurologic damage to progress.
 Therefore, if both folate and cobalamine are deficient,
cobalamine is administered first, followed by folate.
 Blood transfusion with packed RBCs could be needed
in severe cases.
Berhan B. [ Pharmacology Dep't] 34

35. Does deficiency of iron occurs most often in women or
men?
Why?
……………………………………………………
……………………………………………………
………………………………………………………
…….
Berhan B. [ Pharmacology Dep't] 35