This document summarizes drugs that affect blood and their uses. It discusses haematinics like iron, vitamin B12, and folic acid, which are used to treat anaemias caused by deficiencies in red blood cell production. It also covers coagulants and anticoagulants. Coagulants like vitamin K and fibrinogen promote coagulation, while anticoagulants like heparin, low molecular weight heparins, fondaparinux, and oral anticoagulants reduce coagulability of blood and are used to prevent thrombosis. Local haemostatics are used to stop bleeding from accessible sites. Care must be taken with patients on medications or with conditions that can affect haemostasis

1. Drugs affecting blood
Dr. Karun Kumar
Senior Lecturer
Dept. of Pharmacology

2. Haematinics
• Substances required in the formation of blood
• Used for treatment of anaemias
• Anaemia occurs when the balance between
production and destruction of RBCs is disturbed

3. • The disturbance can be caused by :-
1. Blood loss (acute or chronic)
2. Impaired red cell formation due to:
1. Deficiency of essential factors, i.e. iron, vitamin B12, folic
acid.
2. Bone marrow depression (hypoplastic anaemia),
erythropoietin deficiency.
3. Increased destruction of RBCs (haemolytic anaemia)

4. Iron metabolism

5. Oral iron preparations
1. Ferrous sulfate (hydrated salt 20% iron, dried salt
32% iron) is cheapest
Leaves metallic taste in mouth
2. Ferrous gluconate (12% iron)
3. Ferrous fumarate (33% iron); less water soluble
than ferrous sulfate and tasteless
4. Colloidal ferric hydroxide (50% iron)

6. Adverse effects of oral iron
1. Epigastric pain
2. Heart burn
3. Nausea & vomiting
4. Bloating
5. Staining of teeth
6. Metallic taste
7. Constipation

7. Parenteral iron
• Indicated only when:
1. Oral iron is not tolerated (bowel upset too much)
2. Failure to absorb oral iron
3. Non-compliance to oral iron
4. Severe deficiency with chronic bleeding
5. Along with erythropoietin to meet the accelerated
demand

8. • Parenteral iron therapy needs calculation of the total
iron requirement of the patient
• Iron requirement (mg) = 4.4 × body weight (kg) × Hb
deficit (g/dl)
• Parenteral iron preparations :-
1. Iron-dextran
2. Iron isomaltoside-100
3. Ferrous-sucrose
4. Ferric carboxymaltose

9. Use
• Prophylaxis & t/t of iron deficiency anaemia
• Prophylactic administration of supplemental iron is
routinely advised during later part of pregnancy and
to infants
• Also needed in menorrhagic women and during
chronic illnesses
• Iron is given in megaloblastic anaemia along with vit.
B12 /folic acid
• Ferric chloride used in throat paint as astringent

10. Vitamin B12 deficiency
• Due to absence of intrinsic factor secretion by
stomach
– Pernicious anaemia (autoimmune gastric mucosal damage)
– Chronic gastritis
– Gastric carcinoma
– Malabsorption
– ↑ demand or nutritional deficiency

11. • Manifestations of deficiency are:
1. Megaloblastic anaemia (neutrophils with
hypersegmented nuclei, giant platelets)
2. Glossitis, g.i. disturbances  Damage to epithelial
structures
3. Neurological  Subacute combined degeneration
of spinal cord; peripheral neuritis, paresthesias,
depressed stretch reflexes; mental changes—poor
memory, mood changes, hallucinations, etc.

12. Uses
1. Prevention & t/t of B12 deficiency  Confirmed B12
deficiency should be treated by i.m./s.c injection of
cyanocobalamin/ hydroxocobalamin
2. Methylcobalamine, an active coenzyme form of vit
B12 has been especially advocated for neurological
defects in diabetic and other forms of neuropathy

13. Folic acid deficiency
1. Inadequate dietary intake
2. Malabsorption  Coeliac disease, tropical sprue,
regional ileitis, etc.
3. Chronic alcoholism
4. ↑ demand  Pregnancy, lactation, rapid growth
periods, haemolytic anaemia
5. Drug induced  Prolonged therapy with
anticonvulsants (Phenytoin, Phenobarbitone,
Primidone) & OCPs

14. • Manifestations of deficiency are:
1. Megaloblastic anaemia
2. Epithelial damage
1. Glossitis
2. Enteritis
3. Diarrhoea
4. Steatorrhoea
3. General debility, weight loss, sterility

15. Uses
1. Megaloblastic anaemia due to
1. Nutritional folate deficiency
2. ↑ folate demand
3. Malabsorption
4. Antiepileptic therapy
2. Prophylaxis of folate deficiency (during pregnancy
to reduce the risk of neural tube defects in the
newborn)
3. Methotrexate toxicity  Folinic acid (Leucovorin,
citrovorum factor, 5-formyl-THFA) is used

16. • Folic acid should never be given alone to patients
with megaloblastic anaemia because:-
1. Folic acid t/t will improve symptoms of anemia
without affecting neurological defect of vitamin B12;
defects can progress & may become irreversible
2. There is diversion of meagre amount of B12 present
in body to haematopoiesis. It can result in
worsening of neurological defects.

17. Biochemical reactions involving folic acid
and vitamin B12

18. Coagulants
• Substances which promote coagulation
• Indicated in haemorrhagic states
• Haemostasis  Vasoconstriction + Primary
hemostasis + Secondary hemostasis
• Primary haemostasis  Platelets adhere to the
damaged walls of the blood vessel, and also to each
other, to form a platelet plug

19. • Secondary haemostasis  Meshwork of cross-linked
fibrin forms around the platelet plug to stabilize it
• Thrombosis  Primary haemostasis + Secondary
haemostasis
• Coagulation  Secondary haemostasis
• Deficiency of any clotting factor  Fresh whole
blood or plasma; immediate action

20. Normal hemostasis

21. Classification

22. Intrinsic pathway
• Activated by surface contact with foreign body
(Contact pathway) or extravascular tissue
• All factors and activators are contained within
(intrinsic to) the blood
• Responsible for clotting when blood is kept in a glass
tube (in vitro)

23. Extrinsic pathway
• Activated by thromboplastin (tissue factor)
• As a consequence of trauma, a tissue protein (tissue
factor) leaks into the blood from cells outside
(extrinsic to) blood vessels
• Pathways converge with the activation of factor X,
(rate-limiting step in coagulation cascade)
• Activation of factor XIIa(fibrinogen to fibrin)

25. PT aPTT
Intrinsic
pathway
interfered
Normal (12-
14 secs)
Prolonged
Extrinsic
pathway
interfered
Prolonged
(WEPT)
Normal (26-
32 secs)
Common
pathway
interfered
Prolonged Prolonged

26. Vitamin K uses
1. Prophylaxis & t/t of bleeding due to deficiency of
clotting factors
2. Vit. K 1 mg i.m. soon after birth has been
recommended routinely
3. Reverse the effect of overdose of oral
anticoagulants: Phytonadione (K1) is prep. of choice

27. Fibrinogen
• Fibrinogen fraction of human plasma is employed to
control bleeding in
1. Haemophilia
2. Antihaemophilic globulin (AHG) deficiency
3. Acute afibrinogenemic states
• 0.5 g is infused i.v.

28. Antihaemophilic factor
• Concentrated human AHG prepared from pooled
human plasma
• Indications (along with human fibrinogen)
1. Haemophilia
2. AHG deficiency
• Effective in controlling bleeding episodes
• Short lasting action (1 to 2 days)

29. Desmopressin
• V2 receptor agonist analogue of Vasopressin
• Releases factor VIII and von Willebrand’s factor from
vascular endothelium
• Checks bleeding in
1. Haemophilia
2. von Willebrand’s disease

30. Ethamsylate
• Reduces capillary bleeding when platelets are
adequate
• Corrects abnormalities of platelet adhesion, but does
not stabilize fibrin (not an antifibrinolytic)
• Used in prev. & t/t of capillary bleeding in
menorrhagia, after abortion, PPH, epistaxis, malena,
hematuria and after tooth extraction
• S/E  nausea, rash, headache, and fall in BP

31. Haemostasis in dentistry
• Post extraction bleeding from the tooth socket is
usually arrested by a cotton gauze pressure pack held
for 20 to 30 min
• Suturing may be required if bleeding is due to tear
around the socket
• Control of bleeding may need to be aided by the use
of local haemostatics

32. Local haemostatics (Styptics)
• Substances used to stop bleeding from a local and
approachable site
• Effective on oozing surfaces, e.g. tooth socket
• Absorbable materials like
– Fibrin (prepared from human plasma and dried as sheet or
foam)
– Gelatin foam
– Oxidized cellulose (as strips which can be cut and placed in
the wound)
• Provide a meshwork which activates the clotting
mechanism and checks bleeding

33. • Left in situ these materials are abs. in 1–4 weeks
• Cause no foreign body reaction
• Thrombin  Applied as dry powder or freshly
prepared solution to the bleeding surface in
haemophiliacs
• Vasoconstrictors (0.1% Adr solution)  Soaked in
sterile cotton gauze & packed in bleeding tooth
socket to check bleeding when spontaneous
vasoconstriction is inadequate
• Astringents [Tannic acid or metallic salts (Alum, Ferric
chloride)]  Applied for bleeding gums

34. • Many diseases and drugs can affect the vascular
response to injury, platelet function or coagulation to
create haemostatic problems
• When dental surgery is contemplated, careful
planning and consultation with their physician are
needed
1. Vitamin C deficiency
2. Deficient platelet function
3. Haemophilia
4. Anticoagulant medication

35. Vitamin C deficiency
1. Scurvy should be corrected before elective dental
surgery
2. In emergency surgery, careful packing and pressure
can stop the bleed
3. Long term corticosteroid therapy can also
compromise haemostasis by impairing vessel
retraction as well as by reducing platelet count

36. Deficient platelet function
1. Transfusion of platelet rich plasma is indicated
before dental surgery
2. Corticosteroid therapy helps to restore platelet
count in idiopathic thrombocytopenic purpura
3. Aspirin and other NSAIDs are the most important
drugs that inhibit platelet aggregation. A large
number of older individuals now receive long term
low dose aspirin prophylaxis for Ischaemic heart
disease or stroke

37. • Many others receive long term Clopidogrel for a
variety of thromboembolic disorders
• Several patients of arthritis regularly take NSAIDs
• Discontinuation of aspirin for 5 days before dental
surgery should be considered
• In case not possible, proper packing & use of local
haemostatics is needed to prevent excess bleeding

38. Haemophilia
• Minor dental procedures (like scaling) put the
haemophiliac patient at great risk of bleeding
• Patient should be covered before and after the
procedure with i.v. infusion of AHG or factor VIII
along with fibrinogen
• Tranexaemic acid has adjuvant value
• Desmopressin injected i.v. also helps in checking
dental bleeding in haemophiliacs & vW disease

39. Anticoagulant medication
• Any oral surgery in patients on anticoagulant
medication requires due care to avoid excessive
bleeding
• Since the action of i.v. heparin lasts for only 4–6
hours, the extraction can be scheduled at a time
when anticoagulation is minimal
• Low dose s.c. heparin and LMWH therapy does not
↑ dental surgery associated bleeding
• Heparin antagonist  Protamine

40. Anticoagulants
• Drugs used to reduce the coagulability of blood

41. Actions of heparin
1. Anticoagulant  Heparin is a powerful and
instantaneously acting anticoagulant, effective both in
vivo and in vitro
• It acts indirectly by activating plasma antithrombin III
(AT III, a serine proteinase inhibitor)
• Heparin-AT III complex then binds to clotting factors
of the intrinsic and common pathways (Xa, IIa, IXa,
XIa, XIIa and XIIIa) and inactivates them but not
factor VIIa operative in the extrinsic pathway

42. • At low concentrations of heparin, factor Xa mediated
conversion of prothrombin to thrombin is selectively
affected
• The anticoagulant action is exerted mainly by
inhibition of factor Xa as well as thrombin (IIa)
mediated conversion of fibrinogen to fibrin

43. • Low concentrations of heparin prolong aPTT without
significantly prolonging PT
• High concentrations prolong both
• Low concentrations interfere selectively with the
intrinsic pathway, affecting amplification and
continuation of clotting, while high concentrations
affect the common pathway as well

46. 2. Antiplatelet  Heparin in higher doses inhibits
platelet aggregation and prolongs bleeding time
3. Lipaemia clearing  Injection of heparin clears
turbid post-prandial lipaemic plasma by releasing a
lipoprotein lipase from the vessel wall and tissues,
which hydrolyses triglycerides of chylomicra and very
low density lipoproteins to free fatty acids
• These then pass into tissues and the plasma looks
clear

47. Adverse effects
1. Bleeding due to overdose is the most serious
complication of heparin therapy
• Aspirin, other NSAIDs & antiplatelet drugs enhance
heparin induced bleeding
2. Thrombocytopenia is another common problem
• Low molecular weight (LMW) heparins are not safe
in such patients.

49. Advantages of LMWH
1. Better s.c. bioavailability
2. Effects are longer & consistent (once daily s.c. adm.)
3. Dose is given in mg (not in units) can be easily
calculated on body weight basis
4. Chance of haemorrhage is less
5. Lesser antiplatelet action—less interference with
haemostasis
6. Thrombocytopenia is less frequent
7. aPTT/clotting times are not prolonged 
Laboratory monitoring is not needed

50. Indications of LMWH
1. Prophylaxis of deep vein thrombosis and pulmonary
embolism in high-risk patients undergoing surgery;
stroke or other immobilized patients
2. Treatment of established deep vein thrombosis
3. Unstable angina and MI
4. To maintain patency of cannulae and shunts in
dialysis patients, and in extracorporeal circulation

51. Haemodialysis

52. Fondaparinux
• Synthetically produced pentasaccharide segment
present in heparin molecules which binds to AT III
with high affinity to selectively inactivate factor Xa
without binding to thrombin (factor IIa)
• 100% bioavailable on s.c. injection
• Longer acting
• Less likely to cause thrombocytopenia
• Does not require laboratory monitoring
• Uses  Prophylaxis & t/t of DVT, PE, ACS

54. Protamine sulfate
• It is a strongly basic, low molecular weight protein
obtained from the sperm of certain fish
• I.v.  Neutralises heparin weight for weight, i.e. 1
mg is needed for every 100 U of heparin
• Used when heparin action needs to be terminated
rapidly
1. After cardiac surgery
2. After vascular surgery
3. Heparin induced bleeding

55. Direct thrombin inhibitors
• Bivalirudin  Congener of hirudin (polypeptide
anticoagulant secreted by salivary glands of leech)
• Binds to thrombin & inhibits it directly
• Quick onset & short duration (t1/2 25 mins.)
• Not antagonized by Protamine
• Uses  PCI, UA, MI, HIT
• Argatroban  I.v. produces rapid & short-lasting
antithrombin action

56. Oral anticoagulants
• Warfarin and its congeners act as anticoagulants only
in vivo, not in vitro (WEPT)
• Act indirectly by interfering with synthesis of vit. K
dependent clotting factors (II, VII, IX, X, prot. C & S)
• Inhibits vit K epoxide reductase (VKOR) & interferes
with regeneration of the active hydroquinone form
of vit K which acts as a cofactor for the enzyme γ-
glutamyl carboxylase that carries out the final step of
γ carboxylating glutamate residues of prothrombin
and factors VII, IX and X

58. Adverse effects
• Bleeding as a result of extension of the desired
pharmacological action is the most important
problem causing ecchymosis, epistaxis, hematuria,
bleeding in the g.i.t. , Intracranial or other internal
haemorrhages may even be fatal

59. Treatment of bleeding due to oral
anticoagulants
1. Withhold the anticoagulant.
2. Fresh blood transfusion (supplies clotting factors
and replenishes lost blood)
3. Fresh frozen plasma may be used as a source of
clotting factors
4. Vit. K1 (specific antidote); takes 6–24 hours for the
clotting factors to be resynthesized and released in
blood after vit K administration

60. Dose regulation
• Dose must be individualised by repeated
measurement of prothrombin time
• Aim  Achieve a therapeutic effect without unduly
increasing the chances of bleeding
• A INR of 2-4.5 is considered therapeutic for different
indications

61. International Normalized Ratio

62. Drug interactions
A. Enhanced anticoagulant action
1. Broad-spectrum antibiotics  Inhibit gut flora and
reduce vit K production
2. Newer cephalosporins (ceftriaxone, cefoperazone)
cause hypoprothrombinaemia by the same
mechanism as warfarin —additive action
3. Aspirin  Inhibits platelet aggregation and causes
GI bleeding—this may be hazardous in
anticoagulated patients

63. 4. Sulfonamides, indomethacin, phenytoin and
probenecid: displace warfarin from plasma protein
binding
5. Chloramphenicol, erythromycin, celecoxib,
cimetidine, allopurinol, amiodarone and
metronidazole: inhibit warfarin metabolism
B. Reduced anticoagulant action
1. Barbiturates, carbamazepine, rifampin and
griseofulvin induce the metabolism of oral
anticoagulants.
2. Oral contraceptives: increase blood levels of clotting
factors

64. Direct factor Xa inhibitor
• Rivaroxaban  Inactivates factor Xa
• Acts rapidly (within 3-4 hrs.) without a lag period,
and has a shorter duration of action (~24 hours)
• No laboratory monitoring required
• Uses
1. Prophylaxis of DVT & PE following knee/hip
replacement surgery
2. Preventing stroke in patients with AF
3. T/t of DVT & PE

65. Apixaban
• Approved for
1. Prev. of VTE following knee/hip replacement
2. Preventing stroke in patients with AF
3. T/t of DVT & PE

66. Oral direct thrombin inhibitor
• Dabigatran  Reversibly blocks the catalytic site of
thrombin and produces a rapid (within 2 hours)
anticoagulant action
• No laboratory monitoring required
• Uses
1. Prevention of post knee replacement venous
thromboembolism
2. Stroke due to atrial fibrillation

67. Uses of anticoagulants
1. Prophyl. of DVT & PE
1. Following knee/hip replacement surgery
2. High-risk bed ridden
3. Elderly
4. Postoperative
5. Postpartum
6. Poststroke
7. Leg fracture patients
2. T/t of DVT & PE

68. 3. Prophyl. of stroke & systemic embolism in pts. of
nonvalvular AF
4. To cover PCI in pts. of MI & high-risk UA
5. Adjuvant to antiplatelet drugs to prev. reoccl. of cor.
art. following fibrinolytic therapy of MI
6. Combined with antiplatelet drugs in pts. with
prosthetic heart valves, in those undergoing vasc. surg.
or haemodialysis
7. To maintain patency of intravasc. cannulae/catheters
8. To preserve clotting factors in defibrination syndr.

69. Heparin Warfarin
Route of admin. I.v., S.c. Oral
Onset of action Immediate Delayed
Activity In vitro & in vivo In vivo only
Mechanism Activ. Of AT-III ↓ activ. Of c.f.
2,7,9,10
Antagonist Protamine sulphate Vitamin K
Lab control aPTT PT
Drug interact. Few Many
Placental barrier Does not cross Fetal warf. syndrome
Use To initiate therapy For maintenance

70. Fibrinolytic drugs (SURAT)
• Drugs used to lyse thrombi/clot to recanalize
occluded blood vessels (mainly coronary artery)
• Work by activating the natural fibrinolytic system
1. Streptokinase
2. Urokinase
3. Reteplase
4. Alteplase
5. Tenecteplase

71. Mechanism of action

72. Uses of fibrinolytics
1. Acute myocardial infarction
2. Deep vein thrombosis
3. Pulmonary embolism
4. Peripheral arterial occlusion
5. Stroke

74. Anti fibrinolytic drugs
• Drugs which inhibit plasminogen activation &
dissolution of clot, and are used to check bleeding
due to fibrinolysis
1. Epsilon Aminocaproic acid  Blocks plasminogen
activation. Antidote for fibrinolytic agents.
2. Tranexamic acid  7 times more potent.

75. Tranexamic acid
• Preferred for prev./control of exc. Bleeding due to
1. Fibrinolytic drugs.
2. Cardio-pulmonary bypass surgery.
3. Tonsillectomy, prostatic surgery, tooth extraction in
haemophiliacs.
4. Menorrhagia, especially due to IUCD.
5. Recurrent epistaxis, ocular trauma

76. • Main side effects are nausea and diarrhoea.
• Thromboembolic events, disturbed colour vision and
allergic reactions are infrequent
• Headache, giddiness and thrombophlebitis of
injected vein can occur

77. Antiplatelet drugs
(Antithrombotic drugs)
• Drugs which interfere with platelet function and are
useful in the prophylaxis of thromboembolic
disorders
• All of them are likely to accentuate dental surgery
related bleeding

78. Pro & anti-aggregatory factors
• Pro-aggregatory factor  TXA2 (platelets)
↓ blood flow & ↑ platelet aggregation
• Anti-aggregatory factors
1. PGI2 Endothelial
2. NO cells
↑ blood flow & ↓ platelet aggregation

79. Antiplatelet Drugs
Platelets adhere to damaged vasc. Endoth. Via
GP Ia + collagen & GP Ib + vWF (similar to clotting
factor VIII)
↓
Synth. & rel. (degranulation) of TXA2,ADP,5-HT
↓
↑ expression of GP IIb/IIIa rec.
↓
Bind to fibrinogen & cause platelet aggregation

81. 1. NSAIDs inhibit the synthesis of thromboxane A2 by
blocking cyclooxygenase (COX).
2. Clopidogrel, prasugrel, ticagrelor, and others block
the target of ADP, the purine 2Y12 receptor (P2Y12).
3. Epifibatide, tirofiban, abciximab, and other agents
bind to GP-2b/GP3a proteins and prevent
fibrinogen crosslinking of platelets.
4. Dipyridamole inhibits PDE  ↑ cAMP  ↑ PGI2
decreasing platelet aggregation.

82. Classification

83. Aspirin
• It acetylates and inhibits the enzyme COX-1
irreversibly
• TXA2 is the major arachidonic acid product generated
by platelets
• Platelets are exposed to aspirin in the portal
circulation before it is deacetylated during first pass
in the liver, and because platelets cannot synthesize
fresh enzyme (have no nuclei), TXA2 formation is
suppressed at very low doses and till fresh platelets
are formed

84. • Aspirin induced prolongation of bleeding time lasts
for 5–7 days.
• Doses as low as 40 mg/day have an effect on platelet
aggregation
• Maximal inhibition of platelet function occurs at 75–
150 mg aspirin per day.
• Aspirin also ↓ PGI2 synthesis as well. However, since
intimal cells can synthesize fresh enzyme, activity
returns rapidly.

85. • At low doses (75–150 mg/day or 300 mg twice
weekly), TXA2 formation by platelets is selectively
suppressed, whereas higher doses (> 900 mg/day)
may decrease both TXA2 and PGI2 production
• Aspirin inhibits the release of ADP from platelets and
their sticking to each other, but has no effect on
platelet survival time and their adhesion to damaged
vessel wall

87. Ticlopidine
• Alters surface receptors on platelets and inhibits ADP
as well as fibrinogen-induced platelet aggregation
• Blocks P2Y12 type of purinergic receptors through
which ADP mediates adenylyl cyclase inhibition in
platelets
• Activation of platelets is interfered
• Fibrinogen binding to platelets is prevented without
modification of GPIIb/IIIa receptor

88. • No effect on platelet TXA2, but bleeding time is
prolonged
• Synergistic effect on platelets with aspirin
• Superseded by Clopidogrel due to side effects

89. Clopidogrel
• Safer and better tolerated
• Used for TIAs, UA, prev. of stroke and recurrence of
MI
• Aspirin is synergistic in preventing ischaemic
episodes, and is utilized for checking restenosis of
stented coronaries
• Side effects  Diarrhoea, epigastric pain and rashes
• Has replaced Ticlopidine

90. Dipyridamole
• Vasodilator
Inhibits PDE
↓
↑ platelet cAMP
↓
↑ PGI2
↓
Interferes with aggregation

91. • Along with warfarin ↓ thromboembolism in patients
with prosthetic heart valves
• Enhances antiplatelet action of aspirin
• Risk of stroke in patients with transient ischaemic
attacks (TIAs) may ↓ when combined with Aspirin

92. Prasugrel
• Most potent and faster acting P2Y12 purinergic
receptor blocker, that is being increasingly used in
acute coronary syndromes (ACS) and to cover
coronary angioplasty
• Bleeding complications are also more frequent and
more serious
• C/I  Patients with history of ischaemic stroke and
TIAs (greater risk of intracranial haemorrhage)

93. Ticagrelor
• Reversible P2Y12 blocker
• Faster onset & quicker offset of action
• Requires twice daily dosing
• Prophylactic Ticagrelor is recommended in all high
risk ACS patients
• S/E  Shortness of breath, tightness in chest,
nausea, dizziness

94. Glycoprotein (GP) IIb/IIIa receptor
antagonists
• Block GPIIb/IIIa [adhesive receptor (integrin)] on
platelet surface for fibrinogen and vWF through
which agonists like collagen, thrombin, TXA2, ADP,
etc. induce platelet aggregation
• Eptifibatide  Inhibits platelet aggregation; Used as
alternative to Abciximab in ACS & Coronary
angioplasty
• Tirofiban  Used in ACS & Coronary angioplasty
• Antiplatelet action similar to Eptifibatide

95. Abciximab
• Fab fragment of a chimeric monoclonal antibody
against GP IIb/IIIa, which is given along with aspirin +
heparin during coronary angioplasty
• Indications  MI & UA

97. Uses of antiplatelet drugs
1. Coronary artery disease  Low dose aspirin 75–150
mg/day; Aspirin/clopidogrel prophylaxis in post-MI
patients clearly prevents reinfarction and ↓ mortality
2. Acute coronary syndromes (ACSs)  Asp. + LMWH.
Clopidogrel can be used. Prasugrel or Ticagrelor +
Asp. pref. to cover coronary angioplasty
3. Cerebrovascular disease  Aspirin ↓ incidence of
TIAs, stroke in patients with TIAs or pts. with
persistent AF, H/O of stroke in the past.

98. • Clopidogrel also ↓ TIAs & stroke
4. Prosthetic heart valves and arteriovenous shunts 
Antiplatelet drugs, used with warfarin ↓ formation of
microthrombi on artificial heart valves & incidence of
embolism. Also prolong the patency of chronic
arteriovenous shunts.
5. Peripheral vascular disease  Aspirin/clopidogrel
may produce some improvement in intermittent
claudication & ↓ incidence of thromboembolism

99. Hypolipidaemic drugs
• Drugs which lower the levels of lipids and
lipoproteins in blood
• ↑ LDL-CH  Atherogenic
• ↑ HDL-CH  Protective
• ↑ TG  Risk of CAD & stroke irrespective of
cholesterol level

100. Classification

101. Pharmacological treatment
1. HMG-CoA reductase inhibitors (Statins) 
Lovastatin, Simvastatin, Pravastatin, Atorvastatin,
Rosuvastatin, Pitavastatin
2. Bile acid sequestrants (Resins)  Cholestyramine,
Colestipol, Colesevelam
3. Lipoprotein lipase activators (Fibrates) 
Gemfibrozil, Bezafibrate, Fenofibrate.
4. Lipolysis & TG synthesis inhibitor  Nicotinic acid
5. Sterol absorption inhibitor  Ezetimibe

102. MOA & pattern of lipid lowering effect

103. HMG-CoA Reductase inhibitors
(Statins)
• Most efficacious & best tolerated
• Competitively inhibit conversion of 3-Hydroxy-3-
methyl glutaryl coenzyme A (HMG-CoA) to
mevalonate (rate limiting step in CH synthesis) by the
enzyme HMG-CoA reductase
• Compensatory ↑ LDL rec. expr. on liver cells → ↑
rec. mediated uptake and catabolism of IDL and LDL
• Dose dependent lowering of LDL-CH levels

104. MOA of statins

105. Adverse effects
1. S/E  Headache, nausea,
bowel upset, rashes and
sleep disturbances
2. Commonest S/E  Muscle
tenderness
3. Infrequent  ↑ CPK level &
hepatic injury
4. Serious but rare 
Myopathy

106. Use
• 1st choice drugs for lowering ↑ LDL and total CH
levels, with or without raised TG levels
• Efficacy of statins in ↓ LDL-CH associated mortality
and morbidity well established
• Venous thromboembolism following knee
replacement is ↓ by Rosuvastatin
• Additional mechanisms  Improvement in
endothelial function, ↓ LDL oxidation & an anti
inflammatory effect

107. Bile acid sequestrants (Resins)
• Ion exchange resins
• Neither digested nor absorbed in the gut
Bind bile acids in the intestine
↓
Interrupting enterohepatic circulation
↓
Fecal excretion of bile salts & CH
(absorbed with the help of bile salts) ↑
↓

108. ↑ hepatic metabolism of CH to bile acids
↓
↑ LDL receptors expressed on liver cells
↓
Clearance of IDL, LDL & VLDL ↑

110. Lipoprotein-lipase activators
(Fibrates)
• Fibrates activate LPL (enzyme causing degradation of
VLDL resulting in lowering of circulating TGs)
• Effect is exerted through PPARα which enhances
lipoprotein lipase synthesis and fatty acid oxidation
• PPARα may also ↑ LDL receptor expression in liver
• Fibrates ↓ hepatic TG synthesis as well
• S/E  G.i. upset, rashes, body ache, myopathy
• DOC in pts. with ↑ TG levels ± CH levels ↑

111. Nicotinic Acid (Niacin)
• B group vitamin ↓ plasma lipids (2-4 g/day)
• TGs & VLDL ↓; followed by ↓ LDL-CH & total CH
• Most effective drug to raise HDL-CH
• Nicotinic acid reduces production of VLDL in liver by
inhibiting TG synthesis.
• Inhibits lipolysis in adipose tissue & ↑ activity of
lipoprotein lipase that clears TGs

112. Inhibits lipolysis in adipose
tissue
↓
↓ hepatic VLDL synthesis &
production of LDLs in the
plasma

113. Adverse effects
• Large doses poorly tolerated
• Marked flushing, heat and itching (especially in the
blush area) occur after every dose [PGD2 in the skin]
• Aspirin is taken before niacin
• Laropiprant (prostanoid rec. inh.) also ↓ flushing
• Dyspepsia, vomiting & diarrhea; Peptic ulcer
• Long-term effects  Liver dysfunction & diabetes
• Risk of myopathy due to statins ↑

114. Use
1. Used to lower VLDL & TGs and raise HDL levels
2. Adjunctive drug to statins/fibrates
3. Pancreatitis associated with severe
hypertriglyceridaemia
• Due to marked s/e, use restricted to high risk cases
only

115. Ezetimibe
• Interferes with a specific CH transport protein
NPC1L1 in the intestinal mucosa and reduces
absorption of both dietary and biliary CH
• Ezetimibe + low dose statin  As effective in
lowering LDL-CH as high dose of statin alone
• Well tolerated

116. Summary