Unit 6.

d- Pharmacology
LIPID-LOWERING AGENTS
Lipid-Lowering Agents  Caution: the presence of any known bleeding disorder
 Also antihyperlipidemic agents - used to treat because of the risk of excessive blood loss; recent surgery
hyperlipidemia (increased in the level of lipids in the blood. because of the risk of increased bleeding in unhealed
 CAD - Coronary Artery Disease, higher among people with vessels; and closed head injuries because of the risk of
high serum lipid levels. bleeding from the injured vessels in the brain.
Bile Acid Sequestrants Anticoagulants
 Used to decrease plasma cholesterol levels.  Drugs that interfere with the normal coagulation process
 Cholestyramine, colestipol,and colesevelam by interfering with the clotting cascade and thrombin
 Bile acid sequestrants bind with bile acids in the intestine formation.
to form an insoluble complex that is then excreted in the  antithrombin III, argatroban, bivalirudin, desirudin,
feces. fondaparinux, heparin, and warfarin and the two newest
 Bile acids contain high levels of cholesterol. As a result, the oral anticoagulants dabigatran and rivaroxaban
liver must use cholesterol to make more bile acids.  Warfarin causes a decrease in the production of vitamin
 The serum levels of cholesterol and LDL decrease as the K–dependent clotting factors (Prothrombin, FVII, FIX,
circulating cholesterol is used to provide the cholesterol protein C, and protein S) in the liver. The eventual effect is
that the liver needs to make bile acids. a depletion of these clotting factors and a prolongation of
HMG-CoA Reductase Inhibitors clotting times.
 Atorvastatin, lovastatin, pitavastatin, rosuvastatin,  Given orally, onset of action is about 3 days; its effects last
simvastatin for 4 to 5 days.
 The early rate-limiting step in the synthesis of cellular  Heparin blocks the formation of thrombin from
cholesterol involves the enzyme HMG-CoA reductase. If prothrombin.
this enzyme is blocked, serum cholesterol and LDL levels  Injected IV or subcutaneously and has an almost
decrease because more LDLs are absorbed by the cells for immediate onset of action.
processing into cholesterol.  Warfarin overdose - Antidote: Injectable Vitamin K
 Pravastatin, lovastatin, simvastatin - to slow progression of  Promotes the liver synthesis of several clotting factors.
CAD.  Heparin overdose - Antidote: Protamine sulfate
 These 3 agents and atorvastatin - to prevent MI  Forms stable salts with heparin as soon as the two drugs
come in contact, immediately reversing heparin’s
Drugs Affecting Blood Coagulation anticoagulant effects.
Contraindications:
 Hypersensitivity
 Hemorrhagic disorders, recent trauma, spinal puncture, GI
ulcers, recent surgery, intrauterine device placement.
Adverse Effects:
 Bleeding, ranging from bleeding gums with tooth brushing
to severe internal hemorrhage.
Thrombolytic Agents
 Break down the thrombus that has been formed by
stimulating the plasmin system. This process is called clot
resolution.
 alteplase, reteplase, tenecteplase, and urokinase
 Activate the natural anticlotting system—conversion of
Clotting Process plasminogen to plasmin. The activation of this system
 Blood coagulation is a complex process that involves breaks down fibrin threads and dissolves any formed clot.
vasoconstriction, platelet clumping or aggregation, and a  Dissolve that clot to open the vessel and restore blood flow
cascade of clotting factors produced in the liver that to the dependent tissue.
eventually react to break down fibrinogen into insoluble  These drugs are given IV
fibrin threads. When a clot is formed, plasmin acts to break Contraindications:
it down.  Hypersensitivity
 Blood coagulation can be affected at any step in this  Recent surgery, active internal bleeding, cerebrovascular
complicated process to alter the way that blood clotting accident (CVA) within the last 2 months, aneurysm
occurs. Adverse Effects:
Disorders Affecting Blood Coagulation  Bleeding
1. Conditions that involve overproduction of clots, or Clinically Important Drug–Drug Interactions:
thromboembolic disorders (conditions that predispose a  The risk of hemorrhage increases if thrombolytic agents
person to the formation of clots and emboli) are used with any anticoagulant or antiplatelet drug.
2. Conditions in which the clotting process is not working Drugs to Treat Anemias
effectively, resulting in risk for excess bleeding or Anemia
hemorrhagic disorders (excess bleeding; hemophilia, liver Results from some alteration in erythropoiesis, the process of RBC
disease, bone marrow disorders) production, which occurs in the myeloid tissue of the bone marrow.
Antiplatelet Agents  Iron deficiency anemia - this can occur in certain rare GI
 Decrease the formation of the platelet plug by decreasing diseases in which the patient is unable to absorb iron from
the responsiveness of the platelets to stimuli that would the GI tract.
cause them to stick and aggregate on a vessel wall.  Megaloblastic anemias - insufficient amounts of folic acid
 abciximab, anagrelide , aspirin, cilostazol, clopidogrel, or vitamin B12 to adequately create the stromal structure
dipyridamole, eptifibatide, ticlopidine, ticagrelor , and needed in a healthy RBC, causing a slowing of nuclear DNA
tirofiban. synthesis.
 The antiplatelet agents inhibit platelet adhesion and  Pernicious anemia - occurs when the gastric mucosa
aggregation by blocking receptor sites on the platelet cannot produce intrinsic factor and vitamin B12 cannot be
membrane, preventing platelet–platelet interaction or the absorbed.
interaction of platelets with other clotting chemicals.  Sickle cell anemia - chronic hemolytic anemia,
 Anagrelide- blocks the production of platelets in the bone characterized by a genetically inherited hemoglobin S,
marrow. which gives the RBCs a sickle- shaped appearance.
 These agents are used effectively to treat cardiovascular
diseases that are prone to produce occluded vessels; for
the maintenance of venous and arterial grafts; to prevent
cerebrovascular occlusion; and as adjuncts to thrombolytic

Erythropoiesis-Stimulating Agents
 Exogenous erythropoietin
therapy in the treatment of myocardial infarction (MI) and  epoetin alfa and darbepoetin alfa
the prevention of reinfarction after MI.
Unit 6.d- Pharmacology
LIPID-LOWERING AGENTS
 It is important to ensure that the patient has adequate  Hydroxyurea - a cytotoxic antineoplastic drug that is also
levels of the components required to make RBCs, including used to treat leukemia, ovarian cancer, and melanoma.
adequate iron.  increases the amount of fetal hemoglobin produced in the
 Epoetin alfa acts like the natural glycoprotein bone marrow and dilutes the formation of the abnormal
erythropoietin to stimulate the production of RBCs in the hemoglobin S in adults who have sickle cell anemia.
bone marrow.  Given orally, hydroxyurea is absorbed well from the GI
 Indicated in the treatment of anemia associated with renal tract, reaching peak levels in 1 to 4 hours.
failure and for patients on dialysis; for anemia associated  Contraindicated with known hypersensitivity reactions and
with AIDS therapy; and for anemia associated with cancer with severe anemia or leukopenia because it can cause
chemotherapy when the bone marrow is depressed and further bone marrow suppression.
the kidneys may be affected by the toxic drugs  It is cytotoxic and is associated with adverse effects
 Darbepoetin alfa is an erythropoietin-like protein associated with the death of cells, especially in cells that
produced in Chinese hamster ovary cells with the use of are rapidly turning over. There is an increased risk of
recombinant DNA technology. cancer development.
 Treatment of anemias associated with chronic renal failure,
including patients receiving dialysis, anemia induced by
cancer chemotherapy.
 Gained negative publicity after it was used by athletes to
increase their RBC count in the hope that it would give
them more endurance and strength
Agents for Iron Deficiency Anemia
 Although most people get all of the iron they need
through diet, in some situations diet alone may not be
adequate.
 ferrous fumarate, ferrous gluconate, ferrous sulfate,
ferrous sulfate exsiccated, ferumoxytol, iron dextran , iron
sucrose, and sodium ferric gluconate complex
 Iron preparations elevate the serum iron concentration.
They are then either converted to hemoglobin or trapped
in reticuloendothelial cells for storage and eventual release
and conversion into a usable form of iron for RBC
production.
Contraindications:
 Hypersensitivity
 hemochromatosis (excessive iron); hemolytic anemias,
which may increase serum iron levels and cause toxicity;
and peptic ulcer, colitis, or regional enteritis because the
drug can be directly irritating to these tissues and can
cause exacerbation of the diseases.
Adverse Effects:
 Oral iron - GI irritation; melena, N/V, diarrhea,
constipation
 With increasing serum levels, iron can be directly toxic to
the CNS, causing coma and even death.
 Parenteral iron - associated with severe anaphylactic
reactions, local irritation, staining of the tissues, and
phlebitis.
 Iron toxicity - Chelating agent: deferoxamine mesylate
(Desferal), grasp and hold a toxic metal so that it can be
carried out of the body before it has time to harm the
tissues.
 Given IM, subcutaneous, or IV; rash and vision changes are
common
 Clinically Important Drug–Drug Interactions:
Iron absorption decreases if iron preparations are taken with
antacids, tetracyclines, or cimetidine; if these drugs must be used,
they should be spaced at least 2 hours apart.
 Clinically Important Drug–Food Interactions:
Iron is not absorbed if taken with antacids, eggs, milk, coffee, or tea.
These substances should not be administered concurrently.
Agents for Megaloblastic Anemias
 Megaloblastic anemia is treated with folic acid and vitamin
B12.
 Folate deficiencies usually occur secondary to increased
demand (as in pregnancy or growth spurts); as a result of
absorption problems in the small intestine; or secondary to
the malnutrition of alcoholism.
 Folic acid derivatives include folic acid, leucovorin
 Vitamin B12 includes hydroxocobalamin, and
cyanocobalamin

Agent for Sickle Cell Anemia

 Patients with sickle cell anemia are treated with antibiotics
to help fight the infections that can occur when blood flow
is decreased to any area; with pain-relieving activities to
help alleviate the pain associated with the anoxia to
tissues.