CHAPTER 40
LECTURE 10
Drugs for Circulatory
Disorders
Circulatory Disorders
• Drugs used are to maintain, preserve or restore circulation
• Anticoagulants & antiplatelets (antithrombotics),
thrombolytics, antilipemics, peripheral vasodilatiors
• Anticoagulants - prevent formation of clots that inhibit
circulation
• Antiplatelets - prevent platelet aggregation
• Thrombolytics (clot busters) - attack/dissolve formed clots
• Antilipemics - decrease bld. lipid concentration
• Peripheral vasodilators - promote dilation of vessels
narrowed by vasospasm
Circulatory Disorders
Thrombus Formation
• Clot is a Thrombus formed in an arterial or
venous vessel
• thrombophlebitis - Both inflammation and
clots are present
• Some thrombus can be superficial but it’s the
DVT that’s a concern  embolism to lungs.
Circulatory Disorders
Thrombus Formation
•Arterial formation - begins w/ platelet adhesion to
arterial vessel wall  Adenosine diphosphate (ADP)
released from platelets  more platelet aggregation 
Bld. flow inhibited  fibrin, platelets & RBC’s surround
clot  build up of size structure  occludes bld
vessels  tissue ischemia
• The result of Arterial Thrombus is localized tissue
injury from lack of perfusion
Circulatory Disorders
Thrombus Formation
• Venous Formation - Usually from slow bld flow
- Can occur rapidly Stagnation of the blood flow initiate the
coagulation cascade production of fibrinenmeshes RBC’s &
platelets to form the thrombus. Venous thrombus has a long tail that
can break off to produce an embolus. These travel to faraway sites
then lodge  in lung (capillary level)  inadequate O2 & CO2
exchange occur (ie. pulmonary embolism & cerebral embolism)
• Oral & parenteral anticoagulants (Heparin/Warfarin) primarily act
by preventing venous thrombosis
• Antiplatelet drugs primarily act by preventing arterial thrombosis
Circulatory Disorders
Thrombus Formation
• Hemostasis is the normal homeostatic process of
blood clotting.
• Clotting proteins normally circulate in an inactive
state & must be activated to form a fibrin clot.
When there is a trigger - inc. bld viscosity from
bed rest & stasis - the clotting cascade is activated.
• Bld vessel injured  platelets adhering to site of
injury  release of ADP a platelet plug - is ex.
of Intrinsic clotting path.
• Tissue injury (outside bld vessels) = extrinsic
pathway activated
Circulatory
Thrombus Formation
Risk Factors for Deep Vein Thrombophlebitis and
Thromboembolism
• Three factors increasing risk 1) Stasis of venous flow,
2) damage of the endothelium(inner lining of vein), and
3) hypercoagulability of the blood.
• Hx. of thrombophlebitis, abdominal & pelvic surgery, Obesity,
neoplasms (lung), CHF, Advanced age, A-fib, vasospasm, Prolonged
immobility (bed-rest, long trip spinal cord injury, FX. hip), CVA MI
PG, post partum, Estrogen TX (oral contraceptives), IV therapy,
trauma, Sepsis, Venous cannulation, Drug abuse, Cigarette smoking
Excessive vit E intake Hypercoagulable states (Polycythemia, severe
anemias, Dehydration or malnutrition), Antithrombin III deficiency
Circulatory Disorders
Anticoagulants
• Inhibit clot formation - Do NOT dissolve clots
already formed, but prophylactically prevent new
clots
• Used in clients w/ venous/arterial disorders that put
them at inc. risk of clot formation
• Venous = DVT & Pulmonary embolism
• Arterial = Coronary thrombosis (MI), artificial
heart valves, CVA
Circulatory Disorders
Heparin
• A natural substance in the liver that prevents clot
formation.
• Primary use is to prevent venous thrombosis that can lead
to pulmonary embolism (PE) or stroke
• Combines w/ antithrombin III  inactivates thrombin and
other clotting factors then the conversion of fibrinogen to
fibrin doesn’t occur so the clot is prevented
• Poorly absorbed through GI mucosa - given SQ & IV
• Prolongs clotting time - partial thromboplastin time (PTT)
& activated partial thromboplastin time (aPTT) - both bld
tests are monitored during therapy
Circulatory Disorders
Heparin
• Use - DVT, PE, & CVA, Rx of clients w/ heart valve
prosthesis, during CV surgery, post op, during
hemodialysis
* Low doses = prophylactically to prevent DVT
* Full doses = treats a thromboembolism & promotes
neutralization of activated clotting factors = prevents
extension of thrombi & formation of emboli
* If started shortly after formation of a thrombus - heparin
will also prevent it from developing into an insoluble
stable thrombus = reduced tissue damage
Circulatory Disorders
Heparin
• SE - Decreased platelet count =
thrombocytopenia
Hemorrhage - give protamine sulfate IV (an
anticoagulant antagonist)
• DI - Inc. effects w/ ASA, NSAIDs, thrombolytics
Dec. effect w/ NTG
Circulatory - LMWH
•Low Molecular Weight Heparins (LMWHs) recently introduced to prevent venous
thromboembolism
•Binds to Antithrombin III which inhibits the
synthesis of factor Xa & formation of thrombin
- enoxaparin (Lovenox) & dalteparin sodium
(Fragmin)
- more stable dose, lower risk of bleeding, freq. lab
monitoring not required
Circulatory Disorders
LMWHs
• Use - Prevention of DVT after hip & knee replacement
surgery & abd. surgery
• Can be administered at home
• Administered SQ BID
• Available in prefilled syringes w/ attached needles
• Usually given in the abdomen
• Average Rx is 7 to 14 days
• Bleeding less likely to occur
• DI - caution client not to take antiplatelet drugs (ASA)
during therapy
Circulatory Disorders
Warfarin (Coumadin)
• Action - Inhibits activity of vit. K required for the
activation of clotting factors II, VII, IX, & X. Blocking
these factors prevents clot formation
• Use - prophylactically to prevent venous thrombosis, A.
fib., PE, coronary occlusion, thrombophlebitis
• Prolongs clotting time & is monitored by the lab bld. tests
prothrombin time (PT) & International normalized ratio
(INR) - usually before administering the next dose until
therapeutic levels are reached. INR is 1.3 - 2.0 therapeutic
levels on coumadin = 2.0 - 3.0
CIRCULATORY DISORDERS
Warfarin (Coumadin)
• INR is replacing the PT  INR more accurate. Need higher
levels for prosthetic heart valves, cardiac valvular disease and
recurrent emboli.
•
PT not consistent lab to lab or reagents used.
• PT is 1.5 – 2 times the reference value to be therapeutic
• Regular monitoring is required for the duration of drug therapy
•Warfarin is well absorbed through the G.I. tract. Food decreases.
Circulatory Disorders
Warfarin (Coumadin)
• Has a long t1/2 & duration of action - drug accumulation
poss. and can cause internal bldg.
- Observe for: petechiae, ecchymosis, tarry stools,
hematemesis. Monitor menstrual flow
- Teach client importance of bld tests & to look out for
signs of bleeding
• DI - LOTS!!! consult a physician before taking any over
the counter medications
• Vit. K (phytonadione) = antagonist of Warfarin. Used for
OD/ uncontrolled bleeding
Intrinsic Clotting Pathway
The Clotting Cascade
Blood or collagen contact
XII
Tissue trauma
XIIa (H)
XI
Extrinsic Clotting Pathway
Tissue factor
XIa (H)
(W) VII  VIIa
(W) IX
IXa (H)
CA++
PF 3
VIII (W)
Common Pathway
(W) X
Xa (H)
(Next slide)
Common Pathway
Xa (H)
Ca++
PF 3
V (W)
(H) (F)
(W) Prothrombin
Thrombin
Ca++
Fibrinogen
Fibrin (soluble)
CA++
(H)
XIIIa
Fibrin (insoluble)
XIII
Circulatory Disorders
Antiplatelet Drugs
Aspirin, Dipyridamole (Persantine), Ticlopidine (Ticlid)
abciximab (ReoPro), tirofiban (Aggrastat)
• Action: To prevent thrombosis in the arteries by
suppressing platelet aggregation via diff. methods
• Use: Prevention of MI/stroke for clients w/ family hx
- prevention of a repeat MI, stroke in clients having TIA’s
• Persantine & Ticlid = similar to ASA but more expensive
• ReoPro & Aggrastat = mainly for acute coronary
syndromes. Route = IV
Circulatory Disorders
Thormbolytics
• Thromboembolism - Occlusion of an artery or vein caused
by a thrombus or embolus - results in ischemia that causes
necrosis of the tissue distal to the obstructed area.
- it takes about 1 to 2 weeks for the blood clot to
disintegrate by natural fibrinolytic mechanisms
- if new thrombus dissolved quicker damage minimized &
bld flow restored faster  purpose of therapy
• Thrombolytics promote fibrinolytic mechanism (convert
plasminogen to plasmin & destroys the fibrin in the clot) administering a thrombolytic drug = clot disintegrates
Circulatory Disorders
Thrombolytics
• Use = Acute MI - w/ in 4 hrs to dissolve clot & unblock artery, so
decrease necrosis to myocardium & hospital stay is decreased.
• Other uses: Pulmonary embolism, DVT, Noncoronary arterial
occlusion
• Streptokinase, Urokinase, Tissue plasminogen activator (t-PA),
anisoylated plasminogen streptokinase activator complex
(APSAC)
• Streptokinase & Urokinase are enzymes that act to convert
plasminogen to plasmin
• t-PA and APSAC activate plasminogen by acting specifically on
clot.
Circulatory - Thrombolytics
•All 5 drugs induce fibrinolysis (fibrin breakdown)
•Side effects: hemorrhage, allergic reactions (anaphylaxis) &
vascular collapse-more with Streptokinase
•Onset and peak are immediate and rapid, duration can be 12h.
•t-PA most expensive - $2500/tx, short t1/2 (5-7 min.) not
associated with anaphylaxis.
•Aminocaproic acid (Amicar) an antithrombolytic used to stop
bleeding by inhibiting plasminogen activation. Used to stop
bleeding from heart surgery, trauma & abruptio placenta.
Circulatory Disorders
Antilipemics
• Used to Lower bld. lipid levels
• Cholesterol, triglycerides & phospholipids transported in
the body bound to protein in various amounts chylomicrons, very low-density lipoproteins (VLDL),
low-density lipoproteins (LDL), high-density lipoproteins
(HDL) - more protein & less lipid (removes chol. from
bld. stream & deliver it to the liver)
• VLDL & LDL contribute to atheroslerotic plaque in bld
vessels - composed of mainly cholesterol & triglycerides
Circulatory Disorders
Antilipemics
• Nonpharmacologic = before drugs to dec. BP
- Reduce saturated fats & chol intake in the diet
- Exercise
- Body wt. reduction
- Eliminate smoking
• If drug therapy needs to be initiated, clients still need to
make lifestyle changes
• Compliance an issue
Circulatory Disorders
Antilipemics
• Cholestyramine (Questran) - Powder form, Colestipol
(Colestid) - a newer resin - both lower chol.
• Clofibrate (Atromid-S), gemfibrozil (Lopid) - fibric
acid derivatives effective in reducing triglyceride & VLDL
levels.
- Highly protein bound. do not take w/ anticoagulants compete
- Clofibrate - many side effects - dysrhythmias, angina
• Nicotinic acid or niacin (vit B2) - reduces VLDL & LDL
- effective in dec. chol levels, Many SE’s
Circulatory Disorders
Antilipemics
• Statin drugs inhibit enzyme HMG CoA reductase in chol
biosynthesis ( HMG CoA reductase inhibitors) = Dec. the
concentration of chol & dec. LDL & sl. inc. in HDL
• atorvastatin calcium (Lipitor), cerivastatin (Baycol),
fluvastatin (Lescol), lovastatin (Mevacor) - SE = GI disturbances, headaches, muscle cramps &
tiredness (all complaints early in tx.)
- monitor serum liver enzymes
- Annual Eye exams d/t poss cataract formation
- Useful in coronary artery disease (CAD) &
mortality rate
Circulatory - Antilipemics
•If therapy withdrawn, cholesterol levels return to pretreatment
levels  lifetime commitment
•Lovastatin is absorbed with food. High 1st hepatic pass -50%
•Onset and peak occurs in hours , but takes several days to have
a therapeutic effect. Duration is up to 3 weeks.
•NI Monitor blood lipid levels, liver functions, if GI upset
occurs have client take with sufficient water or with meals.
•Desired Lab Values = CHOL <200; triglyceride <150; LDL <
130; HDL > 60
Circulatory Disorders
Peripheral Vasodilators
• Peripheral Vasodilators - Increase bld flow to
extremities
• Peripheral vascular disease is a problem in the
elderly
- Numbness & coolness of extremities, intermittent
claudication (pain/weakness of limb when walking
- symptoms absent at rest), poss. leg ulcers
- Primary cause is hyperlipemia from
atherosclerosis & arteriosclerosis - arteries become
occluded
Circulatory Disorders
Peripheral Vasodilators
• Peripheral vasodilators more effective for disorders
resulting from vasospasm (Raynaud’s disease) than from
vessel occlusion or arteriosclerosis
• Vasodilators have diff. actions but all promote vasodilation
• Isoxsuprine (Vasodilan) - Beta-2 adrenergic agonist causes vasodilation on arteries w/in skeletal muscles,
bronchodilation may also occur
- SE = lightheadedness, dizziness, orthostatic hypotension,
tachycardia, GI distress
Circulatory Disorders
Peripheral Vasodilators
• Pentoxifylline (Trental) - an antihemorrheologic agent improves microcirculation & tissue perfusion
inc. in
tissue O2. Not a vasodilator, but dilates rigid
arteriosclerotic bld vessels - arterioles, capillaries &
venules
- Use = clients w/ intermittent claudication
- Take w/ food
- Avoid smoking d/t nicotine increases vasoconstriction
MATH
The order for medication is 12 mg. The medication you have
is labeled 5 mg per ml. How much do you give?
12mg X 1 ml.
5 mg
= 2.4 ml
You have a vial labeled 40 mg/mL. You need to give 0.1 g.
How much should you give.
Convert 0.1g to mg.
100 mg X 1 mL
40 mg
= 100mg
=
2.5 mL
MATH
You have an order to give 250 mcg. A dosage of 0.2 mg. per
2 ml. is what’s available.
Convert 0.2 mg. to mcg.
250 mcg X
200 mcg
= 200 mcg.
2 ml. = 5 X 2 ml. =
4
10
4
= 2.5 ml.