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 its the
DVT thats 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 & RBCs 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 fibrinenmeshes RBCs &
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 doesnt 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

CA++

Fibrin
(soluble)
(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 TIAs
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 SEs

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 (Raynauds 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 whats available.
Convert 0.2 mg. to mcg.

= 200 mcg.

250 mcg X 2 ml. = 5 X 2 ml. =

200 mcg
4

10

= 2.5 ml.