Circulatory Disorders - Pharmacology

Circulatory disorders impair the flow of blood throughout the body. Circulatory drugs are used to restore and maintain circulation. There are four groups of circulatory drugs.

  1. Anticoagulants and antiplatelets (antithrombotics). Anticoagulants and antiplatelets prevent platelets from clumping together and lower the risk that a patient will develop blood clots.
  2. Thrombolytics. Thrombolytics are sometimes called clot busters because they attack and dissolve blood clots that have already formed.
  3. Antilipemics. Antilipemics decrease blood lipid concentrations.
  4. Peripheral vasodilators. Peripheral vasodilators dilate vessels narrowed by vasospasm.


A clot is a thrombus that has formed in an arterial or venous vessel and is caused by decreased circulation (blood stasis). Anticoagulants such as warfarin and heparin inhibit clot formation but do not dissolve clots that have already formed. Anticoagulants are given to patients who are at risk for deep venous thrombosis and pulmonary embolism. These patients may have had a myocardial infarction (MI, heart attack), a cerebrovascular accident (CVA or stroke), or have an artificial heart valve.

Antiplatelet drugs such as aspirin, dipyridamole (Persantine), and sulfinpyrazone (Anturane) are prescribed for the prevention and formation of blood clots (platelet aggregation).

Patients who have chronic or acute atrial fibrillation are also given anticoagulants to prevent the formation of mural thrombi (blood clots in the heart).

Anticoagulants can be administered orally (coumadin) or parenterally (heparin) to combine with antithrombin III, thus in activating thrombin and other clotting factors. This prevents the formation of a fibrin clot.

Anticoagulants are poorly absorbed through the GI mucosa and destroyed by liver enzymes so it is given subcutaneously or intravenously. Anticoagulants can be given as an IV bolus or infusion. Clotting time is prolonged and partial thromboplastin time (PTT) and activated partial thromboplastintime (aPTT) are monitored during therapy.

Anticoagulants decrease platelet count causing thrombocytopenia. The antidote for heparin is protamine sulfate, which is given intravenously.

When IV therapy is to be discontinued, oral warfarin (Coumadin) or dicumarol is administered simultaneously. However, you must monitor lab values as heparin is gradually stopped and coumadin is added. The dose of Coumadin is adjusted based on PT values.

The International Normalized Ratio (INR) is the laboratory test used to monitor patients on anticoagulant therapy. Normal INR is 1.3 to 2.0 and patients on warfarin therapy are maintained at an INR of 2.0 to 3.0. Monitoring the lab values at regular intervals is required for the duration of drug therapy.

Patients should also be observed for petechiae and ecchymosis, tarry stools, and hematemesis which all could be indicative of occult (hidden) bleeding. The antidote for the oral anticoagulants is Vitamin K (phytonadione) (AquaMEPHYTON).

Low Molecular Weight Heparins (LMWHs) are derivatives of standard heparin and include enoxaparin sodium (Lovenox) and dalteparin sodium (Fragmin). They are used for prevention of deep venous thrombosis (DVT).

Low Molecular Weight Heparins can be administered at home because PTT monitoring is not necessary. They are given subcutaneously in the abdomen twice a day. The average treatment is for 7 to 14 days. The half life of LMWH is two to four times longer than that of heparin. Patients should not take antiplatelet drugs such as aspirin while taking LMWHs. Bleeding is less likely to occur and overdose is rare. However, protamine sulfate is the antidote if necessary and the dose is 1 mg of protamine for every 1 mg of LMWH given.


When a blood clot is mobilized, it is called a thrombus or embolus. It moves through blood vessels eventually causing a blockag called a thromboembolism resulting in decreased blood flow (ischemia) that causes death (necrosis) of tissues in the effected area. Thromboembolisms disintegrate naturally in about two weeks through the fibrinolytic mechanism, which breaks down fibrin.

Thrombolytics are drugs that promote the fibronolytic mechanism if administered within 4 hours following an acute myocardial infarction (AMI). An acute myocardial infarction (heart attack) can be caused by a thromboembolism blocking a coronary artery. This results in decreased circulation to that part of the heart. The ischemic (without oxygen) tissue becomes necrotic (dies) if left without an oxygen supply. Thrombolytics prevent or minimize necrosis that results from the blocked artery and therefore decreases hospitalization time. After thrombolytic treatment, the patient is evaluated for cardiac bypass or coronary angioplasty procedures.

Thrombolytics are also used for pulmonary embolism, deep vein thrombosis, and noncoronary arterial occlusion from an acute thromboembolism.

Commonly used thrombolytics are streptokinase, urokinase, tissue plasminogen activator (t-PA, Alteplase), anisoylated plasminogen streptokinase activator complex (APSAC, Anistreplase), and reteplase (Retavase).

All of these drugs induce fibrin breakdown (fibrinolysis).

Allergic reactions can complicate thrombolytic therapy. Anaphylaxis (vascular collapse) occurs more frequently with streptokinase than with the other thrombolytics.

Reperfusion dysrhythmia or hemorrhagic infarction can result if thrombolytics break up the clot after an MI. The major complication using thrombolytics is hemorrhage. The hemorrhage is stopped by using aminocaproic acid (Amicar) to inhibit plasminogen activation. The use of heparin with thrombolytic medications is commonly done and can prevent formation of new clots but requires intensive care and close monitoring of the patient.


Antilipemics are drugs that lower abnormal blood lipid levels (see Table (Serum lipid values) ). Lipids, composed of cholesterol, triglycerides, and phospholipids, are bound to

Serum lipid values

TABLE : Serum lipid values.

lipoproteins (see Table (Hyperlipidemia: Lipoprotein Phenotype Types II and IV are commonly associated with coronary artery disease.) ) and are transported in the body. These lipoproteins are classified as:

  • Chylomicrons
  • Very low-density lipoproteins (LDL)
  • High-density lipoproteins (HDL).

The HDL (friendly or “good” lipoproteins) has a higher percentage of protein and fewer lipids. HDL removes cholesterol from the bloodstream and delivers cholesterol to the liver. The other three lipoproteins are composed of cholesterol

TABLE : Hyperlipidemia: Lipoprotein Phenotype Types II and IV are commonly associated with coronary artery disease.

Lipoprotein Phenotype Types II and IV are commonly associated with coronary artery disease

and triglycerides and contribute to atherosclerotic plaque in the blood vessels (“bad” lipoproteins).

When cholesterol, triglycerides, and LDL are elevated, the patient is at increased risk for coronary artery disease.

Before antilipemics are administered, patients are treated with nonpharmaco-logical methods to reduce cholesterol and saturated fats in their diet. Total fat intake should be 30%. The patient is also encouraged to exercise. Hereditary factors have a great influence on cholesterol levels and are considered non-modifiable risk factors.

Antilipemics include cholestyramine (Questran), colestipol (Colestid), clofi-brate (Atromid-S), gemfibrozil (Lopid), nicotinic acid or niacin (Vitamin B2).

Clofibrate is not used for long-term treatment because of its many side effects such as cardiac dysrhythmias, angina, thromboembolism, and gallstones.

Nicotinic acid is effective in lowering cholesterol levels, but it too has numerous side effects including GI disturbances, flushing of the skin, abnormal liver function (elevated serum liver enzymes), hyperglycemia, and hyperuricemia. Required large doses make it intolerable for most patients.

Probucol is poorly absorbed and is not as effective as the other antilipemic drugs. Probucol also causes diarrhea and is contraindicated in patients with cardiac dysrhythmias. Cholestyramine lowers cholesterol levels, but causes constipation and peptic ulxcer.

Statin drugs inhibit the enzyme HMG CoA reductase in cholesterol biosynthesis. They inhibit cholesterol synthesis in the liver, decrease the concentration of cholesterol, decrease the LDL, and slightly increase the HDL cholesterol.

Reduction of LDL is seen in as early as two weeks.

Statins include atorvastatin calcium (Lipitor), cerivastatin (Baycol), fluvas-tatin (Lescol), lovastatin (Mevacor), pravastatin sodium (Pravachol), and simvastatin (Zocor).


A common problem in the elderly is peripheral vascular disease. It is characterized by numbness and coolness of the extremities, intermittent claudication (pain and weakness of limbs when walking and symptoms are absent at rest), and possible leg ulcers. The primary cause is hyperlipemia resulting in atherosclerosis and arteriosclerosis. The arteries become occluded.

Peripheral vasodilators increase blood flow to the extremities and are used for venous and arterial disorders. They are more effective for disorders resulting from vasospasm (Raynaud’s disease) than from vessel occlusion or arteriosclerosis (arteriosclerosis obliterans, thromboangiitisobliterans [Buerger’s disease]). Some of the drugs that promote vasodilation include tolazoline (Priscoline), an alpha-adrenergic blocker (Chapter (Nervous System Drugs) ); isoxsuprine (Vasodilan) and nylidrin (Arlidin), beta-adrenergic agonists (Chapter (Nervous System Drugs) ); and cyclandelate (Cyclan), nicotinyl alcohol, and papaverine (Cerespan, Genabid), direct-acting peripheral vasodilators. The alpha blocker prazosin (Minipress) and the calcium channel blocker nifedipine (Procardia) have also been used.

All rights reserved © 2018 Wisdom IT Services India Pvt. Ltd Protection Status

Pharmacology Topics