Interacting drugs

 Bile salts sequestrants - summary

 Bile acid sequestrant (BAS) +

 Anticoagulants  

 anticoagulant effect decreased by cholestyramine

 Digitalis glycosides 

 digitalis glycoside serum levels reduced, possibly reducing the therapeutic effect.

 Gemfibrozil    

  gemfibrozil bioavailability reduced by colestipol

 Glipizide  

  serum glipizide levels decreased by cholestyramine

  Lopanic acid   

    coadministration of cholestyramine resulted in abnormal cholectocystography. Cholestyramine has an apparent high affinity for iopanoic acid

 Phosphate  supplements 

  colestipol interfere with the absorption of oral phosphate  supplements

 Piroxicam 

 piroxicam elimination enhanced by cholestyramine

Propranolol    

 plasma concentration of propranolol and its metabolite reduced

 Tetracyclines

 serum levels of tetracyclines decreased by colestipol

 Thiazides diuretics 

 absorption of serum levels of thizide diuretics decreased

Thyroid hormones 

 loss of efficacy of thyroid and potential hypothyroidism with concurrent cholestyramine -

 Vitamin A, D, E, K 

  malabsorption occur during administration of bile acid sequestrants

Hyperlipoproteinemia. Biliary obstruction

Most common - Constipation at times severe and occassionaly accompanied by fecal impaction

Less common- abdominal pain/distention/cramping. GI bleeding, belching, bloating other adverse reactions include:

Lab test abnormalities- Transcient and modest elevations of AST, ALT, and alkaline phosphatase observed in patients treated with colestipol.

Liver function abnormalities observed with cholestryramine.

CNS- headache, anxiety, vertigo, dizziness, lightheadedness, insomnia, fatigue, tinnitus, syncope

GI -rectal bleeding/pain, black stools, hemorroidal bleeding, duodenal ulcer, peptic ulceration

Hematologic- increased prothrombin time, ecchymosis, anemia

Hypersensitivity- urticaria, dermatitis, asthma, wheezing, rash

Musculoskeletal- backache, muscle/joint pains, arthiritis, osteoporosis

Miscellaneous- anorexia, fatigue, weight loss/gain, increased libido, swollen glands, edema, weakness, shortness of breath, swelling of hands and feet

Hypersensitivity to sequestering resins or any any components of the products, complete biliary obstruction.

Special precautions:

• Monitoring-
• .Determine serum cholesterol levels frequently duringthe first few months of therapy and periodically thereafter.
• Periodically measure serum triglyceride level to detect any significant changes
• Diet- before instituting therapy, vigorously attempt to control serum cholesterol by an appropiate dietary regimen and weight reduction.
• Investigate and treat diseases -contributing to increased blood cholesterol before blood starting therapy (eg. hypothhroidism, diabetes mellitus, nephrotic syndrome, dysproteinemia, obstructive liver disease).
• Cholesterol reduction should occur during the first few months of therapy. Continue therapy to sustain cholesterol reduction. If adequate reduction is not attained, discontinue therapy.
• Malabsorption- because they sequester bile acids, these resins may interfere with normal fat absorption and digestion and may prevent absorption of fat soluble vitamins such as Vitamin A, D E and K.
• With long term therapy, supplemental vitamins A and D may be given in a water miscible form or administered parentrally Chronic use of resins may be associated with increased bleeding tendency due to hypoprothrombimemia associated with Vitamin K deficiency. This will respond to parentral Vitamin K1
• Reduced foliate- reduction of serum and red cell folate has been reported over long term administration of cholestyramine. Consider supplementation of folic acid.
• Hyperchloremic acidosis.- these drugs are chloride anion-exchange resins. Prolonged use may cause hyperchloremic acidosis, especially in younger and smaller patients where relative dosage may be higher.
• Constipation- These agents may produce or severely worsen preexisting constipation. Haemorroids may be aggrevated Avoid constipation in patients with symptomatic coronary artery disease.
•  

Warnings-

• Powder- to avoid accidental inhalation or esipheageal distress, do not take dry. Mix with fluids
• Carcinogenesis- Various alimentary system cancers were more prevalent with cholesyramine
• Pregnancy- safety for use during pregnancy has not beestablished.
• Lactation- excercise caution while administering to a nursing woman.
• Children- dosage schedule have not been established. The effects of long-term administration and effectiveness in mataining cholesterol levels are unknown.

Indications:

Hyperlipoproteinemia. Biliary obstruction

Dosage:

Twice daily

Overdosage:

Symptoms The chief potential harm would be GI tract obstruction. Location and degree of obstruction and status of gut motility of gut detremine treatment.

Overdosage has been reported in a patient taking 150% of the maximum recommended daily dose of cholestyramine for several weeks. No ill efects have been reported

Missed dose

1.  If you miss a dose of this medicine, take it as soon as possible.
2.  However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.
3.  Do not double doses.

BILE SALTS SEQUESTRANTS

1. Medication is taken before meals.

2. Do not take the powder in dry form; mix with beverages, highly fluid soups, cereals or pulpy fruits

3. Swallow colesterol tablets whole; do not cut, crush or chew

4. Medication may interfere with absorption of other drugs taken simutaneously.

Take other drugs 1 hour before or 4 to 6 hours after cholestryramine or colestipol

Pharmacology:

Cholesterol is the major (and probably the sole) precursor of bile acids. During normal digestion, bile salts are secreted via the bile from the liver and gall bladder into the intestines to emulsify the fat and lipid materials in the food, thus facilitating absorption

A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing the enterohepatic cycle. Bile acid sequestering resins bind the bile acids in the intestine in the form of insoluble complex which is excreted in the feces.

This results in partial removal of bile acids from the enterohepatic circulation, preventing their absorption. since these agents are anion-exchange resins, the chloride anions of the resin are replaced by other anions.

These are hydrophylic, but insoluble in water they remain unchanged in the GI tract and are not absorbed.

Medication is taken before meals

Pregnancy:

Safety for use during pregnancy has not been established.use only when clearly needed and when the potential benefits outweigh the potential hazards

Lactation:

Excercise caution while administering to a nursing woman. the possible lack of vitamin absorption may have effect on the nursing infants.

Children

Dosage schedules have not been established. The effects of long term administration and effectiveness in maintaining lowered cholesterol levels are unknown.