1. Chronic Diarrhea: Working with older patients to meet patient specific needs Presented By: Cory Phillips March 24, 2011

2. Case summary JS is an 82 yo WF whose husband presented to the compounding pharmacy looking for paregoric. JS had chronic, severe diarrhea and possibly IBS. The patient had used paregoric in the past, but was unable to find it because the manufacturers stopped supplying the medication. The husband stated that “She had tried everything!” She was set on getting paregoric because she had used this medication for years and it had worked well for her. In her opinion this was the only medication that helped.

3. Patient history 82 yo WF Average height Average weight NKDA KNA No nicotine, alcohol, or recreational drug use Overall good health for an 82 yo woman ROS: chronic diarrhea

4. Primary problem The patient had chronic diarrhea with possible IBS. The manufacturer of paregoric no longer supplies the drug. The patient’s husband presented to the compounding pharmacy in hopes of being able to have paregoric compounded.

5. Background on disease state (IBS) Chronic, episodic GI disorder Affects gut motility Characterized by Abdominal pain Discomfort Defecation disturbances Bloating ~ 10-15% of adult population has symptoms consistent with IBS Prevalence of IBS 2x higher in females than males Symptoms present by age 35

6. Background on disease state (IBS) Causes unknown Alteration in Intestinal motility Visceral hypersensitivity Brain response to visceral stimuli May follow bacterial gastroenteritis in 7-30% of cases

9. Older Generation Uses One of the first agents used for teething in babies Use declined due to known and potential toxic effects of ingredients Used to treat diarrhea or severe withdrawal in neonates born to women addicted to opiates More effective and/or safer agents for the treatment of diarrhea have largely replaced paregoric

10. Mechanism of Action Activity due to opiate agonist morphine Increase smooth muscle tone Antral portion of stomach Small intestine (especially the duodenum) Large intestine Sphincters Decrease secretions Stomach Pancreas Biliary tract Results in constipation and delayed digestion

11. Contraindications/Precautions Sedation Use caution when driving or operating machinery CI Patients with diarrhea secondary to poisoning Infectious diarrhea Use cautiously in pts with GI disease Obstruction Ulcerative colitis Pre-existing constipation Biliary spasms Avoid in pts with severe pulmonary disease Acute or chronic asthma COPD

12. Side Effects (cholinergic) Bradycardia Peripheral vasodilation Problematic in pts with cardiac disease Urinary retention Oliguria Pregnancy Category C

13. Drug Interactions Adverse Reactions Lightheadedness Dizziness Sedation N/V Constipation Ileus GI obstruction Dry mouth Blurred vision Miosis Respiratory depression/arrest Apnea Circulatory depression Coma Shock Cardiac arrest Physical dependence following prolonged use CNS depressants Mixed opiate agonists/antagonists Opiate antagonists

14. Compounding of paregoric

15. Other Options for Diarrhea Individualized treatment Lifestyle changes Dietary changes Cognitive-behavioral therapies Complementary therapies in ajunct to drug therapy Atropine; Difenoxin Atropine; Diphenoxylate Attapulgite Bismuth Subsalicylate Kaolin; Pectin Loperamide Loperamide; Simethicone Opium Tincture Nonpharmacological Pharmacological

16. Summary of Primary Literature No recent literature due to paregoric being an older drug Some early 2000s studies on paregoric in neonatal withdrawal syndrome 2008 Brazilian phase I study investigated the safety of Elixir paregoric® Investigated whether administration causes any noticable toxic effects in healthy volunteers No serious adverse reactions were reported following administration Mild adverse effects resolved themselves

17. Recommendations/Solution The solution was to compound the drug Compounded as a CII prescription The dosage given was 5—10 ml PO 1—4 times per day Recommend the patient see her physician if problem persists Might have IBS which is treated differently than diarrhea alone

18. Conclusion/Follow-up The patient is satisfied with the paregoric which is working well for her.

19. Application Pearls of Wisdom Pharmacists need to be able to work with a variety of patients, including older patients, to meet patient specific needs. It is important for pharmacists to have knowledge of older generation drugs and what they are indicated for. Critical pharmacy problems can be solved when the pharmacist has a strong knowledge of the patient population and drugs associated with this population. Pharmacy should not be limited to what drug manufacturers have to offer. We have access to a plethora of chemicals that can be compounded to fit patient specific needs.

20. References Patient and Preceptor (Dr. Randall Allen) Gold Standard, Inc. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2011. Available at http://clinicalpharmacology-ip.com/Defalt.aspx. Accessed March 19, 2011. Irritable Bowel Syndrome. DISEASEDEX. [database online]. Available at http://www.thomsonhc.com. New York: Thomson Reuters; 2011. Accessed March 19, 2011. MEA de Moraes, Bezerra MM, Bezerra FAF, et al. Safety evaluation of Elixir paregorico® in healthy volunteers: a phase I study. Human & Experimental Toxicity. 2008; 27(10): 751-756.