Harvard-MIT Division of Health Sciences and Technology HST.151: Principles of Pharmocology Instructors: Dr. Carl Rosow, Dr. David Standaert and Prof. Gary Strichartz 1 1. ORGANOPHOSPHATE POISONING A 55 yr old crop duster calls because he has lost control over his chronic twitch, and he is now beginning to have problems with blurry vision and control of his bowels and bladder. He wants to go back to the airfield to finish his crop dusting, but his supervisor makes him call you first. [AChE poisoning, signs] [Treatment] [Selective toxicity of insecticides] 2. ANTICOAGULATION A 50 yr old female is chronically taking warfarin because of a prosthetic mitral valve which was inserted at age 38. Her dose has been stable for many years, and her prothrombin time is usually 5-6 seconds over control (INR 2.9). Three weeks ago, a routine chest X-ray suggested possible tuberculosis. A PPD was positive, so treatment was started with rifampin and isoniazid. This evening she collapsed suddenly at home, and you are called to see her in the Emergency Ward. She is comatose, and a CAT scan shows a large cerebral infarct. INR is 1.2. [Anticoagulant effects, monitoring] [Drug interaction, enzyme induction] 3. ULCERATIVE COLITIS AND SULFASALAZINE You are called to consult on a 20 yr old female for management of recently diagnosed ulcerative colitis. One month prior to admission the patient noted bloody diarrhea and crampy abdominal pain. Proctosigmoidoscopy now reveals diffuse edema, friability and ulcerations consistent with acute ulcerative colitis. Barium enema is normal. You prescribe 1 gram of sulfasalazine po qid and hydrocortisone 100 mg as retention enema bid. Over the next two weeks she improves steadily with complete normalization of her bowel pattern. Two months later you are called again because she was admitted with the sudden onset of weakness, dizziness, chills, abdominal pain and fever. The fever has persisted despite intravenous fluids, antibiotics and systemic steroids and she has now developed a rash and mild jaundice. [Bacterial biotransformation] [Pro-drugs] [Acetylator phenotype]2 4. PHEOCHROMOCYTOMA A 29 yr old female presents to your clinic with a 2 yr. history of headaches, perspiration, chest pain, increased urination and chest pain. Lately, she has been having problems eating because of trouble swallowing and intermittent crampy abdominal pain. Your initial diagnosis of cholelithiasis is further supported by abnormal liver function tests, and you send her for an abdominal ultrasound. When the radiologist presses the transducer up against the right upper quadrant to better visualize a grapefruit-size mass, all of the symptoms the patient has ever experienced present in force. A blood pressure of 250/140 is recorded, and you are voice-paged STAT to the radiology suite. When you arrive, the patient and radiologist are both flushed, diaphoretic and quite uncomfortable; they both look to you for relief. [Diagnosis] [Pathophysiology] [Rx - Acute and Long-term] 5. ASTHMA A patient comes to you in the Medical Walk-In Unit suffering from poorly controlled asthma. He claims that despite regular use of oral theophylline and an albuterol inhaler he is still markedly short of breath. His brother recently left on vacation and left his two dogs with him. Your patient finds that his symptoms are made even worse, or may be brought on from a quiescent state, if he takes the dogs out for a run through the snow. More importantly, he is concerned because his heart is pounding. In between gasps and wheezes he asks you what to do now, and if there is anything you can give him that won't make his heart beat so fast. [Pathophysiology] [Rx Options: Acute treatment vs Chronic Prophylaxis]3 6. POISON CONTROLYou are working the telephone hotline at the Poison Control Center, and your supervisor asks you to review the phone log from the previous 24 hr. a. A 35 yr old man presented to the local EW from his laboratory where he had been working on an enzyme immobilization requiring the use of cyanide. His laboratory technician bumped his arm, and he complained that he felt faint and thought he could taste almonds. b. The Children's Hospital called because a 2 yr. old boy was brought in after probable ingestion of anti-freeze. c. Children's Hospital called again because a 4 yr. old girl ingested a bottle of her grandfather's digoxin tablets. She was having a substantial number of premature ventricular contractions. d. A physician from a local hospital called about a man with abdominal pain, headache and memory loss. He had been admitted with ataxia, a peripheral neuropathy, microcytic hypochromic anemia, and azotemia. Since he is a painter, there was some concern that he was suffering from lead toxicity. He is ultimately found to have an elevated free erythrocyte protoporphyrin level. 7. COCAINE - MI You are the emergency room doctor when a 19 yr. old female is brought in semi-comatose. An unidentified young man accompanies her and says that he was giving her a ride home when she asked to stop at a friend's house. He waited 20 minutes, and when she returned to the car she was acting funny. He brought her to the EW where she passed out. On physical exam she is diaphoretic and responds only to deep sternal rub. Blood pressure is 280/160 and heart rate is 190. Her lungs are markedly bronchospastic with poor air movement peripherally and central wheezes. You think you hear a gallop in addition to her normal heart sounds. The ECG shows evidence for a large evolving myocardial infarction. [Cocaine effects on the heart] [Rx cocaine toxicity]4 8. GLAUCOMA Mr. S presents to you with diminished peripheral vision. He complains that he feels like the world is closing in on him. He also notes that he has trouble looking at lights as they all appear to be surrounded by halos. You perform fundoscopic and gonioscopic exam with tonometry and diagnose glaucoma. Mrs. P is a 65 yr. old female who has become acutely ill in the waiting room. An ophthalmologic assistant had dilated her eyes in preparation for examination. She is now complaining of nausea, diaphoresis and pain in her right eye, which is now red and swollen. [Open vs. closed angle glaucoma] [Appropriate drug rx in each case, rationale] 9. PHARMACOGENETICS A 59 year old male with stable angina was given a prescription for metoprolol. After the first four doses he felt faint. His wife—a nurse—found