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University of Alabama at Birmingham School of Medicine Pharmacology Case #2 MR N. October 4, 2002 MEDICAL RECORD # 0000001 9/25/02 Mr. N, the 80 y.o. husband of Ms. N, has the following medical problems: 1. Angina pectoris. 2. Hypercholesterolemia. 3. Hypertension. 4. COPD. 5. Tobacco abuse. 6. Peripheral vascular disease. 7. Degenerative joint disease. 8. Status post left herniorraphy. 9. Status post bilateral cataract extractions. 10. Insomnia. Current Medications 1. Nitroglycerin 0.4 mg sl prn chest pain. 2. Isosorbide mononitrate mg po q 8 am and 2 pm. 3. Ipratropium bromide metered-dose inhaler 2 puffs qid. 4. Metoprolol 25 mg po bid 5. Enteric-coated aspirin 81 mg qd. 6. Benazapril 20 mg po bid. 7. Multiple vitamins one tablet po qd. 8. Docusate calcium 100 mg po bid prn constipation. 9. Amitriptyline 25 mg po hs prn sleep. Interval History Mr. N comes in with his wife, Mrs. N (Case #1), for a routine visit. He continues to smoke 1 pack of cigarettes daily and notes no change in his typical 1 block dypsnea on exertion. Weekly bouts of moderately severe substernal chest tightness radiate into the left upper extremity and are associated with nausea and diaphoresis. These symptoms are precipitated by exertion and emotional upset and are relieved by rest and sublingual nitroglycerin. He describes no change in the frequency, severity or associated symptoms and denies palpitations, orthopnea, paroxysmal nocturnal dypsnea, ankle edema or easy fatiguibility. Mr. N is independent in his self-care Activities of Daily Living (ADL’s), but requires assistance from his wife for banking, shopping and transportation (i.e., Instrumental ADL’s). The patient reports tolerating a low fat, low cholesterol diet since the last appointment on 7/7/02. Memory impairment, falls, urinary incontinence and difficulty walking are denied, but Mr. N complains of urinary hesitancy, diminished stream and constipation. Physical Examination The patient is robust, obese older man in no acute distress. BP 165/60, P 72, sitting; T 97o, Wt 200 lbs (no change since 7/7/02) 1 University of Alabama at Birmingham School of Medicine Skin: Good skin turgor w/ moist mucus membranes. Neck: Supple with a right carotid bruit and no jugular venous distention. Chest: Increased AP diameter with hyperresonant lung fields and diminished breath sounds throughout. (+) Bibasilar rales. Heart: Point of maximum impulse not palpable with a soft S1 and a physiologically split S2. (+) S4G, a 2/6 systolic ejection murmur is best appreciated at the apex and base. Abdomen: Benign. Rectum: Good sphincter tone, a 2(+) smoothly enlarged prostate, brown hemoccult (-) stool. Extremities: Bony hypertrophy of the right greater than left knees without effusions or signs of acute synovitis. Dependent rubor and absent pedal pulses in the feet. Laboratory Electrocardiogram: normal sinus rhythm, normal electrical axis, left atrial enlargement and Q waves consistent with an old inferior wall myocardial infarction. Urinalysis and serum electrolytes, glucose and BUN/creatinine are within normal limits. PSA 4.5. Fasting lipid panel: Cholesterol 300, HDL cholesterol 32, LDL cholesterol 153, triglycerides 165. Note: Mrs. N also comes today. Review her medical history from Case #1. 2 University of Alabama at Birmingham School of Medicine Questions 1. Comment on each medicine Mr. N is taking. (Be familiar with the class of drug, route of administration, duration of action, side-effect profile). 2. Comment on his history, physical examination and laboratory values. Note any abnormalities and consider if any are drug-induced. 3. What approach to his lipid/cardiovascular status would be reasonable? (do not worry about details here yet, since we will cover antianginal, antihypertensive and hypolipidemic drugs in the next section of the course) 4. If his COPD worsened, what drug could be used to improve his symptoms? 5. Mrs. N complains of pain in her right knee. What would you suggest to relieve her pain? 3 University of Alabama at Birmingham School of Medicine Answers. 1. Current Medications Nitroglycerin 0.4 mg sl prn chest pain. – anti-anginal vasodilating nitrate, fast-acting, sublingual route of administration to avoid first-pass metabolism and give rapid onset of action, used during an acute attack of angina. Isosorbide mononitrate 10 mg po q 8 am and 2 pm.—anti-anginal vasodilating nitrate, long-acting, taken orally, used prophylactically every day, but with a drug-free interval at night to diminish the development of tolerance; often causes severe headaches when taken initially, but tolerance develops to this side-effect, also causes orthostatic hypo tension and reflex tachycardia if not taken with a beta blocker. Ipratropium bromide metered-dose inhaler 2 puffs qid. -- muscarinic antagonist, unable to enter bloodstream or CNS because of quarternary ammonium ion,, inhaled to block ACh receptors on pulmonary smooth muscle cells and bronchi; decreases bronchoconstriction and bronchial secretions. Metoprolol 25 mg po bid – beta-1 adrenergic receptor antagonist, taken orally, relieves anginal pain, lowers heart rate, lowers myocardial O2 demand, improves survival postMI, side-effects include bronchospasm at high doses due to blockade of pulmonary beta2 adrenergic receptors, bradycardia, hypotension, fatigue, depression, impotence. Enteric-coated aspirin 81 mg qd. – taken orally at this low dose prophylactically to diminish platelet activity, reduce risk of cardiovascular accident; inhibits irreversibly COX-1 and COX-2; side-effects at this dose minimal, gastric irritation. Benazapril 20 mg po bid. -- ACE inhibitor, taken orally, reduces production of Angiotensin II, which is a vasoconstrictor, and reduces breakdown of bradykinin, which is a vasodilator; Used as a vasodilator and natriuretic agent to reduce hypertension, improve survival after MI, reduce symptoms of congestive heart failure; side-effects include cough, hypotension, angioedema, renal insufficiency, hyperkalemia, sodium loss. Multiple vitamins one tablet po qd. – everybody should take a Flintstone multivitamin once a day; my favorite is Barney. Docusate calcium 100 mg po bid prn constipation – stool softener, helps eliminate pain at excretion, taken orally as needed, detergent action allows water to enter stool. Amitriptyline 25 mg po hs prn sleep – inhibits reuptake of serotonin and norepinephrine, thus increasing actions of serotonin and norepinephrine, takes several weeks to become effective in treating depression; causes sedation, inhibition of muscarinic receptors, histamine 1 receptors, alpha1and alpha 2 adrenergic receptors; side-effects: antimuscarinic effects (blurred vision, dry mouth, urinary retention, constipation, tachycardia, sweating, agitation), postural hypotension. 2. Mr. N has chronic obstructive pulmonary disease (presumably due to his chronic smoking), stable angina, peripheral vascular disease, untreated pure hypercholesterolemia, poorly controlled hypertension, symptoms of urinary obstruction & constipation (aggravated by his use of the highly anticholinergic amytriptyline as a sedative). His risk factors for coronary heart disease need considerable work in order to reduce his risk of having another MI. The use of amitriptyline in this patient is probably contraindicated because of its less wellknown propensity to depress cardiac contractility, to increase the QT interval on his EKG, and to increase blood pressure and heart rate. These tendencies probably 4 University of Alabama at Birmingham School of Medicine underlie reports in the medical literature of new cardiovascular events in coronary artery disease patients taking tricyclic antidepressants. 3. He needs to stop smoking and probably add a statin to lower is cholesterol. Additional antihypertensive therapy is warranted. Diet and exercise modification would help. 4. Poor pulmonary function probably requires addition of albuterol (switch him to CombiVent that contains albuterol plus ipratropium) and possibly low-dose theophylline. 5. Mrs. N is at risk for gastric distress already as a result of prednisone therapy. NSAIDs are likely to aggravate that problem. She may need to try rest and ice on her knee. Alternatively, COX-2 selective drugs (expensive) or acetaminophen are options. 5 University of Alabama at Birmingham School of Medicine Some additional tidbits for faculty moderator consideration only: left herniorraphy: PRIOR SURGICAL REPAIR OF A LEFT INGUINAL HERNIA. right carotid bruit: THE SOUND MADE BY TURBULENT BLOOD FLOW THROUGH A PARTIALLY OBSTRUCTED CAROTID ARTERY; A MANIFESTATION OF PT'S PERIPHERAL VASCULAR DISEASE & ATHEROSCLEROSIS. 1 block dypsnea: A FANCY TERM FOR SHORTNESS-OF-BREATH AFTER WALKING 1 BLOCK ON A LEVEL SURFACE, A ROUGH MEASURE OF THE SEVERITY OF HISLUNG DISEASE. Increased AP diameter with hyperresonant lung fields: THESE ARE THE PHYSICAL FINDINGS IN SOMEONE W/ EMPHYSEMA (I.E., OVEREXPANDED POORLY VENTILATED LUNGS). PROBABLY, HE NEEDS COMBIVENT (IPATROPRIUM + ALBUTEROL) & LOW-DOSE THEOPHYLLINE & MUST STOP SMOKING. Point of maximum impulse not palpable with a soft S1 and a physiologically split S2. (+) S4G, a 2/6 systolic ejection murmur is best appreciated at the apex and base: THE POINT OF MAXIMUM IMPULSE LOCALIZES THE APEX OF THE HEART & IS A ROUGH MEASURE OF VENTRICULAR SIZE. IN PERSONS W/ EMPHYSEMA, YOU DON'T OFTEN FEEL IT BECAUSE OF THE OVERINFLATED LUNGS. ALSO BECAUSE OF THE OVERINFLATION, THE FIRST HEART SOUND (S1) IS SOFTER THAN NORMAL. THE S4G (S4 GALLOP) IS A NONSPECIFIC PRESYSTOLIC SOUND OF UNKNOWN SIGNIFICANCE IN AN OLDER ADULT. THE MURMUR IS ONE RELATED TO AORTIC VALVE STENOSIS, PROBABLY MILD. HE WILL NEED ANTIBIOTICS PRIOR TO ANY INVASIVE PROCEDURE (E.G., COLONOSCOPY, TOOTH EXTRACTIONS, ETC). Dependent rubor and absent pedal pulses in the feet: THESE ARE SIGNS OF THE PATIENT'S OVERALL TENDENCY TO ATHEROSCLEROSIS. THE FIRST TERM APPLIES TO THE FLUSHING OF THE LOWER EXTREMITIES OFTEN SEEN IN PATIENTS W/ADVANCED PERIPHERAL VASCULAR DISEASE WHEN THE FEET ARE IN A DEPENDENT (I.E., BELOW THE LEVEL OF THE HEART) POSITION. TREATMENT W/ PENTOXIPHLLIN? STOP SMOKING! Cholesterol 300, HDL cholesterol 32, LDL cholesterol 153, triglycerides 165. (All abnormal? What is normal?): THIS PATIENT HAS AN ELEVATED TOTAL CHOLESTEROL, A LOW HIGH DENSITY LIPOPROTEIN CHOLESTEROL (HDL) AND A HIGH LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL), WHICH IS VERY UNFAVORABLE FOR FUTURE HEART ATTACKS, STROKE AND OTHER VASCULAR EVENTS. HE PROBABLY NEEDS TO BE TREATED W/ A STATIN, AS WELL AS THE DIET HE'S ON. Supported by a grant from the Association of American Medical Colleges and the John A. Hartford Foundation. 6