Blood Pressure and Drugs

1. Blood Pressure and Drugs Sarah Fu (sarah.fu@mail.utoronto.ca) Meng Xue Shi (mengxue.shi@mail.utoronto.ca) Shuhua Situ (shuhua.situl@mail.utoronto.ca) Monica Tran (mo.tran@mail.utoronto.ca) Presentation Date: Friday, September 21, 2012 PHM142 Fall 2012 Instructor: Dr. Jeffrey Henderson

2. Blood Pressure • Measure of systolic and diastolic pressure • Pressure against the blood vessels • Proportional to blood flow • Transport of nutrients and O2 • Removal of waste and CO2 • Distribution of Hormones

3. Hypertension • Blood pressure above 140/90 • Risk increases with age • 2011 – 44% men and women ages 45-64 • 2011 – 45% men and women ages 65+

4. Dangers of Hypertension • Blindness • Stroke • Heart attack • Heart failure • Kidney damage • High salt diet • Obesity • Hereditary • Stress Causes

5. Renin-Angiotensin Aldosterone System

6. ACE Inhibitors Liver A H H A: Enalapril

7. ACE Inhibitors Liver A B H H A: Enalapril B: Esterase

8. ACE Inhibitors Liver B A H H A: Enalapril B: Esterase

9. ACE Inhibitors Liver B A H H A: Enalapril B: Esterase

10. ACE Inhibitors Liver B A H H A: Enalapril B: Esterase

11. ACE Inhibitors Liver B H C H H B: Esterase C: Enalaprilat

12. ACE Inhibitors Action of Benazeprilat H H H

15. Adverse effects <1% during clinical trials • Hypotension • Chest pain • Abdominal pain • Anemia >1% during clinical trials • Fatigue • Headache • Dizziness • Nausea

16. Hypotension • Common in institutionalized elderly • Orthostatic Hypotension • baroreflex failure or volume depletion • Systolic bp decrease >20mm Hg • Diastolic bp decrease >10mm Hg • Associated with hypertension, increased age and diabetes mellitus

17. Orthostatic Hypotension • Symptoms • Blurred vision, headache, nausea, dizziness • Risks • Increased incident of cerebral vascular disease • Mild cardio-infarction • Coronary heart disease • Heart failure • Cardio-vascular mortality

18. Treatments • Medicinal • Pyridostigmine (Mestinon) • Fludrocortisone (Florinef) • Midodrine (ProAmatine) • Non-Medicinal • Consumption of salt • Consumption of extra fluids • Head of bed elevated • Physical Activity • Abdominal binder

19. Midodrine • Vasopressor • Increases standing systolic bp • Metabolite desglymidodrine • α1-agonist • Activation of α-adrenergic receptors • Arterial and venous vasoconstriction • Elevates blood pressure

20. Enzymatic cleavage Midodrine Desglymidodrine Glycine Desglymidodrine Vasoconstriction – Increase BP  γ α β α1-adrenergic receptor s Cytosol Phospholipase C Increase in calcium Nucleus

21. Adverse Effects • Supine hypertension • Scalp paresthesias • Pilomotor reactions (goosebumps) • Urinary urgency • Headaches

22. Hypotension Summary • Systolic BP drop >20mm Hg or diastolic BP drop >10mm Hg • Midodrine: major metabolite desglymidodrine which activates adrenergic receptors • Vasopressor effect that causes activation and constriction of the arterial system Hypertension Hypertension: BP > 140/90 ACE converts angiotensin I (inactive) into angiotensin II (active) to increase blood pressure Angiotensin II is responsible for vasoconstriction, thirst, and releases aldosterone for retention of Na+ Majority of ACE inhibitors (Enalapril), when activated, bind by the carbonyl group Enalaprilat (active form) inhibits ACE, which vasoconstriction, thirst, and stops the release of aldosterone

23. References • Ace Inhibitors. 09/15/12. <<http://www.uic.edu/classes/pcol/pcol425/restricted/Skidgel/ACE%20Inhibitors%20handout%202011.pdf>. • Adrenal Gland. <http://te-deum.blogspot.ca/2012/08/recovering.html>. • Barrios, V., Escobar, C., (2010). Antihpertensive and organ-protective effects of benazepril. Expert Review of Cardiovascular Therapy, 12, 1653-1724. • Burt, V.L., Whelton, P., Roccella, E.J., Brown, C., Cutler, J.A., Higgins, M., … Labarthe, D. (1995). Prevalence of hypertension in the US adult population. Hypertension, 25, 305-313. • Canadian Health Measures Survey: Blood pressure in adults. 09/13/12. <http://www.statcan.gc.ca/daily-quotidien/100217/dq100217b-eng.htm>. • eCPS. 09/15/12. <https://www-e-therapeutics-ca.myaccess.library.utoronto.ca/cps.showMonograph.action#>. • Figueroa, J.J., Basford, J.R., and Low, P.A., (2010). Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleveland Clinic Journal of Medicine, 7(5), 298-306 • High blood pressure, by age group and sex. 09/15/12. <http://www.statcan.gc.ca/tables-tableaux/sum-som/l01/cst01/health03a-eng.htm>. • Hypertension in Canada, 2010. 09/15/12. <http://www.phac-aspc.gc.ca/cd-mc/cvd-mcv/ccdss-snsmc-2010/pdf/CCDSS_HTN_Report_FINAL_EN_20100513.pdf>. • Jabary, N.S., Sarabia, R., Sanchez, T., and Gordillo, R. (2007). Midodrine treatment in the management of severe orthostatic hypotension after hemangioblastoma surgery. ActaNeurochirurgica, 149, 303-306 • Kaplan, N.M., & Victor, R.G. (2009). Kaplan’s Clinical Hypertension (10th ed.). Philadelphia: WoltersKluwer • Liver. 09/13/12. <http://www.pawelmazur.org/blog/wp-content/uploads/2010/07/liver.jpg>. • Nature of Code Blood Vessels. 09/13/12. <http://itp.nyu.edu/~ek1388/myblog/?p=904>. • Oldenburg, O., Kribben, A., Baumgart, D., Philipp, T., Erbel, R., and Cohen, M. V., (2002). Treatment of orthostatic hypotension. Current Opinion in Pharmacology, 740-746 • Perazella, M.A. (2003). Efficacy and safety of midodrine in the treatment of dialysis-associated hypotension. Expert Opinion Drug Safety, 2(1), 37-47 • Sherwood, L. (2007). Human Physiology (6th ed.). Belmont: Thomson Broks/Cole. • Swann, P., Stehouwer, M., and Tukker, J., (1995). Molecular mechanism for the relative binding affinity to the intentinal peptide carrier. Comparion of three ACE-inhibitors: enalapril, enalaprilat, and isinopril. Biochimica et BiophysicaActa, 1236, 31-38.