Mechanismofaction-VCU.doc

Cardiovascular Pharmacology - Antihypertensive Agents Edward JN Ishac. Ph.D. Professor, Dept. Pharmacology Toxicology Office: Smith Bldg, Room 742 Email: eishac@vcu.edu Tel: (804) 828 2127 Objectives: Demonstrate an understanding of antihypertensive agents with respect to: 1. Subcategories (drug classes) and the specific mechanisms 2. Major pharmacokinetic characteristics of each drug class 3. Primary adverse effects of each drug class 4. Unique characteristics of individual agents 5. Similarities and differences in the hemodynamic effects of the drug classes 6. Differences among populations in response to drug classes 7. Advantages or disadvantages of using combinations from different drug classes 1. Blood Pressure Regulation: Physiology Franks formula, BP regulation: BP = CO x TPR CO = HR x SV Baroreceptor reflex: oppose changes in BP, rapid, moment-to-moment BP adjustments Renal system: Control of Na and H2O balance, responsible for long-term BP control Figure 1. Regulation of blood pressure 2. Definition of Human Hypertension (HT) A sustained elevation of systolic and/or diastolic BP above an arbitrarily defined level (systolic 139 mmHg and/or diastolic 89 mmHg) - secondary HT may be cured by surgical procedures (early diagnosis of cause) - primary (essential) HT is a lifelong disease, needs longterm control treatment 3. Classification of Hypertension (HT) 3.1. Based on severity systolic (mmHg) diastolic (mmHg) Normal 120 and 80 Pre-hypertension 120 - 139 or 80 - 89 Stage 1 Hypertension 140 -159 or 90 - 99 Stage 2 Hypertension 160 or 100 - Represents 15-20% of general population, 50% of individuals 60 years - 45 – 60 million in US - CV mortality risk doubles with each 20/10 mm Hg BP increment 3.2. Based on pathogenesis 3.2.1. Secondary HTs ( 10%) -neurogenic HT caused by brain damage -cortisol overproduction: hypophysis or adrenal gland tumor -aldosterone overproduction: adrenal gland tum