Antihypertensive Drugs 59-291 Section 3, Lecture 1 Antihypertensive Drugs 50 million people in the United States suffer from high blood pressure (hypertension) Hypertension: Systolic BP >= 140 mmHg, Diastolic BP >= 90 mmHg Untreated hypertension: Damages blood vessels Accelerates atherosclerosis Left ventricular hypertrophy Ischemic heart disease, stroke, heart failure and kidney failure

Hypertension Primary; 95%: No underlying disease risk factors Obesity, Lack of exercise, Metabolic syndrome; (abdominal obesity, hyperlipidemia, insulin resistance), excessive dietary salt intake, excessive alcohol intake Secondary; 5% caused by consequence of other disease; chronic kidney disease, pheochromocytoma, hyperaldosteronism

Classification of BP was presented in the Seventh Report of the Joint National Committee on the Prevention, Detection, and Treatment of High Blood Pressure; 2003 Table 10-1. Classification of Blood Pressure for Adults and Follow-up Recommendations Blood Pressure Classification SBP1 mm Hg DBP2 mm Hg Follow-up Recommendations Normal <120 and <80 Check again in 2 years Prehypertension 120-139 or 80-90 Check again in 1 year Stage 1 hypertension 140-159 or 90-99 Confirm within 2 months Stage 2 hypertension >160 or >100 Evaluate within 1 week to 1 month3

Blood Pressure Regulation BP is influenced by cardiac output and peripheral vascular resistance and regulated by sympathetic nervous system (short term regulation) and kidneys (long term control) BP=CO x PVR Cardiac output: CO = Stroke volume x heart rate Increased by activation of b1 receptors Kidneys regulate blood volume and CO PVR: resistance to blood flow through arteriols; Cross sectional area depends on arteriolar smooth muscle tone Activation of a1 receptors causes vasoconstriction

Blood Pressure Regulation: BP= CO x PVR

CO= Stroke Volume x Heart Rate  By sypm. Stimulation of 1 receptors in the heart ;kidneys also play a role in CO by their role in regulating blood volume which determine cardiac filling pressure and stroke volume

PVR (Peripheral Vascular resistance)- resistance to blood flow through the arterioles Symp. Stimulation of -receptors- contraction of vascular smooth muscle leading to elevated BP. In addition, the release of angiotensin II and vasopressin also induce vasoconstriction Note: Symp. Regulation of BP Short term via baroreflex BP due to altered posture/physical activity Symp.  via CO  and PVR 

The Long term regulation of BP by the kidneys. -via regulation of plasma V and renin-angiotensin-aldosterone system Normotensive- BP  excretion of Na+  H2O > BP normal Hypertensive- BP regulation is defective PVR is  but it is unknown whether this is the cause or effect of hypertension. Sites of pharmaceutical intervention 4- major categories of drugs: 1- diuretics 2-sympatholytics 3- ACE inhibitors 4- vasodialtors

vasodilators a-antagonists b-antagonists b-antagonists b-antagonists Angiotensin II receptor antagonists b-antagonists CNS-directed sympatholytics b-antagonists ACE inhibitors Angiotensin II receptor antagonists diuretics

Practice Questions Explain how stimulation of b1 receptors increases BP. Increase heart rate increase CO increase BP

Explain “Prehypertension” condition and the follow up recommendation for this condition. SBP 120-139 or DBP 80-90 Check again in 1 year

What type of drugs decrease PVR? Vasodilators Angiotensin II receptor antagonists a blockers