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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

59-291 Section 3, Lecture 1

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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

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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

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

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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 1 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 1 receptors causes vasoconstriction

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Blood Pressure Regulation:

BP= CO x PVR

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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

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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

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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

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vasodilators

-antagonists

-antagonists

-antagonists

-antagonists

Angiotensin II receptor antagonists

Angiotensin II receptor antagonists

CNS-directed sympatholytics

ACE inhibitors

diuretics

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Practice Questions

• Explain how stimulation of 1 receptors increases BP.

• Increase heart rate

• increase CO

• increase BP

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• Explain “Prehypertension” condition and the follow up recommendation for this condition.

• SBP 120-139 or

• DBP 80-90

• Check again in 1 year

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• What type of drugs decrease PVR?

• Vasodilators

• Angiotensin II receptor antagonists blockers