1. Antihypertensive Drugs
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

2. 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

3. 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 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
or 80-90
Check again in 1 year
Stage 1 hypertension
or 90-99
Confirm within 2 months
Stage 2 hypertension
>160
or >100
Evaluate within 1 week to 1 month3

4. 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

5. Blood Pressure Regulation:
BP= CO x PVR

6. 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

7. 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 

8. 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

9. 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

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

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

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