ACEI: angiotensin-converting Enzyme inhibitor A II ant: angiotensin II receptor antagonist
-blocker BP
ACEI AII ant.
Ca-Blocker
Alternative Medicine
RENIN-ANGIOTENSIN SYSTEM (RAS)
Antihypertensive Agents
Zhu Yi Zhun, Dept. of Pharmacology, SPFDU Email:
Hypertension
• Incidence: 10-20% in adults
e.g. 5 millions Americans have hypertension.
Diagnosis of Hypertension
• is based on repeated, reproducible measurements of elevated blood pressure.
• BP 140/90 mm Hg
Management of Hypertension
Antihypertensive Therapy
ACE: Angiotensin Converting Enzyme
ACE INHIBITOR
Originally found in snake venom The synthesized inhibitors are competitive inhibitor tightly bound to the Zn2+ ions of the ACE preventing the access of the ACE substrates to the active site of ACE Inhibit Angiotensin II synthesis Inhibit Bradykinin degradation Captopril was the 1st ACE inhibitor introduced to the market. Ramipril, Enalapril, Moexipril, Lisinopril etc. have been synthesized thereafter.
Classification of Hypertension
-- Primary (Essential) Hypertension (PH): About 90%-95%. Onset 25-55 years. No cause can be established for 95% cases of PH.
Classification of Blood Pressure
Systolic Blood Diastolic Blood
Pressure (mm Hg) Pressure (mm Hg)
Normal
< 130
<85
High Normal
130-139
85-90
Hypertension
Stage 1 (mild)
Vasodilator
-blocker
Angiotensinogen
Peripheral Resistance
Cardiac Output
Renin Angiotensin I
ACE inhibitors
ANG II blocker
Angiotensin II
BBPP
al blood
flow
Angiotensin II Renal blood
flow
Regulation of Blood Pressure
Brain Stem
Sympatholytic drugs
Sympathetic Stimulation
Aldosterone Diuretics
Adrenoceptors
Sodium Retension
Complications of untreated hypertension
• Hypertensive cardiovascular disease • Hypertensive cerebrovascular disease and dementia • Hypertensive renal disease • Aortic dissection • Atherosclerotic complication
-- Secondary Hypertension (SH): About 5%-10%. Cause: Renal disease Hormonal (e.g. Estrogen) therapy Renal vascular hypertension Hypertension associated with pregnancy Hypercalcemia, hyper- or hypothyroidism etc.
140-159
90-99
Stage 2 (moderate)
160-179
100-109
Stage 3 (severe)
>180
>110
BP= CO x PVR
CO: Cardiac Output;
PVR: Peripheral Vascular Resistance.
Regulation of Blood Pressure
Brain Stem
BP= CO x PVR
Sympathetic Stimulation
Aldosterone
Adrenoceptors
Sodium Retension
Peripheral Resistance
Cardiac Output
BP
Angiotensinogen
Renin Angiotensin I
68% are aware of their diagnosis. 53% are receiving treatment. Only 27% are under control of the 140/90 mm Hg threshold.
Hypertension
• is usually asymptomatic
• is associated with increased risk from ischemic heart disease, cerebrovascular accidents, heart and renal failure.
End organ damage
Therefore, it is important to treat hypertension and reduce mortality and morbidity of these conditions
ANGIOTENSINOGEN
KININOGENS
RENIN
KALLIKREINS
ANGIOTENSIN I
ANG II blocker
ANGIOTENSIN II
ACE
BRADYKININ
INACTIVE
ACE inhibitor METABOLITES
AT 1 RECEPTOR
AT 2 RECEPTOR