Antihypertensive Drugs. Hypertension. Hypertension is not a disease It is an arbitrarily defined disorder to which both environmental and genetic factors contribute Major risk factor for: cerebrovascular disease myocardial infarction heart failure peripheral vascular disease
The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many years. The myocardial fibers have undergone hypertrophy.
This left ventricle is very thickened (slightly over 2 cm in thickness), but the rest of the heart is not greatly enlarged. This is typical for hypertensive heart disease. The hypertension creates a greater pressure load on the heart to induce the hypertrophy.
Diastolic Range (mm Hg)
Systolic Range (mm Hg)
Long-term goal of antihypertensive therapy:
Reduce mortality due to hypertension-induced disease
MAP = CO X TPR
Blood pressure is controlled by an integrated system
AP = CO x TPR
Treatment of hypertension seeks to lower CO and/or TPR.
Sit or stand up quickly, BP fallsneural responses reestablish normal BP or Sudden increase in stroke volume, BP rises, neural responses reestablish normal BP
Sympathetic nervous control
Blood volume too high, RenalSympathetic vasoconstriction reducedMore fluid enters kidney, more urine formed Lowers BP via lower blood volume
Blood pressure too low, Renal
Sympathetic vasoconstriction risesLess fluid enters kidney, less urine formedRaises BP by higher blood volume
If BP too low, increase BP by increasing __________
Kidney cells secrete _______Converts angiotensinogen to angiotensin I_______________________in lung converts angiotensin I to angiotensin II….
Regulates BP by Changing:
Directly – by allowing more or less fluid
to enter kidney tubules
Indirectly – Reabsorbing more fluid that
was already destined to be urine
Vasoconstriction / vasodilation
- Thiazides and congeners.
- Loop diuretics.
- Potassium-sparing diuretics.
2) Sympatholytic drugs
- Centrally acting antiadrenergic agents.
- Adrenergic neuron blocking agents.
- Alpha adrenergic blockers.
- Beta adrenergic blockers.
- Alpha-beta adrenergic blockers.
- Nitric oxide releasers.
- Potassium channel openers.
- Calcium channel blockers.
4) Angiotensin inhibitors and antagonists.
- Angiotensin Converting Enzyme (ACE) inhibitors.
- Angiotensin receptor antagonists.
After 6-8 weeks of continuous therapy intravascular volume and cardiac output return towards normal while peripheral vascular resistance decreases.
- Mechanisms of this decrease are probably related to
a depletion of body Na+ stores which leads to:
a) a decrease of interstitial fluid volume
b) a fall in smooth muscle Na+ concentration that in turn decreases intracellular Ca++ concentration
c) a change in response of cell surface receptors to vasoconstrictor hormones
b) Na reabsorption by kidney (hemodynamic effect on kidney and drop in aldosterone secretion). This reduces blood volume and preload c) release of NE (which lowers TPR and CO) d) cardiac contractility
AT1 R antagonists
Normal Reduced Increased
vasomotor center of the medulla which inhibits the sympathetic
in blood pressure.
(ie methyldopa in pregnant hypertensive patients).
a reduced sympathetic nerve firing rate.