SIMPLE MECHANISMS OF ACTIONS - HYPERTENSION MEDICATIONS
NOTE: In addition to the information presented here, other mechanisms are also involved in the antihypertensive effects of most of these hypertension medications.
The graphic below on the left is
(a) - representation of the sympathetic nervous system and its actions on body tissues such as heart, kidney, and blood vessels.
(b) - The chemical actions involved in blood pressure regulations.
7, 8, 9 is an enlarged representation of the synaptic space between the nerve and the cell (blood vessel, heart, etc). Catecholamines (dopamine, norepinephrine in the postganglionic nerve endings, and epinephrine from the adrenal gland) all induce vasoconstriction by activating the post synaptic alpha 1 receptor.
Norepinephrine is released from the nerve and acts on the post synaptic alpha receptor. This induces vasoconstriction. The pre synaptic alpha 2 receptor provides feedback to inhibit additional release of norepinephrine.
Agonists - This class of medications attach and activate the receptor.
Antagonists - This class of medications attach to the receptor, but does not activate the receptor. Therefore, this class of medications blocks the receptor and antagonize the natural receptor agonist.
Alpha Receptor Action: Blood Vessel -
vasoconstriction (narrows vessel).
Beta Receptor Action: Kidney - increase renin secretion; Heart - increase heart rate, contractility, conduction, excitation; Lung - increase bronchodilation (opens lungs); Blood Vessel - vasodilation (opens vessel).
Alpha Adrenergic Agonists (central acting)
Examples: clonidine, methyldopa, guanabenz
These meds acts by stimulating the central alpha receptors which depresses or inhibits sympathetic nerve activity (decreasing catecholamine [norepinephrine] release). This central action also causes side effects such as dry mouth, sedation, decreased alertness, and rebound hypertension when stopped abruptly.
Examples: inversine (mecamylamine)
Acetylcholine is released from the preganglionic nerve which binds to and stimulates the nicotinic receptors on the cell bodies of the postganglionic nerve. This causes increased sympathetic tone and vascular contraction which increases cardiac output and blood pressure.
These meds block the ganglion of the nerve which blocks the acetylcholine binding and stimulation of the receptors.
Adrenergic Neuron Antagonists (periherally acting)
Examples: reserpine, rauwolfia, guanadrel.
Interferes with the release of norepinephrine at the sympathetic nerve endings (peripheral).
This results in a decrease in peripheral resistance which lowers blood pressure.
Alpha Adrenergic Blockers
Examples: minipress, hytrin, cardura
The effect is due to the blocking of the post synaptic alpha receptor.
This prevents norepinephrine from acting on the receptor.
The pre synaptic alpha 2 receptor is not affected, allowing the feedback
inhibition of additional norepinephrine release.
Beta Adrenergic Blockers
Examples: propranolol, metoprolol
Beta receptors stimulations causes increase renin secretion, increase heart rate, contractility, conduction, excitation, increase bronchodilation, and vasodilation (opens vessel).
These meds competes with catecholamines (norepinephrine) for binding to the beta adrenergic receptors in vascular smooth muscles and in the heart. This blocking of the beta receptors results in decreasing beta stimulation and the effects of the catecholamines. Blood pressure is decreased.
Beta Adrenergic Blockers
Examples: propranolol, metoprolol
Beta receptors stimulations causes increase renin secretion. This blocking of the beta receptors results in decreasing beta stimulation and renin secretion. Blood pressure is decreased.
Alpha & Beta Adrenergic Blockers
Examples: coreg, normodyne, trandate
Also see information on alpha blockers and beta blockers.
The ratio of alpha blocking and beta blocking may be variable depending on the specific medication.
Plasma renin activity decreases and catecholamine (norepinephrine) increases.
Blood pressure decreases mainly by decreasing vascular resistance.
Inhibition of Renin
These medications inhibit the production of renin , angiotensin I, and angiotensin II.
Angiotensin Converting Enzyme (ACE) Inhibitors
Accupril, monopril, vasotec, zestril
These meds block the production of angiotensin I to angiotensin II. This decreases aldosterone and its sodium retention and decreases angiotensin II and its vasoconstriction. Renin release increases.
Angiotensin II Receptor Blockers
Examples: Avapro, Cozaar, Diovan
These meds bind to the AT1-receptors and thereby interfere with the binding of angiotensin II to the angiotensin II receptor. By blocking angiotensin II (which is a vasoconstrictor and which increase synthesis and release of aldosterone), these meds cause a decrease in vascular resistance and thereby decreases blood pressure. Renin release increases.
Aldosterone Receptor Antagonist (mineralcorticoid* receptor blocker)
The effect is due to the binding to the mineralcorticoid receptor and blocking the binding of aldosterone to the receptor. If aldosterone binds to these receptors found in tissues (including blood vessels, heart, kidney, and brain), blood pressure is increased by the increase sodium reabsorption (retention).
By blocking the negative feedback regulation of aldosterone on renin, the increase plasma renin increases serum aldosterone. The increased renin and aldosterone levels do not overcome the effects of the aldosterone receptor antagonist.
a. Glucocorticoids (cortisol, hydrocortisone)
b. *Mineralocorticoids (aldosterone) - causes kidney to reabsorb sodium and
water, and secretion of potassium)
c. Androgens (testosterone)
e. Progestagens (progesterone)
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Calcium Channel Blockers
Examples: norvasc, procardia.
These meds inhibit calcium influx in heart and blood vessel smooth muscle cells. The decrease in calcium in the cells decreases the muscle contraction resulting in decreased myocardial contractility and dilation of the blood vessels (vasodilation). This causes decreased peripheral resistance and a decrease in blood pressure.
Thiazide & Related Diuretics
Examples: lasix, hydrochlorothiazide.
These meds increase water loss from the body by inhibiting sodium/chloride reabsorption in the kidneys. Thiazides also increase potassium excretion by the kidneys. By reducing water (extracellular fluid volume), the blood pressure is lowered. Thiazides also cause vasodilation which reduces peripheral vascular resistance.
Vasodilators (direct relaxation of vascular smooth muscles)
Examples: hydralazine, minoxidil.
These meds cause direct relaxation of vascular smooth muscles and produces decreased vascular resistance.
The mechanism of action of hydralazine is not known.
Minoxidil increases potassium conductance in vascular smooth muscle and the resultant hyperpolarization reduces calcium entry.
The direct vasodilation causes the body to respond by increasing heart rate and cardiac output. The renin-angiotensin system causes aldosterone release which results in sodium and fluid retention.
Beta blockers can help the increased heart rate and cardiac output.
Diuretics can help the fluid retention.
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