Antihypertensive Agents Flashcards
Blood pressure =
Cardiac Output (CO) X Peripheral Vascular Resistance (PVR)
How do blood pressure adjustments occur?
rapid: CNS reflexes
longer term: kidney
the sympathetic nervous system innervates:
heart, veinules and arterioles
What are the primary peripheral sites of blood pressure control?
And what would you want to do at each of these sites to lower blood pressure?
arterioles (dilate)
veins (dilate)
heart (decrease contractility, decrease heart rate)
kidneys (decrease fluid retention)
pharmacological targets on vascular smooth muscle
Presynaptic:
alpha 2 (inhibit NE release, so you would want to stimulate them)
AT1 (promotes NE release, so you would want to block it)
beta 2 (promotes NE release, so you would want to block it)
On vascular smooth muscle:
alpha 1: (promotes contraction, so you would want to inhibit it)
AT1: (promotes contraction, so you would want to inhibit it)
ETA (endothelial type a receptor: promotes contraction, so you would want to inhibit it)
beta 2 (promotes relaxation, so you would want to activate)
NP (natriuretic peptide: promotes relaxation, so you would want to stimulate)
endothelial cells (can generate NO)
ETb
Mas
BK: stimulate all 3 because they can generate NO
what are the general antihypertensive drug categories?
sympatholytic agents
vasodilators
vasopeptidase inhibitors
diuretics
What do sympatholytic agents do?
interfere with sympathetic control of blood pressure
in the CNS: decrease CO, decrease PVR, decrease VR via the alpha 2 adrenoceptor
in arterioles via alpha 1 receptors: dilate
venules: alpha 1
heart: beta 1 (also beta 1 receptors in juxtaglomerular apparatus that affect RAAS)
What do vasopeptidase inhibitors do?
inhibit angiotensin II formation (or receptor actions) and decrease aldosterone secretion
prevent breakdown of bradykinin and natriuretic peptides
inhibit metabolism of endogenous vasodilator and natriuretic peptides
What do diuretics do?
promote sodium excretion and water removal from the body (inhibit renal absorption of sodium & water)
What are the side effects (and why) of virtually all drugs that dilate arteries/arterioles?
flushing: blood vessels in face dilate
palpitations: vasodilator decreases bp, body tries to bring it back up, increase sympathetic activation to compensate, increase heart rate –> reflex tachycardia
dizziness: postural hypotension if veins are dilated or you drop blood pressure too much - not enough blood getting back to CNS
headache: dilate cerebral blood vessels - activates cerebral stretch receptors –> welcome to headache ville.
peripheral edema: dilate pre-capillary sphincters, more fluid will be pushed out b/c pressure is increased in capillaries
what is the rationale for combination of HTN drugs?
if you decrease BP with a sympatholytic, renal blood flow will decrease, then renin secretion will increase, then aldosterone secretion will increase so body will end up holding onto fluid. you need to give a diuretic to prevent that from happening. Body won’t have the larger dropping blood pressure b/c kidneys will start holding onto fluid.
If you decrease BP w/a diuretic, decrease blood volume, which drops blood pressure, the baroreceptor reflex will activate sympathetic reflex, b/c body can’t retain water, sympathetic nervous system will constrict blood vessels 7 activate the heart, so try to bring BP back up so also give sympatholytic agent
if you block one pathway, body’s mechanisms will stop drop in bp via other methods - have to use other pathways -comb meds.
what do sympatholytic agents do?
inhibit cardiovascular effects of the sympathetic nervous system
renal mechanisms will tend to counter the actions of these drugs
