Antihypertensives Flashcards
What are the two types of hypertension?
primary: no known cause
secondary: specific cause (maybe pheochromocytoma of the adrenal gland that produces catecholamines)
What provides acute BP control?
baroreceptor, chemoreceptor, atrial stretch reflexes
What provides long-term BP control?
RAAS system
What is the most important factor affecting blood pressure?
vessel diameter
Ohm’s Law: pressure = flow x resistance
What is the function of arterial baroreceptors?
rapid adjustment of BP; protective mechanism to maintain perfusion of brain/heart; buffer rapid deviations in BP from the set-point determined by renal pressure natriuresis
What is the function of chemoreceptors?
slow adjustment of BP; BP has to be low enough that your body starts producing byproducts recognized by these receptors (acidosis)
What is the function of the atrial stretch reflex?
receptors sensitive to increase in volume; increase HR, dilation of afferent arterioles, decrease ADH and increase ANP
What are endothelial factors involved in BP control? Name the two major factors.
factors released by endothelial cells lining the blood vessels
nitric oxide: relaxation
endothelin: constriction
How does NO cause vasodilation?
endothelial-derived nitric oxide synthase (eNOS) synthesizes NO from arginine and oxygen; NO diffuses out of cell & acts on smooth muscle; converts cGTP to cGMP which relaxes the vessel
How does endothelin cause vasoconstriction?
amino acid peptide released from damaged endothelial cells; prevents bleeding from torn arteries
African Americans are less reactive to which medications?
RAAS meds (ACEIs, ARBs)
What are the 4 targets of antihypertensive therapy?
fluid balance (Na & water
renin-angiotensin system
central & peripheral SNS control
vascular smooth muscle tone
How do diuretics function overall?
deplete body Na stores; reduces blood volume; initially decreases CO; CO returns to normal after 6-8 weeks & PVR declines
How do thiazides work?
inhibit Na/Cl transporter in the distal tubule and early collecting duct
How do loop diuretics work?
act on Na/K/2Cl transporter in the thick loop of Henle where substantial reabsorption of Na occurs
Which drug types work on the RAAS system?
AT1R blockers (ARBs)
ACEIs
renin inhibitor or beta1 adrenergic antagonist
How do renin inhibitors work?
renin levels are high in HTN pts
beta1 blockers stop production of renin
aliskiren is a direct competitive renin inhibitor
How do ACEIs work?
inhibit angiotensin I conversion to angiotensin II conversion to aldosterone; inhibit breakdown of bradykinin (increase Na & water excretion, decrease PVR)
adverse effects of ACEIs
dry cough: bradykinin
hyperkalemia: inhibition of aldosterone secretion
angioedema: substance P
hypotension in presence of hypovolemia
How do ARBs work?
vasodilate; increase Na & water excretion; reduce plasma volume; decrease cellular hypertrophy; increase plasma renin & renin activity
*don’t affect AT2 that is responsible for remodeling
How do beta adrenergic receptor antagonists treat HTN?
decrease CO (HR & contractility); decrease renin secretion; decrease central sympathetic outflow; reset baroreceptors
function of beta1 receptors
cardioselective (increase HR, conduction, contraction, EF); increase renin release by JG cells
function of beta2 receptors
smooth muscle relaxation; increase renin release by JG cells
function of alpha1 receptors
vasoconstriction; contraction of smooth muscles
*antagonist drugs cause dilation of arterioles & capacitance veins
function of alpha2 receptors
inhibits release of NE; indirectly works in CNS
mechanism of action of reserpine
depletes NE from adrenergic nerve endings; inhibits reuptake of NE; decreases PVR and CO
mechanism of action of clonidine & methlydopa
decrease sympathetic outflow; increase vagal activity to the heart; decrease PVR & CO
mechanism of action of Ca+2 channel blockers
block voltage sensitive L-type Ca+2 channels; relax VSM & decrease PVR; decrease MAP (reflex increase sympathetic discharge and HR)
mechanism of action of hydralazine
requires NO; affects arterioles; decreased PVR/MAP
mechanism of action of minoxidil
affects arterioles; decreased PVR
mechanism of action of nitroprusside
direct vasodilator; generates NO which activates guanylyl cyclase and increases cGMP; affects veins & arteries to reduce preload & afterload
mechanism of action of nitroglycerin
affects veins; generates NO which activates guanylyl cyclase to increase cGMP
mechanism of action of epoprostenol
direct vasodilator via cAMP; counteracts TXA2
