Antihypersensitives Flashcards
What are antihypersentitives
drugs used when the goal is to lower blood pressure (treat hypertension)
which drugs are considered antihypertensives (10)
clonidine
propanolol
metoprolol
prazosin
sodium nitroprusside
verapamil
enalapril
lostartan
hydrochlorothiazide
furosemide
what can happen if hypertension is left untreated?
damage to blood vessels
renal failure
heart disease
stroke
anatomy of blood pressure control
arteries = resistance
veins = capacitance
heart = rate/cardiac output
kidney = blood volume
how do the kidneys help regulate blood pressure
- longterm BP regulation
- regulates blood volume by pulling water in or out
- works via the renin angiotensin system
- key regulator of BP = angiotensin II
baroreceptors detect bloodpressure changes in…
carotid artery and aorta - monitor the stretch of blood vessels (more stretched = higher BP)
how does the renin-angiotensin-aldosterone system regulate BP
decreased BP in renal arteries - renin secretion cleaves angiotensinogen to angiotensin I - ACE cleaves it to angiotensin II- causes increased aldosterone to increase BV
more angiotensin II in the bloodstream leads to…
- constriction of blood vessels
- increased aldosterone - Na+ and water retention - increased blood volume
how do the kidneys contribute to increasing arterial pressure
- when pressure decreses the kidneys secrete renin
- renin produces angiotensin I
- ACE cleaves it to angiotensin II
angiotensin II leads to aldosterone secretion (for salt and water retention) and vasoconstriction - both these factors cause arterial pressure to increase
blood pressure grades
ideal BP = 90-119/60-79
pre-hypertensive = 120-129/60-79
hypertension stage 1 = 130-139/80-89
hypertension stage 2 = 140/90 or higher
what is the goal of antihypertensive therapy
- intervene to decrease BP and prevent organ damage
- interferes with mechanisms regulating BP
- balance toxicity and risk of not treating
- use monotherapy or combined therapy
which antihypersensitives are centrally acting (effect at level of CNS)
clonidine
how does clonidine act as a centrally acting antihypersensitive
- targets receptors that regulate BP in the CNS
- decreases NE levels in the CNS which decreases SNS activity and therefore decreases BP
- dilates blood vessels
adverse effects of clonidine as an antihypertensive
bradycardia
constipation (a2 in GI tract)
sedation
impaired concentration (a2 CNS effect)
which antihypertensives are considered peripherally acting (PNS)
beta-blockers (propanolol and metoprolol)
alpha blockers (prazosin)
effects of betablockers (propranolol and metoprolol) on blood pressure
- block B1 receptors in heart - dereased CO
- block B1 receptor in kidney - decreased renin release and therefore decreased PVR
toxicities of betablockers
bradycardia (B1 antagonism)
bronchoconstriction
effects of alphablockers (prazosin) on blood pressure
- block a1 receptors found in arteries
- prevent vasoconstriction
- can lead to salt and water retention so often need to be administered with beta blockers or diuretics
which BP regulating drugs can be classified as vasodilators
- a1 antagonists (prazosin)
- NO donors (sodium nitroprusside)
- Ca2+ blockers (verapamil)
how do vasodilators work to lower BP
- relax arterial smooth muscle to decrease PVR
- might get compensatory responses from baroreceptors and renin-angiotensin system
- work best when combined with anti-hypersensitive that oppose these responses
mechanism of NO donord to vasodilate - e.g sodium nitroprusside
- NO activates cGMP
- cGMP cleaves myosin-PO4 to myosin
- myosin causes relaxation of smooth muscle cells
toxicities associated with NO donors
hypotension
cyanide accumulation
mechanism of Ca2+ channel blockers - e.g. verapamil
- decreased Ca2+ influx into arterial smooth muscle casues vasodilation (Ca2+ initiates contraction but now this is blocked)
- also inhibits cardiac Ca2+ channels
adverse effects of calcium channel blockers
bradycardia (low heart rate)
hypotension (low BP)
Angiotensin converting enzyme (ACE)
- enzyme that converts angiotensin I to II
- also inactivates bradykinin
Angiotensin II - Key regulator of BP in the kidneys
- binds to AT1 and AT2 receptors
- very potent vasoconstrictor
- increases secretion of aldosterone (from adrenal gland) and ADH (from pituitary gland)
- causes NE release
how does angiotensin II cause vasoconstriction
- activates AT1 receptor to increase IP3 and DAG
- at presynaptic AT1 causes NE release
- at smooth muscle AT1 IP3 causes increase Ca2+ release - contraction of SM
how does angiotensin II regulate blood volume
- activates aldosterone which increases Na+ reabsorption into blood (H2O follows)
- activates ADH which increases permeability of collecting duct in kidney, increases H2O reabsorption
what happens when ACE inhibits bradykinin
- bradykinin is a vasodilator, when inhibited by ACE causes BP to increase
how does bradykinin work as a vasodilator
causes increased NO (EDRF) to relax blood vessels
where do ACE inhibitors work to treat high BP
- block angiotensin I to II conversion
- inactivates bradykinin
which drugs are considered angiotensin inhibitors
- ACE inhibitors (e.g. Enalapril)
- AT1 receptor blocker (e.g. Losartan)
properties of Enalapril
- an ACE inhibitor
- prodrug metaboilized in liver to become activated
- works to lower BP
- side effects = hypotension, hyperkalemia, dizziness, headache
- can cause a cough by blocking bradykinin
properties of Losartan
- an AT1 receptor blocker
- prodrug?
- side effects = hypotension, hyperkalemia, dizziness, headache
what is the role of diuretics
- drugs that decrease BP by depleting body Na+ (H2O follows)
- ACE inhibitors enhance their efficiency (e.g. enalapril)
- in mild-moderate hypertension can use them alone
- in severe hypertension need a powerful one or combine it wirth a sympatholytic and vasodilator
diuretics examples
acetazolamide
osmotic agents
loop agents
thiazides
aldosterone antagonists
ADH antagonists
how do loop agents work as diuretics
- powerful diuretic
- works at the loop of henle
- targets sodium and inpacts potassium
how do thiazides work as diuretics
- decrease the water being reabsorbed at the DCT because there is a higher salt concentration
Hydrochlorothazide - thiazide diuretic
- inhibits NaCl transport in DCT
- absorbed well orally
- inexpensive and effective
- toxicities include hypokalemia (K+ depletion), gout and hyponatremia (dehydration)
Furosemide - loop agent diuretic
- inhibits co-transporter of Na+, K+ and Cl- in loop of Henle (NaCl reabsorption inhibited)
- rapid and short acting
- used for severe hypertention and pulmonary edema
- toxicities include hypokalemia (K+ depletion), gout, hyponatremia (dehydration) and ototoxicity (hearing loss)
what are ways to help lower blood pressure before drug intervention
- Na+ restriction
- weight loss
- exercise
initial monotherapy to treat high BP
- thiazide diuretic (mild-moderate)
- ACE inhibitor, AT1 receptor blocker
- Ca2+ channel blocker
- B blockers
- a1 blockers, centrally acting sympatholytics
combination “stepped” therapy to treat high BP
- used in severe hypertension
- drugs added in stepwise fashion untol optimal BP is achieved
- first lifestyle changes implimented
- next add these drugs one at a time as needed in this order: Diuretics, ACE inhibitors/ARB, Ca2+ channel blocker, sympatholytic/vasodilator
problems with combination “stepped” therapy to treat high BP
- lack of patient compliance
- side effects common
- drugs are expensive
- disease is asymptomatic
bradycardia is an adverse effect of which drugs
- a2 agonists: clonidine
- B-blockers: propanolol, metoprolol
- Ca2+ channel blockers: verapamil
