Hypertension Pharmacology Flashcards
diuretics mechanism of action
reduction of extracellular volume and cardiac output
alteration of total body sodium is believed to cause decreased vascular resistance
decrease in plasma volume of 5% corresponds to effective treatment
distal convoluted tubule diuretics
thiazides such as hydrochlorothiazide, chlorthalidone, or metalazone
loop diuretics
furosemide, bumetanide, thacrynic acid
K+ sparing diuretics
spironolactone, epelrenone, triamterene, amiloride
mechanism of thiazide diuretics
inhibits the Na/Cl symporter in the distal convoluted tubule
side effects of distal convoluted tubule diuretics
impotence
fluid and electrolyte imbalances
impaired glucose tolerance
increased cholesterol
hyperkalemia
hyponatriemia,
hypercalcemia
mechanism of loop diuretics
furosemide, torsemide, bumetanide
inhibits the Na/K/2Cl symporter in the thick ascending limb of the loop of Henle
used for volume ovefrload, especially in chronic kidney disease patients
side-effects of loop diuretics
fluid and electrolyte imbalances
volume depletion
ototoxicity
hyperuricemia
hyperglycemia
increased LDL and triglycerides
mechanism of K+ sparing diuretics
triamterene, amiloride, spironolactone
triamterene and amiloride inhibit renal empithelial Na channels in the late distal tubule and collecting duct
spironolactone and eplerenone antagonize the mineralcorticoid receptor on epithelial cells in the late distal tubule and collecting duct
side effects of K+ sparing diuretics
amiloride and triamterene - hypokalemia, nausea
spironolactone - hyperkalemia, gynecomastia
using diuretics as treatment
proven efficacy and safety
often a first line treatment
avoid hypokalemia as the reduction in mortality from using diuretics is reduced if the diuretic causes the patient to have hypokalemia
types of sympatholytic drugs
centrally acting
alpha-adrenergic receptor antagonists
beta-receptor antagonists (blockers)
centrally acting sympatholytics
methyldopa, clonidine, guanabenz
mechanism of methyldopa
replaces norepinephrine in secretory vesicles of adrenergic neurons
although it is a potent vasoconstrictor, it acts centrally on the brain to inhibit central adrenergic outflow
mechanism of clonidine
stimulates the centrally located alpha2-receptor
side effects of centrally acting agents
methyldopa - sedation, dry mouth, decreased energy, depression, liver toxicity
clonidine, guanabenz, guanfacine - sedation/somnlocence, dry mouth, depression, bradycardia, withdrawal if high doses are stopped suddenly
alpha1-receptor blockers
prazosin, terazosin, doxazosin
blocks the alpha1-receptor
main effect of alpha-1 blockers
decreased peripheral vascular resistance
side effects of alpha1-receptor blockers
first dose phenomenon of orthostatic hypotension
water retention
possible CHF when given as monotherapy
usually used in conjunction with other agents for treatment of hypertension, primarily beta-blockers
beta-blocker mechanism of action
atenolol, metobrolol - selective beta1 blockers
propranolol, timolol - beta1 and beta2 blockers
beta1 blockade leads to slower heart rate and decreased contractility, which decreases renin release
beta2 blockade leads to bronchoconstriction, slight increase in peripheral vascular resistance (slight vasodilation)
side effects of beta-blockers
bradycardia, hyperkalemia, fatigue, cold extremities, and bronchospasm
may have adverse effect on lipid panel, and blunt symptoms of hypoglycemia
used preferably in patients with CAD, not for sole use in patietns with hypertension and heart failure
labetolol and carvedilol
block beta receptors and some alpha-1 receptors
drugs affecting the RAAS
ACE inhibitors - catopril, enalapril, lisinopril, quinapril, ramipril, benazepril, fosinopril
ARBs - losartan, candesartan, irbesartan, valsartan
mechanism of action of ACE inhibitors
block the conversion of angiotensin I to the active angiotensin II by inhibiting ACE
mechanism of action of ARBs
block the angiotensin II receptor type I
found in myocrdial tissue, brain, and kidney, smooth muscle cells, and adrenal glomerulosa cells
difference from ACE inhibitors is that it leads to decreased bradykinin
inhibits angiotensin less than ACE inhibitors as well
effects of ACE inhibitors and ARBs
decreased intravascular volume
possible increase in cardiac output
decreased peripheral vascular resistance
side effects of ACE inhibitors
cough, hyperkalemia, renal failure, fetal toxicity, angioedema
side effects of ARBs
hyperkalemia
renal failure
fetal toxicity
rare angioedema and no cough
ACE-I/ARB treatment population
hypertensive patients, particularly those with heart failure, diabets/proteinuria, or CAD/post MI
effects of efferent arteriole constriction
increased glomerular capillary pressure
decreased peritubular capillary pressure
decreased nephrone plasma flow but increases GFR
effects of efferent arteriole dilation
decreased glomerular capillary pressure
increased peritubular capillary pressure
increased nephron plasma flow
decreased GFR
types of calcium channel blockers
phenylalkylamines
benzothiazepine
dihydropyridine
CCB mechanism of action
block the L-type calcium channel preventing the influx of calcium
since contraction of the smooth muscle is dependent on calcium, less intracellular calcium results in less contraction
decreases peripheral vascular resistance
dihydropyridine vs. non-dihydropyridine classes of CCBs
dihydropyridines - more peripheral effect
non-dihydropyridines - also affect the smooth muscles but have varying effects on the heart
dihydropyridines
nifedipine, amlodipine, felodipine, nisoldipine, nitrendipine
large decrease in peripheral vascular resistance
some increase in cardiac output
metabolized by the CP-450 system
side effects of dihydropyridines
heaches
flushing
dizziness
GERD
constipation
peripheral edema
benzothiazepine
diltiazem
decreases cardiac output
decreases peripheral vascular resistance
metabolized by the CP-450 system
may inhibit the clearance of other drugs
side effects of benzothiazepine
edema
headache
nausea
dizziness
constipation
diarrhea
bradycardia
phenylalkylamines
verapamil
decreases cardiac output
decreases vascular resistance but not as much as diltiazem
metabolized by the CP-450 system
may inhibit clearance of other drugs
target population of CCBs
safe in patients with diabetes, renal insufficiency, lipid problems, and asthma
use with caution in patietns with heart disease and conduction abnormalities
possibly synergistic with other agents, so it is a good add-on therapy
peripheral vasodilators
hydralazine
minoxidil
sodium nitroprusside
hydralazine mechanism of action
lowers blood pressure through relaxation of arteriolar smooth muscle
minoxidil mechanism of action
activates a potassium channel in vascular smooth muscle, causing K+ efflux which hyperpolarizes and relaxes smooth muscle cells
nitroprusside mechanism of action
metabolized by blood vessels to nitric oxide
nitric oxide activates guanyl cyclase which makes cGMP and vasodilates the blood vessels
effects of peripheral vasodilators
increased intravascular volume
increased cardiac output
major decrease in peripheral vascular resistance
side effects of hydralazine
headache
nausea
flushing
angina
edema/heart failure
drug induced lupus
side effects of minoxidil
sodium and H2O retention
tachycardia/angina/heart failure
hypertrichosis
effusions
side effects of nitroprusside
hypotension
cyanide and thicyanate toxicity
manifests as severe lactic acidosis
anorexia
fatigue
confusion
psychosis
target population of peripheral vasodilators
used in patients with difficult to control blood pressure
often on multiple agents, which allows some control of the side effects of the vasodilators
aliskiren
a direct renin inhibitor
can cause dizziness, hyperkalemia, and rash
should be used in people who have resistant hypertension or intolerant of other medication
treating hypertensive emergencies
look for end organ damage - CNS, heart, kidneys, eyes
lower BP by about 20% from the mean arterial BP presentation to prevent ischemia
agents - nitroprusside, labetolol, hydralazine, enalaprilat, nicardipine
