Module 3 Hypertension Flashcards
what are classes of drugs used in the treatment of hypertension
calcium channel blockers
angiotensin converting enzyme inhibitors
angiotensin receptor blockers
thiazide diuretics
alpha 1 adrenergic antagonists
what percentage of americans are hypertensive
15% and largely asymptomatic
what is considered hypertension
above 120/80 is prehypertensive
140/90 is stage 1 hyper tensive
160/100 is stage 2 hypertnesive
what is the etiology of hypertension
unknown (primary or essential)
known (secondary) less than 5 %
-chornic renal or vascular disease
-endocrine (pheochromocytoma, primary aldoseronism)
-drugs/food (glucocorticoids, sympathomimetic amines)
-white coat
what is pheochromocytoma
neoplasia of chromatin cells causing the over production of catecholamines
glucocorticoids do what
sodium retinaing action
Blood pressure is the equation of what
TPR x CO
total peripheral resistance x cardiac output
cardiac output is the equation of what
cardiac output = Heart Rate x Stroke Volume
what are the two mechanisms to decrease blood pressure
decrease total peripheral resistance (relax vasucalr smooth muscle) (decrase TPR)
-calcium channel blockers
-antiotensin converting enzyme (ACE) inhibitors
-angiotensin receptor blockers (ARBs)
-alpha 1 adrenergic antagonists
decreaes the amount of blood pumped from the heart per beat (decrease co) (Strookve volume)
-thiazide diuretucs
contraction of vascular smooth muscle is done how
initiated by depolarization of the cell membrane potential and actiivation of voltage gated calcium channels
-this causes calcium ions to come into the smooth muscle an causes additional cacium release from a sarcoplasmi reticulum
calcium then binds to protein calmodiun
the calcium calmodiun compelx then stimulate the enzume myosin light chain kinase that phosphrylates the mysotin lifght chain of the contractile protins
this bnds myosin light chain to aciin and brings about smooth msucle contraction
drugs taht block the calcium channel do whay
inhibit contraction adn this decrase peripheral resistance
what are examples of calcium channel blockers
amlodipine and nifedipine
act to block smooth msucle calcium channels and inhibit contraction
amlodipine is used when in hypertension
stage 1 and in combinationn for stage 2
first line therapy - mroe effective in african americans and geriatric aptients
what are side effects of amlodipine and nifedipine
hypotension and relfex tachycarida
lower leg edema
risk of orthostatic hypotension
what is reflex tachycarida
with a fall in blood pressure the body compensates by increasing heart rate
what happens with a fall in blood pressure normally in kidneys
kineyes secrete enzyme called renin
renin converts angiotensinogen (peptide made in the liver) to angiotensin 1
in the blood, enzume called angiotensin convertin enzyme convers angiotensin I to angiotensin II
antiotension II causes vasoconstriction thus increasing total peripheral resistance
increaes aldosterone production by the adrenal gland
aldosterone increases sodium reabsorptin by the kidneys and potassium excretion
increase in na absorption means and increase in water reabsoptin which increases blood volume
ace also breaks down bradykinin to inactive peptides
how do ace inhibitors work
ace inhibitors decrease angiotnein II productin and this decrease antiogensin II indicued vasocontriction
-they inhibit aldosterone syntehsis resulting in less blood volume
decrease potassium excretion
so tehy increase blood potassium (hyperkalemia)
-also increase bradykinin which has a proinflamatory action which can result in dry cough that is non productive and angioedema
how do arbs (angiotensin receptor blocker) work
inhibit vasoconstriction and aldosterone syntheis do not affect bradykinin breakdown
so couhg and angioedema is not a side effect of arbs
what are examples of ace inhibitors
captopril and enalapril
what are examples of arbs
losartan and valsartan
what are the therapeutic uses of ace inhibiotrs and arbs
-hypertension stage 1 and in combination for stage 2
-more effective in Caucasian and young people (less so in geriatric)
-congestive heart failure
-diabetic neuropathy
what are side effects of ace inbitors
hyperkalemia
caution with k+ supplements
dry cough and andioedema
contraindicated in all trimesters of pregnancy
what are side effects of arbs
hyperkalemia
caution with k+ supplemnts
contraindicated in all tirmestsof pregnancy’s
felta hypotension and potential kidney damage.,
what do diuretics do inblood pressure
decraese blood volume by increasing water exrestion frin the kiney
what are exmaples of diuretics
furosemide
hydrochlorothiazie
where does furosemide act
acts on teh loop of henle in the kidney and is the most efficacious direetct
also used in the treatment of congestive heart failture
where does hydrocholothiazide work
actrs on teh distal tubule and is used in treatment of hypertension
what is the action of hydrochlorothiazide
kidney diuretic action
increaes urine output thus reducing blood volume and this stroke volume
smooth msucle relaxation reducing TPR
what are the therapeutic uses of hydrochlorothiazide
first line therapy
african and geriatirc patients
-used in monotherapy or combined with calcium channel blcokers, ace inhib or arbs
what are the side effects of hydrochlortiazide
hypokalemia - offset acei/arb
sulfonamide sensitivity (such as sulfa abx)
caution in pregnany
contrction of vascular smooth mscule occurs by binding of norepi to what
binding to alpha 1 adrenegic receptors
increase in heart rate is from binding of norpi to what
to cardiac beta 1 receptors
what happens when alpha 1 recetpor is stimulated by epi or norepi
the production of ip3 through gq protein
ip3 then causes calcium release from the sarcoplasmic reticulum
the relase calcium then binds to calmodium leading to the phosphyrlation fo mysoin light chain kinase and myosin light chaain and contraction
what does alpha adrenergic blocker (antagonist) do
causes venous dilation thus reducing vascualr resistance
inhiibits catecholamine induced vascualr constirction
example of alpha adrenergic blocker
prazosin
what is the therapeudic use of prazosin
essential hypertension used in combination for stage 1 and 2
not commonly used anymore
benign prostatic hyperplasia relieving obstructive symptoms
how does prazosin releive urinary obstruction
reducing the tone of the prostate by relaxing teh uretra increaing the urnary stream
what is heart failure
patholoogicl state in which the heart is unable to pump blood at a rate necessary to meet the requirements of teh body
the resuling symptoms fatigue, shortnes sof rbeath, pulmonary congestion and edema results from inadequate perfusion of tissue and retention of fluid
what is afterload
the arterial resistance that the heart needs to pump against
increases with vascualr constirction (hypertension)
what is preload
the amount of stretch of the cardiac ventricular chamber referred to as end diastoluc pressure (EDV)
increased venous return of blood to the ventrilce (blood volune) increases EDV
what is contractillity
the force of cardiac contraction
what is cardiac output
amount of bloood ejected from heart over time
what is stroke volume
amount of blood ejected from heart during one beat
what factors effect stroke volume
contractility
afterload
heart rate
cardiac output
lv wall integrity
valvular competnece
preload
what are factors that decrase stroke volume
-coronary artery diease, MI, arrhythias affect contractility decrasing it
-hypertension increases the resistnacne the heart needs to pymp against thus increasing afterload
-direct damage to walls and values of the heart (mitral valve stenosis)
-venous constrition and increased venous return to heart will increase preload, increase myocaridal wall stress
when cardiac output falls, a number of compensatory systems are activated including what
increased sympathetic activirt will increaes heart rate and contraction (sympathetic stimulation of the veins increaes venous return to the heart and this increases diasolic volume
this is accompanied by an increase in the heart 0 cardiac hypertrophy
what are the long term consequenses of compensatory systems in heart failure
vasocoonstriction of the synpathetic system increases afterloaf which increases the resistance against which the heart pumps
-there is also an increase in diasolic volume
-the resuction in renal blood flow activates the renin angiotensino II system leaving to further fascular contriction and increase in aferload
-the also increases aldosterone release from the adrenal gland resuling in an increase in sodium and water reabsrption
this further increasses end diasolic volume
-the increased wall stress can impair caridac contractin resuling in a further drop in cardiac output
-catecholamies such as epinephrine directly damage the heart
to treat heart failure, what does digoxin do
directly incrases the force of cardiac contraction or other ionotropic agents
to treat heart failure what do beta blockers do
beta adrenergic antagoists or beta blockers will protect the heart from damage caused by catecholamies
vasodialators, angiotension converting enzume inhibitors and angiotensin recetpor antatognistsdoes what to heart failiure
reduce afterload and ventricular wall stres
what do diuretic do in heart failutre
reduced preload and reduce edema
what do ionotropic drugs do
increase cardiac contractility
increase in intracellualr calcium
what are the three groups of iontropuic drugs
dobutamine
inathrionine
digonxin
what is dobutamine and its action
a beta 1 adrenergic receptor agonist
increases cyclinc amp and stmulates camp dependent protien kinase
this increases calcium influc throguh ca channel into the myocyte enhanxcing contraction
what is inamrionone and its action
a phosphodiesterade inhibitior
phosphodiesterase enzymes break down cyclic amp
by inhibiting breakdwon of clyclic amp inamrionr increases intracellular camp increaesing ca
what is digoxin adn what does it do
binds to and inhibits the sodium potassium atpase
this increaes intraceulular soudium whihc then increases inctracellular calcium
what is the pharmacology of digoxin
increase contraction which is positive inotrophy increasing cardiac output
decreases preload, end diasolic voliume and heart oxygen demand
increases cholinteric activity slowing heartrate
if there is an increase in cardiac output then what doe sthis do to compensatory ssytems
decrease compensations
so decrease preload, edv anbd heart ocygen demand
increaes parasymp activity slows heart rate
what is the therapeutic use of digozin
second line drug in treating heart failure
low output heart failure with accompanying atrial fibrillation
end stage heart failure
acei, arbs, beta blocker first line of defense
what are side effects of digoxin
k+ and digondn compete for same biiding site on na/k atpase
caution with k wastering diruretics (furosemide) enhanced digozin toxicity
less k = more digoxin binding
narrow therapeutic infex (easy to reach toxin blood level)
cardiac arrhythmias
gi anorexia, nausea, vomiting
cns fatigue, weakness and confusion
mostly eliminated unchanged by kindey so caution in kidney damage pt
life threatenign digoxin toxicity is treated with what
atropine and digoxin antibodies (muscarinin antagonist) and bind to digoxin in boood and remove from body
dobutamine is considered what
beta adrenerigc receptor agonist
inamrinon is considered what
pde inhibitor
what is the pharmacology of dobutamine and inamrinon
only used in late stage heart failure since they increase mortality
increaes contraction (increase co)
use limited to advanced heart failure (ICU)
may increase mortality in chf patients
parasoxical use of beta blockers
what is used for patient in icu for treating pt w/ acute heart failure
nitroglycerin an na nitroprusside
nitroglycerin and na nitroprusside are considered what
direct acting vasodilators
what is the pharmacology of direct acting vasodulators (nitroglycerin and na nutroprusside
venous dilation (nitrogly) decrease preload (edv) reduign pulmonary edema and improving breathing
arterial and venous sialtion afterload and preload decreased (na nitroprusside)
what are side effects and considerations of nitroglycerin and na nitroprusside
used in icu in acute heart failure indlucing pulmonary edema (difficulty breathing and extreme fatigue and swelling of legs and ankles)
nitroprusside is convered to cyanide and thiocyanate (cyanide toxicity)
what is now considered first line drugs in treating congestive heart failure
ace inhibitor and arbs
both ace inhibtiors and arbs decrease afterload andn preload and this do what
increase cardiac output increasing water excretion reducing edema
ace i and arbs are given with what when heart failture is first diagnosed
beta blockers
what is the pharmacology of ace i and arbs in heart failure
first line therapy in chf pt reducing mortality
both decrease afterload and preload increasing cardiac output
both decrease aldosterone syntheiss decreasing edema
what are the side effects of abrs and aceinhib
hyperkalemia because inhibit aldosterone sysntheiss
dry cough and andioendema in ace inhibitors
both contrainsidcaed in prengnacy
both contraindicated in pt with bilateral renal stenosis bc these pt need angiotensin II in order to maintain normal kidney function
diureticsc decrase preload how
by decreaing blood volume
what is the pharmacology of furosemide and hydrochlorothiazide
reduce plasma volume decreasing preload
loop direetc furosemide prefered bc greater diuretic action
decrease pulmonary (dyspenia) and peripheral edema
what are side effects of diuretics
electrolyte K+ loss is major concern
hypokelemia
what do beta blockers do
decrease contraction and this decrease cardiac output
what are examples of beta blockers
metoprolol and carvedilol
beta adrenergic receptor blockers
what is the therapeutic use of bta blockers
parasoxical benefical action and decrease mortality
mechanism to decrease catecholamine induced apoptosis of cardiac myocytes (exact mech not known) - with remodeling there are changes in the expression of ion channels and contractile protiens in the heart
use with ace i or arbs and diuretics
what are the side effects of beta blockers
cardiac contraction and excitatoin depression (prevent the binding of catecholamines to beta 1 recepotr in heart
they caase depression of cardiac contractio and exxcitation in heart
-asthma and copd as pt needed catecholamine simulation of b2 in the lungs - need to use beta 1 selective drug such as metorprolol
-masking hypoglcemia in diabetes - mask effect of catecholamine release from hypoglycemia (increase hr and dizziness) so may not realize have hypo
entresto does what
is a new drug that acts partially by increasing blood levels of BNP
it has been shown to reduce mortality and hosptual visits with pt w heart failure
nitric ozxide does waht
is a chemical released from teh endothrlisum assocuated with vasulcar smooth muscle
it enters into smooth muscle and stimualted the prodiction fo cgmp
cgmp activates cgmp dependent protien kinase that caues a relaxation of vasular smooth msucel
what does brain naturtic peptide (BNP) receptor do
is a cell membrane glynylele cyclase
binding of bnp to the receptor incrases cgmp in vascular smooth muscle
this results in decrreases in arterial resistance afterlaod and pulmary congestion from preload
