antihypertensives - RAAS (exam 2) Flashcards
high blood pressure stage 1
systolic: 130-139
diastolic: 80-89
high blood pressure stage 2
systolic: 140 or higher
diastolic: 90 or higher
hypertensive crisis
systolic: higher than 180
diastolic: higher than 120
essential hypertension
95%
no underlying cause
secondary hypertension
underlying cause
causes of secondary HTN
renal (parenchymal, vascular, other)
endocrine
other
predisposing factors of HTN
age
family history of CV disease
sedentary lifestyle and psycho-social stress
smoking
high cholesterol diet
obesity and weight gain
co existing disorders
high intake of alcohol
why is HTN considered the silent killer?
most of the time there is no specific complaints/manifestations other than the high BP
clinical manifestations of HTN
morning occipital headache
dizziness
fatigue
manifestations of severe HTN
epistaxis
blurred vision
routine tests for HTN
ECG
urinalysis
blood glucose, serum K, Cr, eGFR and Ca
lipid profile
optional tests for HTN
urinary albumin excretion
albumin/Cr ratio
why do we treat HTN?
to target organ damage
organ damage in the heart caused by HTN
left ventricular hypertrophy
angina/MI
HF
organ damage in the brain caused by HTN
stroke
transient ischemic attack
diseases caused by organ damage from HTN
CKD
PAD
retinopathy
the goal of BP management
reduce the risk of CVD related morbidity and mortality manifested as organ damage
lifestyle modifications to help treat CVD
weight loss
low sodium diet
physical activity
blood pressure =
cardiac output x peripheral vascular resistance
cardiac output =
stroke volume x heart rate
drugs that decrease HR or heart contractility will
decrease cardiac output
drugs that cause vasodilation will
decrease peripheral vascular resistance
drugs that decrease blood volume will decrease
cardiac output and PVR
agents that target RAAS
Angiotensin concerting enzyme I (ACE) inhibitors
angiotensin II receptor blockers (ARBs)
direct renin inhibitor
diuretics used to treat HTN
thiazides
loops
K sparing
vasodilators used to treat HTN
calcium channel blockers (CCBs)
direct vasodilators
agents that target the sympathetic nervous system to treat HTN
beta blockers
alpha 1 blockers
alpha 2 blockers
most medications reduce SBP by an average of
5-10 mmHg
first line medications for treatment of HTN
ACE inhibitors
ARBs
CCBs
thiazides
direct renin inhibitor example
aliskiren (tekturna)
ACE inhibitor examples
benazepril (lotensin)
captopril (capoten)
enalapril (vaster)
fosinopril (monopril)
lisinopril (Prinivil, Zestril)
quinapril (accupril)
ramipril (altace)
ARB examples
candesartan (atacand)
irbesartan (Avapro)
losartan (cozaar)
olmesartan (Benicar)
telmisartan (micardis)
valsartan (diovan)
azilsartan (edarbi)
angiotensin II stimulates
sympathetic activity
tubular Na, Cl reabsorption, K excretion, H2O retention
aldosterone secretion
arteriolar vasoconstriction
ADH secretion –> H2O reabsorption
the result of the RAAS system activation
water and salt retention
effective circulating volume increases
ACEIs cause
vasodilation
reduction of aldosterone secretion
reduction of ADH secretion
ADEIs cause an increase in _____________ which can contribute to _________________
but buildup of this in the lungs can lead to ________________
bradykinin levels
vasodilation
cough and angioedema
ARBs are more specific for
blocking angiotensin I effects which limits side effects
ARBs were hypothesized to be less effective than ACEIs however they have
similar clinical efficacy
ACE inhibitors and ARBs are typically _______________ but can cause ____________ in certain situations
renal-protective
AKI
constriction of afferent arteriole leads to
a decrease in GFR
constriction of the efferent arteriole leads to
an increase in GFR
what blood test is used as a surrogate for GFR?
creatinine clearance
when an ACE/ARB is used, there is vasodilation of the __________________ which leads to a _____________ in glomerular pressure and _______________
efferent arteriole
reduction
decrease in GFR
addition of an ACEI or ARB leads to only a small reduction in ___________, meaning the drug is __________
GFR
renal-protective by reducing excessive glomerular pressure
In patients with renal stenosis or volume depletion, taking an ACEI/ARB can cause a
major reduction in GFR leading to AKI
ACEI/ARBs can lead to
hyperkalemia due to a reduction in aldosterone
when an ACEI/ARB is used there is a reduction in _________________ leading to a reduction in __________________ causing hyperkalemia
aldosterone secretion
K excretion
does ACEI/ARBs cause hyponatermia?
although there is an increase in sodium excretion, they do NOT cause hyponatremia
ADRs of both ACEIs and ARBs
hyperkalemia
increase serum creatinine
what is a normal increase in SCr when taking an ACE/ARB?
30%
ADRs of ACE inhibitors
dry cough
angioedema
contraindications for ACEI/ARBs
pregnancy
bilateral renal stenosis
can you combine RAAS medications for therapy?
NOT REALLY
only in extreme situations such as HF or CKD with proteinuria
Captopril consists of a _____________ and binds to
thiol group
taste buds leading to taste disturbance
there is an increased risk of ____________ with captopril
skin rash
why does captorpil have to be taken on an empty stomach?
it interacts with foods
ACE inhibitors with no thiol group replaced by an ester group
enalapril
quinapril
benazepril
fosinopril
ramipril
ACE inhibitors with an ester are considered ___________ because ______________
prodrugs
hydrolysis of the ester is required for therapeutic activity
enalaprilat
active metabolite of enalapril
given IV for treating hypertensive crisis
lisinopril
lysine derivative of enalapril
carboxylic acid group replaces ester
NOT a prodrug
ACE inhibitor prodrugs are converted into the active form in the
GI and liver by esterase enzymes
lisinopril is excreted
mostly unchanged
all ACE inhibitors are excreted ____________ except for _____________
via kidneys
fosinopril
fosinopril is excreted by ______________ and does not
hepatobiliary route
accumulate in renal failure
candesartan, olmesartan and azilsartan are ______________ which are converted into active form by __________________
ester prodrugs
gastrointestinal hydrolase enzymes
active metabolite of losartan?
losartan is converted to it by what enzymes?
EXP-3174
CYP2C9 and CYP3A4
losartan’s active metabolite is ______________ more potent than losartan
10-40x
irbesartsan is metabolized by
CYP2C9 to inactive metabolites
excretion of ARBs
mixed renal and hepatobiliary elimination
due to variable half lives or ARBs, they are dosed
once a day or sometimes BID
direct renin inhibitor MOA
inhibits renin (responsible for conversion of angiotensinogen to angiotensin I)
ADRs of direct renin inhibitors
diarrhea
PK of direct renin inhibitors
minor CYP3A4 metabolism
long half life
when a direct renin inhibitor is added to ACEI/ARB therapy in diabetic patients with CKD,
it increases cardiovascular events
under the condition of hyperkalemia, aldosterone release is mediated by
a direct effect of potassium on cells in the zona glomerulosa
factors of dual negative feedback control of aldosterone secretion
blood volume
plasma potassium concentration
aldosterone release leads to
increased absorption of sodium and water
increased potassium secretion
increased blood volume and bp
does ACTH control aldosterone?
no
aldosterone antagonists
usually prescribed with diuretic
for those with uncontrolled HTN, diabetes or HF
enzyme that controls cortisol expression
11 beta - HSD2
