ACE Inhibitors & Angiotensin Antagonists Flashcards
How do ARBs impact the urate transporter?
- it BLOCKS the urate transporter
- uricosuric effect (increased uric acid excretion, reduces gout risk)
ACE INHIBITOR CONTRAINDICATIONS
- PREGNANCY
- typically not used in pts with Scr > 2.5 (high doses in pts w/ renal insufficiency may = neutropenia)
- typically not good in BLACKS
Breakdown of ARB impact
blocks AT1 –> blocks release of norepi –> decreases sympathetic action
Renin released due to
- Drop in BP
- Low NaCl in the distal tubule of the kidney
- . Activation of specific receptors in JG cells
angiotensin II stimulates the adrenal cortex which
- releases aldosterone
- increases BP
BLOCKED BRADYKININ CAUSES
- PGE2/PGI2 = vasodilation = increased vascular permeability
- bronchoconstriction = COUGH
- natriuresis
ARB examples
- losartan (cozaar)
- valsartan (diovan)
angiotensin II can modulate baroreceptor reflex which
increases BP WITHOUT reflex bradycardia
Angiotensin II Receptor Type 1 (AT1) Blockers end in
-sartans
angiotensin II causes
widespread vasoconstriction
Liver releases
angiotensinogen
angiotensin II activates thirst center (pituitary gland) which
- causes release of antidiuretic hormone (ADH, vasopressin)
- drink more –> increase volume
- increases BP
ADVERSE EFFECTS OF ARBS
- hypotension
- hyperkalemia («< ACE-Is)
- teratogenic potential (2nd + 3rd trimester)
Selectively block effects of ANG II does 3 things
- reduce BP
* **SANS: inhibit stimulation of NE system (fast pressor effects)
* **RAAS: reduce secretion of aldosterone (slow pressor effect)
* **prevent cardiac hypertrophy - reduce renal vasoconstriction
- no effects on bradykinin system (cough and angioedema less prevalent)
ACE inhibitor examples
- lisinopril (zestril)
- enalapril (vasotec)
- captopril (capote)
enalapril (vasotec)
- prodrug (has ester that needs to be cleaved)
- similar to lisinopril
why ace-inhibitors not good in Blacks
- due to low circulating renin
- but use to treat DN and heart failure
ADH causes
aquaporins to move to the collecting duct plasma membrane, which increases water reabsorption
AT1 Receptor is blocked by
ARBs
WHEN BLOCK ACE-I
-INCREASES CONCENTRATION OF BRADYKININ
SANS definition
sympathetic autonomic nervous system
Angiotensin Receptor 1 (AT1) coupled to _____ and causes (3 things)
Gq GPCR (but also Gi);
- vasoconstriction of smooth muscles
* **PLC –> Ca increase
* **activation of Ca channels
* **reduce NO synthesis - Increases BP
* **increase aldosterone production (adrenal medulla) - Cardiac hypertrophy
angiotensin II causes constriction of smooth muscle cells which
increases BP
captopril (capote)
- useful for supine HTN-orthostatic hypotension
- short acting (t1/2= < 3 h)
- side effect = rash
angiotensin II does (5 things)
- stimulates the adrenal cortex
- causes constriction of smooth muscle cells
- activates thirst center (pituitary gland)
- can modulate baroreceptor reflex
- causes cardiovascular hypertrophy
ACE inhibitors end in
-pril
inhibition of renin (direct and indirect) contraindications
- PREGNANCY and nursing mothers
- use with ARBs or ACEIs in pts with kidney impairment or diabetes because of kidney impairment risk, low BP and high K+ in blood
RAAS definition
renin-angiotensin-aldosterone system
CLINICAL USES OF ARBS
- HTN
- Congestive heart failure
- diabetic nephropathy
- stroke prophylaxis
ACE INHIBITOR CLINICAL USES
- HTN
- Heart failure with reduced ejection fraction (left ventricular systolic dysfunction)
- MI (dampened SNS response)
- slows down progression of diabetic nephropathy
HOW DO ACE INHIBITORS SLOW DOWN PROGRESSION OF DIABETIC NEPHROPATHY
- act on efferent arteriole of the kidney
- this reduces pressure in the glomerulus
- diminishes proteinuria
lisinopril (zestril)
- most commonly used
- well tolerated
- t1/2 = 12h
- not a pro-drug (available mixed with HCTZ - Zestoretic)
Kidney releases
renin
The release of renin
increases BP
direct inhibition of renin by
- aliskiren (Tekturna)
- **10 years old
- **used alone or in combination to treat HTN
- **benefit: may decrease carotid arterial stiffness vs HCTZ
Indirect inhibition of renin
impacts beta 1 blockers (blocks B1-AR mediated release)
Mechanism
- enzyme reaction (kidney - renin, liver - angiotensinogen)
- angiotensin I
- enzyme reaction (ACE in pulmonary blood)
- angiotensin II
- stimulation of adrenal cortex to secrete aldosterone
ACE-I ADVERSE EFFECTS
- first dose hypotension (fainting, orthostatic hypotension)
- hyperkalemia (via aldosterone effect)
- acute renal failure
- dry cough
- angioedema
Most relevant diuretics
- thiazides
- K sparing (aldosterone)
- loop diuretics
Renin is released by ____________ cells in the _______
juxtaglomerular; kidney
angiotensin-converting enzyme located in
pulmonary blood
ACE-I drug-drug interactions
- food/antacids reduce bioavailability
- NSAIDs may reduce effectiveness (renal)
- K+ supplements
- may increase plasma levels of digoxin and lithium
aldosterone stimulates
Na uptake on the apical cell membrane in the distal convoluted tubule and collecting ducts
angiotensin II causes cardiovascular hypertrophy which
- increases contraction
- increases BP
