ACE/ARBs/Diuretics Flashcards
RAAS Pathway
1) ___ cleaves angiotensinogen into ___
2) angiotensin-converting enzyme (ACE) converts ___ to ___
3) angiotensin II is converted to ___ which binds to target cells to increase ___ absorption, ___ excretion, ___ retention
- renin, angiotensin I
- angiotensin I, angiotensin II
- aldosterone
- Na, K, fluid
renin release in HTN
renin is released by ___ cells in the kidney:
1) due to drop in ___ in pre-glomerular arteries ( < ___ mmHg systomic BP)
2) due to low ___ in the distal tubule of the kidney
3) increased ___ nervous activity (B1), or other signaling mechanisms
juxtaglomerular
BP, 90
NaCl
sympathetic
Renin Inhibitor: Aliskiren (Tekturna)
action: direct inhibitor of renin and thus decreases formation of ___
clincal use: not first-line for hypertension - effective in reducing renin leading to a drop in ___
contraindicated in ___ and ___ mothers
Note: drugs that block ___ receptors inhbit release of renin due to interaction with ___ receptors on juxtaglomerular cells in kidney
- angiotensin I
- BP
- pregnant, nursing
- beta1, beta 1
ACE Inhibitor Classes
1) sulfhydryl-containing structurally related to ___
2) dicarboxyl-containing structurally related to ___
3) Phosphorous-containing structurally related to ___
- captopril
- enalapril
- fosinopril
ACE Inhibitor Classes
many ACE inhibitors are ester containing ___
pro-drugs
ACE Inhibitors
Lisinopril (Prinivil, Zestril)
- well tolerated
- not a ___
Enalapril (Vasotec)
- ___ hydrolyzed to active diacid ___
- PO and IV
Captopril (Capoten)
- ___ containing, not a ___
- useful for supine hypertension-orthostatic ___
- ___ acting
- SE: rash, neutropenia, agranulocytosis
- prodrug
- prodrug, enalaprilat
- thiol, prodrug
- hypotension
- short
Fosinopril Sodium (Monopril)
- ___ containing
- ___ , cascade ester
- phosphonate
- prodrug
ACE Inhibitors
actions: inhibit ___
- reduce ___ due to angiotensin III
- reduce mycardial mitogenic activity and thus decrease myocardial ___ and remodeling
- reduced ___ and ___ retention caused by aldoseteron release
- reduce totaly ___ resistance
Clinical Use:
- ___ monotherapy for HTN and HF
- beneficial for patients of HF or CKD (restabilize renal function)
Problems
- cough, angiodema, hyperkalemia
- should not be used in ___
- ACE-i/ARBs are used in renal artery stenosis but not if GFR drops by more than ___ %
- ___ may reduce effectiveness
- ACE
- vasocontriction
- hypertrophy
- water, Na
- peripheral
- 1st line
- pregnancy
- 30%
- NSAIDs
ACE Inhibitors: AE
- ACE inactivates ___
- bradykinin produces ___ , mediated by prostaglandins
- ___ block production of prostaglandins and may decrease ACE inhibitor ___ effects due to decreased bradykinin effect
- Cough and ___ of lips and tongue due to accumulation of ___ (black population)
- hyperkalemia due to decreased production of ___ ; risk is increased with potassium supplements or ___ sparing diuretics
- bradykinin
- vasodilation
- NSAIDs, hypotensive
- angiodema, bradykinin
- aldosterone
- K
ARBs - “-sartans”
- block ___ receptors with a much higher affinity for the ___ receptor versus the ___ receptor
Rank of potency
candesartan = ___ > irbesartan = ___ > telmisartan = ___ = EXP 3174 (active metabolite of ___ ) > ___
- angiotensin II, AT1, AT2
- omesartan, eprosartan, valsartan, losartan, losartan
Design of ARBs based on ___ of angiotensin II
- essential HTM, all administerd PO, excreted in the ___
- carboxy terminus
- feces
ARB SAR
- acidic group: ___ acid or ___ acid
- substituted ___ or ___ equivalent
- a second ___ group in some cases
- o-Phenylcarboxylic, carboxylic
- imidazole, isosteric
- carboxylic acid
ARB
Action
- ___ antagonist at angiotensin II receptor ( ___ ) - blocks effects of ___ produced by ACE and by local tissue enzymes
- reduction in angiotensin II mediated ___
- decrease ___ resistance; decrease ___
- decrease ___ secretion; __ and __ retention, and ___
- decrease ___ activity from angiotensin II stimulation (thus reduce renin release)
- decreased ___ and ___ remodeling
- decrease ___ apoptosis
- reduce total ___ resistance
- competitive, AT1, angiotensin II
- vasocontriction
- peripheral, afterload
- aldosterone, salt, water, preload
- sympathetic
- vascular, mycardial
- cardiomyocyte
- peropheral
ARB
Clinical Use:
- often used in patients who do not tolerate ___ inhibitors
- ___ - combined with sacubitril
- ___ monotherapy for HTN
AE: hypotension, hyperkalemia, lower rate of ___ but may still occur, fetal pathologies, reduction in GFR
Note: ARBs do not inhibit the breakdown of ___ like ACE inhibitors, not associated with ___
- both ACE-Is and ARBs are less effective in ___ as HTN monotherapy but appropriate for ___
- ACE
- valsartan
- 1st line
- angiodema
- cough
- AA
- HF
ARB
particularly useful in patients
- with diabetes (compared to ___ )
- with ischemic heart disease (compared to direct ___ )
- patients with CKD (diminish proteinuria and stabilize ___ function)
- thiazides
- vasodilators
- renal
Aldosterone (Mineralocorticoid) Receptor Antagonists
Spironolactone, Eplerenone
MOA: ( ___ sparing diuretic)
- aldosterone receptor antagonist (collecting tubules of nephron), thus blocks reabsorption of ___ and mildly decreases ___
- effectiveness in HF likley not primarily due to diuretic effect. May be related to increased production of ___ in diseased heart promoting development of cardiac hypertrophy, remodeling, and fibrosis and maintenance of normal ___ levels thus decreasing the risk of ___
- K
- Na, BP
- aldosterone , K, arrhythmias
Aldosterone (Mineralocorticoid) Receptor Antagonists
Clincal Use:
- chronic HF - reduces mortality
- aldosteronism, HTN, not ___ for HTN but used to reduce ___
AE
- ___ kalemia
- spironolactone: lack of specificity and interaction with other steroid receptors (antiandrogen effects: ___ and ___ )
- monotherapy, hypokalemia
- hyperkalemia
- gynecomastia, impotence
HTN Treatment Strategies
First line
- diuretics ( ___ )
- ___ Inhibitors
- ___ blockers
- L-type ___
- thiazides
- angiotensin converting enzyme
- angiotensin II receptor
- CCB
HTN Treatment Strategies
Secondary Agents
- diuretics ( ___ , ___ sparing - including ___ antagonists)
- sympatholytics ( ___ blockers, combined ___ ___ blockers, ___ blockers, ___ CNS acting agonists)
- direct renin inhibitor ( ___ )
- loop, K+, mineralocorticoids
- B, B, a1, a1, a2
- aliskiren
Thiazides: cholrthalidone + HCTZ
action:
- diuretic blocking the ___ on the ___ convoluted tubule
- initially: related to diuretic effect ( reduce blood ___ and cardiac ___ )
- long term thiazides lower ___ vascular resistance
Clinical Use: ___ monotherapy for mild moderate HTN; often combines with sympatholytic or vasodilator
particularly effective in ___ population
Problems: hypokalemia, metabolic alkalosis, hyperuricemia, hypercalcemia, hyper ___ , hyper ___
- sodium chloride symporter, distal
- volume, output
- peripheral
- 1st line
- black
- hyperglycemia, hyperlipidemia
Other Diuretics
loop diuretics are NOT recommended as first line monotherapy for the management of HTN
- potent but, ___ acting
K sparing diuretics are NOT recommended as first line monotherapy for the management of hypertension because they are ___ and associated with ___
- short
- weak
- hyperkalemia
HTN in pregnancy
managment: ___
Beta blockers: ___ and ___ (and other beta blockers)
Drugs to avoid:
- ___ , ___ , direct ___
- ___ (mineralocorticoid) receptor antagonist
- methyldopa
- labetalol, metoprolol
- ACE, ARBs, renin
- aldosterone
