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Flashcards about ATII Blockers and nitrates.
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ATII Blockers and nitrates
Blockers and nitrates are the main focus.
Effects of ATII Blockers and Nitrates
Reduced Blood Pressure, Renin Release, Lowered Sodium Excretion, Vasoconstriction, Aldosterone Secretion, Sodium and Fluid Retention, Increased Peripheral Resistance, Increased Cardiac Output, Elevated Blood Pressure
Renin metabolism pathway
A biochemical pathway that regulates blood pressure, controlling the conversion of angiotensinogen to angiotensin I, and then to angiotensin II, influencing vascular tone and fluid balance.
Angiotensin I
ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE-HIS-LEU
Angiotensin II
ASP-ARG-VAL-TYR-ILE-HIS-PRO-PHE-HIS-LEU
Angiotensin III
ARG-VAL-TYR-ILE-HIS-PRO-PHE
ARB Mechanism
ARB bind and inhibit angiotensin II (ATII) type 1 receptor (AT1).
AT1 Activation
causes vascular smooth muscle contraction, sodium and water retention, and aldosterone secretion.
ARBs Uses
ARBs are used to treat hypertension, heart failure, diabetic nephropathy and for patients who cannot tolerate ACE inhibitors.
Examples of ARBs
EXP3174, Valsartan, Telmisartan, Candesartan, Olmesartan, Azilsartan, Irbesartan
ARB SAR
Imidazole ring mimics His6 in angiotensin II. Butyl/propyl substituent mimics Ile. Biphenyl group has ortho acidic substituent (tetrazole is best).
Losartan
a Prodrug that is converted to its active form, EXP3174, in the liver. It is primarily used for hypertension and to protect against kidney damage in diabetic patients.
Metabolite of Losartan
Losartan 5-carboxylic acid derivative
ARBs Requiring Hydrolysis (Prodrugs)
Olmesartan medoxomil, Candesartan cilexetil, Azilsartan medoxomil
Active Metabolite ARBs
Olmesartan, Candesartan, Azilsartan
ARBs Characteristics
Highly variable bioavailability, high protein binding, primarily fecal elimination unchanged, Interactions with other antihypertensive drugs, contraindicated in pregnancy/nursing.
Organic nitrates
Nitroglycerin, Isosorbide dinitrate, Pentaerythrityl tetranitrate, Isosorbide mononitrate, Amyl nitrite, Sodium nitroprusside, Nicorandil
Organic nitrate mechanism & use
Prodrugs for nitric oxide (NO). Causes relaxation of vascular smooth muscle cells. Decreases cardiac preload and increases coronary blood flow. Used for treating angina (prophylactic and acute), hypertension, and heart failure. Nitrate tolerance can develop.
Organic nitrates Characteristics
Lipophilic nitrate esters, are very well absorbed, has a wide variety of dosage forms, metabolically activated to deliver NO and has interactions.
Big Picture
These drugs act on renin-angiotensin-aldosterone-system (RAAS) or generate nitric oxide directly. DDIs with each other or diuretics can be beneficial or harmful. They have similar mechanism-based DDIs