Angiotensin interfering drugs Flashcards
Inhibition of renin release
-Beta blockers (ie propanolol), alpha 2 agonists (clonidine, methyldopa)
Propanolol
- Beta blocker
- inhibits renin release and thus angiotensin levels, which decreases vascular resistance
- also decreases CO
- AE: normal B blocker AE’s; rebound hypertension if stopped abruptly
Clonidine
- Alpha 2 agonist
- inhibits renin release and thus angiotensin levels, which decreases vascular resistance
- also decreases CO
Methyldopa
- Alpha 2 agonist
- inhibits renin release and thus angiotensin levels, which decreases vascular resistance
- also decreases CO
Ace Inhibitors (General)
- ACE INHIBITORS → ↓Ang II & ↑bradykinin
- 3 classes; all end in “pril”
- captopril, enalapril, lisinopril
Captopril
- Class 1 ACE inhibitor (only one)
- sulfhydryl (-SH)
- active as is; no further metabolism required
- additional AE: also neutropenia, loss taste, oral lesions
ACE inhibitor Mechanism
↓Ang II & ↑bradykinin
- ↓vasoconstriction → ↓TPR → ↓BP
- ↓aldosterone synthesis, release
- ↓central sympathetic output, ↓thirst, ↓vasopressin, ↓ACTH
- ↓renal proximal tubule NaCl reabsorption and ADH release
- ↓mitogenic activity
- ↑bradykinin which ↑vasodilation → ↓BP
- no hypotension-induced reflex sympathetic activation (tachycardia) → safe @ ischemic heart disease [Ang II mediates centrally-mediated resetting of baroreceptors by ↑NE; removing Ang II → no tachycardia]
ACE inhibitor uses and admin
Orally active
- Hypertension, heart failure, diabetic nephropathy, MI (reduces remodeling), DBM II
- HTN; drug of choice @ diabetes (β blockers impair insulin sensitivity)
- CHF ** ↓ mortality
- diabetic nephropathy (by ↓BP)
- post-MI (blocks mitogenic remodeling)
- not as effective in AA , b/c of salt intake → “low renin state” → ↓efficacy of ACE inhibitors
- low Na → ↑responsiveness to ACE inhibitors
- synergy w/ diuretic (↑Na loss)
ACE inhibitors AE and contraindications
AE, all:
- dry cough, skin rash (↑bradykinin)
- hyperkalemia (esp. in patients taking K+-sparing diuretics) → MI
-hypotension
- acute renal failure (↓glomerular filtration)
- teratogen @ 2nd, 3rd trimesters
- angioedema
- Captopril: also neutropenia, loss taste, oral lesions
Contraindications:
- pregnancy (all trimesters), renal failure, hyperkalemia, bilateral renal stenosis, pre-existing hypo-tension, severe aortic stenosis or obstructive cardiomyopathy
ENALAPRIL
- Class 2 ACE inhibitor
- prodrug, active after hepatic metabolism (most common class)
- ↓efficacy @ ↓liver fxn.
- pretty much every drug ending in “pril” except for captopril and lisinopril
LISINOPRIL
- Class 3 ACE inhibitor (only one)
- H20 soluble (active as is)
- renal excretion
ALISKIREN
- Renin Inhibitor
- Mechanism: block formation of Ang I by inhibiting renin
- Use: Hypertension
- last line; poor bioavailability
- AE: Induces Reactive Renin Release
- Also, hypotension, acute renal failure, angioedema, rash, diarrhea, cough
- Contraindications: pregnancy, hyperkalemia, cyclosporine therapy, history of angioedema
- in patients also using ACE inhibitors or ang receptor blockers, contraindicated for patients with diabetes because of the risk of hypotension, renal impairment, and hyperkalemia
Renin Inhibitor
Aliskiren, blocks formation of Ang I by inhibiting renin
Angiotensin interfering drugs, strategy
- Inhibit renin release (inhibit sympathetic nervous system)
- Inhibit renin
- Inhibit ACE
- ARBs
- Aldosterone antagonists
Angiotensin receptor (AT1) antagonists
=ARBs
-LOSARTAN, VALSARTAN
all AT1 receptor antagonists end in “sartan”
