Pharm management of HTN I - Lee Flashcards
BP aka MAP equation
BP = CO x TPR
- increase bp by increasing CO and/or TPR
- vascular tone also affects TPR
CO equation
CO = HR x SV
effects of angiotensin II
- arteriole smooth muscle vasoconstriction
2. aldosterone release
ACE
converts ang I to angII
renin
converts angiotensinogen to angI
ACE inhibitors
- prevent conversion of angI to angII
- prevent breakdown of bradykinin (vasodilator), which stimulates lung irritation
- for HTN, heart failure, diabetic neuropathy
- teratogen for pregnancy***
- not for when renal perfusion is low in stenosis (exacerbates issue)*
adverse effects
-acute renal failure (too low BP and stenosis), hyperkalemia from aldosterone suppression, dry cough, angioedema, severe hypotension in hypovolemic patients, skin rash, and altered/loss taste**
drug interactions
- hyperkalemia if used with K+ supplements/diuretics
- NSAIDs blocking bradykinin mediated vasodilation
- NSAIDs also reducing prostaglandins –> vasoconstriction decreasing renal blood flow
captopril, enalapril, fosinopril, lisinopril
- all are ACE inhibitors –> preventing conversion of angI to angII
- prevent inactivation bradykinin
- all given orally
- all excreted by kidney –> renal damage requires dose adjustment
- all have same indications –> HTN, heart failure, diabetic neuropathy**
- same contraindications –> pregnancy (teratogenic), bilateral renovascular disease, hyperkalemia
- only half life changes**
captopril
- not prodrug**
- half life = 2hr.**
- have to give multiple doses per day
enalapril
- prodrug –> dicarboxyl containing
- half life = 11 hr. ** (better for compliance)
fosinopril
- prodrug –> phosphorous containing group
- half life = 11.5 hr. **
- excreted in urine and bile*
lisinopril
- prodrug –> phosphorous containing
- half life = 12 hr. **
angiotensin II receptor blockers (ARB)
- block AT1 receptors* for angII
- no effect on bradykinin metabolism** - more selective to angiotensin
- oral bioavailability usually low (<50%)
indications –> HTN
-can be combined with other drugs
contraindications –> 2nd and 3rd trimester of pregnancy (can reduce fetal renal function causing neonatal death)
side effects –> cough and angioedema, but less than ACE inhibitors
drug interactions
- with ACEI, sacubitril/valsartan increases risk of serious angioedema (more common in african americans*)
- K-sparing diuretics or K supplements –> hyperkalemia
- NSAIDs –> worsen renal failure
- lithium toxicity*
FETAL TOXICITY**
losartan, candesartan, valsartan
- all are ARB –> block AT1 receptors** (block angII activity)
- same indications –> HTN, heart failure, diabetic neuropathy, intolerance to ACE inhibitors (angioedema, cough)*
- same contraindications –> pregnancy, use with aliskiren in diabetic patients*
- adverse effects –> dry cough, hyperkalemia, skin rash, hypotension, altered taste*
losartan
- for sure indicated with diabetic patients
- go to drug if patient has angioedema or cough**
candesartan
-contraindicated in breast feeding like the others**
valsartan
-indicated in left ventricular dysfunction or failure after MI*****
ARB + Neprilysin inhibitor
- double effects if combined with other drugs
- Sacubitril (neprilysin inhibitor) combined with valsartan (ARB)**
- sacubitril –> decreases vasoconstriction, Na+ retention, and maladaptive remodeling
- valsartan –> inhibits angII effects and release of aldosterone
- indications –> treat heart failure with reduced ejection fraction** (HFrEF) –> greater effect with drug combination (reduced death from CV causes and slowed progression of HF)
- contraindications –> pregnancy**
adverse effects –> hypotension, hyperkalemia, cough, angioedema*
drug interactions –> same as ARB
what is neprilysin?
- neutral endopeptidase that degrades vasoactive & natriuretic peptides, bradykinin & adrenomedullin
- metabolizes ANP, BNP, CNP
aliskiren** - renin inhibitors
- binds renin & inhibits cleavage of angI from angiotensinogen**
- for HTN (not drug of 1st choice bc expensive)*
- not used with other ACE inhibitors or ARB in diabetics
- use for someone with problems with ACE inhibitors**
- side effects of fetal/neonatal death in 2nd/3rd trimester
- GI adverse side effects**
aliskiren + hydrochlorothiazide (diuretic)
- combination therapy
- for patient whos BP is not controlled well enough by either of these drugs alone or if it is controlled well with hydrochlorothiazide but has hypokalemia
- not indicated for initial therapy
- discontinue if pregnant
