Pharm management of HTN I - Lee

Question 1

BP aka MAP equation

Answer 1

BP = CO x TPR

• increase bp by increasing CO and/or TPR
• vascular tone also affects TPR

Question 2

CO equation

Answer 2

CO = HR x SV

Question 3

effects of angiotensin II

Answer 3

1. arteriole smooth muscle vasoconstriction

2. aldosterone release

Question 4

ACE

Answer 4

converts ang I to angII

Question 5

renin

Answer 5

converts angiotensinogen to angI

Question 6

ACE inhibitors

Answer 6

• 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

Question 7

captopril, enalapril, fosinopril, lisinopril

Answer 7

• 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**

Question 8

captopril

Answer 8

• not prodrug**
• half life = 2hr.**
• have to give multiple doses per day

Question 9

enalapril

Answer 9

• prodrug –> dicarboxyl containing

- half life = 11 hr. ** (better for compliance)

Question 10

fosinopril

Answer 10

• prodrug –> phosphorous containing group
• half life = 11.5 hr. **
• excreted in urine and bile*

Question 11

lisinopril

Answer 11

• prodrug –> phosphorous containing

- half life = 12 hr. **

Question 12

angiotensin II receptor blockers (ARB)

Answer 12

• 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**

Question 13

losartan, candesartan, valsartan

Answer 13

• 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*

Question 14

losartan

Answer 14

• for sure indicated with diabetic patients

- go to drug if patient has angioedema or cough**

Question 15

candesartan

Answer 15

-contraindicated in breast feeding like the others**

Question 16

valsartan

Answer 16

-indicated in left ventricular dysfunction or failure after MI*****

Question 17

ARB + Neprilysin inhibitor

Answer 17

• 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

Question 18

what is neprilysin?

Answer 18

• neutral endopeptidase that degrades vasoactive & natriuretic peptides, bradykinin & adrenomedullin
• metabolizes ANP, BNP, CNP

Question 19

aliskiren** - renin inhibitors

Answer 19

• 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**

Question 20

aliskiren + hydrochlorothiazide (diuretic)

Answer 20

• 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