Therapeutics of Hypertension Part 3

Question 1

Angiotensin Inhibitors

Answer 1

all work at diff parts of RAAS system
Angiotensin converting enzyme inhibitors (ACEi) * Inhibits conversion for angiotensin I to angiotensin II (potent vasoconstrictor)
Angiotensin II receptor blockers (ARBs)
* Block effects of angiotensin II by binding to target receptors
Renin inhibitors
* Inhibits conversion of angiotensinogen to angiotensin I

Question 2

Angiotensin Converting Enzyme Inhibitors (ACEi)

Answer 2

First-line treatment option for HTN
Additional benefit with history of:
* Diabetes w/ proteinuria
* Heart failure
* Post MI
* Chronic kidney disease
Good option for PM dosing to ensure “BP dipping” overnight
HTN effects by vasodilation, reduced PVR, and increased diuresis

Question 3

Angiotensin Converting Enzyme Inhibitors (ACEi) frequency

Answer 3

all at least once daily in PM except for captopril which is twice or three times a day dosing
want to start these on the lowest dose possible

Question 4

Angiotensin Converting Enzyme Inhibitors

Answer 4

Adverse effects
* Angioedema
* Cough (up to 20%) - due to excess of bradykinin (dry, no productive)
* Hyperkalemia
* Acute renal failure w/ severe bilateral renal artery stenosis
Contraindications
* History of angioedema on an ACEi (do not try a diff ACE-I)
* Concomitant use of aliskiren in patients w/ DM
* Pregnancy/breastfeeding

Question 5

Angiotensin II Receptor Blockers (ARBs)

Answer 5

First-line treatment option for HTN
Often “back-up” if an ACEi isn’t tolerated for other indications
* Doesn’t block bradykinin breakdown → less cough than ACEi
* Can use with history of angioedema due to ACEi
Good option for PM dosing to ensure “BP dipping” overnight
HTN effects by vasodilation, reduced PVR, and increased diuresis

Question 6

Angiotensin II Receptor Blockers (ARBs) frequency

Answer 6

all at least once daily in PM
eprosartan and losartan once or twice daily dosing

Question 7

Angiotensin II Receptor Blockers

Answer 7

Adverse effects
* Angioedema
* Hyperkalemia
* Acute renal failure w/ severe bilateral renal artery stenosis
Contraindications
* History of angioedema on an ARB
* Concomitant use of aliskiren in patients w/ DM
* Pregnancy/breastfeeding

Question 8

ACEi/ARB Monitoring

Answer 8

baseline: potassium and renal function
1-2 weeks after initiation: *Check BMP within 1 week for elderly; in low risk patients or patients with potassium < 4.5mEq/L can wait 3-4 weeks before initial assessment
3-4 weeks after initiation: **Only needed if elevated SCr or potassium at 1-2 weeks
every 6-12 months
Consider holding or reducing dose if potassium >5.5 mEq/L or SCr increase >30%

Question 9

Direct Renin Inhibitors

Answer 9

Agent(s): aliskiren
NOT first line for HTN: Very expensive and no better than ACEi/ARBs
Doesn’t block bradykinin breakdown → less cough than ACEi
Avoid in pregnancy
Concomitant use with an ACE-I or ARB contraindicated in patients with diabetes

Question 10

Direct Renin Inhibitors frequency

Answer 10

once daily dosing

Question 11

Direct Renin Inhibitors AEs

Answer 11

Monitoring: Potassium, BUN, SCr
Adverse Effects
* Diarrhea
* Musculoskeletal effects (CK increase)
* Dizziness
* Headache
* Hyperkalemia
* Renal insufficiency/ARF
* Orthostatic hypotension

Question 12

Angiotensin Inhibitors Clinical Pearls

Answer 12

Discuss contraceptive methods with women of childbearing age
Do not combine drug classes due to risk of adverse effects
Assess patients risk for hyperkalemia (CKD, other medications, etc)
Educate patient on dietary sources of potassium (bananas, food seasoning, etc)
ACEi/ARBs often preferred over other first-line agents in the presence of other compelling indications

Question 13

Calcium Channel Blockers (CCBs)

Answer 13

Inhibit influx of calcium across cardiac and smooth muscle cell membranes → coronary and peripheral vasodilation
Subclasses:
* Dihydropyridines - more vasodilation
* Nondihydropyridines - more negative ionotropic effects
* Overall similar effect on BP
First line for HTN

Question 14

Dihydropyridine CCBs

Answer 14

Patient populations with additional benefit:
* Reynaud’s syndrome
* Elderly patients w/ isolated systolic HTN (related to vascular stiffness)
More potent vasodilators than nondihydropyridine CCBs
* Vasodilation → baroreceptor-mediated tachycardia (drop in pressure –> body reacts by increasing HR)
* No effect on atrioventricular node conduction
Avoid short-acting dihydropyridines (IR nifedipine/nicardipine) - can cause severe tachycardia

Question 15

Dihydropyridine CCBs frequency

Answer 15

all once daily dosing except for isradipine and nicardipine SR

Question 16

Dihydropyridine CCBs AEs

Answer 16

Adverse effects:
* Reflex tachycardia, flushing, dizziness, headache, peripheral edema(dose-related), gingival hyperplasia
Warnings:
* Increased risk of angina/MI in patients with obstructive coronary disease due to reflex tachycardia
Drug interactions:
* Grapefruit juice
* CYP3A4 enzyme inducers/inhibitors

Question 17

Nondihydropyridine CCBs

Answer 17

diltiazem ER and verapamil ER dosed once or twice daily dosing
Many formulations available and start/max doses differ by product
Not AB rate as interchangeable/equipotent due to differences in release mechanisms and bioavailability

Question 18

Nondihydropyridine CCBs Patient Population Benefit

Answer 18

Patient populations with additional benefit:
* Supraventricular tachyarrhythmias (Afib)
* Pts w/ angina who can not tolerate a beta blocker
Slows AV node conduction and decreases in heart rate
* Negative ionotropic effects!
Extended-release formulations preferred for HTN

Question 19

Nondihydropyridine CCBs AEs

Answer 19

Adverse effects:
* Bradycardia, headache, dizziness, AV node block, systolic heart failure, gingival hyperplasia, constipation (verapamil>diltiazem)
Drug interactions:
* Concomitant use of beta blockers (increases risk of heart block) - HR goes too low
* Grapefruit juice
* CYP3A4 enzyme inducers/inhibitors (3A4 substrates)
Contraindications
* Heart block
* Left ventricular dysfunction

Question 20

CCB Clinical Pearls

Answer 20

No routine laboratory monitoring required
Check for drug interactions
CCBs are first line for HTN
Peripheral edema is dose-dependent
Extended release formulations are preferred
Nondihydropyridine CCB formulations are NOT interchangeable
If a CCB is needed in the setting of heart failure choose amlodipine

Question 21

Beta Blockers

Answer 21

NOT first line for HTN unless a compelling indication is present
* Examples of compelling indications include heart failure and CAD
Patient populations with additional benefit:
* Tachyarrhythmias, tremors, migraines, thyrotoxicosis
Decreases heart rate + force of contraction → Decrease in
CO
Avoid abrupt cessation - titrate off of over a couple weeks, if not, get rebound increase in HR and BP

Question 22

Beta Blockers - Cardioselective

Answer 22

selective to beta receptors in heart, no effect on lungs
atenolol, betaxolol, bisoprolol, metoprolol tartrate, metoprolol succinate, nebivolol (NO induced vasodilation)
all dosed once daily except for metoprolol tartrate which is twice daily dosing

Question 23

Beta Blockers - Nonselective

Answer 23

go to other beta receptors throughout the body
nadolol, propranolol IR, propranolol LA
all dosed once daily except for propranolol IR which is twice daily
avoid in bronchospastic airway disease

Question 24

Beta Blockers - Intrinsic Sympathomimetic Activity (ISA)

Answer 24

acebutolol, penbutolol, pindolol
all dosed twice daily except for penbutolol which is once daily
avoid in heart failure and IHD
these are used if a pts HR is too low to start on a beta blocker

Question 25

Beta Blockers - Mixed Alpha/Beta

Answer 25

carvedilol and labetolol both dosed twice daily
more BP lowering with these

Question 26

Beta Blockers AEs

Answer 26

Adverse effects:
* Bronchospasm, bradycardia, fatigue, exercise intolerance, depression
Can masked signs/symptoms of hypoglycemia (don’t mask hunger + sweating)
Use with caution in patients with:
* Peripheral artery disease (carvedilol preferred) - b/c also causes vasodilation
* Reactive airway disease (use selective BBs)
Contraindications:
* Second or third degree heart block
* Decompensated heart failure
* Post-MI (ISA BBs only)
* Severe bradycardia
* Sick sinus syndrome