HTN Agents--MOA & Clinical Use

Question 1

ACE inhibitors (Angiotensin Converting Enzyme)
suffix, MOA, clinical use, SE, monitoring, avoid, extra

Answer 1

• Suffix: -pril
• MOA: competitively inhibits ACE
• Clinical use: first-line HTN; avoid in Black pts unless specific comorbidity
• SE: cough, angioedema, hyperkalemia
• Monitor: SCr, K+
• Avoid: NSAIDs, in pregnancy, concomitant use of aliskiren (pts w/ DM)
• Extra: all ACEi are prodrugs except for lisinopril & captopril; take in evening to avoid BP “dipping” overnight

• MOA: ACE converts angiotensin I to angiotensin II (potent vasoconstrictors)
• Clinical use: specific comorbidity/SE like HF, CKD stage 3+, albuminuria, secondary stroke prevention
• SE: ACE inhibitors block the degradation of bradykinin (ACE enzyme breaks down bradykinin)–the accumulation of bradykinin can cause coughing & angioedema of the lips; ACEi also inhibits aldosterone secretion (angiotensin II acts on adrenal gland to release aldosterone), which can cause hyperkalemia (aldosterone normal function is to reabsorb sodium and get rid of potassium)
• Monitor: ACEi needs to be stopped if SCr falls by >30% (can be restarted if SCr improves); K+ needs to be monitored b/c SE of hyperkalemia
• Avoid: bradykinin causes vasodilation (partly b/c of prostaglandins), NSAIDs block prostaglandins, which can reduce effectiveness of ACEi
• Extra: use lisinopril & captopril in pts w/ liver disease (prodrug activation occurs in liver)

Question 2

What drug class(es) should be used for Black patients?
1. Black pts w/ DM?
2. Black pts w/ CKD?
3. Black pts w/ HF?

Answer 2

• Thiazide or CCB
  1. Thiazide or CCB
  2. Follow CKD guidelines: ACEi if albuminuria present or if stage 3-5
  3. Follow HF guidelines: basically ACE/ARB/ARNI, diuretics or BB

Question 3

ARB (Angiotensin II Receptor Blocker)
suffix, MOA, clinical use, SE, monitoring, avoid

Answer 3

• Suffix: -sartan
• MOA: competitive antagonist at angiotensin II receptor
• Clinical use: first-line HTN (typically used if ACEi is not tolerated); avoid in Black pts unless specific comorbidity
• SE: hyperkalemia
• Monitor: SCr, K+
• Avoid: NSAIDs, in pregnancy, concomitant use of aliskiren (pts w/ DM)

• MOA: angiotensin II acts directly on blood vessels (vasoconstriction) and adrenal gland (stimulates release of aldosterone); by blocking angiotensin II from binding to the receptors, vasoconstriction does not occur and aldosterone is not released
• SE: aldosterone secretion is inhibited, so potassium accumulates which can cause hyperkalemia; cough & angioedema less of an issue b/c ARBs do not block the breakdown of bradykinin
• Monitor: ARBs needs to be stopped if SCr falls by >30% (can be restarted if SCr improves); K+ needs to be monitored b/c SE of hyperkalemia

Question 4

1. Which organ releases angiotensinogen?
2. Renin?
3. ACE?
4. Aldosterone?

Answer 4

1. Liver
2. Kidney
3. Lungs
4. Adrenal gland

Question 5

Aldosterone Receptor Antagonist/Mineralocorticoid Receptor Antagonist (MRA)
drug(s), MOA, clinical use, SE, monitoring, avoid, extra, admin

Answer 5

• Drugs: spironolactone, eplerenone
• MOA: selectively blocks mineralocorticoid receptors
• Clinical use: resistant HTN (step 3); used to reduce hypokalemia; HF
• SE: hyperkalemia, gynecomastia (spironolactone)
• Monitor: K+, SCr
• Avoid: in pregnancy; RAAS agents & NSAIDs
• Extra: do not start if K+ >5mEq/L; hold or reduce dose if K+ >5.5mEq/L or SCr >25%
• Admin: take in AM

• MOA: Mineralocorticoid receptors are located in the kidney, heart, blood vessels, and brain; aldosterone in heart/vasculature causes vasoconstriction, endothelial cell dysfunction, inflammation, hypertrophy, remodeling, and fibrosis; blocking the receptors can cause hyperkalemia (b/c blocks reabsoprtion of sodium), and appears to prevent myocardial and vascular fibrosis; effectiveness mostly due to heart/vasculature receptor blocking, not diuretic effect; K+ decreases risk of arrhythmias
• SE: if gynecomastia, switch pt to eplerenone
• Monitor: SCr (can worsen renal function)
• Avoid: agents increase risk of hyperkalemia
• Admin: take in AM to avoid nocturnal diuresis

Question 6

Thiazide
drug(s), MOA, clinical use, SE, monitoring, avoid, extra, admin

Answer 6

• Drugs: chlorthalidone, HCTZ, indapamide, metolazone
• MOA: inhibit sodium and chloride reabsorption in distal convuluted tube
• Clinical use: first-line HTN
• SE: hypokalemia, hyperuricemia
• Monitor: K+, SCr, uric acid
• Avoid: pts w/ sulfa allergy, anuria, uncontrolled gout
• Extra: more effective in pts w/ CrCl >30mL/min
• Admin: take in AM

• MOA: initial decr in BP due to diuretic effect, long-term lowers peripheral vascular resistance
• Clinical use: may need another agent to balance out hypokalemia (typically potassium-sparing diuretic)
• Extra: if pt CrCl <30mL/min then use loop diuretic
• Admin: take in AM to avoid nocturnal diuresis

Question 7

Renin inhibitors
drug(s), MOA, clinical use, SE, monitoring, avoid

Answer 7

• Drug: aliskiren
• MOA: direct inhibitor of renin
• Clinical use: not first-line HTN (expensive)
• SE: hyperkalemia, orthostatic hypotension, renal insufficiency, musculoskeletal effects!!!
• Monitor: K+, SCr
• Avoid: in pregnancy, concomitant use of ACEi/ARB in pts w/ DM

• MOA: renin converts angiotensinogen to angiotensin I, this process is inhibited

Question 8

Calcium Channel Blockers (Dihydropyridine)
suffix, MOA, clinical use, SE, avoid, extra

Answer 8

• Suffix: -dipine
• MOA: inhibits influx of Ca++ across blood vessels (only works on blood vessels)
• Clinical use: first-line HTN (pts w/ Reynaud’s, elderly pts w/ isolated systolic HTN), angina
• SE: reflex tachycardia, peripheral edema (dose-related), gingival hyperplasia
• Avoid: grapefruit juice, interacts w/ CYP3A4 inducers
• Extra: use amlodipine if CCB is needed in HF; incr risk of angina/MI in pts w/ obstructive coronary disease (specifically immediate-release)

• MOA: Ca++ contracts, so blocking calcium from entering arteries prevents contraction/vasoconstriction, leading to vasodilation (decr BP); more potent vasodilators than NonDHP; decr afterload
• Clinical use: works in pts w/ Reynaud’s b/c relaxes vessels which incr supply of blood and oxygen to the heart; works w/ angina b/c reduces oxygen demand in the heart
• SE: peripheral edema is dose-related; vasodilation leads to reflex tachycardia (amlodipine does not have relflex tachycardia)
• Extra: risk of angina/MI increased due to reflex tachycardia
• Molecular: allosteric binding site (outside of pore), drugs cause tonic block (bind to closed channels and prevent them from opening)

Question 9

Calcium Channel Blockers (Non-Dihydropyridine)
drug(s), MOA, clinical use, SE, avoid, extra

Answer 9

• Drugs: diltiazem ER, verapamil ER (phenylalkylamine)
• MOA: inhibits influx of Ca++ across blood vessels and heart (smooth and cardiac muscle); negative inotropic effects
• Clinical use: first-line HTN, pts w/ Afib, pts w/ angina who cannot tolerate beta blocker
• SE: bradycardia, systolic HF, constipation
• Avoid: concomitant use of beta blockers, pts w/ heart block, grapefruit juice, CYP3A4 inducers
• Extra: formulations are not interchangeable, extended-release preferred

• Drugs: diltiazem (benzothiazepine) some tonic block and some frequency-dependent block; verapamil (phenylalkylamine) inhibitory effect on heart is frequency-dependent block (channel has to open for drug to enter and bind pore)
• MOA: extracellular Ca++ triggers cardiac & vascular smooth muscles to contract, nonDHPs work on cardiac (heart) and smooth (arteries) muscles so less contraction occurs; HR and BP decreased; has ionotropic effects= slows HR and weakens heart’s contraction; antiarrhythmic (blocking of cardiac)
• Clinical use: works w/ angina b/c reduces oxygen demand in the heart
• SE: bradycardia b/c MOA is to slow HR
• Avoid: concomitant use of beta blocker b/c both slow HR, could cause heart to stop, HF b/c SE of edema & pts w/ HF already have a lot of fluid built up and need to reduce it

Question 10

Order these CCB drugs from most potent to least potent in terms of inhibiting the heart: DHP, verapamil, diltiazem

Answer 10

1. verapamil
2. diltiazem
3. DHP

Question 11

Order these CCB drugs from most potent to least potent in terms of vasodilation: DHP, verapamil, diltiazem

Answer 11

1. DHP
2. Verapamil
3. Diltiazem

Question 12

Which drug classes should patients avoid if they have uncontrolled gout?

Answer 12

Thiazides, loop, potassium-sparing
Basically diuretics increase risk of developing gout

Question 13

Which drug classes should be taken in the morning

Answer 13

diuretics

Question 14

Which drug classes should be taken in the evening

Answer 14

ACEi, ARB

Question 15

Which drug classes have renal considerations

Answer 15

Thiazide & loop