Hypertension Drugs

thiazides: MOA

inhibit sodium and chloride reabsorption in the DCT

thiazides: PK

chlorthalidone has a longer half-life and duration of action than HCTZ

thiazides: AE

• increased uric acid, gout

• hyponatremia, hypokalemia, hypomagnesemia

• hyperglycemia

• hypercalcemia

thiazides: precautions

• gout flare

• photosensitivity

• hyperlipidemia

• hyperglycemia

• SLE-exacerbation

thiazides: monitoring

• BP

• SCr/BUN

• electrolytes (Na, K, Mg, Ca)

• uric acid

thiazides: DDI

• dofetilide

• lithium

• topiramate

thiazides: clinical pearls

• take in morning

• caution in patients with sulfa allergy

• HCTZ ineffective if CrCl < 30 mL/min

thiazides: dosing

• chlorthalidone (Thalitone, Hemoclor) → 12.5-25 mg daily

• hydrochlorothiazide (Inzyrqo) → 25-50 mg daily

• indapamide (Lozol) → 1.25-2.5 mg daily

ACE inhibitors: MOA

inhibit ACE, preventing conversion of angiotensin I to angiotensin II; causes decreased plasma renin activity and aldosterone

ACE inhibitors: AE

• orthostatic hypotension

• hyperkalemia

• angioedema

• dry cough

ACE inhibitors: precautions

• prior to surgery

• bilateral renal artery stenosis

• hyperkalemia

ACE inhibitors: CI

• angioedema due to previous ACEi

• pregnancy

• avoid in combination with ARB or DRI

ACE inhibitors: monitoring

• BP

• SCr/BUN (2-4 weeks after initiation or dose titration)

• serum potassium

ACE inhibitors: dosing

• benazepril (Lotensin) → 10-40 mg daily

• captopril (Capoten) → 6.25-50 mg two or three times daily

• fosinopril (Monopril) → 10-40 mg daily

• enalapril (Vasotec) → 5-40 mg daily

• lisinopril (Prinivil, Zestril) → 10-40 mg daily

• quinapril (Accupril) → 10-80 mg daily

• ramipril (Altace) 2.5-20 mg daily

ACE inhibitors: combination therapy

• lisinopril/HCTZ (Zestoretic)

• benazepril/HCTZ (Lotensin HCT)

• amlodipine/benazepril (Lotrel)

ARB: MOA

direct antagonism of angiotensin II (AT2) receptors, causes vasoconstriction

ARB: AE

• orthostatic hypotension

• hyperkalemia

ARB: precautions

• angioedema

• prior to surgery

• bilateral renal artery stenosis

• hyperkalemia

ARB: CI

• pregnancy

• avoid in combination with ACEi or DRI

ARB: clinical pearls

losartan has uricosuric properties

ARB: monitoring

• BP

• SCr/BUN (2-4 weeks after initiation or dose titration)

• serum potassium

ARB: dosing

• losartan (Cozaar) → 25-100 mg daily

• candesartan (Atacand) → 8-32 mg daily

• valsartan (Diovan) → 40-320 mg daily

• telmisartan (Micardis) → 20-80 mg daily

• irbesartan (Avapro) → 150-300 mg daily

• olmesartan (Benicar) → 20-40 mg daily

ARB: combination therapy

• amlodipine/valsartan (Exforge)

• amlodipine/olmesartan (Azor)

• losartan/HCTZ (Hyzaar)

• nebivolol/valsartan (Byvalson)

CCB: MOA

block L-type voltage channel, inhibiting calcium influx across cell, causes coronary (non-DHP) and peripheral (DHP) vasodilation

DHP CCB: clinical effects

• decreases BP

• reflex tachycardia

DHP CCB: dosing

• amlodipine (Norvasc) → 2.5-10 mg daily

• felodipine (Plendil) → 2.5-10 mg daily

• nifedipine (Procardia XL, Adalat CC) → 30-90 mg daily

non-DHP CCB: clinical effects

• decreased BP

• decreased inotropy

• decreased chronotropy

non-DHP CCB: dosing

• verapamil (Calan SR, Verelan) → 40-120 mg three times daily (IR), 120-360 mg daily (ER)

• diltiazem (Cardizem, Cardizem CD, Cartia XT, etc.) → 30-90 mg every 6 hours (IR), 120-360 mg daily (ER)

DHP CCB: clinical pearls

• substrates of CYP3A4

  • avoid grapefruit juice

• felodipine:

  • avoid meals high in fat or carbohydrates

  • take without food or with small meal

• amlodipine and felodipine can be used in HFrEF

non-DHP CCB: clinical pearls

• can be used for treatment of supraventricular tachycardias (ex: AF)

• avoid use with beta blockers

• avoid use in HFrEF

• substrate of CYP3A4 and P-gp

  • avoid grapefruit juice

• more DDI than DHP CCB

non-DHP CCB: DDI

• verapamil:

  • CYP3A4 inhibitor → atorvastatin, colchicine, simvastatin

  • P-gp inhibitor → colchicine, dofetilide

• diltiazem:

  • CYP3A4 inhibitor → atorvastatin, budesonide, colchicine, simvastatin

non-DHP CCB: drug-disease interactions

• verapamil:

  • use with caution in renal impairment

  • may cause acute liver injury

    • reduce dose by 20% in cirrhosis

    • monitor ECG

  • avoid use in HFrEF

  • use with caution in GI disorders

• diltiazem:

  • use with caution in liver disease

  • mild elevations in transaminases 1-8 weeks after initiation

  • avoid use in HFrEF

DHP CCB: AE

• reflex tachycardia

• hypotension

• dizziness

• flushing

• GI effects

• headache

• lower extremity edema

• gingival hyperplasia

non-DHP CCB: AE

• bradycardia

  • AV node block

• hypotension

• dizziness

• headache

• GI effects

  • constipation

• gingival hyperplasia

• acute liver injury

DHP CCB: monitoring

• BP

• HR

• DDI

• drug-disease interactions

• AST/ALT, alk phos, bilirubin

non-DHP CCB: monitoring

• BP

• HR (PR interval)

• DDI

• drug-disease interactions

• SCr

• AST/ALT, alk phos, bilirubin

MRA: MOA

competes with aldosterone for receptor sites at DCT, potassium sparing, used in hyperaldosteronism

spironolactone: AE

• hyperkalemia

• increased SCr/BUN

• gynecomastia

• impotence

• irregular menses

• GI effects (N/V, diarrhea, cramps)

eplerenone: AE

• GI effects (N/V, diarrhea, cramps)

• increased SCr/BUN

• hyperkalemia

eplerenone: precautions

• moderate to severe hepatic impairment

• dose adjustment in patients with moderate CYP3A4 inhibitors

spironolactone: CI

• pregnancy

• hyperkalemia

eplerenone: CI

• strong CYP3A4 inhibitors

• T2DM with microalbuminuria

• serum potassium > 5.5 mEq/L at initiation

• SCr:

  • > 2 mg/dL in men

  • > 1.8 mg/dL in women

  • CrCl < 50 mL/min

spironolactone: monitoring

• BP

• SCr/BUN

• serum potassium within first week of initiation

spironolactone: dosing

(Aldactone) 12.5-100 mg daily

eplerenone: monitoring

• SCr within 3-7 days of initiation:

  • moderate CYP3A4 inhibitor

  • ACEi/ARB

  • NSAID

• serum potassium within first week of initiation, then every month

eplerenone: dosing

(Inspra) 50-100 mg daily

beta blockers: indications

• not first line for HTN

• HFrEF (carvedilol, metoprolol succinate, bisoprolol)

• AF, ventricular arrhythmias

• chronic coronary syndromes, angina

• acute coronary syndromes

beta blockers: AE

• bradycardia

• hypotension

• exercise intolerance

• PR interval prolongation (AV block)

• bronchospasm (non-selective)

• mask symptoms of hypoglycemia

• CNS:

  • vivid dreams

  • depression

  • somnolence

  • fatigue

  • sexual dysfunction

beta blockers: CI

• cardiogenic shock

• second/third degree heart block

• sinus bradycardia, decompensated HF, reactive airway disease, SBP < 100 mmHg, first degree AV block

beta blockers: clinical pearls

• “start low, go slow”

• succinate formulation can be split

• avoid abrupt withdrawal (wean off)

• continue during surgical procedures

beta blockers: monitoring

• BP

• HR

beta blockers: dosing

• metoprolol tartrate (Lopressor) → 12.5-200 mg twice daily

• metoprolol succinate (Toprol XL) → 12.5-400 mg daily

• carvedilol (Coreg) → 3.125-50 mg twice daily

• labetalol (Normodyne) → 100-1,200 mg twice daily

• propranolol (Inderal) → 80-160 mg daily

• bisoprolol (Zebeta) → 1.25-10 mg daily

• nebivolol (Bystolic)

• atenolol (Tenormin)

• esmolol (Brevibloc)

beta blockers: cardioselective

• atenolol

• metoprolol

• bisoprolol

• nebivolol

• esmolol

beta blockers: non-selective

propranolol

beta blockers: mixed

• carvedilol

• labetalol

beta blockers: DDI

• metoprolol:

  • CYP2D6 substrate

• carvedilol:

  • CYP2D6 substrate

  • P-gp inhibitor

• propranolol:

  • CYP2D6 substrate

  • CYP1A2 substrate

• bisoprolol:

  • CYP3A4 substrate

amiloride: MOA

blocks sodium channels in late DCT and collecting duct, inhibits sodium reabsorption, potassium sparing (used as an alternative to spironolactone)

amiloride: AE

• hyperkalemia

• may decrease sodium and chloride

• may increase BUN

amiloride: precautions

• DM

• SCr > 1.5 mg/dL

• BUN > 30 mg/dL

amiloride: CI

avoid use if CrCl < 45 mL/min

amiloride: dosing

(Midamor) 5-10 mg daily

aprocitentan: MOA

blocks endothelin (ET1) from binding to ETA/ETB receptors, prevents vasoconstriction

aprocitentan: AE

• hepatotoxicity

• fluid retention, peripheral edema

• reduction in Hb/Hct

aprocitentan: CI

• pregnancy

• eGFR < 15 mL/min/m²

• Child Pugh class B or C

• baseline AST/ALT > 3 times ULN

aprocitentan: dosing

(Tryvio) 12.5 mg daily

vasodilators: MOA

direct vasodilation of arterioles

minoxidil: AE

• fluid retention

• sinus tachycardia

• pericardial effusion/tamponade

• hypertrichosis

minoxidil: dosing

(Loniten) 5-40 mg daily

hydralazine: AE

• lupus-like syndrome

• flushing

• edema

• reflex tachycardia

• headache

• rash

• agranulocytosis

hydralazine: CI

coronary artery disease

hydralazine: dosing

(Aprezoline) 25-300 mg daily

alpha-1 RA: MOA

competitively inhibit postsynaptic alpha-1 AR, causes vasodilation

alpha-1 RA: AE

• orthostatic hypotension

• edema

• CNS effects

• myasthenia

• decreased WBC

alpha-1 RA: precautions

history of acute MI, HR, or angina

alpha-1 RA: clinical pearls

• associated with orthostatic hypotension, especially in older adults (first-dose effect)

• can be used as a second line agent in patients with BPH

alpha-1 RA: dosing

• doxazosin (Cardura) → 1-16 mg daily

• terazosin (Hytrin) → 1-20 mg daily

aliskiren: MOA

direct renin inhibitor

aliskiren: AE

• diarrhea

• hyperkalemia

• increased SCr/BUN

• andioedema

aliskiren: CI

• pregnancy

• cannot be used with ACEi or ARB in patients with DM

aliskiren: clinical pearls

• not used often

• weak antihypertensive properties

• DDI → CYP3A4 substrate

alpha-2 receptor agonists: MOA

stimulates alpha-2 receptors in brain stem, reduces sympathetic outflow, decreases PVR and HR

alpha-2 receptor agonists: AE

• hypotension

• bradycardia

• CNS:

  • drowsiness

  • headache

  • fatigue

  • dizziness

• edema

• xerostomia

• constipation

• urinary incontinence

alpha-2 receptor agonists: CI

hepatic disease

alpha-2 receptor agonists: clinical pearls

• clonidine available as pill and patch

• last line due to adherence and adverse effects

• avoid abrupt discontinuation (rebound HTN)

• methyldopa is safe in pregnancy

  • dose adjustment if CrCl < 50 mL/min

alpha-2 receptor agonists: dosing

• clonidine (Catapres) → 0.2-2.4 mg daily

• methyldopa (Aldomet) → 500-3,000 mg daily