Hypertensive Urgency Pharmacotherapy

Definition

• Systolic BP ≥180 mmHg and/or diastolic BP ≥110 mmHg
• No symptoms or evidence of acute end-organ damage
• Urgent but not emergency situation

Causes

• Medication nonadherence
• Undiagnosed/undertreated hypertension
• Abrupt medication discontinuation (clonidine, beta blockers)
• Illicit drug use (cocaine, amphetamines)
• Medication effect (NSAIDs, steroids, SSRIs)
• Pain, anxiety
• Volume overload (renal failure, hyperaldosteronism)

Evaluation

• Repeat BP measurements to confirm
• Thorough history and physical exam
• Assess for symptoms of end-organ damage:
  • CNS: headache, altered mental status, focal deficits
  • Cardiac: chest pain, dyspnea, arrhythmia
  • Renal: hematuria, oliguria
  • Retina: vision changes, retinal hemorrhage
• Diagnostic tests:
  • Basic metabolic panel
  • Urinalysis
  • ECG
  • Cardiac enzymes if indicated
• Identify precipitating causes

Goals of Therapy

When it comes to managing blood pressure, it is important to do so gradually and systematically. Lowering blood pressure (BP) over a period of 24 to 48 hours is generally recommended for optimal results. The main goal during this process is to reduce the mean arterial pressure by approximately 25% within the first few hours.

It is crucial, however, to avoid excessive reductions in blood pressure, exceeding the recommended 25% mark. This is necessary to prevent the risk of inadequate blood supply (ischemia) to vital organs, which could lead to further complications. Therefore, finding the right balance is key.

To start, the target BP should be lowered to a level of 160/100 mmHg. Once this initial target is achieved, it is common practice to transition to an oral medication regimen for continued management of blood pressure in an outpatient setting. This gradual transition ensures a smoother adjustment, allowing for long-term maintenance of healthy blood pressure levels.

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Management of previously treated hypertension

• If a patient was on a previous regimen, reinitiate that regimen
  • Consider titrating to a higher dose.

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Untreated Hypertension: Initiating Antihypertensive Therapy

• In patients not currently taking antihypertensive medications, the choice of initial agent(s) should take into account patient-specific factors, comorbidities, and compelling indications that favor certain drug classes.
• In patients without compelling indications, reasonable options for initial monotherapy include thiazide diuretics, ACE inhibitors, ARBs, and dihydropyridine calcium channel blockers. Based on evidence from head-to-head trials, ACE inhibitors, ARBs, and dihydropyridine CCBs may be preferred over thiazide diuretics.

Below is the table detailing the compelling indications for the use of specific antihypertensive agents:

Compelling Indication	Recommended Agents
Heart failure	Diuretics (e.g., thiazides, loop diuretics), ACE inhibitors, ARBs, beta blockers, aldosterone antagonists
Post-myocardial infarction (MI)	Beta blockers, ACE inhibitors, ARBs
Diabetic nephropathy	ACE inhibitors, ARBs
Chronic kidney disease (CKD)	ACE inhibitors, ARBs
Chronic kidney disease (CKD) with proteinuria	ACE inhibitors, ARBs
Stroke prevention	Thiazide diuretics, ACE inhibitors, ARBs
Atrial fibrillation with rapid ventricular response	Non-dihydropyridine calcium channel blockers (e.g., diltiazem, verapamil)
Pregnancy or planning pregnancy soon	Methyldopa, labetalol, nifedipine extended-release, amlodipine

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1. Medication choice should also account for comorbidities like CKD, orthostatic hypotension, and patient factors such as age, frailty, and pregnancy/childbearing potential. Frequent monitoring and up-titration is key during initiation.
2. If blood pressure is ≥20/10 mmHg above goal, starting with two drugs is reasonable. Preferred combinations include a RAS inhibitor with a CCB or thiazide diuretic. Single pill combinations may improve adherence.

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Oral Antihypertensive Agents

Captopril:

• ACE inhibitor
• Onset 15-30 minutes, peak 1-2 hours
• Duration 4-6 hours
• Dose: 25-50 mg PO
• Advantages: Rapid onset, well-tolerated
• Avoid in pregnancy, bilateral renal artery stenosis

Lisinopril

• Class of Agent: Lisinopril belongs to the class of drugs known as ACE inhibitors (Angiotensin-Converting Enzyme inhibitors).
• Onset: Lisinopril typically starts working within 1 to 2 hours after taking the medication.
• Duration: The effects of Lisinopril can last for 24 hours.
• Dosing: The typical starting dose of Lisinopril for hypertension is 10 mg once daily, with the dosage adjusted based on the individual’s response.
• Advantages: Lisinopril is effective in managing high blood pressure, reducing the risk of heart attack and stroke, and improving heart failure symptoms. It is generally well-tolerated and can be used in various patient populations.

Losartan

• Class of Agent: Losartan is an angiotensin II receptor blocker (ARB).
• Onset: The effects of Losartan can generally be seen within 6 hours
• Duration: The duration of action for Losartan is approximately 24 hours.
• Dosing: The usual starting dose of Losartan for hypertension is 50 mg once daily, with the dosage adjusted if necessary.
• Advantages: Losartan is effective in lowering blood pressure, reducing the risk of stroke, and managing certain heart conditions. It is well-tolerated and can be used in patients with diabetes or kidney problems.

Furosemide

• Class of Agent: Furosemide is a loop diuretic.
• Onset: Furosemide typically starts working within 30 minutes of oral administration or within 5 minutes if given intravenously.
• Duration: The effects of Furosemide can last for 4 to 6 hours.
• Dosing: The recommended starting dose for Furosemide varies depending on the condition being treated but is usually between 20-80 mg taken orally or intravenously.
• Advantages: Furosemide is effective in treating edema (fluid retention) associated with congestive heart failure, liver disease, or kidney disorders. It can help reduce symptoms such as swelling and shortness of breath.

Chlorthalidone

• Class of Agent: Chlorthalidone is a thiazide-like diuretic.
• Onset: Chlorthalidone typically starts working within 2 hours after oral administration.
• Duration: The duration of action for Chlorthalidone is approximately 24 to 72 hours.
• Dosing: The usual starting dose of Chlorthalidone is 25 mg to 50 mg once daily, with the dosage adjusted if necessary.
• Advantages: Chlorthalidone is effective in reducing blood pressure and managing edema. It is often used in the treatment of hypertension and can help improve overall cardiovascular health.

Hydrochlorothiazide

• Class of Agent: Hydrochlorothiazide is a thiazide diuretic.
• Onset: Hydrochlorothiazide generally starts working within 2 hours after oral administration.
• Duration: The effects of Hydrochlorothiazide can last for 6 to 12 hours.
• Dosing: The typical starting dose of Hydrochlorothiazide for hypertension is 12.5 mg to 25 mg once daily, with the dosage adjusted based on the individual’s response.
• Advantages: Hydrochlorothiazide is effective in lowering blood pressure, managing fluid retention, and can be used in various conditions, including hypertension, edema, and heart failure. It is often well-tolerated and is available in combination with other medications for enhanced effectiveness.

Clonidine:

• Central α2 agonist
• Onset 30-60 minutes, peak 2-4 hours
• Duration 6-12 hours
• Dose: 0.1-0.2 mg PO
• Advantages: Oral route, no dose adjustment in renal impairment
• Disadvantages: Rebound hypertension with abrupt discontinuation

Labetalol:

• Nonselective Beta-1 and Beta-2 receptor antagonist, minor alpha blocking activity
• Pros: PO/IV Push/Cont. Infusion, more-peripheral BB, quick onset
• Cons: Not for CHF or > 1st degree AV block, caution in bronchospastic disease
• Onset 30 minutes, peak 2-4 hours
• Duration 6-12 hours
• Dose: 200-400 mg PO
• Avoid in reactive airway disease, heart block

Metoprolol – Selective Beta-1 receptor antagonist

• Pros: Inexpensive, rapid onset, great for ACS or maintenance in CHF
• Cons: Hepatic metabolism, HR effect > BP effect

Amlodipine:

• Dihydropyridine calcium channel blocker
• Onset 2-4 hours, peak 6-12 hours
• Duration >24 hours
• Dose: 5-10 mg PO
• Advantages: Once daily dosing, few drug interactions
• Avoid in severe LV dysfunction

Hydralazine –

• Dosing: 10–50 mg orally, 2–4 times/day
• Pharmacokinetics: T1/2 = 3–7 hours, bioavailability ~26–50%
• Interferes with calcium transport, causing vasodilation
• Pros: PO/IV Push, rapid onset, short duration
• Cons: Multiple doses, lupus-like syndrome

Drug	Class	Onset	Duration	Dose	Advantages	Disadvantages
Captopril	ACE inhibitor	15-30 min	4-6 hours	25-50 mg PO	Rapid onset, well-tolerated	Avoid in pregnancy, bilateral renal artery stenosis
Lisinopril	ACE inhibitor	1-2 hours	24 hours	10 mg once daily	Effective, well-tolerated	–
Losartan	Angiotensin II receptor blocker (ARB)	6 hours	24 hours	50 mg once daily	Effective in lowering BP, well-tolerated	–
Furosemide	Loop diuretic	30 min	4-6 hours	20-80 mg PO/IV	Effective in treating edema, reduces fluid retention	–
Chlorthalidone	Thiazide-like diuretic	2 hours	24-72 hours	25-50 mg once daily	Reduces BP, helps manage edema	–
Hydrochlorothiazide	Thiazide diuretic	2 hours	6-12 hours	12.5-25 mg once daily	Lowers BP, manages fluid retention	–
Clonidine	Central α2 agonist	30-60 min	6-12 hours	0.1-0.2 mg PO	Oral route, no dose adjustment in renal impairment	Rebound hypertension with abrupt discontinuation
Labetalol	Nonselective Beta-1 and Beta-2 receptor antagonist, minor alpha blocking activity	30 min	6-12 hours	200-400 mg PO	Multiple administration routes, quick onset	Not for CHF or > 1st degree AV block, caution in bronchospastic disease
Metoprolol	Selective Beta-1 receptor antagonist	1-2 hours	6-12 hours	25-50 mg PO	Rapid onset, great for ACS or maintenance in CHF	HR effect > BP effect
Amlodipine	Dihydropyridine calcium channel blocker	2-4 hours	>24 hours	5-10 mg PO	Once daily dosing, few drug interactions	Avoid in severe LV dysfunction
Hydralazine	Vasodilator	0.5-1 hour	up to 12 hours	10-50 mg orally, 2-4 times/day	Rapid onset, short duration, various administration routes	Multiple doses, lupus-like syndrome,

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Monitoring and Follow-up

• Frequent BP monitoring initially
• Assess for response to treatment and adverse effects
• Provide strong recommendations for outpatient follow-up
• Long-term lifestyle modifications – exercise, diet, sleep, stress management
• Ensure transition to an effective oral antihypertensive regimen