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Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC)

• JNC 8 recommends using thiazide diuretics, calcium channel blockers, ace inhibitors or angiotensin II receptor agonists as monotherapy or in combination as first line treatment of hypertension.

Diuretics

• Diuretics are the generally the first line of treatment for patients with mild HTN (BP 140–149 / 90–99).
•  Patients with mild HTN are usually treated with a single diuretic medication.
• Diuretics effectively treat 50% of patients with mild to moderate HTN and can be combined with other HTN medications.

Thiazide Diuretics

• Thiazide diuretics are recommended as first line treatment for HTN.  They are cheap and effective first line therapy.

Why does it work?

• Initially – lower plasma volume
  • Thiazides decrease Na+ resorption at the distal convoluted tubule by inhibiting the Na+/Cl- transporter.  This results in a loss of Na+ and fluid.
• Long term –  peripheral vascular dilation and no one is sure exactly why

Other effects

• Decrease in serum K
• Decrease in serum Na
• Decrease in serum Mg
• Increase in serum Ca
• Increase Uric acid (think gout)
• Increase glucose (pay attention in the diabetic patient)

When to use

• HTN
• Heart failure
• Kidney stone with idiopathic hypercalcemia (Increase Ca+)
• Nephrogenic diabetes insipidus (Increase Ca+)

Contraindications

• Hypotension
• Sulphur allergy
• Gout
• Renal failure
• Hypokalemia
• Pay attention with diabetic patients

Examples

• Hydrochlorothiazide – HCTZ
  • Dose – 12.5 mg or 25 mg po daily
• Chlorthalidone
  • Dose – 12.5 mg or 25 mg po daily

Non Thiazide Diuretics

• These have the same physiologic effect as thiazides, but different chemical properties.

Examples

• Metolazone
  • Initial dose for adult HTN is 1 tablet per day or 1/2 mg per day

Loop Diuretics

• Powerful but short acting diuretics.

Why does it work?

• Lower plasma volume.  Loop diuretics act on the ascending loop of Henle inhibiting the Na+/K+/2Cl – transporter.  This is the site where most of the Na is reabsorbed.
• Increase prostoglandin production causing a decrease in vascular resistance

Other effects

• Hyperuricemia (gout)
• Decreased serum K
• Decreased serum Mg
• Decreased serum Ca

When to use

• Situation with severe edema
  • Acute pulmonary edema
  • Congestive heart failure (first line)
• Hyperkalemia
• Acute renal failure
• Anion overdose

Side effects

• Ototoxicity (reversible)

Examples

• Furosemide (Lasix)
  • Initial dose for adult HTN is 40 mg BID
• Ethacrynic Acid
• Bumetanide

Potassium Sparing Diuretics

Why does it work?

• They block sodium exchange sites
• Or they are aldosterone antagonists which prevents specific proteins from being created that are part of the sodium potassium exchange pump

When to use

• Used mainly as a secondary agent with another diuretic which may lower the potassium
• Situation with severe edema
  • Acute pulmonary edema
  • Congestive heart failure

Other effects

• Hyperuricemia (gout)
• Decreased Mg

Examples

• Epithelial sodium channel blockers
  • Amiloride
• Aldosterone antagonists
  • Spironolactone

Side effects

• Frequency
• Hyperkalemia

Calcium Channel Blockers (CCBs)

• JNC 8 recommends calcium channel blockers to be a first-line treatment either as monotherapy or in combination with thiazide-type diuretics, ACE inhibitors, or angiotensin II receptor antagonists for all patients regardless of age or race.

Why does it work?

• CCBs block the voltage gated calcium channels in blood vessels and cardiac muscle.
• Preventing Ca from entering the cells reduces muscle contractility
  • This leads to vasodilation
    -This leads to decreased cardiac contractility
• Reduces AV node conduction and therefore heart rate
• Reduces aldosterone production

Classes of CCBs

• Dihydropyridine
  • Names end in “one”
  • Higher rate of peripheral vasodilation
  • Peripheral vasodilation can lead to reflexive tachycardia
• Non-dihydropyridine
  • More selective for myocardium

When to use

• HTN
• Angina
• Arrhythmia (supraventricular tachyarrhythmias)

Examples

• Verapamil
• Diltiazem
• Amlodipine – less effective on cardiac tissue
• Nifedipine – less effective on cardiac tissue

Side effects

• Headache
• Peripheral edema
• Bradycardia

Angiotensin Converting Enzyme Inhibitors (ACE inhibitors)

•  JNC 8 recommends using these as first line medication for HTN either alone or in combination.

Why does it work?

• Inhibits angiotensin converting enzyme thereby slowing production of angiotensin II which causes vasoconstriction especially in the kidneys
• Reduces vasoconstriction
• Reduces aldosterone secretion

When to use

• HTN
• CHF
• DM (may lower risk of end stage renal disease as well as MI)
• Chronic Kidney disease

Examples (end in “pril”)

• Captopril
  • Initial dose is 25 mg BID
• Enalapril
  • Initial dose is 5 mg daily
• Ramipril

Side effects

• Cough
• Hyperkalemia
• Teratogenic

Angiotensin Receptor Blockers (ARBs)

• JNC 8 recommends using these as first line medication for HTN either alone or in combination.

Why does it work?

• These drugs block the angiotensin receptor
• Reduce vasoconstriction
• Reduce aldosterone secretion

When to use

• HTN
• CHF
• Chronic kidney disease
• DM (may lower risk of end stage renal disease as well as MI)

Examples

• Candesartan
• Irbesartan
• Losartan
  • Initial dose is 50 mg daily

Side effects

• Less cough than ACEIs
• Hyperkalemia
• Teratogenic

β Receptor Antagonists (Beta Blockers)

• Catecholamines (most notably epinephrine and norepinephrine) have several different receptor sites they bind to.  One class of receptors is known as the  β receptors.  This group is divided further into β1 and  β2.  These drugs have varying affinities for β1 and  β2 receptors so they will produce slightly different results.

Why does it work?

• Beta blockers drugs compete with catecholamines to bind to β receptors.
• Once a receptor is occupied by a β receptor antagonist that receptor is blocked and can not be used by a catecholamine.
• This prevents sympathetic cardiac stimulation
• Reduce heart rate
• Reduce cardiac contractility
• Decrease renin production (lowering plasma volume)

When to use

• HTN
• Angina
• CHF
• Post MI to prevent a second MI

Examples

• Metoprolol (Lopressor)
  • Initial dose for Metoprolol XR is 25 mg daily
• Carvedilol
  • Initial dose of Carvedilol XR is 20 mg daily
• Atenolol
• Propranolol
• Labetalol

Contraindications

• Asthma
  • A β2 blockade results in an increase in airway resistance.  Beta blockers should generally be avoided in asthma patients however if necessary use drugs with a high affinity for β1 receptors and a low affinity for β2 receptors.  This group would include metoprolol and atenolol

Side effects

• Bradycardia
• Hypoglycemia
• Nausea and vomiting

α Receptor Antagonist (α Blockers)

• In addition to beta receptors, catecholamines also bind to alpha receptors.  This class is also split into two groups α1 and α2

Why does it work?

• Like beta blockers, alpha blockers compete with catecholamines.  In this case however they compete at the α receptors rather than at the β receptors.  These receptors cause different reactions within the cells, so the drugs have different effects.
• Prevents sympathetic vasoconstriction.

When to use

• HTN as a second medication
• Benign prostatic hyperplasia (BPH)

Examples

• Prazosin
• Terazosin

Side effects

• Postural hypotension especially when beginning therapy

Renin Inhibitors

• Juxtaglomerular cells secrete renin in response to to low blood volume
• Angiotensinogen + renin = angiotensin I
• Angiotensin I + angiotensin converting enzyme = angiotensin II
• Angiotensin II causes vasoconstriction and stimulates aldosterone secretion causing the kidneys to reabsorb more Na+ and water.

Why does it work?

• Inhibits activity of renin which prevents the production of Angiotensin II
  Reduce vasoconstriction
• Reduce aldosterone secretion which then prevents the formation of K+/Na+ exchange in the kidney

When to use

• HTN as a second medication

Example

• Aliskiren

Side effects

• Diarrhea

Contraindications

• Do not use in combination with an ACEI or an ARB as it may lead to kidney damage

Central Sympatholytic Acting Drugs

• Similar to beta and alpha blockers but work along a different pathway.
• Do not stop these medications quickly as blood pressure may rise to dangerous levels due
• Do not use in pregnancy

Why does it work?

• Centrally working α2 adrenergic agonist
• Create a reduction in sympathetic tone
• Decreases heart rate
• Decreases renal vascular resistance

When to use

• HTN
• Many other noncardiac uses
  • ADHD
  • Tourette’s syndrome
  • Alleviate opioid withdrawal

Examples

• Clonidine (Pregnancy schedule C do not use)
• Methyldopa (Pregnancy schedule B used commonly in pregnancy)

Side effects

• Dry mouth
• Sedation
• Sluggishness
• Impotence in men

Vasodilators

Why does it work?

• Directly affect smooth muscle of the arteries decreasing peripheral resistance

Examples

• Hydralazine
  • Causes a release of nitric oxide but also causes an increase in heart rate
• Nitroprusside
  • Causes a release of nitric oxide and has a long list of adverse effects
• Minoxidil
  • Opens K+  channels creating hyperpolarization of and therefore relaxation of smooth muscle
  • Used topically to regrow hair

When to use

• Hypertensive emergencies
• Minoxidil used to treat hair loss

Side effects

• Angina
• Tachycardia, Bradycardia
• Hypotension
• Headache
• Flushing

Treatment Protocols

See algorithm

• In the US a low dose thiazide diuretic is often the drugs of choice for initial treatment.

 

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