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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
- This leads to vasodilation
- 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.
Study tip
Google docs for spell checking medical writing.