Arterioles (resistance)

Venous system (capacitance)

Heart (pump output)

Kidneys (blood volume)

Elderly, obese, african americans

For whom ACE inhibitors may not be very effective

Inhibit sodium reabsorption fro DCT

May stimulate excretion of potassium in distal tubule

Can result in a 10-15 mm Hg reduction in SBP

Blocks NKCC2 in ascending loop of henle

Greater urine loss than thiazides

"high ceiling diuretics"

Diuretic of choice in severe heart failure and pulmonary edema

Ex) furosemide, bumetanide, torsemide, ethacrynic acid

Ex) spironolactone, amiloride, triamterene)

Both are relatively weak diuretics, and are often used in conjunction with thiazide diuretics

Antagonize effects of aldosterone at cortical collecting tubule

Aldosterone will increase ENaC number, so this is also indirectly inhibiting ENaCs

Inhibit vasopressin V2 receptors, which promote synthesis and translocation of aquaporin 2 in the collecting duct

Water isn't retained - urine is dilute and urinary output increase, plasma Na levels rise

Major clinical use is to treat hyponatremia rather than HTN

Ex) Conivaptan (IV), and Tolvaptan (oral)

Those with depressed heart function should not depress it more with a beta blocker

Can also cause bronchoconstriction, so contraindicated in asthma patients

reduce BP by inhibiting a1 receptors on arterioles and venules, leading to relaxation

No adverse lipid/metabolic effects from B blockers

Postural hypotension common in patients after first dose, so initial dose should be administered after bedtime

Competitive inhibitor of DOPA decarboxylase

Converted to methylNE by dopamine B hydroxylase which replaces NE in storage vesicles 

High affinity for presynaptic a2 receptors (AGONIST)

direct acting alpha 2 adrenergic agonist

Reduces sympathetic outflow

Blocks norepinephrine uptake by adrenergic neurons, leading to the depletion in transmitter content and strength of adrenergic output in the periphery

Can cause significant depression

Calcium channel blockers

K channel openers

Because of the tendency to cause reflex tachycardia (verapamil and diltiazem excluded), the agents best work in conjuction with other agents that oppose reflex actions

They are also negative chronotropes and inotropes because they affect calcium channels in the heart as well 

Therefore, you wouldn't want to use these drugs in CHF

Dilate arterioles, not veins

Reduce afterload

Opens K sensitive channels leading to membrane hyperpolarization

Drop in BP may lead to reflex tachycardia

Can lead to edema due to increased sodium and water retention; co therapy with a b-blocker (less renin) and a diuretic may reduce side effects

Side effect - hirsutism (Rogaine)

Weaker vasodilator than minoxidil 

Mechanism of action unknown (stimulation of cGMP levels?)

Prolonged exposure can lead to tolerance and lupus like symptoms

Combo of hydralazine and isosorbide dinitrate approved for CHF in AA, but should work for others too

Initially give diuretic or B blcoker in combination; if this doesn't work, additional agents

Being replaced with individual therapy 

Beta blockers sed, and verapamil/diltiazan

Might lean toward B blockers because beneficial effect on angina too

Plasma glycoprotein synthesized in many organs 

Only known substrate of renin

Decapeptide formed by proteolysis of angiotensinogen by renin

Weak vasoconstrictor activity

peptide with potent vasodilator activity

Substrate for ACE, which converts bradykinin to inactive fragment

1. Medullary thick ascending limb of Henle

2. Distal tubule

3. Collecting Duct

Renin inhibition drug

Poor bioavailability (~2.5%)

Also has reactive renin release which releases more renin that can overcome inhibition

Do not induce reflex sympathetic activation, and can safely be used in patients with ischemic heart disease

Also reduces breakdown of bradykinin (vasodilator activity), but also side effects: dry cough and skin rash

Active as is (don't require metabolism)

Captopril 

prodrugs - must be de-esterified by hepatic metabolism

All currently used ACE inhibitors are Class II minus Class I and Class III

Water soluble

Not metabolized

Lisinopril

Excreted unchanged by kidneys

hypotension (overdoing it), hyperkalemia, acute renal failure (reduction in glomerular filtration), tertaogenesis, angioedema (rare but can be fatal)

Hyperkalemia probably most common side effect

Ex: losartan, valsartan

orally-active nonpeptide AT1 receptors antagonists

Same as ACE inhibitors, but smaller incidence of side effects

(no effects on bradykinin)

Lower incidence of angioedema