Antihypertensives and Diuretics Study Guide

Question 1

Describe the mechanism of action of ACE inhibitors?

Answer 1

• ACE inhibitors block the conversion of angiotensin I to angiotensin II

(angiotensin II is a potent vasoconstrictor responsible for arterial smooth muscle constriction, increased aldosterone secretion , and sympathetic nervous system stimulation)

Question 2

Describe the renin-angiotensin-aldosterone system. (a good explanation, but kind of long)

Answer 2

A decrease in GFR slows the rate of infiltrate through the ascending loop of Henle which causes increased reabsorption of sodium and chloride ions.

The reduced concentration of sodium is sensed by the macula densa-a thick short segment of the ascending limb.

Sensing this change, the macula densa does 2 things: 1) decreases resistance to blood flow in the afferent arterioles which raises glomerular hydrostatic pressure and
2) increases renin released from the juxtaglomerular cells.

Renin acts as an enzyme to increase the formation of angiotensin I an inactive polypeptide.

Two amino acids are split from Angiotensin I to form angiotensin II. This action occurs almost entirely in the lungs by the converting enzyme. Angiotensin II is a very potent vasoconstrictor with duration of action of 1-2 minutes because of rapid inactivation by angiotensinases.

Vasoconstriction occurs intensely in the arterioles and much less in the veins.

Angiotensin acts directly on the kidneys to cause salt and water retention and causes the adrenal glands to secrete Aldosterone with also increases salt and water reabsorption by the kidneys.

Question 3

What is the role of angiotensin converting enzyme?

Answer 3

to convert angiotensin I to angiotensin II

…hopefully we’ll get questions like this on the test…

Question 4

What are the CV effects of captopril? What are the side effects?

Answer 4

CV effects:
- captopril lowers systemic BP without alterations in cardiac output or heart rate

(d/t decreases in sodium and water retention)

side effects:
- Rash or pruritus (10%)

• loss of taste
• hyperkalemia.
• angioedema (rare, but the worst side effect)

Question 5

Describe the pharmacokinetics of nipride.

Answer 5

• nipride interacts with oxyhemoglobin, dissociating immediately and forming methemoglobin while releasing cyanide and NO.
• NO activates the enzyme guanylate cyclase present in vascular smooth muscle, resulting in increased intracellular concentrations of cGMP.
• cGMP inhibits calcium entry into vascular smooth muscle cells and may increase calcium uptake by the smooth endoplasmic reticulum to produce vasodilation.
• As such, NO is the active mediator responsible for the direct vasodilating effect of nipride.
• nipride spontaneously generates NO, thus it functions as a prodrug .

Question 6

What is an angiotensin receptor blocker? How does it work and where? Name one.

Answer 6

• ARB’s produce antihypertensive effects by blocking the vasoconstrictive actions of angiotensin II without affecting ACE activity.
• It blocks the binding of angiotensin II to the AT₁ receptors found principally in vascular smooth muscles.
• Losartan is an ARB

Question 7

What is the MOA of hydrochlorothiazide?

Answer 7

inhibition of sodium reabsorption in the distal tubule

Question 8

What is the site of action for hydrochlorothiazide?

Answer 8

distal renal tubule

Question 9

What is the clinical use of hydrochlorothiazide?

Answer 9

lowers blood pressure by reducing extracellular fluid volume (edema)

Question 10

What are side effects of hydrochlorothiazide?

Answer 10

• hypochloremic metabolic acidosis
• dysrhythmias
• skeletal muscle weakness
• ileus
• potentiation of NDNMB

Question 11

Hydrochlorothiazide is what type of diuretic?

Answer 11

a thiazide diuretic

Question 12

What is the MOA of furosemide?

Answer 12

inhibits the reabsorption of sodium and chloride

Question 13

What is the site of action of furosemide?

Answer 13

• the medullary and ascending limbs of the loops of Henle

- distal renal tubule

Question 14

What is the clinical use of furosemide?

Answer 14

• diuresis with subsequent mobilization of excess fluids (edema, plural effusions, and ascites)
• reduction in blood pressure

Question 15

What are side effects of furosemide?

Answer 15

• ototoxicity (hearing loss or tinnitis)
• hypotension
• large loss of electrolytes (K, Cl, Mg, Na, Ca)

Question 16

Furosemide is what type of diuretic?

Answer 16

a loop diuretic

Question 17

What is the MOA of ethacynic acid?

Answer 17

inhibits the reabsorption of sodium and chloride

Question 18

What is the site of action of ethacynic acid?

Answer 18

• medullary and ascending lims of the loop of Henle

- distal renal tubule

Question 19

What is the clinical use for ethacynic acid?

Answer 19

diuresis with subsequent mobilization of excess fluids (edema, pleural effusions, ascites

(alternative diuretic for patients with allergy to sulfonamides)

[only starred that last line cause i thought it was pretty cool]

Question 20

What are the side effects of ethacynic acid?

Answer 20

• GI reactions with oral med (abdominal pain, anorexia, N/V, diarrhea, dry mouth) (pretty common)
• ototoxicity (hearing loss or tinnitis)
• hypotension
• large loss of electrolytes (K, Cl, Mg, Na, Ca)

basically the same as with lasix, except for the GI complications with the oral version.

Question 21

Ethacynic acid is what type of diurectic?

Answer 21

a loopy diuretic

Question 22

What is the MOA of mannitol?

Answer 22

• increases plasma osmolarity which draws intracellular fluid to the extracellular spaces
• results in acute expansions of intravascular volume

Question 23

What is the clinical use for mannitol?

Answer 23

• prophylaxis against acute renal failure
• acute oliguria
• increased ICP
• increased IOP (intraocular pressure)

Question 24

What is the site of action for mannitol?

Answer 24

• typically used to decrease brain bulk or to increase renal blood flow to the medulla
• i suppose the site is everywhere

Question 25

What are the side effects of mannitol?

Answer 25

• may cause pulmonary edema in patients with oliguria secondary to heart failure
• prolonged use may cause hypovolemia, electrolyte disturbances, and plasma hyperosmolarity

Question 26

Mannitol is what type of diuretic?

Answer 26

an osmotic diuretic

Question 27

What is the MOA of urea?

Answer 27

its small molecular size causes reabsorption of more than 60% of urea filtered by the glomerulus

Question 28

What are side effects of urea?

Answer 28

• crosses the BBB and can cause rebound increases in ICP
• high incidence of thrombosis and tissue necrosis at injection site

(sounds like a great drug…)

Question 29

Urea is what type of diuretic?

Answer 29

an osmotic diuretic

Question 30

What is the MOA of potassium-sparing diuretics, such as triamterene or amiloride?

Answer 30

• acts directly on renal tubular transport mechanisms in the distal convoluted tubules, independent of aldosterone, to produce diuresis
• causing an increase in urinary excretion of Na, Cl, and bicarb, and increases urine pH
• inhibits potassium secretion in the distal renal tubules

Question 31

What are the clinical uses of triamterene or amiloride?

Answer 31

• used in combination with loop or thiazide diuretics to augment diuresis and limit potassium loss

Question 32

What are side of effects of triamterene and amiloride?

Answer 32

• hyperkalemia

Question 33

Triamterene and amiloride are what types of diurectics?

Answer 33

potassium sparing

Question 34

What is the MOA of spironolactone?

Answer 34

causes loss of sodium bicarb and calcium while saving potassium and hydrogen ions by antagonizing aldosterone

Question 35

What is the clinical use of spironolactone?

Answer 35

• weak diurectic and antihypertensive response when compared with other diuretics
• so, if you don’t need the big guns…

Question 36

Spironolactone is what type of diuretic?

Answer 36

an aldosterone antagonist

Question 37

What is the MOA of acetazolamide?

Answer 37

the inhibition of carbonic anhydrase has different effects in different parts of the body…

in the eye:
- decreased secretion of aqueous humor

in the kidneys:
- self-limiting urinary excretion of Na, K, bicarb, and water

in the CNS:
- the resultant diuresis may decrease abnormal neuronal firing

Question 38

What is the clinical use of acetazolamide?

Answer 38

• lowering intraocular pressure
• control of some types of seizures
• prevention and treatment of acute altitude sickness
• diuresis and mobilization of excess fluid
• prevention of renal calculi

Question 39

Acetazolamide is what type of diuretic?

Answer 39

a carbonic anhydrase inhibitor

Question 40

What is the MOA of nicardipine?

Answer 40

• dihydropyridine calcium channel blocker
• preventing calcium entry into the vascular smooth cells by extracellular allosteric modulation of the L-type voltage gated calcium ion channels

Question 41

What is the site of action for nicardipine?

Answer 41

• peripheral arterioles, with minimal effects on venous capacitance vessels.
• Lack effecs on the SA node & AV node
• minimal myocardial depressant effects.

** Of all DHP CCBs, this one has the most vasodilating effects, with the greatest effects in the coronary arteries **

Question 42

Clinical uses for nicardipine?

Answer 42

• hypertension
• only dihydropyridine CCB available in IV form
• can be used as a tocolytic drug (uterine contraction repressant)

Question 43

Side effect of nicardipine?

Answer 43

• reflex tachycardia

Question 44

What is the MOA of hydralazine?

Answer 44

• activates guanylate cyclase to produce vascular relaxation.

Hydralazine can also cause hyperpolarization of isolated arteries and interfere with mobilization of Ca2+ in vascular smooth muscle

Question 45

What is the site of action for hydralazine?

Answer 45

• direct relaxant effect on vascular smooth muscle

dilation effect on arterioles are greater than on the veins

Question 46

Clinical uses for hydralazine?

Answer 46

• decreases SBP
• vasodilator effects more pronounced on the coronary, cerebral, renal, and splanchnic circulations
• may be vasodilator of choice in heart failure patients with renal dysfunction who cannot tolerate an ACE inhibitor
• best for hypertensive emergencies in pregnancy

Question 47

Side effects of hydralazine?

Answer 47

• sodium and water retention if a diuretic is not given concomitantly
• reflex tachycardia
• possible MI in patients with CAD
• H/A, nausea, flushing, etc

Question 48

What is the MOA of nipride?

Answer 48

• direct acting, non selective peripheral vasodilator that causes relaxation of arterial and venous vascular smooth muscle
• interacts with oxyhemoglobin, dissociating immediately and forming methemoglobin while releasing cyanide and nitric oxide (NO).
• NO actives the enzyme guanylate cyclase present in vascular smooth muscle, resulting in increased intracellular concentrations of cGMP.
• cGMP inhibits calcium uptake by the smooth endoplasmic reticulum to produce vasodilation and decreasing BP.

Question 49

What is the MOA of digitalis?

Answer 49

• a cardiac glycoside that selectively and reversibly inhibits the sodium-potassium ion transport system located in the cardiac cell membranes
• the resulting increase in sodium ion concentration in cardiac cells leads to decrease extrusion of calcium ions by the sodium pump mechanism.

(it is presumed that this increased intracellular concentration of calcium ions is responsible for the positive inotropic effects of cardiac glycosides. Conceptually, increased amounts of calcium ions become available to react with contractile proteins to generate a greater force of myocardial contraction. The positive inotropic effects produced by cardiac glycosides occur without changes in heart rate and are associated with decreases in left ventricular preload, afterload, wall tension, and oxygen consumption in the failing heart)

Question 50

What is the MOA of milrinone?

Answer 50

positive inotrope:

• inhibits intracellular phosphodiesterase III (the enzyme that metabolizes cAMP)
• the buildup of cAMP activates protein kinase in myocardial cells
• the activated protein kinase then phosphorylates L-type calcium channels on the plasma membrane, allowing increased calcium influx into the cell

vasodilator:

• when smooth muscles accumulate cAMP, the myosin light chain kinase (the enzyme responsible for initiating actin and myosin) is inhibited
• without that activity, vascular smooth muscle is relaxed and dilated

Question 51

What is the clinical use of milrinone?

Answer 51

• acute left ventricular dysfunction / acute cardiac failure (ie after an MI)
• weaning from cardiopulmonary bypass

(patients that would benefit from combined inotropic and vasodilator therapy)

Question 52

Side effects of milrinone?

Answer 52

• ventricular arrhythmias
• hypotension
• headache

Question 53

What are the signs and symptoms of digitalis toxicity?

Answer 53

• anorexia
• N/V (d/t excitation of the CTZ)
• visual disturbances
• amblyopia
• jaw pain (similar to trigeminal neuralgia)
• altered mental status
• arrhythmias