7 - Hypertension

Question 1

Diagnosis of HTN

Answer 1

Two or more Diastolics >40

Systolic >90

Pulse pressure >65

Question 2

Stage 2 HTN

Answer 2

S >160

D>100

Question 3

Essential HTN

Answer 3

90% of cases, no identifiable cause

Increased PVR

Normal CO

Question 4

Diuresis

Answer 4

an increase in urine volume

Question 5

Natriuresis

Answer 5

Increase in Renal sodium

Question 6

Clinical uses for diuretics

Answer 6

HTN, edema, CHF

Kidney disease, cirrhosis

Hypercalcemia

Diabetes insipidus

Question 7

Acetazolamide SOA

Answer 7

PCT

(NaHCO₃)

Question 8

Mannitol (or other osmotic agents) SOA

Answer 8

PCT – H20

Question 9

Furosamide SOA

Answer 9

Thick ascending limb

Question 10

Thiazides SOA

Answer 10

DCT (early)

(NaCl)

Question 11

Aldosterone SOA

Answer 11

Collecting tubule

(NaCl)

Question 12

ADH antagonists SOA

Answer 12

Collecting tubule

(H20)

Question 13

Adenosine SOA

Answer 13

Affererent arteriole, PCT, Thick ascending limb, Collecting duct

Question 14

Acetazolamide class, MOA

Answer 14

Carbonic anhydrase inhibitor

Inhibit the formation of CO2 and H20 (from H2CO3) out in the lumen

→ CO2 and H2O are excreted

Prevent the reformation of H2CO3 in the PCT cell

Question 15

Hemodynamic effect of long-term administration of diuretics

Answer 15

HR and CO are unchanged

Plasma volume = decreased/unchanged

TPR = decreased

Renin = increased

Question 16

Mechanism for long term vasodilation with long term diuretics

Answer 16

unknown

Question 17

Diuretics that act in the loop of henle

Answer 17

Furosamide

Bumetanide

Ethacrynic acid

Question 18

Loop diuretics MOA

Answer 18

Inhibit the Na-K-2Cl symporter in the lumenal membrane

Question 19

Loop diuretics - Effect on K+ dynamics

Answer 19

No accumulation of K

No K+ outflux back into lumen

NO Mg+ and Ca++ entry

Question 20

How and where do Mg++ and Ca++ enter the cell in response to K outflux?

Answer 20

From the lumen of the Thick Asc. Limb via the paracellular route

Question 21

Net ionic effects of loop diuretics

Answer 21

Increases excretion of all:

Na/ Cl / K / Mg / Ca

Question 22

Increased ____ from loop diuretics is due to PG formation

Answer 22

RBF

Question 23

Duration of action of loop diuretics depends on ____

Answer 23

Renal function

Question 24

Toxicities of loop diuretics

Answer 24

Dehydration

Hypokalemic Met. Acidosis

Ototoxicity

Hyperuricemia

Hypomagnesemia

Question 25

CI's for loop diuresis

Answer 25

Sulfa allergy

Question 26

\_\_\_\_ are more effective antihypertensives than loops in patients with \_\_\_\_\_\_\_\_\_

Answer 26

Thiazides Normal renal function

Question 27

Thiazide MOA

Answer 27

Interfere with the **NCC (Na-Cl Cotransporter**) in the DCT --\> net excretion of Na (with water following)

Question 28

Thiazides reduce the formation of

Answer 28

calcium stones in idiopathic hypercalcuria

Question 29

Net ionic effects of thiazides

Answer 29

increase excretion of Cl, Na, K, and HCO3 (high doses only) Reduce the excretion (Ca+)

Question 30

Thiazide diuretics

Answer 30

Chlorthiazide HCTZ Trichlormethiazide Methylclothiazide Polythiazide Cyclothiazide

Question 31

Thiazide-like diuretics

Answer 31

Chlorthalidone Indapamide Metolazone

Question 32

Thiazides may open...

Answer 32

Ca++ activated K+ channels | (leading to vasodilation)

Question 33

Why decrease in peripheral resistance with thiazides?

Answer 33

Negative Na balance

Question 34

What effect does K have on vascular state

Answer 34

K outflow hyperpolarizes the vascular smooth muscle --\> increases vasodilation

Question 35

In patients with renal insufficiency, thiazides...

Answer 35

lose the anti-hypertensive effect

Question 36

Thiazide diuretics may cause these conditions

Answer 36

* Hypokalemia, Hyponatremia, Hypochloremic Alkalosis * Hyperuricemia, Hyperlipidemia, Hypercalcemia * Erectile dysfunction

Question 37

CI's for thiazides

Answer 37

sulfa allergies

Question 38

Diuretics that act on the collecting tubule

Answer 38

Potassium-sparing Amiloride Trimterene Eplerenone Spironolactone

Question 39

Amiloride MOA

Answer 39

Inhibit apical Na channels in collecting tubule \*\*Reduced Na entry also reduces K+ excretion

Question 40

Clinical use for amiloride

Answer 40

Adjunct Tx with Thiazide or Loop for **CHF or HTN** *has some efficacy in reducing BP* Also used in Cirrhosis and edema due to secondary hyperaldosteronism

Question 41

Amiloride toxicities

Answer 41

Hyperkalemia Hyperchloremic met. acidosis

Question 42

CI's for amiloride

Answer 42

K+ supplementation ACE inhibitors

Question 43

Triamterene MOA

Answer 43

Inhibit apical Na+ channels in collecting tubule also reduces K excretion (d/t reduced sodium entry)

Question 44

Clinical use for triamterene

Answer 44

**Edema** associated with CHF, Cirrhosis, nephrotic symdrome, or hyperaldosteronism

Question 45

Triamterene does not have efficacy in...

Answer 45

lowering BP when used as monotherapy use in combo!

Question 46

Toxicities for triamterene

Answer 46

Hyperkalemia, Hyperchloremic metabolic acidosis

Question 47

CI's for triamterene

Answer 47

Kidney stones K supplementation ACE inhibitors

Question 48

Both triamterene and Amiloride are secreted in the

Answer 48

PCT

Question 49

\_\_\_\_ increases urinary excretion of Mg++ but ____ does not.

Answer 49

Triamterene does Amiloride doesn't

Question 50

Other class of drugs that act on the collecting ttubule

Answer 50

Aldosterone antagonists

Question 51

Counteract thiazide postassium loss with

Answer 51

amiloride or triamterene

Question 52

Drug that controls the number of Na channels in the membrane

Answer 52

antagonist

Question 53

Aldosterone works in the

Answer 53

nucleus to alter gene transcription

Question 54

AIP

Answer 54

aldosterone induced proteins upregulated with increased aldosterone

Question 55

Function of AIP's

Answer 55

controls proteins that traffic Na channels in and out of the membrane Influences the amount of channels in membrane

Question 56

Aldosterone antagonists downstream effects

Answer 56

Block aldosterone from binding receptor and inducing AIPs and downregulate Na channels for reabsorption from the lumen LESS REABS. OF SODIUM FROM LUMEN

Question 57

Aldosterone antagonists

Answer 57

aldosterone spironolactone

Question 58

Spironolactone MOA

Answer 58

* blocks acions of aldosterone * blocks 5a reductase (5a-reductase creates active metabolites of aldosterone)

Question 59

Clinical use of spironolactone

Answer 59

**HTN** or CHF with other diuretics

Question 60

Aldosterone and RAAS play a role in pathogenesis of

Answer 60

CHF

Question 61

Tox's with spironolactone

Answer 61

Hyperkalemia HyperCL met acidosis Gynecomastia, impotence, BPH

Question 62

CI's for spironolactone

Answer 62

K supplements, ACE inhibitors (promote K retention) Chronic renal insufficiency

Question 63

More selective mineralocorticoid receptor antagonist

Answer 63

Eplerenone

Question 64

Eplerenone MOA

Answer 64

selective antag of MCR in kidney heart BV and brain

Question 65

Eplerenone uses

Answer 65

HTN alone or combo

Question 66

Eplerenone therapeutic effect should be observed within

Answer 66

4 weeks

Question 67

Tox's for eplerenone

Answer 67

hyperkalemia Hypertriglyceridemia

Question 68

CI's for eplerenone

Answer 68

K supps, K sparing diuretics, ACE inhibitors Chronic renal insufficiency Diabetes associated with microalbuminemia CYP450 3A4 inhibitors (ketoconazole)