Week 2 - Hypertension

Question 1

What is normal blood pressure?

Answer 1

when correctly measured is < 120/80 mmHg (<115 mmHg systolic is probably truly healthy)

A truly healthy, normal BP is a systolic < 115 mmHg but it is controversial at what point pharmacotherapy should be initiated to lower a BP (until > 150 mmHg which everyone agrees is too high at any age)

Question 2

Define HTN

Answer 2

sustained (repeated measures) blood pressure >140/90 mmHg

Question 3

Stage 1, 2, and 3 HTN

Answer 3

Stage 1: systolic BP from 140 - 159 and diastolic BP in the 90’s
Stage 2: systolic BP from 160 – 179 and diastolic BP in the 100 - 109 range
Stage 3: systolic BP ≥180 and diastolic BP≥110 (stage 3 may also be referred to as malignant hypertension)

Question 4

Atherosclerotic: myocardial infarction and stroke and HTN

Answer 4

elevated blood pressure accelerates atherosclerosis in all arteries (happens in the arterial wall)

Question 5

Cardiac Outcomes of HTN

Answer 5

higher pressures increases the workload on the heart which results in heart failure
- can cause both systolic heart failure (impaired contraction and pumping) and diastolic heart failure (impaired relaxation and filling)

Question 6

Renal Outcomes of HTN

Answer 6

The kidneys are uniquely susceptible to elevated arterial pressures since they use them to filter blood and make urine.
- sustained, elevated blood pressure leads to chronically damaged kidneys and can eventually lead to the need for dialysis

Question 7

What are the known complications of an untreated, sustained elevation in BP?

Answer 7

atherosclerosis (MI and stroke)
heart failure
kidney damage

Question 8

BP and Genetics

Answer 8

a bell curve distribution in a healthy population dictated largely by genetics: other factors just modulate

Most all of the genetic contribution to hypertension involves sodium handling

Question 9

Other factors that affect BP

Answer 9

Na+ intake, stress, obesity, kidney disease, atherosclerosis (high cholesterol, smoking)

Question 10

Non-pharmacologic Txs of HTN

Answer 10

sodium restriction, sodium restriction, sodium restriction

and then weight loss, smoking cessation and stress management

Question 11

Goal of diuretics

Answer 11

get rid of sodium

Question 12

B - blockers

Answer 12

reduce cardiac output

dampen cardiac contractility

Question 13

Ace and ARBs

Answer 13

reduce Angiotensin 2 to give vasodilation

Question 14

Calcium Channel Blockers (CCBs)

Answer 14

forces arterial relaxation

Question 15

What are diuretics?

Answer 15

substance that promotes the excretion of urine:

caffeine, yerba mate, nettles, cranberry juice, alcohol

Question 16

What are Natriuretics?

Answer 16

substance that promotes the renal excretion of Na+

This is what we really need.

Question 17

LOOP diuretics are more potent

Answer 17

because they are working upstream in the loop of Henle
Furosemide (prototype)
Bumetanide
Torsemide
Ethacrynic acid
*Pt should NOTICE the effect of these drugs - if not, not the right dose (go to restroom within an hour after taking)
** Only used in pts with markedly advanced kidney disease, when thiazides no longer work

Question 18

Thiazide Diuretics

Answer 18

active in distal convoluted tubule. Some commonly used:

Chlorothiazide (prototype)
Hydrochlorothiazide
Chlorthalidone
Metolazone

Question 19

MOA of Thiazides

Answer 19

inhibit Na+ and Cl- transporter in distal convoluted tubules
increased Na+ and Cl- excretion
Natriuretic effect on Na+ reduces circulating blood volume and relaxes vascular smooth muscle in the wall of arteries
- increased K+/Mg2+ excretion
- decrease Ca2+ excretion
beware of hypokalemia

Question 20

Side Effects of Thiazides

Answer 20

• hypokalemia
• hyponatremia
  Hyperglycemia (very mild effect and rare at the low doses which are used for hypertension) - diminished insulin secretion, elevated plasma lipids (minor)
  Hyperuricemia (may be a factor in patients with gout)
  Hypercalcemia (reduced Ca++ excretion in kidney can be helpful in patients with history of kidney stones)
  *TEST WITHIN 6 MONTHS

Question 21

Pharmacokinetics of thiazides:

Answer 21

• orally administered, generally fairly poorly absorbed
• onset of action in ~ 1-2 hours but BP effects takes several days for full effect after initiation initiated
• wide range of t1/2 (half life) amongst different thiazides, generally considerably longer than loop diuretics and can all be dosed once daily
• free drug enters tubules by filtration and by organic acid secretion
• Working in the kidney

Question 22

MOA of Loop Diuretics

Answer 22

enter proximal tubule via organic acid transporter
inhibits apical Na-K-2Cl transporter in thick ascending loop of henle (these drugs really make you pee)
competes with Cl- binding site
enhances passive Mg2+ and Ca2+ excretion
increased K+ and H+ excretion in CCD
inhibits reabsorption of ~25% of glomerular filtrate

Question 23

Pharmacokinetics of Loop Diuretics

Answer 23

orally administered, rapid absorption. (preferred over thiazides in patients with moderate-severe chronic kidney disease)
rapid onset of action for both diuresis and BP effect. Preferred over thiazide agents when patients have reduced kidney function (eGFR< 30)
increase toxicity lithium (causes retention of lithium)
may have additive toxicity with other ototoxic drugs but only at high doses of intravenous formulations
inhibitors of organic acid ion transport decrease potency (NSAID’s like ibuprofen, naproxen) - of unclear clinical implication

Question 24

Side Effects of Loop Diuretics

Answer 24

* hypokalemia
hyperuricemia (bad for gout patients)
 metabolic alkalosis (at higher doses)
* hyponatremia
 ototoxicity (with higher doses of intravenous formulations)
Mg2+ depletion
*REPEAT LEVEL TESTING WITHIN 1 MONTH

Question 25

Renin-Angiotensin Inhibitors for Hypertension: ACE-I and ARBs

Answer 25

*RAS inhibitors are among the best tolerated of the antihypertensive drugs.

ARBs are even better tolerated (less cough and risk for angioedema).

The direct renin inhibitor (DRI) aliskiren is one of the newest BP drugs, but there are no completed or ongoing RCTs of aliskiren monotherapy.

Question 26

Why is “Dual RAS blockade” CI’d?

Answer 26

“Dual RAS blockade” either with an ACEI plus an ARB or with aliskiren plus an ACEI or ARB—is now contraindicated.
1-More hypotension,
2-Accelerate the decline in renal function,
3-Cause more hyperkalemia

Question 27

ARB

Answer 27

blocks the receptors in BVs from receiving Angiotensin 2

Question 28

ACE

Answer 28

block production of angiotensin 2

Question 29

Which is better, ARB or ACE?

Answer 29

Clinically they are equally effective

Question 30

Common ACEs

Answer 30

Lisinopril, Enalapril, Captopril, Ramipril

Question 31

Common ARBs

Answer 31

Losartan, Irbesartan, Valsartan, Candesartan

Question 32

Side Effects of ACEs/ARBs

Answer 32

All RAS inhibitors are contraindicated in pregnancy (can cause birth defects)
MC:
- ACEIs is a dry cough, which is more common in black patients and more common still in Asian patients.
If a cough develops in a patient taking an ACEI who needs RAS blockade, an ARB should be substituted.
- Angioedema (swelling of soft tissue, commonly around face/throat which can be life threatening) is much more common with ACE-I than ARB and more common in African Americans
- ACE-Is and ARBs have an equal incidence of hyperkalemia which is dose dependent
Because of unique effects in the vasculature of the kidney, ACE-Is and ARBs can cause small reductions in kidney function which are usually transient.
** Paradoxically, they are the drugs of choice for patients with hypertension and chronic kidney disease