Lecture 8 - Drugs Used to treat high blood pressure II

Question 1

What is the agonist effect of alpha 1 receptor? What is the antagonist effect of the alpha 1 receptor?

Answer 1

Agonist: vasoconstriction
Antagonist: vasodilation

Question 2

What is the agonist effect of beta 1 receptor? What is the antagonist effect of the beta 1 receptor?

Answer 2

Agonist: promotes contraction in the heart
Antagonist: dilation in the heart

Question 3

What is the agonist effect of beta 2 receptor? What is the antagonist effect of the beta 2 receptor?

Answer 3

Agonist: promotes dilation in vascular smooth muscle
Antagonist: constrictes airway of vascular smooth muscle

Question 4

Increased intracellular Ca2+ is the main signal for smooth muscle ____. It can arise from plasma membrane Ca2+ channels or activation of Gq-coupled cascade such as alpha 1.

Answer 4

contraction

Question 5

What drug is commonly used for anti-hypertensive purposes which blocks the voltage sensitive calcium channels, blocking a way you could generate a calcium signal?

Answer 5

Amlodipine

Question 6

What is RAAS?

Answer 6

• Renin angiotensin aldosterone system

Question 7

What 3 functions does RAAS control?

Answer 7

• blood volume
• salt balance
• blood pressure

Question 8

What is ARBs and ACEIs?

Answer 8

ARB: Angiotensin receptor blockers
ACEI: Angiotensin converting enzyme inhibitor

Question 9

What enzyme is secreted by the kidneys that processes angiotensinogen to Angiotensin I ( AT1)?

Answer 9

Renin

Question 10

What is the function of ACE and where it does it happen?

Answer 10

• converts AT1 to AT2
• happens in the circulation in the lungs

Question 11

Is AT1 or AT2 a powerful vasoactive peptide that causes vascular smooth muscle control and aldosterone release from teh adrenal cortex?

Answer 11

AT2

Question 12

How is the RAAS pathway stimulated?

Answer 12

if your blood pressure is reduced; triggers your kidneys to release renin.

Question 13

AT2 will restore blood pressure by acting directly on ____ and aldosterone will restore blood pressure by acting directly on ____ triggering changes in our water and salt balance.

Answer 13

Blood vessels; kidneys

Question 14

AT2 causes vaso____ and aldosterone release at the same time; can’t do it individually.

Answer 14

constriction

Question 15

Which steroid hormone promotes reabsorption of Na+ and H20 in the kidney (preserved blood volume and increases blood pressure)?

Answer 15

aldosterone

Question 16

Memorize the following pathway on the purple side

Answer 16

Question 17

Renin is secreted by the kidney in response to ____ blood pressure by the stimulation of adrenergic stimulation.

Answer 17

low

Question 18

Renin release is stimulated by ____ receptors

Answer 18

Beta 1

Question 19

ACE or ARB exists primarily as a membrane bound protein in the pulmonary capillary endothelium?

Answer 19

ACE

Question 20

Angiotensin II effects are primarily mediated by the ATII receptor usually called the ____ receptor

Answer 20

AT1 receptor; also known as AT2 type 1 receptor

Question 21

AT1 receptors are GCPRs, coupled to the ____ signaling cascade.

Answer 21

Gq

Question 22

In adrenal cortex, Ca2+ signals trigger synthesis/release of ____ (steroid hormone; lipid soluble)

Answer 22

aldosterone

Question 23

Does aldosterone have a intracellular or extracellular signaling pathway?

Answer 23

intracellular

Question 24

What are the key transcriptionsal targets in the nephron?

Answer 24

• Na+/K+ pump
• Epithelial Na+ channel (ENaC)
• NCC (Na+/Cl- symporter)

Question 25

Receptors for aldsoterone are found in the ____ convoluted tubule; when they are active, they promote trancription of target genes (the 3 target genes in the nephron)

Answer 25

distal

Question 26

Is captopril an ACE, aldosterone antagonist, or ARB (AT1 blocker)?

Answer 26

ACE

Question 27

What drug acts as an enzyme inhibitor and binds to ACE to prevent the cleavage of ATI to AT, as a consequence, it reduces all of the downstream RAAS signals (ATII and aldosterone?

Answer 27

Captopril

Question 28

What are the side effects of Captopril?

Answer 28

* Most common is dry cough; ACE is responsible for the breakdown of a inflammatory mediator called Bradykinin (peptide hormone), ACE cleaves bradykinin and breaks it down.

Question 29

In you ____ ACE, you have excess amounts of Bradykinin, triggering cough in patients.

Answer 29

inhibit

Question 30

Is Losartan an ACE, aldosterone antagonist, or ARB (AT1 blocker)?

Answer 30

AT1 blocker (ARB)

Question 31

Losartan and other ARBs have a vaso____ effect. They inhibit powerful vaso____ effects of ATII.

Answer 31

dilatory; constrictive

Question 32

ARB's inhibit vasoconstrictive effects of AT2 by ____ the GCPRs in vascular muscle and ____ the production of aldosterone.

Answer 32

inhibiting; inhibits

Question 33

In vascular smooth muscle, AT1 receptors mediate vaso____.

Answer 33

constriction

Question 34

Is spironolactone an ACE, aldosterone antagonist, or ARB (AT1 blocker)?

Answer 34

Aldosterone antagonist

Question 35

Spironolactone acts as a ____ antagonist for aldosterone

Answer 35

competitive

Question 36

Aldosterone antagonists have what kind of effects?

Answer 36

* acts as a diuretic by inhibiting aldosterone effect (i.e., no reabsorption of sodium or water)

Question 37

Answer 37

RELATIVE RISK REDUCTION OF MAJOR CARDIOVASCULAR EVENTS: 1 – (13209/137319)/(14068/128259) = ~12% ABSOLUTE RISK REDUCTION = (14068/128259) – (13209/137319) = 1.3% NNT = 74 RELATIVE RISK REDUCTION OF ALL CAUSE MORTALITY: 1-(9775/138298)/(9998/129700) = ~8% ABSOLUTE RISK REDUCTION = (9998/129700) – (9775/138298) = 0.64% NNT = 156

Question 38

It is common to use anti-hypertensice drugs in combination therapy because they can have ____ effects on blood pressure.

Answer 38

additive