Lecture 10: Drugs to Treat High BP II

Question 1

What are the three types of adrenergic receptors?

Answer 1

• Alpha 1
• Beta 1
• Beta 2

Question 2

What are the effects when an agonist binds to alpha 1 receptors?

Answer 2

Vasoconstriction of organs that are no required for the fight of flight response

Question 3

What are the effects when an antagonist binds to alpha 1 receptors?

Answer 3

Vasodilation of organs that are not required for the fight or flight response

Question 4

What are the effects when an antagonist bind to beta 1 receptors?

Answer 4

Increased cardiac contractility and rate

Question 5

What are the effects when an antagonist binds to beta 1 receptors?

Answer 5

Decreases cardiac contractility and rate

Question 6

What are the effects when an agonist binds to beta 2 receptors?

Answer 6

Relaxation of airway vascular smooth muscle

Question 7

What are the effects when an antagonist binds to beta 2 receptors?

Answer 7

Constriction of the airway vascular smooth muscle

Question 8

Where are beta 1 receptors found?

Answer 8

In the heart

Question 9

Where are Beta 2 receptors found?

Answer 9

In the lungs

Question 10

What is the main effect of beta blockers?

Answer 10

Decrease cardiac output by decreasing contractility and heart rate

Question 11

What does RAAS stand for?

Answer 11

Renin Angiotensin Aldosterone System

Question 12

What does the RAAS system control?

Answer 12

It controls blood volume, salt balance and blood pressure

Question 13

What drugs target the RAAS system?

Answer 13

• Angiotensin receptor blockers (ARBs)

* Angiotensin Converting Enzyme inhibitors (ACEis)

Question 14

What is Renin secreted by?

Answer 14

The kidney

Question 15

What does Renin do?

Answer 15

It cleaves Angiotensinogen to Angiotensin I

Question 16

What does ACE stand for?

Answer 16

Angiotensin Converting Enzyme

Question 17

What does ACE do?

Answer 17

Cleaves Angiotensin I (ATI) to Angiotensin II (ATII)

Question 18

What does ATII do?

Answer 18

It causes vasoconstriction of vascular smooth muscles and aldosterone release

Question 19

What is Aldosterone?

Answer 19

A steroid hormone that promotes reabsorption of Na+ and H2O in the kidney increasing blood volume

Question 20

Where does ATI come from?

Answer 20

The cleavage of Angiotensinogen by Renin

Question 21

Where does ATII come from?

Answer 21

ACE converting ATI to ATII

Question 22

What causes Aldosterone to be secreted?

Answer 22

ATII

Question 23

Where is Aldosterone produced?

Answer 23

In the adrenal glands

Question 24

What is the release of Renin stimulated by?

Answer 24

B1 activation due to low blood pressure

Question 25

What is the end goal of the RAAS system?

Answer 25

To increase blood volume and blood pressure

Question 25

What is the end goal of the RAAS system?

Answer 25

To increase blood volume and blood pressure

Question 26

How do beta 1 blockers reduce BP?

Answer 26

By reducing cardiac output and by decreasing renin secretion

Question 27

What is the signal pathway that increases release of Renin?

Answer 27

Adrenaline binds to B1 receptors activating Gs which activates AC and cAMP resulting of increased renin secretion

Question 28

How do B1 antagonists affect Renin secretion?

Answer 28

They will block B1 agonists from starting the Gs cascade suppressing renin secretion and RAAS system

Question 29

Where does ACE primarily exist?

Answer 29

In the pulmonary capillary endothelium as a membrane bound protein

Question 30

What receptor does ATII bind to?

Answer 30

The ATI receptor

Question 31

What kind of G receptors are ATI receptors that bind to ATII?

Answer 31

Gq receptors

Question 32

What are the two main target tissues of ATII?

Answer 32

* The Adrenal cortex | * Vascular smooth muscle

Question 33

What does the Adrenal Cortex release?

Answer 33

Aldosterone

Question 34

What does ATII do the adrenal cortex and vascular smooth muscle?

Answer 34

Causes the release of aldosterone from the adrenal cortex and vasoconstriction of vascular smooth muscle

Question 35

What is the intracellular pathway that leads to release of Aldosterone in the adrenal glands?

Answer 35

* ATII binds to ATI receptors which are Gq linked * Increased calcium binds to calmodulin * Calmodulin triggers synthesis and release of aldosterone

Question 36

What is the intracellular mechanism that ATII causes vasoconstriction?

Answer 36

* ATII binds to ATI receptors which are Gq linked * Increased calcium binds to calmodulin * Calcium Calmodulin activates MLCK * MLCK which phosphorylates the MLC causing constriction of the muscles

Question 37

How is Aldosterone able to interact with its receptor and why?

Answer 37

Aldosterone must cross the plasma membrane to interact with its receptor because it is a steroid hormone

Question 38

What is the intracellular cascade that allows aldosterone to work?

Answer 38

* Aldosterone crosses the membrane to bind with receptor * Receptor causes unbinding of chaperone protein * Translocates to the nucleus * Affects transcription of target genes * Generates mRNA and proteins * Leads to biological effects

Question 39

Which part of the kidney does Aldosterone target?

Answer 39

The Distal convoluted tubule

Question 40

Which three parts of the DCT does Aldosterone target?

Answer 40

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

Question 41

What is the net effect of aldosterone?

Answer 41

To promote Na+ and therefore water reabsorption to increase BP

Question 42

What does NCC do?

Answer 42

Transports sodium into the epithelial cell of the nephron so that the sodium potassium exchange pump can pump sodium into the interstitium blood

Question 43

What does aldosterone do to the sodium transported in the DCT?

Answer 43

Causes them to be upregulated in order to increase water reabsorption

Question 44

What level does aldosterone, a steroid hormone act?

Answer 44

At the level of gene transcription

Question 45

What is the main ACE inhibitor drug?

Answer 45

Captopril

Question 46

What do ACE inhibitors do?

Answer 46

The prevent the cleavage of ATI to ATII

Question 47

What does the prevention of ATI converting to ATII by ace inhibitors do?

Answer 47

Prevent the Vasoconstriction and aldosterone secretion of ATII

Question 48

What is the most common side effect of ACE inhibitors and why?

Answer 48

Dry cough because ACE also causes the breakdown of bradykinin which causes bronchoconstriction

Question 49

What is the overall effect of ACE inhibitors?

Answer 49

By blocking Vasoconstriction and Aldosterone secretion it decreases BP

Question 50

What is the main ATI blocker (ARB)?

Answer 50

Losartan

Question 51

What binds to ATI receptors?

Answer 51

ATII

Question 52

What is the effect of ARBs?

Answer 52

They have a vasodilatory effect

Question 53

Why do ARBs have a vasodilatory effect?

Answer 53

Because they block the ATI receptors and don't allow ATII to bind

Question 54

Why are ARBs better tolerated than ACE inhibitors?

Answer 54

Because they don't have the dry cough side affect cause by bradykinin not being broken down

Question 55

What is the main Aldosterone Antagonists?

Answer 55

Spironolactone

Question 56

What is Spironolactone?

Answer 56

A competitive antagonist of the aldosterone receptor

Question 57

What do Aldosterone Antagonists do?

Answer 57

The prevent aldosterone receptors from being activated

Question 58

What are the effects of Aldosterone inhibitors?

Answer 58

They have diuretic actions be stopping the reabsorption of Na+