Lecture 7 - Drugs to treat high blood pressure I

Question 1

What is blood pressure?

Answer 1

• is it generated by the beating of the heart and the resistance of the circulatory system.
• it changes during the cardiac cycle.

Question 2

When is our systolic pressure measured?

Answer 2

Pressure at the peak of ventricular contraction

Question 3

When is our diastolic pressure measured?

Answer 3

• minimum pressure during ventricular relaxation/dialation

Question 4

Hypertension increases the risk for which diseases?

Answer 4

• Renal failure
• coronary disease
• heart failure
• stroke
• dementia

Question 5

Blood pressure is the calculation of?

Answer 5

• Cardiac output x peripheral vascular resistance

Question 6

The more your cardiac output, the ____ your blood pressure

Answer 6

higher

Question 7

The stiffer your blood vessels are, the more ____ they are to blood flow leading to ____ blood pressure

Answer 7

ressitant; higher

Question 8

What does RAAS stand for?

Answer 8

• Renin-Angiotensin-Aldosterone System

Question 9

What is the most commonly used drug on the kidney?

Answer 9

Thiazide diuretics

Question 10

What is the function of sodium chloride co-transporter?

Answer 10

• reabsorbs sodium and chloride and co-transports them into the cell and then sodium is transported again back into the interstitium-blood via the sodium potassium pump

Question 11

What is the function of thiazides?

Answer 11

inhibit NaCl reabsorption in the distal convoluted tubule by blocking Na+/Cl- transporter.

Question 12

What is the function of thiazides?

Answer 12

inhibit NaCl reabsorption in the distal convoluted tubule by blocking Na+/Cl- transporter.

Question 13

Why is blocking reabsorption of Na+ bad?

Answer 13

• reabsorption of Na+ = reabsorption of water; keeping sodium inside the tubule also blocks the ater from being reabsorbed, leading to peeing causing a loss of water = reduced blood volume and decreased blood pressure

Question 14

What is a commonly used thiazide?

Answer 14

Bendroflumethaizide

Question 15

Which receptors are G-protein coupled receptors that are activated by catecholamines like adrenaline and noradrenaline?

Answer 15

Adrenergic receptors

Question 16

Why are adrenergic receptors important?

Answer 16

They regulate blood pressure.

Question 17

Which subtypes of adrenergic receptors are present in the heart?

Answer 17

• Beta 1 (only 1 heart)
• receptors are responsible for acceleration of heart rate and causing the heart to pump harder during a flight or fight response

Question 18

Which receptor does calcium bind to on the sarcoplasm particulum to allow calcium to tbe released from the sarcoplasm?

Answer 18

ryanodine receptor

Question 19

When calcium is released, it triggers the ____ filaments in our cardiac muscle to ____.

Answer 19

myofibrils; contract

Question 20

The stimulation of adrenergic receptors activates the ____ type calcium channels so more calcium comes in by ____ the type ____ channels. It accelerates the rate of calcium re-uptake causing the heartbeat to get ____ and leads to your heart beating/pumping ____ blood. It also phosphorylates a protein known as phospholamban which ____ the circuit pump.

Answer 20

• L-type
• autophosphorylation
• L-type
• smaller
• more
• inhibits

Question 21

Which adrenergic receptors are present in the lungs?

Answer 21

Beta 2 receptors (2 lungs in the body)

Question 22

Beta 2 receptors in the lungs cause bronchioles to ____ and enhanced perfusion of skeletal muscle during a fight or flight response

Answer 22

dilate

Question 23

In cardiac muscle, what are the 3 key targets of PKA?

Answer 23

• voltage-gated Ca2+ channels (L-type)
• Ryanodine receptors
• serca pumps

Question 24

Voltage-gated Ca2+ channels (L-type) ____ intracellular Ca2+ during a heart beat

Answer 24

increase

Question 25

Ryanodine receptors ____ Ca2+ release from intracellular stores during a heartbeat.

Answer 25

increase

Question 26

What pumps clean up Ca2+ by taking it up into ER stores during the termination of a heartbeat?

Answer 26

SERCA pumps

Question 27

What is the key target in vascular/bronchiolar smooth muscle? | Hint: MLCK

Answer 27

Myosin Light Chain Kinase

Question 28

Myosin Light Chain Kinase is a protein which enables ____ of smooth muscle. Phosphorylation by PKA causes smooth muscle to ____ (dilate bronchioloes, dilate vessels).

Answer 28

constriction; relax

Question 29

Protein Kinase in smooth muscle will phosphorylate myosin light chain kinase by ____ its activity and making the ____ of muscle weaker.

Answer 29

inhibiting; contraction

Question 30

Phosphorylation of Myosin Light Chain kinase promotes ____ (contraction/dilation)

Answer 30

contraction

Question 31

Gq signaling cascade releases IP3 which causes the release of calcium from calcium channels in vascular muscle or bronchioles. Calcium acts through ____ which binds to MLCK. When ____ is activated, it phosphorylates the MLC allowing smooth muslce ____ to occur.

Answer 31

calmodulin; calmodulin; contraction

Question 32

MLCK is a ____ dependent protein kinase

Answer 32

Ca2+ - calmodulin

Question 33

MLCK activity is ____ by B2-adrenoceptor activation

Answer 33

inhibited

Question 34

* Beta 1 receptors ____ contraction in the heart * Beta 2 receotors ____ contraction in smooth muscle (bronchioles and lungs) and in blood vessels during a flight or fight reaction

Answer 34

promote; inhibit

Question 35

Beta blockers are ____ antagonists of adrenergic receptors Some examples include adrenaline, noradrenaline, propranolol (non-selective), atenolol (B1 selective), carvedilol (B and a inhibition) and prazosin (alpha 1 selective)

Answer 35

competitive

Question 36

Anti-hypertensive effects of beta-blockers are mediated primarily by a ____ in cardiac output and ____ of renin secretrion

Answer 36

decrease;inhibition

Question 37

True or False: Inotropic effects the strength of contraction of the Heart

Answer 37

True

Question 38

True or False: Chronotropic influences the rate at which your heart beats.

Answer 38

True

Question 39

Some beta blockers such as carvedilol have non-specific inhibition of alpha receptors, which leads to an additional effect on ____ resistance (due to vasodilation).

Answer 39

peripheral

Question 40

Some beta blockers such as carvedilol have non-specific inhibition of alpha receptors, which leads to an additional effect on ____ resistance (due to vasodilation).

Answer 40

peripheral

Question 41

What is the side effect of non-specific beta blockers in bronchial smooth muscle?

Answer 41

bronchospasm

Question 42

Why are beta blockers with acitivy on beta 2 receptors to be avoided in patients with asthma or other respiratory issues?

Answer 42

* If you take beta 2 receptors, it causes your bronchioles to relax/dilate so by taking a beta blocker your are inhibiting the relaxation and bronchioles become constricted, making it harder to breathe. * If someone is taking a beta blocker to treat high blood pressure and they also have asthma, a negative outcome is that you inhibit beta 2 receptors causing an astham exacerbation.

Question 43

Inhibition of ____ receptors would cause dilation, while the inhibition of ____ 2 would cause constriction

Answer 43

alpha;beta

Question 44

Why do we not use Beta 2 blockers to treat high blood pressure?

Answer 44

beta2 blockade can trigger blood vessel constriction

Question 45

Why do we use a non-specific beta blocker to treat high blood pressure?

Answer 45

they block beta1 and reduce blood presure by reducing cardiac output and reducing renin release

Question 46

Explain the signaling cascade for alpha1- receptor

Answer 46

->GDP - GTP exchange on Galpha,q subunit and dissociation of Galpha and Gbeta/gamma ->Galpha,q activates PLC -> PLC cleaves PIP2, releasing IP3 and DAG -> IP3 triggers Ca2+ release from ER, via IP3 receptor -> Ca2+ is sensed by Calmodulin ->Ca2-Calmodulin binds and activates Myosin Light Chain Kinase -> Myosin Light Chain Kinase phosphorylates Myosin Light Chain -> This allows for muscle contraction.

Question 47

In tissues that don't require increased blood flow during a fight or flight response, ____ receptors are the primacy adrenergic receptors.

Answer 47

alpha 1

Question 48

Stimulation of alpha1 receptors triggers smooth muscle ____. ____ causes vasodiliation.

Answer 48

contraction; inhibition

Question 49

Alpha 1 receptors signal through ____ cascade.

Answer 49

Gq

Question 50

Protein kinase C can promote ____ of vascular muscle by phosphorylating a protein called the ____ kinase which then inhibits a MLCP (myosin light chain phosphatase). If MLCP is inhibited, muscle ____ is longer and more efective.

Answer 50

constriction; Rho; contraction

Question 51

is Propranolol selective or non-selective?

Answer 51

non-selective

Question 52

Is atenolol Alpha1 selective or beta1 selective?

Answer 52

Beta1 selective

Question 53

Is carvedilol beta inhibition or alpha inhibition?

Answer 53

alpha and beta inhibition

Question 54

Is prazosin alpha1 selective or beta1 selective?

Answer 54

alpha 1