Lecture 7 - Drugs to Treat High Blood Pressure

Question 1

how is blood pressure generated?

Answer 1

by the beating of the heart, and the resistance of the circulatory system

Question 2

pressure at the peak of ventricular contraction is called ___

Answer 2

systolic pressure

Question 3

minimum pressure during ventricular relaxation is called ___

Answer 3

diastolic pressure

Question 4

what is the equation for blood pressure?

Answer 4

BP = (cardiac output)(peripheral vascular resistance)

Question 5

what is cardiac output?

Answer 5

volume of blood per unit time

Question 6

what is peripheral vascular resistance?

Answer 6

the resistance that the heart is working against

Question 7

what are the three main sites/mechanisms where drugs regulate blood pressure?

Answer 7

1) the heart
2) resistance vessels
3) the renin-angiotensin-aldosterone system (RAAS)

Question 8

how does the RAAS alter blood pressure?

Answer 8

feeds back onto the diameter and pressure of resistance vessels

Question 9

what are thiazide diuretics?

Answer 9

drugs that increase water loss and have a direct vasodilatory effect

Question 10

what is the mechanism of action of thiazide diuretics?

Answer 10

they inhibit the sodium chloride cotransporter (NCC), preventing sodium reabsorption, increasing water in the urine

Question 11

where is the Na+/Ca++ cotransporter (NCC) located?

Answer 11

the distal convuluted tubule in the kidneys

Question 12

a commonly used thiazide

Answer 12

bendroflumethiazide

Question 13

GPCRs that are activated by catecholamines like adrenaline and noradrenaline

Answer 13

adrenergic receptors

Question 14

what are the two main subtypes of adrenergic receptors?

Answer 14

alpha and beta

Question 15

what are beta-1 adrenergic receptors and what do they do?

Answer 15

the predominant adrenergic receptors located in the heart that are responsible for acceleration of the heart rate and cause the heart to pump harder

Question 16

list the steps in the beta-1 receptor signaling cascade?

Answer 16

• coupled to the Gs signaling cascade
• increased PKA
• increased free intracellular Ca++ via ryanodine receptors
• increased contractility

Question 17

what are the effects of a beta-1 receptor agonist?

Answer 17

increased cardiac contractility

Question 18

what are the effects of a beta-1 receptor antagonist?

Answer 18

decreased cardiac contractility

Question 19

both beta-1 and beta-2 receptors are coupled to the Gs signalling cascade, but their effects are different because ___

Answer 19

different effectors are present

Question 20

in cardiac muscle, the key targets of PKA are:

Answer 20

• voltage gated Ca++ channels
• ryanodine receptors
• SERCA pumps

Question 21

what are ryanodine receptors?

Answer 21

receptors located on the sarcoplasmic reticulum which increase Ca++ release from intracellular stores during a heartbeat

Question 22

what are SERCA pumps?

Answer 22

pumps located on the sarcoplasmic reticulum which ‘clean up’ Ca++ by taking it up into SR stores during the termination of a heartbeat

Question 23

what are beta-2 adrenergic receptors and what do they do?

Answer 23

the predominant adrenergic receptors in the lungs and some vasculature which cause bronchioles to dilate, and enhanced perfusion of skeletal muscle

Question 24

in vascular/bronchiole smooth muscle, the key targets of PKA are:

Answer 24

• myosin light chain kinase (MLCK)

Question 25

this protein enables constriction of smooth muscle

Answer 25

myosin light chain kinase (MLCK)

Question 26

phosphorylation of MLCK by PKA causes:

Answer 26

smooth muscle to relax (dilate bronchioled, dilate vessels)

Question 27

MLCK activation is enabled by ___

Answer 27

intracellular Ca++ (binding to calmodulin)

Question 28

MLCK activity is inhibited by ___

Answer 28

beta-2 adrenoceptor actiation (phosphorylated MLCK is inhibited and does not promote contraction)

Question 29

what are beta blockers?

Answer 29

competitive antagonists of adrenergic receptors

Question 30

propranolol

Answer 30

non-selective beta blocker (competitive antagonist), can cause bronchospasm/vasoconstriction as a side effect of targetting beta-2 receptors

Question 31

adrenolol

Answer 31

beta-1 selective beta blocker, decreases cardiac contractions = reduces BP, minimal side effects

Question 32

carvedilol

Answer 32

non selective beta blocker which inhibits both beta and alpha receptors, has an additional effect on peripheral resistance due to alpha receptors

Question 33

anti-hypertensive effects of beta-blockers are mediated primarily by:

Answer 33

• a decrease in cardiac output
• inhibition of renin secretion

Question 34

inotropic

Answer 34

influences cardiac contractility

Question 35

chronotropic

Answer 35

influences heart rate

Question 36

why would non selective beta-blockers, like propanolol, not be prescribed to patients with asthma?

Answer 36

because of the risk of experiencing bronchospams as a side effect

Question 37

what are alpha adrenergic receptors?

Answer 37

Gq coupled receptors, the primary adrenergic receptors in tissues that do not require increased blood flow during a fight-or-flight response

Question 38

stimulation of alpha-1 receptors triggers ___

Answer 38

smooth muscle contraction (vasoconstriction)

Question 39

inhibition of alpha-1 receptors triggers ___

Answer 39

vasodilation

Question 40

describe the alpha-1 receptor signalling cascade

Answer 40

• increased IP3
• increase in Ca++-calmodulin dependent protein kinase (CaM)
• phosphorylates/activates MLCK
• increase muscle contraction (vasoconstriction)

Question 41

rho kinase

Answer 41

inhibits MLCK phosphatase