Hypertension Flashcards

1
Q

What is hypertension?

A

High blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What causes hypertension?

A
  • Salt and volume retention
  • Excess aldosterone can increase the amount of sodium in blood – increasing water
  • Vasoconstriction
  • Adrenaline/noradrenaline
  • Endothelium dysfunction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does angiotensin 2 do?

A
  • Causes vasoconstriction of blood vessels
  • Makes kidney reabsorb more salt and water
  • Influence adrenal cortex which stimulates aldosterone
  • Impacts brain – release of anti-diuretic hormone VASOPRESSIN – increases volume
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How do the kidneys work?

A
  • Blood comes in through bowmans capsule
  • Filtered in glomerulus
  • Reabsorption via NHE/SGLT (PCT)
  • Leftover stuff goes through loop of henle
  • Then through NKCC channels – target of loop diuretics – make kidney pass more fluid
  • Then through distal convoluted tubule (DCT) NCC channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 3 targets of the kidney/nephron

A
  • SGLT
  • NKCC channel
  • NCC channel
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Diuresis vs natriuresis

A
Diuresis = passing out water
Natriuresis = passing out sodium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are baroreceptors?

A

• Receptors that sensor pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where can baroreceptors be found

A
  • Aortic arch

* Carotid sinus nerve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How do baroreceptors work

A

• LOW pressure detected = sends signals to the brain via vagus nerve to stimulate brain to send messages to increase heart rate and vasoconstriction etc

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

current Treatments for hypertension

A
  1. ACE inhibitor
  2. Low-cost angiotensin 2 receptors blocker
  3. Calcium channel blocker
  4. Thiazide like diuretic - work on DCT
  5. Spironolactone – aldosterone antagonist
  6. Alpha and beta blockers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the limitations for current therapy?

A
  • Already many treatment options so a new medication needs something special
  • Medication adherence for blood pressure medications is poor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which drugs can we repurpose for hypertension?

A
  • Entresto – meta-analyses show that it lowers blood pressure more than ARB alone
  • Vericiguat = Victoria trial for heart failure suggested that vericiguat lowers blood pressure more than placebo
  • SGLT2 inhibitors = reduce blood pressure
  • Synthetic natriuretic peptide agonist – mimics natural natriuretic peptides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Tell me about natriuretic peptide agonists

A
  • Currently available as intravenous agents
  • Like neprilysin inhibitor it aims to increase the beneficial effects of natriuretic peptides
  • e.g., increases natriuresis and diuresis and lower arterial tone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

An example of a natriuretic peptide agonist

A

• Cenderitide was tested In heart failure and blood pressure – shown small reduction in blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What drug can give a prolonged effect for high blood pressure? Help with adherence

A

Angiotensin vaccines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do vaccines help with adherence

A

• You give it once or twice and then done

17
Q

Give an example of an angiotensin vaccine trial

A
  • A phase 2 trial showed the effect of single dose angiotensin 2 vaccine lasting 14 weeks
  • Trial did not reach phase 3 BECAUSE:
  • The BP effects were small compared to ACEi
  • Results not reproducible
  • Can’t reverse effects maybe?
18
Q

New treatment - What is firibastat?

A

Brain aminopeptidase a inhibitor

19
Q

What does the Renin Angiotensin Aldosterone system do? RAAS

A
  • Elevates blood volume via:
  • Working on kidneys: Sodium and water reabsorption
  • Working on blood vessels = vasoconstriction
  • Heart
  • Brain
20
Q

How does RAAS affect the brain?

A

• Through the angiotensin process

21
Q

How does brain control BP through RAS

A
  • Increase in vasopressin – antidiuretic
  • Activation of sympathetic premotor neuron activity
  • Inhibition of the Baroreflex – baroreflex usually keeps pressure low
22
Q

What is new in the angiotensin process?

A
  • APA converts angiotensin 2 into 3

* APN converts angiotensin 3 into 4

23
Q

What is APA

A

• Aminopeptidase A

24
Q

What is APN

A

• Aminopeptidase N

25
What does angiotensin 3 do?
* It is produced in the brain * Angiotensin 2 and 3 have a similar affinity for angiotensin 1 and 2 receptors * They also have similar affinity for non-angiotensin 1 and 2 binding sites * Increases arterial pressure
26
What is EC33 – Aminopeptidase inhibitor
* EC33 is a drug which STOPS APA so stops angiotensin 3 being made * Angiotensin 2 ability to increase pressure is also reduced by aminopeptidase inhibitor (APA inhibitor)
27
What is RB150
* Known as firibastat * A drug which crosses the blood brain barrier STOPS APA * Decreases blood pressure
28
Clinical trial data on firibastat
* Phase 2 showed trials showed the higher the blood pressure the greater the firibastat BP lowering effect * Acts as antihypertensive agent and NOT as a hypotensive agent
29
Summary of hypertension
* Significant room for repurposing other cardiovascular drugs to use in hypertension * Potential for medicines that help more than one cardiovascular condition = SGLT2 inhibitors * Vaccines are an interesting development to improve drug adherence