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Cardiovascular > Hypertension > Flashcards

Hypertension Flashcards

1
Q

What is hypertension?

A

High blood pressure

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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
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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
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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
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5
Q

What are the 3 targets of the kidney/nephron

A
  • SGLT
  • NKCC channel
  • NCC channel
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6
Q

Diuresis vs natriuresis

A 
Diuresis = passing out water
Natriuresis = passing out sodium
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7
Q

What are baroreceptors?

A

• Receptors that sensor pressure

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8
Q

Where can baroreceptors be found

A
  • Aortic arch

* Carotid sinus nerve

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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

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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
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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
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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
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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
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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

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15
Q

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

A

Angiotensin vaccines

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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
Q

What does angiotensin 3 do?

A
  • 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
Q

What is EC33 – Aminopeptidase inhibitor

A
  • 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
Q

What is RB150

A
  • Known as firibastat
  • A drug which crosses the blood brain barrier STOPS APA
  • Decreases blood pressure
28
Q

Clinical trial data on firibastat

A
  • 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
Q

Summary of hypertension

A
  • 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

Cardiovascular (4 decks)

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