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Pharm > Lecture 10: Drugs to Treat High BP > Flashcards

Lecture 10: Drugs to Treat High BP Flashcards

1
Q

What is Blood Pressure Generated by?

A

Beating of the heart and resistance of the circulatory system

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2
Q

What is Systolic Pressure?

A

The pressure at the peak of ventricular contraction

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3
Q

What is increased blood pressure associated with?

A

A higher hazard ratio for most cardiovascular outcomes

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4
Q

What will increase blood pressure?

A

Increased beating of the heart or higher resistance of the vasculature

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5
Q

Where are the three places where drugs regulate blood pressure?

A
  • The heart
  • Resistance vessels
  • RAAS (Renin-Angiotensin-Aldosterone System)
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6
Q

What are the main effects of the RAAS?

A

Regulates blood volume and peripheral resistance

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7
Q

What is the main organ in the body that regulates fluid balance?

A

The kidneys

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8
Q

Which part of the Nephron is targeted by Thiazide Diuretics?

A

The Distal Convoluted Tubule

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9
Q

How do Thiazide Diuretics work?

A

They inhibit sodium and chloride reabsorption in the distal convoluted tubule

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10
Q

Which transporter do Thiazides work on?

A

The Sodium Chloride transporter (NCC)

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11
Q

How does the NCC work?

A

It brings Na+ and Cl- from the lumen of the nephron into the cell of the nephron and then the sodium potassium exchange pump takes sodium out of the cell into the blood

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12
Q

What happens with water when sodium is reabsorbed in the kidneys?

A

Sodium reabsorption drives water reabsorption

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13
Q

How does Thiazide affect blood pressure?

A

By blocking NCC they block sodium uptake with is coupled to water uptake and water uptake increases blood pressure

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14
Q

What is the commonly used Thiazide?

A

Bendroflumethiazide

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15
Q

What kind of receptors are Adrenergic Receptors?

A

G-protein coupled Receptors (GPCRs)

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16
Q

What are Adrenergic Receptors activated by?

A

Catecholamines like adrenaline and noradrenaline

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17
Q

What are the two subtypes of adrenergic receptors?

A

Alpha and Beta receptors

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18
Q

What are the predominant adrenergic receptors in the heart?

A

B1 receptors

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19
Q

What are B1 receptors in the heart responsible for?

A

Acceleration of the heart rate and causing the heart to pump harder during a fight or flight response

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20
Q

What kind of alpha G protein are Adrenergic receptors coupled to?

A

Gs

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21
Q

What are the key substrates that get phosphorylated in the heart?

A
  • Voltage-gated ca2+ channels (L-type)
  • Ryanodine receptors
  • SERCA pumps
22
Q

What is the first step during the beating of the heart?

A

Voltage gated calcium channels allow a small amount to calcium into the cell

23
Q

What does the calcium that enters the heart cells during depolarization do?

A

Triggers calcium release by binding to ryanodine receptors

24
Q

What do SERCA pumps do?

A

They reuptake the calcium

25
Q

How does PKA affect the calcium reuptake pump?

A

It increases its overall activity

26
Q

Where is Beta 2 the prominent adrenergic receptor?

A

In the lungs and some vasculature

27
Q

What do beta 2 receptors do?

A

Cause bronchioles to dilate and enhance perfusion of skeletal muscle during a flight-or-fight response

28
Q

What G signalling cascade are Beta 1 and Beta 2 coupled to?

A

The Gs signalling cascade

29
Q

What is the key difference between the Beta 1 and Beta 2 signalling cascade?

A

Their effects are different in the tissues because different effectors are present

30
Q

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

A
  • Voltage gated Ca2+ channels that increase Ca2+ during a heartbeat
  • Ryanodine receptors that increase Ca2+ release from intracellular stores during a heartbeat
  • SERCA pumps remove Ca2+ by taking it into the ER
31
Q

What are the targets of PKA in Vascular/Bronchiolar smooth muscle?

A

PKA phosphorylates myosin light chain kinase causing smooth muscle to relax

32
Q

What do Beta Blocker do at the receptor?

A

Beta blockers are competitive antagonist of adrenergic receptors

33
Q

Which adrenergic receptors are used to treat hypertension?

A

Beta blockers

34
Q

Why would administering beta blockers work to treat HBP?

A

Because they would decrease cardiac output by blocking calcium activity in the heart by decreasing the force of contraction

35
Q

What does Ionotropic refer to?

A

Changes in the contractility of the heart

36
Q

What does Chronotropic refer to?

A

Changes in heart rate

37
Q

What do alpha adrenergic receptors have a role in?

A

Peripheral resistance

38
Q

What is the problem with some beta blockers like Carbedilol?

A

They have non-specific inhibition of alpha receptors as well as beta receptors

39
Q

What harms may arise from using beta blockers?

A

Inhibiting Beta 2 receptors can cause bronchial spasm

40
Q

Where are Alpha Adrenergic receptors present?

A

In tissues that don’t require increased blood flow during the fight or flight response

41
Q

What does activation of alpha adrenergic receptors lead to?

A

Constriction of blood vessels

42
Q

How do Beta blockers with non-specific alpha effects affect alpha adrenergic receptors?

A

They inhibit the constriction of blood vessels not needed in the fight or flight response leading to peripheral vasodilation reducing blood pressure

43
Q

Which type of G receptor are alpha adrenergic receptors coupled to?

A

Gq receptors

44
Q

What occurs when alpha receptors are activated?

A

They are g-coupled do they then go on to increase calcium in the cell through IP3. The calcium binds to calmodulin which binds to MLCK and increases the contraction of smooth muscle

45
Q

What does blocking of alpha adrenergic receptors cause?

A

It blocks the activation of calcium calmodulin so that it cannot activate MLCK and activate smooth muscle constriction which doesn’t allow vessels around blood vessels not needed to constrict during fight or flight

46
Q

What is the main mechanism by which beta blockers reduce blood pressure?

A

By reducing cardiac output

47
Q

What receptors need to be targeted in order to have an effect on cardiac output?

A

Beta one receptors

48
Q

What is a Beta 1 selective beta blocker?

A

Atenolol

49
Q

What do non-selective beta blockers target?

A

Both beta 1 and beta 2

50
Q

What do nonselective beta blockers do?

A

They reduce cardiac output but also have to potential to block dilation in the lungs causing bronchospasm

51
Q

What is the benefit of Carvedilol?

A

It reduces peripheral resistance by causing vasodilation in tissues with alpha adrenoreceptors and reduce cardiac output

Pharm (31 decks)

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