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Y2 Pharm (LCRS1) > Drugs of the Cardiovascular System – The Vasculature > Flashcards

Drugs of the Cardiovascular System – The Vasculature Flashcards

1
Q

Name three drug classes that interfere with the renin-angiotensin system.

A

Renin inhibitors ACE inhibitors Angiotensin receptor blockers

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2
Q

Describe the action of aldosterone in collecting duct tubule cells.

A

Aldosterone passes through the plasma membrane and binds to mineralocorticoid receptors intracellularly and increases the synthesis of Na+ channels and Na+/K+ pumps This causes an increase in sodium reabsorption Water follows down its osmotic gradient

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3
Q

What are the uses of ACE inhibitors?

A
  • Hypertension
  • Heart Failure
  • Diabetic Nephropathy
  • Progressive Renal Insufficiency
  • Patients at high risk of cerebrovascular disease
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4
Q

Give an example of an ACE inhibitor.

A

Enalapril

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5
Q

What are the anti-hypertensive effects of ACE inhibitors?

A

They reduce the production of angiotensin II, which is a potent vasoconstrictor It also reduces the production of aldosterone, thus reducing salt and water retention This means that there is a decrease in blood volume, hence a decrease in venous return

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6
Q

What law links venous return to contractility?

A

Starling’s Law

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7
Q

What is diabetic nephropathy caused by?

A

It is due to significant damage to the kidney glomerulus because of toxic products NOTE: hyperglycaemia increases the risk of exposure to oxygen free radicals

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8
Q

Why are ACE inhibitors used in diabetic nephropathy?

A

ACE inhibitors reduce the angiotensin II-mediated vasoconstriction of the efferent arteriole This reduces the blood pressure at the glomerulus and hence reduces the accumulation of toxic products at the glomerulus

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9
Q

Give an example of an angiotensin receptor blocker.

A

Losartan

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10
Q

Explain the most common side effect of ACE inhibitors?

A

COUGH ACE also breaks down bradykinin If bradykinin levels build up then this can cause a cough

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11
Q

State some other side effects of ACE inhibitors and ARBs. Briefly explain them

A
  • Hypotension - over supression of A2, less vasoconstriction and less aldosterone mediated fluid retention
  • Hyperkalaemia - less activity of Na+/K+ ATPase because less aldosterone, K+builds up in circulation
  • Renal failure in patients with renal artery stenosis - A2 usually constricts the efferent arteriole to compensate for the stenosed renal artery, no efferent constriction = no gomerular pressure = no GFR
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12
Q

Describe the excitation-contraction coupling of vascular smooth muscle cells.

A

Depolarisation causes the opening of voltage-gated calcium channels (VGCC)

This leads to calcium influx

This causes Ca release from the SR

The calcium then binds to calmodulin forming a Ca2+-CaM complex

This complex activates Myosin Light Chain Kinase (MLCK), and the MLCK-mediated phosphorylation leads to smooth muscle contraction

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13
Q

What type of calcium channel blocker is more selective for blood vessels? Give an example.

A

Dihydropyridines – amlodipine

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14
Q

Give an example of non-rate limiting and a rate limiting CCB.

A

Non-rate limiting: Amlodipine Rate limiting: Verapamil

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15
Q

Which part of the calcium channel do the different CCBs bind to?

A

Dihydropyridines bind to the extracellularly component of the L-type calcium channel Verapamil binds to the intracellular component so for a CCB to have an effect on the heart it needs to be able to penetrate the membrane and act on the receptor inside the cell

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16
Q

Why are non-rate slowing CCBs preferred to rate-slowing CCBs in the treatment of hypertension and heart failure?

A

They have a more powerful effect on vascular smooth muscle and dont cause any negative ionotropy

17
Q

What type of receptor is a beta adrenoceptor?

A

G-protein coupled receptor (Gs protein linked)

18
Q

What are the effects of noradrenaline that cause an increase in blood pressure?

A

Increase in heart rate and cardiac contractility (leads to an increase in CO) via beta-1 receptors in the heart

Stimulation of beta-1 receptors in the kidneys promotes renin release –> increase in angiotensin II

Stimulation of alpha-1 receptors causes peripheral vasoconstriction

19
Q

What is hypertension in younger patients normally caused by?

A

Increased sympathetic drive

20
Q

State some uses of beta-blockers.

A
  • Angina
  • Cardiac dysrhythmias
  • Chronic heart failure
  • Hypertension
  • Also thyrotoxicosis,
  • glaucoma,
  • anxiety states,
  • migraine prophylaxis,
  • benign essential tremor
21
Q

Give an example of a cardio-selective beta-blocker.

A

Atenolol

22
Q

What are mixed beta-alpha blockers? Give an example.

A

They are beta-1, beta-2 and alpha-1 blockers Carvedilol You get extra vasodilation due to alpha-1 blockade

23
Q

Give an example of an alpha-1 blocker.

A

Prazosin

24
Q

Give an example of a non-selective alpha blocker.

A

Phentolamine

25
Q

Why is it important for alpha-1 blockers to be selective?

A

Alpha-2 receptors are the negative feedback receptors of the SNS Blocking them will result in enhancement of sympathetic activity so exxagerated relfex tacchycardia

26
Q

What is step 1 in the NICE guidelines for treatment of hypertension?

A

< 55 years = ACEi + ARB >55 years or Afro-Caribbean of any age = CCBs + thiazide-type diuretics

27
Q

What is step 2 in the NICE guidelines for treatment of hypertension?

A

ACEi & CCB or ACEi & thiazide diuretic

28
Q

What is step 3 in the NICE guidelines for treatment of hypertension?

A

ACEi & CCB & Thiazide diuretic

29
Q

What is step 4 in the NICE guidelines for treatment of hypertension?

A

Further diuretic therapy (low-dose spironolactone)

or

Alpha or beta-blocker

30
Q

What is spironolactone?

A

It is an aldosterone receptor antagonist

31
Q

What is chronic heart failure?

A

Impaired cardiac function due to ischaemic heart disease, hypertension or cardiomyopathy that results in fluid retention, oedema and fatigue Importantly - cardiac output doesn’t meet body’s demand

32
Q

Which drugs are normally used on patients with chronic heart failure?

A

ACEi ARB Beta-blockers Spironolactone

33
Q

Why are over 55s and afro-Caribbeans given different guidelines for hypertension?

A

ARBs, ACEi, CCBs, Diuretics have similar efficacy ARBs and ACEi are more well tolerated than CCBs and diuretics However, afro-caribbeans have lower renin:A2/aldosterone ratio suggesting their hypertenion is less linked to renin Older you get the less dependent on renin your hypertension becomes as it is more related to atherosclerosis

Y2 Pharm (LCRS1) (34 decks)

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