Drugs and the cardiovascular system: The vasculature

Question 1

identify the mechanisms regulating vascular tone and peripheral vascular resistance

Answer 1

vasoconstriction - decreased radius and flow, increased resistance
Vasodilation - increased radius and flow, decreased resistance

Question 2

What is vascular tone

Answer 2

Arteriolar smooth muscle normally displays a state of partial constriction

Question 3

How is blood pressure calculated

Answer 3

Cardiac output x Total peripheral resistance

Question 4

What is the clinical definition of hypertension and what is an important risk factor for

Answer 4

BP consistently above 140/90 mmHg

Single most important risk factor for stroke, causing about 50% of ischaemic strokes
Major risk factor for myocardial infarction (MI) + chronic kidney disease (KD)

Question 5

What is the first step in hypertension treatment

Answer 5

<55 - ACE inhibitor OR angiotensin receptor blocker (ARB)

> 55 / afro caribbean - Calcium channel blocker (CCB) or thiazide-like diuretic

Question 6

What is the second step in hypertension treatment

Answer 6

CCB + ACEi or ACEi + thiazide type diuretic

Afro caribbean - ARBs preferred to ACEi

Question 7

What is the third step in hypertension treatment

Answer 7

Combination of ACEi/ ARB with CCB and thiazide-like diuretic is recommended

Question 8

What is the fourth step in hypertension treatment/ treatment for resistant hypertension

Answer 8

Consider low-dose spironolactone

Consider beta-blocker or alpha blocker

Question 9

What is the mechanism of action for ACEi

Answer 9

Inhibit the somatic form of angiotensin converting enzyme (ACE)
Prevent the conversion of angiotensin I to angiotensin II by ACE

Question 10

What are the uses of ACEi

Answer 10

Hypertension
Heart failure
Post-myocardial infarction
Diabetic nephropathy 
Progressive renal insufficiency 
Patients at high risk of cardiovascular disease

Question 11

Give an example of an ACEi

Answer 11

Enalapril

suffix -pril is indicative

Question 12

How does hypertension lead to an increased CO

Answer 12

Increased TPR directly contributes to increased BP and increased venous return leads to increased cardiac contractility (via Starling’s Law) and thus CO.

Question 13

How does heart failure lead to oedema

Answer 13

Increased vasoconstriction increases the afterload and increases cardiac work. Increased venous return leads to long term fluid retention and congestion, leading to oedema.

Question 14

Give an example of a angiotensin receptor blocker (ARB)

Answer 14

Losartan

Question 15

Give the mechanism of action for ARBs

Answer 15

Antagonists of type 1 (AT1) receptors for Ang II, preventing the renal and vascular actions of Ang II

AT1 found on vessels, kidney and adrenaline glands
Reduction in vasoconstriction, salt and water retention and aldosterone secretion (and thirst via SNS/CNS)

Question 16

What are the uses of ARBs

Answer 16

Hypertension

Heart failure

Question 17

What are the side effects of ACE inhibitors and ARBs

Answer 17

COUGH (ACEi - due to bradykinin accumulation as ACE usually converts it to inactive metabolites)

Hypotension
Hyperkalaemia (care with K supplements or K-sparing diuretics)
Renal failure in patients with renal artery stenosis

Question 18

Describe the excitation-contraction process of smooth muscle contraction

Answer 18

1. Membrane depolarisation opens voltage-gated calcium (Ca2+) channels (VGCCs)
2. Ca2+ enters & binds to calmodulin (CaM)
3. Ca2+-CaM complex binds to & activates myosin light chain kinase (MLCK)
4. MLCK mediated phosphorylation
5. smooth muscle contraction

Question 19

What are the two types of calcium channels blockers and describe them

Answer 19

dihydropyridines (DHPs)
More selective for blood vessels
Also licensed for prophylaxis of angina

Non-DHPs
Rate-limiting

Question 20

Give an example of the two types of calcium channels blockers and their inotropic effects

Answer 20

Dihydropyridines (DHPs)
Amlodipine (no negative inotropy)

Non-DHPs
Verapamil (large negative inotropic effect)

Question 21

Which of the calcium channel blockers would you use to treat hypertension?

Answer 21

Dihydropyridines
inhibits Ca2+ entry into vascular smooth muscle cells
Decreased TPR and BP

Question 22

Why are alpha blockers used as anti-hypertensives

Answer 22

Blockade alpha1 receptors

Block vasoconstriction, reduce blood pressure

Question 23

What are the targets of prazosin and phentolamine

Answer 23

Alpha blockers
Prazosin targets a1 receptors
Phentolamine targets a1 and a2 receptors

Question 24

Why are ACEi and ARBs contraindicated for renal failure patients with renal artery stenosis

Answer 24

Glomerular pressure must be sufficient enough to drive GFR
ANG II controls this pressure usually. When pressure drops, ANG II is released and constricts the efferent arteriole so blood cannot leave the glomerulus effectively and GFR is restored

Patients with renal failure cannot regulate their glomerular pressure

Question 25

Why are elderly and afro Caribbean given CCBs as first line

Answer 25

Low plasma renin activity

elderly - Hypertension is usually due to atherosclerosis, RAAS desensitises

Question 26

Compare RASi to CCBs

Answer 26

CCBs reduce SBP more than RAS inhibitors
RAS inhibitors decrease heart failure
RAS inhibitors increase stroke
No difference for all-cause death

Question 27

Compare RASi to thiazides

Answer 27

Thiazides reduce SBP more than RAS inhibitors
RAS inhibitors increase heart failure and stroke
No difference for all-cause death

Question 28

Compare RASi to beta blockers

Answer 28

No difference in SBP reduction
RAS inhibitors reduce CV events and stroke
No difference for all-cause death