PHARM 12: Drugs + CVS - VASCULATURE

Question 1

what is meant by vascular tone

Answer 1

when Arteriolar S.M. normally displays a state of partial constriction

Question 2

link BP , TPR and CO in an equation

Answer 2

BP= CO x TPR

Question 3

What is hypertension?

Answer 3

• blood pressure consistently above 140/90 mmHg

Question 4

step 1: How would you treat Hypertension

Answer 4

• under 55s = Angiotensin converting enzyme (ACE) inhibitor OR angiotensin receptor blocker (ARB)
• over 55s or afro-Caribbean’s = Calcium channel blocker (CCB) or thiazide-like diuretic

Question 5

step 2: How would you treat Hypertension

Answer 5

• CCB or thiazide-like diuretic + ACEi or ARB

- ARBs preferred to ACEi for AfroCaribbean’s

Question 6

step 3: How would you treat Hypertension

Answer 6

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

Question 7

step 4: How would you treat Hypertension

Answer 7

Resistant Hypertension:

• Consider low-dose spironolactone
• Consider beta-blocker or alpha blocker

Question 8

how does RAS lead to hypertension?

i.e what can stimulate RAS ?

Answer 8

• decrease in renal Na+ reabsorption
• causes decrease in renal perfusion pressure
• increases SNS

Question 9

how do ACE inhibitors work?

Answer 9

• they inhibit conversion of ATI –> AT II by ACE

- AT II = potent vasoconstrictor

Question 10

give example of an ACE inhibitor

Answer 10

enalapril

Question 11

When might be ACE inhibitors used?

Answer 11

• hypetension
• heart failure
• post myocardial infarction
  diabetic nephropathy
  progressive renal insufficiency

Question 12

why would Increased TPR and venous return worsen heart failure/ hypertension?

Answer 12

• increased TPR –> increased vasoconstriction (BP) causes Increased BP
  + (HEART) increases after load –> increasing cardiac work
• increased venous return -> (BP) causes increased cardiac contractility + CO (HEART) causes long term fluid retention + congestion –> leads to oedema

Question 13

what are potential side effects of ACEi + ARB?

Answer 13

• Cough (ACEi)
• hypotension (both)
• fetal injury
• renal failure (if has renal artery stenosis)
• urticaria
• hyperkalaemia =

Question 14

Whats the difference between Dihyropyridines (non rate limiting )
and Non DHPs (rate limiting)

Answer 14

• DHPS = more selective for blood vessels

Question 15

Whats the difference between amlodipine and verapamil?

Answer 15

Amlodipine: does not cause any negative inotropy

verapamil: causes large -ve inotropic effect

so Amlodipine is better to use for hypertension

Question 16

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

Answer 16

DHPs (Amlodipine)

Question 17

How would DHP work to treat hypertension?

Answer 17

• DHPs –> inhibit Ca2+ entry into vascular smooth muscle cells
• decrease in TPR + BP

N.B. Powerful vasodilation can lead to reflex tachycardia and
increased inotropy thus increased myocardial oxygen demand

Question 18

How would alpha blockers work to treat hypertension?

Answer 18

alpha 1 –> causes vasoconstriction

if alpha 1 blocked –> causes vasodilation by reducing Ca2+ influx

Question 19

peripheral reisistance is mainly driven by _________

Answer 19

arteriolar constriction

Question 20

What are effects of AT II ?

Answer 20

• stimulates aldosterone production –> which promotes salt and water retention
• potent vasoconstrictor
• stimulates thirst

Question 21

how would AT II receptor blockers treat heart failure?

Answer 21

• more vasodilation –> less force need to pump blood out of heart
• reduce salt and water retention –> decreases venous return
• venous return = preload –> drives CO
• decrease CO

note: can also decrease congestion of the heart

Question 22

how would AT II receptor blockers treat hypertension?

Answer 22

• reduce vasoconstriction
• reduce salt and water retention –> decreases venous return
• venous return = preload –> drives CO
• decrease CO

–> causes decrease in BP

Question 23

why does ACEi cause cough as a side effect?

Answer 23

ACEi –> prevents break down of bradykinin

which accumulates and initiates cough

Question 24

why does ACEi cause hyperkalaemia as a side effect?

Answer 24

aldosterone promotes insertion of Na-K atlases into kidney cells
if you block ACE - you get less aldosterone
so you get less channels
so teure is less uptake of K+ –> into kidney cells
so there is an increase in accumulation of K+ in the blood
results in hyperkalaemia

Question 25

• why does ACEi cause renal failure (if has renal artery stenosis)

Answer 25

• people with renal failure
  have a low GFR
  angiotensin –> constricts the afferent arteriole –> and increases the pressure of the glomerulus –> which improves the GFR

However
but if this is inhibited –> the ability to vasoconstrictor the afferent article is lost –> so there is low pressure in the glomerulus –> which causes renal failure

Question 26

describe the process of normal smooth muscle contraction

Answer 26

1. memb depolarization open s VGCC
   Ca2+ enters a+ binds to Calmodulin (CAM)
2. Ca-CAM complex binds to and activates MLCK
3. MLCK mediated phosphorylation –> causes smooth muscle contraction

Question 27

elderlies + afro carribeans –> you give CCB as 1st step hypertensive.

Why?

Answer 27

a) because tends to have low renin hypertension
- they would have low plasma renin
- so ACEi –> has less of an effect
- and so you would require too much dose

b) older you get the more dependent BP gets on atherosclerosis rather than RAS
so ACEi –> would have less of an effect