Drugs and the vasculature

Question 1

What do the varicosities along the length of the sympathetic nerve do primarily?

Answer 1

Release NA to stimulate vasoconstriction

Question 2

What are examples of VSM mediators that increase Ca2+ and stimulate a VSM contraction?

Answer 2

Angiotensin 2 -> AT1r
PGG2, PGH2 -> TP (T prostanoid receptor)
ET1 -> ET A/B

Question 3

What are examples of endothelial cell agonists that stimulate a relaxation from the increase in Ca2+?

Answer 3

NO
CNP - C type naturietic peptide
PGI2
EDHR - endothelial hypopolarising factor

Question 4

What is blood pressure generally mediated by?

Answer 4

CO and TPR

Question 5

What’s the vascular tone like in hypertensive patients?

Answer 5

Raised base vascular tone leading to more TPR leading to a higher BP

Question 6

What type of vessel contributes the most to blood pressure regulation?

Answer 6

Arterioles

Question 7

What blood pressure is considered hypertensive

Answer 7

140/90mmHg

Question 8

What is the first step of hypertension treatment?

Answer 8

Single therapy:
If under 55 give ACEi or ARD (angiotensin receptor blocker) but if over 55 or afro caribbean of any age then give CCB or thiazide diuretic

Question 9

What is the second step of hypertension treatment?

Answer 9

Dual therapy using either ACEi and CCB or ACEi and thiazide diuretic

Question 10

What is the third step of hypertension treatment?

Answer 10

Give ACEi, CCB and thiazide diuretic

Question 11

What is the 4th and final step of hypertension treatment

Answer 11

Just giving symptomatic relief using a low dose spironolactone (diuretic therapy) and a beta blockade or alpha blockade

Question 12

Give an example of an ACE inhibitor drug (ACEi)

Answer 12

Enalapril (they often have ‘-ipril’ endings)

Question 13

What stimulates the renin angiotensin system?

Answer 13

LOW renal Na+ reabsorption
LOW renal perfusion pressure
HIGH SNS activation

Question 14

What does ACEi do?

Answer 14

It decreases angiotensin II production and increases bradykinin

Question 15

What are the uses of an ACe inhibitor?

Answer 15

Hypertension
Heart failure
Post MI
Diabetic nephropathy
Progressive renal insufficiency
High CVS disease risk patients

Question 16

How do ACE inhibitors treat hypertension?

Answer 16

• They reduce TPR by more bradykinin and less AngII. Lower TPR due to less AT1R mediated vasoconstriction leading to less BP and more bradykinin vasodilation.
• There is sodium retention due to less Na+ retention in the kidneys via blocked actions of AngII on the AT1R in the kidneys and less aldosterone secretion as blocked AT1R in the adrenal medulla
• Thirst drive due to less SNS activation of thirst in the brain via AT1R

Question 17

How do ACE inhibitors treat heart failure?

Answer 17

• Reduce TPR - less vasoconstriction via AT1R in the peripheral vasculature so less TPR so less afterload on the heart so ionotropic effects of the heart decrease
• Reduce preload - venodilation by bradykinin

Question 18

What is an example of an angiotensin receptor blocker drug

Answer 18

Losartan

Question 19

What does an angiotensin receptor blocker drug do?

Answer 19

Prevent binding of Angiotensin ii to AT1 receptors

Question 20

What are angiotensin receptor blocker drugs used for

Answer 20

Hypertension and heart failure

Question 21

What are side effects of ARBs ?

Answer 21

Hypotension, Hyperkalaemia, Foetal injury, Renal failure in patients with renal artery stenosis

Question 22

What are side effects of ACEis?

Answer 22

Cough, Urticaria/angiodema (rarely), Hypotension, Hyperkalaemia, Foetal injury, Renal failure in patients with renal artery stenosis

Question 23

Why do ARBs and ACEis cause hyperkalaemia?

Answer 23

Aldosterone promotes K+ loss so aldosterone inhibitors produce a hyperkalaemia

Question 24

How do ARBs and ACEis cause renal failure in patients with renal artery stenosis?

Answer 24

Glomerular filtration is maintained by AngII

Question 25

Give examples of calcium channel blockers?

Answer 25

Amlodipine, verapamil

Question 26

How are smooth muscle contractions caused? How do they happen?

Answer 26

Membrane depolarisation opens VGCC, Ca2+ enters and binds to calmodulin (CaM), and the Ca2+-CaM complex activates MLCK, MLCK mediated phosphorylation causes VSM contraction

Question 27

What are the two different types of calcium channel blocker?

Answer 27

Dihydropyridines - non rate limiting and non-DHPs which are

Question 28

Why is amlodipine used to treat hypertension

Answer 28

a calcium channel blocker that doesn’t have a ionotropic effect on the heart

Question 29

What do DHPs do to decrease BP?

Answer 29

They inhibit Ca2+ entry into the VSMCs so less contraction of the cells so less TPR so less BP

Question 30

How can a powerful vasodilation lead to increased myocardial O2 demand

Answer 30

Powerful vasodilation -> reflex tachycardia -> increased ionotropy -> increased myocardial oxygen demand

Question 31

Why are ACE and ARB first line treatments for hypertension in patients under 55?

Answer 31

Because there is good patient adherence which is linked to less side effects and there is not much difference between the amoutn ACEi and ARB decrease BP

Question 32

Why are CCB and thiazide diuretics first line treatments for hypertension in patients over 55 and in afro caribbean patients??

Answer 32

This group of people have a different drug schedule due to low plasma renin activity so ACEi doesn’t work as well

Question 33

What are examples of alpha blocker drugs?

Answer 33

Prazosin and phentolamine

Question 34

What type of drug is prazosin

Answer 34

An alpha 1 antagonist

Question 35

What type of drug is phentolamine? How does this work?

Answer 35

An alpha1/alpha 2 antagonist.
The alpha 2 blocking leads to neg feedback of NA release so there is an enhanced NA release and SNS response leading to increased HR