Pharmacology of Hypertension

Question 1

What are the 5 major cardiovascular risk factors?

Answer 1

Hypertension
Hypercholsterolaemia
Family history
Diabetes
Smoking

Question 2

What is the Q-risk?

Answer 2

Calculator that predicts the likelihood of cardiovascular event

Question 3

Why is it difficult to get people to take hypertension medication?

Answer 3

No immediate effects
It will improve your health status in the future e.g. 5-10 years time
But it may give you side effects on the day
Difficult to see the benefits of the drug

Question 4

When do you begin hypertension medication?

Answer 4

Stage 1 hypertension: evidence of end organ damage, 10 year risk > 10% or have a cardiovascular disease

Stage 2 hypertension

Question 5

How do you define stage 1 hypertension?

Answer 5

Systolic between 130-150

Question 6

How do you define stage 2 hypertension?

Answer 6

Systolic over 150

Question 7

What do NICE guidelines suggest for hypertension if you are Black or over 55?

Answer 7

Calcium Channel Blockers

Question 8

Why are you not given ACEi if you are black or over 55?

Answer 8

Less likely to be hypertension where renin is significant

Question 9

What is the relationship between plasma clearance and elimination half life?

Answer 9

As plasma clearance (ml/min/kg) decreases elimination half life increases

Time to peak plasma levels increase

Conc. of drugs with a long half life remains fairly stable

Question 10

What is the mechanism of action of calcium channel blockers?

Answer 10

Prevents entry of calcium into smooth muscle of arteries, prevent contraction, causing vasodilation

Question 11

What is clearance?

Answer 11

Clearance is the measure of the ability of the body to eliminate a drug. Clearance by means of various organs of elimination is additive. Elimination of drug may occur as a result of processes that occur in the liver, kidney, and other organs.

Question 12

What is elimination half-life?

Answer 12

Elimination half-life is the length of time required for the concentration of a particular drug to decrease to half of its starting dose in the body.

Question 13

What is the time to peak plasma levels?

Answer 13

Time to peak concentration is the time required for a drug to reach peak concentration in plasma. The faster the absorption rate, the lower is the time to peak plasma concentration.

Question 14

What are the differences between amlodipine and felodipine?

Answer 14

Amlodipine has a much longer half life : never a moment when you do not have the drug in your system - accumulates
Dosed accordingly

Question 15

How do ACEi work?

Answer 15

Inhibits angiotensin converting enzyme mainly in the lung

Prevents the conversion of angiotensin I –> 2 (potent vasoconstrictor)

Reduces aldosterone production - decreasing sodium reabsorption

Question 16

What is a common side effect of ACEi?

Answer 16

Cough

Question 17

What medication is given if someone develops a cough whilst taking ACEi?

Answer 17

ARBs

Angiotensin receptor blockers

Question 18

Why do ACEi cause a cough?

Answer 18

ACE also breaks bradykinin

Stopping the enzyme increased bradykinin concentration causing a cough

Question 19

Why does ARB not cause a cough?

Answer 19

You limit angiotensin directly and the enzyme is left to work - still breaks down bradykinin

Question 20

Why do ACEi impact renal function?

Answer 20

To perfuse glomerulus, afferent arteriole must be open and efferent arteriole needs to be smaller to generate pressure

Angiotensin II keeps the efferent arteriole slightly closed

ACEi causes efferent arteriole to relax - reduced glomerular perfusion

Question 21

Why do ACEi impact serum potassium?

Answer 21

Less aldosterone causes potassium retention

The job of aldosterone is to retain sodium at the expense of potassium

Spirolactone stops aldosterone binding its receptor has the same effect

Question 22

What is the mechanism of action of indapamide?

Answer 22

Block sodium/chloride transporter in the distal tubule

Enables the reabsorption of any remaining sodium

Increases water reabsorption in the distal tubule

Increased urine output
Decreased cardiac output

Question 23

What happens after you take thiazide diuretics for a while?

Answer 23

After a while a mechanism adapts to overcome the reduction in cardiac output

Cardiac output goes back to normal

So in reality they work by decreasing total peripheral resistance

Question 24

Why do diuretics increase serum potassium?

Answer 24

More sodium delivered to the distal tubule

Reabsorbs sodium at the expense of potassium