Treatment of Hypertension

Question 1

how do you treat stage 1 hypertension?

Answer 1

In stage one hypertension if the patient has end organ damage, CV disease, renal disease, diabetes or a 10 year CV risk then lifestyle modifications or theraputic intervention. If not then still lifestyle modifications and monitor BP.

Question 2

How do you treat stage 2 hypertension

Answer 2

Lifestyle modifications and theraputic interventions.

Question 3

Name the antihypertensive therapeutics agents (ABCD)

Answer 3

• Angiotensin converting enzyme inhibitors
• Angiotensin 2 receptor blockers
• Diuretics
• Calcium Channel blockers
• alpha-adrenergic receptors blockers
• beta-adrenergic receptor blockers
• Potassium- sparing diuretics

Question 4

Describe the role of the kidneys in blood pressure

Answer 4

They control body water and salt balance which determines extracellular fluid volume and hence BP

Question 5

What are the ion transporters in the kidneys and where are they located?

Answer 5

• Proximal convoluted tubule - Sodium/Hydrogen exchanger
• Thich ascending limb - NKCC (Sodium/potassium/chloride exchanger)
• Distal convoluted tubule - NCC (Sodium/chloride exchanger)
• Collecting ducts - (epithelial sodium channel)

Question 6

Where is the main area angiotensin 2 works on absorption of sodium?

Answer 6

Proximal convoluted tubule

Question 7

Where does aldosterone stimulate sodium absorption?

Answer 7

Collecting duct

Question 8

Describe the function of ACE inhibitors in reducing BP

Answer 8

1st/2nd line treatment. They block the angiotensin converting enzyme which will decrease vasoconstriction (decreasing TPR), decrease water and salt retention which decreases ECV. All of which decrease BP

Question 9

Describe the other pathway ACE is involved in and the effect that ACE inhibitors have

Answer 9

Involved in the kinin-kallikrein system. It breaks down bradykinin into an inactive metabolite. Therefore ACE inhibitors increase the levels of bradykinin which is a vasodilator and therefore decreases the TPR further and therefore decreases BP.

Question 10

Name some ACE inhibitors and their side potential side effect

Answer 10

Ramipril, enalapril and lisinopril. Since increase bradykinin can cause bronchoconstriction it can cause a dry cough, so patients are often then perscribed ARB instead

Question 11

Describe the function of Angiotensin 2 receptor blockers

Answer 11

Prevent angiotensin 2 from binding to their receptors, this therefore causes decreased vasoconstriction and decreased water and salt retention which all decrease BP. However there is not effect on bradykinin so no dry cough

Question 12

Name some examples of angiotensin 2 receptor blockers

Answer 12

Losartan, Valsartan and Candesartan

Question 13

What are diuretics, their main action in reducing BP and the three main types

Answer 13

• Substances that help get rid of water by targeting sodium absorption. They reduce BP by decreasing ECV and the three main types are:
• Loop diuretics,
• Thiazide diuretics
• K+ sparing diuretics

Question 14

What is the method of action of loop diuretics

Answer 14

Absorbed in GI tract and then secreted by PCT, they inhibit the NKCC (Na+/K+/2cl- co-transporter) in the thick ascending limb of loop of Henle which causes a reduction in the reabsorption of Na+, K+ and Cl-. Most powerful diuretics.

Question 15

Name examples of loop diuretics and what they are used for?

Answer 15

Furosemide and Bumetanide. Used in:

• Hypertension where renal function is impaired
• Acute pulmonary oedema,
• Chronic HF
• Cirrhosis of liver
• Nephrotic syndrome
• Renal failure.

Question 16

What is the mechanism of action of Thiazide diuretics? and their common side effect

Answer 16

They are less powerful than loop. They inhibit the NCC causing a reduction in sodium and calcium reabsorption as well as causing vasodilators. Excreted in urine.

• They can cause erectile dysfunction

Question 17

Name some examples of Thiazide diuretics

Answer 17

Bendroflumethiazide and hydrochlorothiazide

Question 18

Name the two different postassium sparing diuretics and their action and name some examples

Answer 18

1) Aldosterone Antagonists (sprinolactone and eplerenone) - competitively inhibit the MLR to decrease sodium reabsorption
2) ENaC inhibitors (Amiloride and triamterene) - Block the epithelial sodium channel reducing sodium reabsorption.

Question 19

What are some of the complications of potassium sparing diuretics?

Answer 19

They have limited diuretic action alone but powerful when used with loop/thiazide diuretics. However they reducing the driving force for potassium secretion which would cause hyperkalaemia alone. If combined with loop diuretics then it balances the plasma potassium.

Question 20

Describe features of selective alpha 1 adrenoceptor antagonists and name two examples

Answer 20

Doxazosin and Terazosin

• Inhibit alpha 1 receptors which decreases vasoconstriction, therefore decreasing TPR and BP. Causes less tachycardia than older drugs but is only used in severe hypertension

Question 21

Describe features of non-selective beta-adrenoceptor antagonists and name an ecample

Answer 21

Propanaolol (blocks beta 1 and 2 adrenoceptors)
- Causes decrease in renin release, HR and force of contraction which decreases CO and therefore decreases BP however the side effects are bronchoconstriction which is important in asthmatics

Question 22

Describe features of selective beta 1 adrenoceptor antagonists and name an example.

Answer 22

Atenolol

- Blocks beta 1 receptors causing decrease in HR, force of contraction and renin release. It is excreted by the kidneys

Question 23

Beta blockers decrease renin release, what does this do?

Answer 23

Decrease angiotensin two which causes a decrease in vasoconstriction and salt retention and therefore further decrease in BP

Question 24

Why are beta blockers not first line treatment?

Answer 24

Less tolerated by ACE inhibitors/ARBs and less evidence to support routine use but they can be useful for hypertensive patients who have the additional need for a beta blocker such as those with angina or heart failure.

Question 25

Describe the depolarisation in conductive cardiac tissue

Answer 25

• F type calcium channels open allows for slow influx of Na, this causes a small depolarisation which opens T-type voltage gated calcium channels which causes further depolarisation as Ca enters. This causes L-type voltage gated calcium channels to open causing a large depolarisation. Depolarisation spreads through gap junction to all cells of heart.

Question 26

Name the calcium channel blockers and their effects

Answer 26

Rate limiting - Verapamil and Diltiazem.
Dihydropyridine - Amlodipine and lercanidipine.
Cardiac effects - Decrease contractility, HR and conduction velocity which decreases CO.
Smooth Muscle effects - Decreases coronary artery and peripheral vessel constriction which decreases TPR.