Hypertension 2

Question 1

Describe the complexity of hypertension treatment

Answer 1

• Monotherapy is sufficient in only 55% of cases
• In more severe cases 2 or 3 drugs have to be used simultaneously
  
  • each drug must belong to a different class

Question 2

What are the 7 classes of antihypertensive drugs?

(2a’s, 2b’s, 2c’s, 1d)

Answer 2

1. Angiotensin Converting Enzyme Inhibitors (ACE inhibitors)
2. Angiotensin II Receptor Antagonists (AIIRAs)
3. Beta-Blockers
4. Peripheral Alpha-Blockers
5. Centrally Acting Alpha-Agonists
6. Calcium Channel Blockers
7. Diuretics

Question 3

What is diuresis?

Answer 3

• Increased or excessive production of urine

Question 4

What are diuretics?

Answer 4

• Cause excretion of water and electrolytes
• In kidney, water reabsorption is dependent primarily on Na+ reabsorption
  
  • therefore, a diuretic is an agent which inhibits tubular Na+ reabsorption, resulting in increased excretion of these ions and consequently water

Question 5

What is the role of the kidney in the regulation of Blood Pressure?

Answer 5

• Help to regulate the blood pressure by increasing or decreasing the blood volume
• The important site for renin-angiotensin-aldosterone system
• Long-term control of blood pressure
• Blood filtered at the nephron

Question 6

What is the function of Kidney Tubules?

Answer 6

• Post-nephron tubular structures are responsible for reabsorption of Na+ (and water) from urine depending on the need

Question 7

What are the three classes of diuretics?

Answer 7

• Thiazide Diuretics (e.g. hydrochlorothiazide)
• ‘Loop’ Diuretics (e.g. Furosemide)
• Competitive Inhibitors of Aldosterone

Question 8

What is Aldosterone?

What does Aldosterone Bind to?

What does Aldosterone Complex Bind to?

Answer 8

• Aldosterone acts as a typical steroid hormone released from adrenal gland
• Aldosterone binds to a cytoplasmic receptor that is transported to the nucleus
• The aldosterone/receptor complex binds to DNA to enhance the synthesis of a Na+, K+-ATPase and a Na+ channel involved in a Na+ and K+ transport in the distal tubule and collecting ducts

Question 9

What is the MOA of beta-blockers in decreasing BP?

Answer 9

• Decreasing arterial blood pressure by reducing cardiac output (blocking sympathetic stimulation of the heart)
• Can be used in combination with diuretic
• Inhibit the release of renin from the kidneys (partly regulated by beta1-adrenoceptors in the kidney)

Question 10

What does decreasing circulating plasma renin lead to?

Answer 10

• Decreasing circulating plasma renin leads to a decrease in angiotensin II level and subsequently aldosterone, enhancing renal loss of Na+ and H2O and further decreases BP

Question 11

What are the effects of Beta-Blockers on the heart?

Answer 11

• Bind to beta-adrenoceptors located in cardiac tissue
• Heart has both b1 and b2 adrenoceptors (b1 predominant)
  
  • bind to NA that is released from sympathetic adrenergic nerves
  • in addition they bind NA and A that circulate in the blood
• b-blockers prevent NA from binding by competing for the receptor binding site

Question 12

What are the effects of Beta-Blockers on the Vasculature?

Answer 12

• Vascular smooth muscle has b2-adrenoceptors that are normally activated by NA released by sympathetic nerves or by circulating A
• beta-blockers have minor vascular effects because of their specificity to B1 receptors

Question 13

What are the Adverse Effects of Beta-Blockers?

Answer 13

1. Cold hands and feet
   
   • Raynaud’s
     
     • reduction in CO
2. Swollen ankles
   
   • Fluid escapes from blood vessels quickly
3. Slow heartbeat
   
   • Bradycardia
4. Difficulty breathing
   
   • Non-selective Beta-Blockers
5. Joint Pain
6. Halluciation
   
   • Metoprolol can cause BBB - interaction with CNS - vivid dreams
7. Lethargy
8. Impotence