Pharmacology of Hypertension

Question 1

What are angiotensin converting enzyme (ACE) inhibitors used for?

Answer 1

• ACE inhibitors are used to treat hypertension, heart failure, and acute myocardial infarction

Question 2

What is the primary drug target of angiotensin converting enzyme (ACE) inhibitors?

Answer 2

• Angiotensin converting enzyme

Question 3

What is the drug target type of angiotensin converting enzyme (ACE) inhibitors?

Answer 3

• Enzyme antagonist

Question 4

What is the location of action of angiotensin converting enzyme (ACE) inhibitors?

Answer 4

• Endothelium (Lungs & Kidneys)

Question 5

What is the mechanism of action of angiotensin converting enzyme (ACE) inhibitors?

Answer 5

• Inhibit the angiotensin converting enzyme
• Prevent conversion of angiotensin I to angiotensin II by ACE
• Decrease sympathetic nervous stimulation
• Decrease vasoconstriction
• Decrease Blood Pressure

Question 6

What are the main adverse effects of angiotensin converting enzyme (ACE) inhibitors (6)?

Answer 6

• Cough
• Hypotension
• Hyperkalaemia
• Foetal injury
• Renal failure
• Urticaria / Angioedema

Question 7

Give 3 examples of angiotensin converting enzyme (ACE) inhibitors.

Answer 7

• Ramipril
• Lisinopril
• Perindopril

Question 8

What considerations should be taken when prescribing angiotensin converting enzyme (ACE) inhibitors?

Answer 8

• Hepatic considerations:
  
  • Most ACE inhibitors (not lisinopril) are pro-drugs (they require hepatic activation to generate metabolites required for therapeutic effects)
• Renal considerations:
  
  • eGFR and serum potassium must be regularly monitored when prescribing ACE inhibitors

Question 9

What are angiotensin receptor blockers used for?

Answer 9

• Angiotensin receptor blockers are used to treat hypertension, delay progression of diabetic nephropathy, and treat congestive heart failure

Question 10

What is the primary drug target of angiotensin receptor blockers?

Answer 10

• Angiotensin receptor

Question 11

What is the drug target type of angiotensin receptor blockers?

Answer 11

• Receptor antagonists

Question 12

What is the location of action of angiotensin receptor blockers?

Answer 12

• Kidneys and Vasculature

Question 13

What is the mechanisms of action of angiotensin receptor blockers?

Answer 13

• Angiotensin receptor blockers act as non-competitive antagonists at AT1 receptor
• Decrease sympathetic nervous stimulation

Question 14

What are the main adverse side effects of angiotensin receptor blockers (4)?

Answer 14

• Hypotension
• Hyperkalaemia
• Foetal injury
• Renal failure

Question 15

Give 3 example of angiotensin receptor blockers.

Answer 15

• Losartan
• Irbesartan
• Candesartan

Question 16

What considerations should be taken when prescribing angiotensin receptor blockers?

Answer 16

• Hepatic considerations:
  
  • ​Losartan & Candesartan are pro-drugs (they require hepatic activation to generate the active metabolites required for therapeutic effects)
• Other medication options:
  
  • Most trials indicate that angiotensin receptor blockers are not as effective anti-hypertensive agents as ACE inhibitors

Question 17

What are calcium channel blockers used for?

Answer 17

• Calcium channel blockers are used to treat hypertension and angina

Question 18

What is the primary drug target of calcium channel blockers?

Answer 18

• L-type calcium channel

Question 19

What is the drug target type of calcium channel blockers?

Answer 19

• Ion channel antagonist

Question 20

What is the location of action of calcium channel blockers?

Answer 20

• Heart and Blood vessels

Question 21

What is the mechanism of action of calcium channel blockers?

Answer 21

• Block L-type calcium channel (predominantly on smooth muscular vescels)
• Decrease in calcium influx
• Inhibition of myosin light chain kinase & prevention of cross-bridge formation
• Vasodilation
• Decrease in blood pressure

Question 22

What are the main adverse effects of calcium channel blockers (4)?

Answer 22

• Ankle oedema
• Constipation
• Palpitations
• Flushing / Headaches

Question 23

Give 2 examples of calcium channel blockers.

Answer 23

• Amlodipine
• Felodipine

Question 24

What type of calcium channel blockers demonstrate a higher degree of vascular selectivity?

Answer 24

• Dihydropyridine type calcium channel blockers

Question 25

What are thiazide / thiazide-like diuretics used for?

Answer 25

* Thiazide / Thiazide-like diuretics are used to suppress lactation and to treat hypertension and edema

Question 26

What is the primary drug target of thiazide / thiazide-like diuretics?

Answer 26

* Sodium / Chloride co-transporter

Question 27

What is the drug target type of thiazide / thiazide-like diuretics?

Answer 27

* Transport protein antagonist

Question 28

What is the location of action of thiazide / thiazide-like diuretics?

Answer 28

* Kidneys

Question 29

What is the mechanism of action of thiazide / thiazide-like diuretics?

Answer 29

* They block the Na⁺/Cl^- cotransporter in the early DCT * Na⁺/Cl^- reabsorption is inhibited * Increased osmolarity of the tubular fluid * Decrease osmotic gradient for water reabsorption in the collecting duct * Decrease in volume of fluid in body * Decrease in bloop pressure

Question 30

Why is there an increase in calcium reabsorption with using thiazides?

Answer 30

1. Calcium is **reabsorbed across the lumen membrane down its concentration gradient** that is generated by the activity of the **sodium calcium exchanger** 2. **Blocking the entry of sodium** into the cell through the Na⁺/Ca²⁺ exchanger , whilst the Na⁺/K⁺still works means that the **return of sodium into the cell via the Na⁺/Ca²⁺ ​ is increased** 3. This **reduces sodium calcium concentration** in the cell and therefore **increases the potential for calcium** to be removed from the tubular fluid

Question 31

What are the main adverse effects of thiazide / thiazide-like diuretics (6)?

Answer 31

* Hypokalaemia * Hercalcaemia * Metabolic alkalosis (increased H⁺ excretion) * Hyponatraemia * Hyperuricemia * Hyperglycaemia (hyperpolarised pancreatic β-cells)

Question 32

Give 2 examples of thiazide / thiazide-like diuretics.

Answer 32

* Bendroflumethiazide (thiazide diuretic) * Indapamide (thiazide-like diuretic)