Anti-hypertensives (details)

Question 1

What are the 2 MOAs of ACE-inhibitors?

Answer 1

1) Blocks the conversion of ANGI to ANGII by inhibiting ACE
This causes ANGII levels to drop and ANGI levels will increase

2) Prevent the breakdown of bradykinin into an inactive state
Bradykinin is usually broken down by ACE. Bradykinin will activate the formation of prostaglandins and nitric oxide.

Question 2

What is the effect of the decrease in ANGII levels?

Answer 2

1) Decrease in vasoconstriction
2) Decrease in aldosterone secretion
3) Less sodium retention
4) Less water retention and thus decrease in blood volume

(salt gets secreted and water follows salt)

Question 3

What are the clinical uses of ACE inhibitors?

Answer 3

1) Hypertension
2) Cardiac failure
3) Following a myocardial infarction
4) Renal insufficiency

If you give patients ACE inhibitors after an MI, it has a protective effect for subsequent mortality

Question 4

What are the adverse effects of ACE inhibitors?

Answer 4

1) Severe hypotension
2) Acute renal failure
3) Hyperkalemia
4) Angioedema
4) Dry cough

Question 5

What is the contraindication for ACE inhibitors

Answer 5

Pregnancy

Question 6

What is the MOA of AT1 blockers?

Answer 6

They block Angiotensin II type 1 receptors so that Angiotensin II cannot mediate its effects

Question 7

What is the advantage of AT1 blockers over ACE inhibitors?

Answer 7

There is less/no dry cough because it no longer affects the pathway involving bradykinins

Question 8

What is the contraindication of AT1 blockers?

Answer 8

Pregnancy

Question 9

What is the MOA of beta-blockers?

Answer 9

Blockade of beta 1 receptors –> reduction of activation of calcium channels –> limited calcium influx (blocks CICR) –> no formation of calcium-calmodulin complex –> no activation of MLCK (myosin light chain kinase) –> relaxation of cardiac muscles –> reduce contractility of the heart

Question 10

What is CICR?

Answer 10

CICR = calcium-induced calcium release

The initial entry of calcium via the calcium channels is too limited for calcium-calmodulin complexes to form and for downstream pathways to be activate. But the presence of calcium in the cytoplasm would activate the sarcoplasmic reticulum, which contains a lot of calcium, to release more calcium, which will then cause a large increase in the amount of calcium, thus allowing for the formation of calcium-calmodulin complexes and thus the activation of myosin.

Question 11

What is the contraindication for beta blockers?

Answer 11

Asthma (note that it’s a RELATIVE rather than an absolute contraindication)

• Asthma = higher potential for the occurrence of bronchoconstriction
• Usually adrenaline will act on the beta 2 receptors in the bronchial smooth muscles to mediate bronchodilation
• Usage of beta 2 blockers = adrenaline can no longer act on beta 2 receptors to mediate bronchodilation, which is bad in asthma where there’s more bronchoconstriction
• Therefore, don’t give a non-selective beta-blocker

Question 12

What are the 3 main types of beta-blockers?

Answer 12

1) Non-selective beta blockers

2) Cardioselective beta blockers
- Targets beta 1 receptors and thus has less off-target effects because the heart is the main organ which has beta 1 receptors

3) Mixed (3rd generation) beta blockers
- Has slightly different selectivity based on the dose given.
- Low dose and/or fast metabolisers = beta 1 selective
- High dose/ slow metabolisers = non-selective (binds to beta 1 and beta 2), and thus becomes contraindicated in asthma.

Question 13

Name 3 non-selective beta blockers

Answer 13

1) Propanolol
2) Pindolol
3) Carvedilol

Question 14

Name 3 cardioselective (beta 1 receptor) beta blockers

Answer 14

1) Atenolol
2) Bisoprolol
3) Metoprolol XL (metoprolol succinate)

Question 15

Name 1 mixed (3rd generation) beta blocker

Answer 15

Nebivolol

Question 16

What are the clinical uses of beta blockers?

Answer 16

1) Hypertension
2) Cardiac failure
3) Following myocardial infarction
4) Abnormal heart rhythm
5) Anxiety disorders

Question 17

What are the adverse effects of beta blockers?

Answer 17

1) Hypotension
2) Bradycardia
3) AV nodal block (reduces tachycardia, but too much is not good)
4) Reduced exercise capacity
5) Bronchoconstriction (especially in asthmatics)
6) CNS effects (rare): vivid dreams, clinical depression

Question 18

Which part of the nephron do thiazides work on?

Answer 18

Distal convoluted tubule

Question 19

What is the MOA of thiazides?

Answer 19

1) Inhibits NaCl reabsorption by blocking the Na+/Cl- transporter
2) Enhance Ca2+ reabsorption in the DCT (reduces urine calcium, increases blood calcium)

Question 20

What are the clinical uses of thiazides?

Answer 20

1) Hypertension
2) Congestive heart failure
3) Nephrolithiasis due to idiopathic hypercalciuria (ie: high amount of calcium in the urine)
4) Nephrogenic diabetes insipidus

Question 21

What are the adverse effects of thiazides?

Answer 21

1) Hypokalemic metabolic alkalosis
2) Hyponatremia
3) Hyperuricemia
4) Hyperglycemia
5) Hyperlipidemia
6) Hypercalcemia

Question 22

What drug class should NOT be taken together with thiazides?

Answer 22

NSAIDs

Action of thiazides depend on renal prostaglandin synthesis. NSAIDs interfere with the actions of thiazides by reducing prostaglandin synthesis.