ACE inhibitors, Angiotensin Receptors Inhibitors And Diuretics

Question 1

What is the vascular endothelium and what are its functions?

Answer 1

A single layer of cells on the inner surface of blood vessels.

Barrier, clotting, angiogenesis, inflammation, vasoconstriction/vasodilation

Question 2

What potent mediators does endothelium contain?

Answer 2

Vasodilators and vasoconstrictors

Question 3

What does the renin-angiotensin-aldosterone system (RAAS) regulate?

Answer 3

Blood pressure, blood volume and electrolyte balance

Question 4

Under what three circumstances would renin be released?

Answer 4

• Reduced sodium delivery to distal convoluted tubule
• Reduced perfusion pressure in the kidney
• Sympathetic stimulation

Question 5

What hormones are involved in the RAAS?

Answer 5

• Atrial natriuretic Peptide (ANP)
• Vasopressin/antidiuretic Hormone (ADH)
• Aldosterone

Question 6

What protease Enzymes are involved in the RAAS?

Answer 6

Wouldn’t you like to know cowboy 🤠

Question 7

What is Angiotensin 2?

Answer 7

An active octapeptide that is a potent vasoconstrictor which increases blood pressure

Question 8

What does Renin and ACE convert?

Answer 8

Renin - Angiotensinogen to Angiotensin 1
ACE - Angiotensin 1 to Angiotensin 2

Question 9

Angiotensin 2 activates AT1 receptors which cause what?

Answer 9

• Contraction of vascular smooth muscle
• Secretion of aldosterone
• Increased reabsorption of sodium
• norepinephrine release
• Stimulation of cell growth in arteries and heart

Question 10

What are some examples of ACE inhibitors?

Answer 10

Ramipril, perindopril, captopril, lisinopril

Question 11

Where is ACE mainly expressed and what are ACE inhibitors mechanism of action?

Answer 11

In the lungs.

1. Binds to the zinc atom in the active site of ACE preventing conversion of Angiotensin 1 to Angiotensin 2.
2. Reduction of circulating Angiotensin 2 lowers blood pressure

Question 12

What drug interactions are there with ACE inhibitors?

Answer 12

Diuretics/CCBs -> effect increased (can be used in resistant hypertension)
Potassium sparing diuretics -> hyperkalaemia
Lithium -> Lithium toxicity
NSAIDSs -> impedes antihypertensive effects

Question 13

What are the adverse effects of ACE inhibitors?

Answer 13

• Dry cough (buildup of bradykinin usually cleaved by ACE) - major compliance issue
• Can cause foetal injury and death - MUST NOT BE USED IN PREGNANCY

Question 14

What are examples of angiotensin receptor blockers (ARBs), what is their mechanism of action and what is their advantage over ACE inhibitors?

Answer 14

Candesartan, Irbesartan, losartan.

Selectively block Antgiotensin AT1 receptors, reducing Angiotensin 2 mediated effects.

Do not cause dry cough.

Question 15

What is the main contraindication of ARBs?

Answer 15

Pregnancy

Question 16

What is the name of the only direct renin inhibitor and how does it work?

Answer 16

Aliskiren, binds to active site of renin, prevents cleavage of angiotensinogen to angiotensin 1
(Can be used as ARB adjunct)

Question 17

What are the function of the kidneys?

Answer 17

Eliminate waste products from the blood while recycling electrolytes and water, and regulating blood pressure.

Question 18

What are examples of Thiazide(-like) diuretics and how do they reduce blood pressure?

Answer 18

Hydrochlorothiazide, indapamide.
Reduce BP by increasing sodium and water excretion

Question 19

What are the indications of thiazides and thiazide-like diuretics?

Answer 19

Management of CVD
Indapamide also possesses vasodilatory properties (can also be used for HF)

Question 20

What are the side effects of thiazides and thiazide like diuretics?

Answer 20

• Can evoke compensatory renin release
• potential hypokalaemia
• can elevated blood glucose, and cholesterol levels
• Can reduce insulin sensitivity
• Can potentate the effect of loop diuretics

Question 21

What are examples of loop diuretics, what is their mechanism of action and where do they act on?

Answer 21

Furosemide, Bumetanide, Torsemide

Increased excretion of sodium, potassium, chloride, magnesium and calcium ions and water - act on the water-impermeable thick ascending limb (TAL) of the loop of henle

Question 22

Loop diuretics are preferred in which patients?

Answer 22

Renal impairment, as thiazides ineffective in CrCLl <3mL/min

Question 23

What are the adverse effects of loop diuretics?

Answer 23

• Electrolyte abnormalities
• Inc. blood glucose like thiazides
• Can cause ototoxicity

Question 24

What are the two types of potassium sparing diuretics?

Answer 24

Sodium channel blockers (e.g. Amiloride) and Aldosterone receptor antagonists (e.g. Spironolsctone, Eplerone)

Question 25

What are the adverse effects of potsssium-sparing diuretics?

Answer 25

• Hyperkalaemia
• Aldosterone antagonists -> Gynaecomastia in men (Not Eplerone as is specific)

Question 26

What are examples and the mechanism of action of ADH antagonists?

Answer 26

Conivaptan and Tolvaptan.
Significant water loss without high electrolyte loss (antagonism of V2 receptor)

Question 27

What is the adverse effect of ADH antagonists?

Answer 27

Hypernatraemia if excessive doses used