Haematology and immunology: Pharmacology - Vasoactive peptides

Question 1

List 5 vasoconstrictor vasoactive peptides

Answer 1

1. Angiotensin II
2. Vasopressin
3. Endothelins
4. Neuropeptide Y
5. Urotensin

Question 2

List 7 vasodilatory vasoactive peptides

Answer 2

1. Bradykinin and related kinins
2. Natriuretic peptides
3. Vasoactive intestinal peptide
4. Substance P
5. Neurotensin
6. Calcitonin gene-related peptide
7. Adrenomedullin

Question 3

What are kinins?

Answer 3

Potent vasodilator peptides

Question 4

Describe the pathway for kinin formation and metabolism

Answer 4

Tissue and plasma kininogens are converted to kinins by the action of kallikreins
They are then metabolised to inactive fragments by kinanases I and II (kininase II = ACE)

Question 5

What are the major physiologic and pathologic effects of kinins?

Answer 5

1. Arteriolar dilation in heart, skeletal muscle, kidney, liver, and intestine
2. Venoconstriction
3. Contraction of visceral smooth muscle
4. Oedema (due to arteriolar vasodilation and increased capillary permeability)
5. Four classic symptoms of inflammation: redness, local heat, swelling, and pain (by stimulating nociceptive afferents in skin and viscera)

Question 6

What is the pathophysiology of hereditary angioedema? What is the inheritance pattern?

Answer 6

Deficiency/dysfunction of C1 esterase inhibitor (C1-INH) which is a protease inhibitor important in complement, coagulation and kallikrein-kinin systems
Results in increased kallikrein activation and bradykinin formation
AD inheritance

Question 7

Mechanism of action and clinical uses of icatibant

Answer 7

Bradykinin2-receptor antagonist
Used to treat hereditary angioedema (may also be useful in drug-induced angioedema)

Question 8

Subtypes, distribution and effect of vasopressin receptors

Answer 8

V1A: vascular smooth muscle (vasoconstriction)
V1B: anterior pituitary (ACTH release)
V2: renal tubule cells (increased water resorption in collecting tubules), extrarenal (regulation of coagulation factor VIII and vWF release)

Question 9

What is the mechanism of action and clinical application of desmopressin?

Answer 9

Selective V2 receptor agonist: decreases water excretion by acting on renal tubular cells, increases factor VIII and vWF by acting on extrarenal receptors
Used in pituitary diabetes insipidus, paediatric primary nocturnal enuresis, haemophilia A, and von Willebrand disease

Question 10

Give two examples of vasopressin analogues used to treat vasodilatory shock

Answer 10

AVP
Terlipressin

Question 11

What is an ARNI and what is it used for? Give an example

Answer 11

Combination medication used in HFrEF: angiotensin receptor blocker with neprilysin inhibitor
E.g. Entresto (valsartan and sacubitril)

Question 12

What eight factors can stimulate ANP release?

Answer 12

1. Atrial stretch via mechanoreceptors
2. Volume expansion
3. Lying down (standing to supine position)
4. Exercise
5. Sympathetic stimulation (via a1-adrenoceptors)
6. Endothelins
7. Glucocorticoids
8. Vasopressin

Question 13

Five effects of ANP

Answer 13

1. Increased natriuresis
2. Increased diuresis
3. Inhibition of renin and aldosterone release
4. Inhibition of vasopressin release
5. Vasodilation and decreased BP

Question 14

Three effects of BNP

Answer 14

1. Increased natriuresis
2. Increased diuresis
3. Hypotension

Question 15

Effects of CNP

Answer 15

Potent vasodilator, less natriuretic/diuretic effects when compared with ANP and BNP

Question 16

Endothelin effects

Answer 16

1. Vasoconstriction
2. PGI2 and NO release from endothelium (initial transient hypotension)
3. Positive inotropy and chronotropy
4. Decreased GFR and Na+/H2O excretion
5. Bronchoconstriction
6. Increased RAAS, vasopressin and ANP

Question 17

Six effects of substance P

Answer 17

1. Vasodilation (via NO release from endothelium)
2. Venoconstriction
3. Increased GI motility
4. Bronchoconstriction
5. Increased salivary gland secretion
6. Diuresis/natriuresis