Vasopressors

Question 1

Fill in the blanks

Answer 1

Question 2

Why could norepinephrine be containdicated in patients that are hypovolemic?

Answer 2

usually already in a state of increased vascular tone from endogenous catecholamine release - could impede venous return and decreased CO if exacerbated by norepinephrine

Question 3

What are the dopaminergic receptros affected by dopamine?

Answer 3

D1 - postsynaptic - cause vasodilation

D2 - presynaptic - inhibit norepinephrine release, indirectly promoting vasodilation

Question 4

List the different dose dependent effects of dopamine

Answer 4

Low dose - dopaminergic receptors (D1 and D2)&raquo_space; vasodilation
Medium dose - beta adrenergic receptors&raquo_space; increased HR, contractility, some vasodilation
High dose - alpha adrenergic receptors&raquo_space; vasoconstriction

Question 5

How does dobutamine affect the BP?

Answer 5

usually unchanged

Question 6

How does ephedrine work?

Answer 6

Actually not a direct catecholamine

Sympathomimetic amin&raquo_space; increases norepinephrine release from sympathetic nerve endings

can lead to tachyphylaxis with prolonged use - i.e., depleting norepi stores of the body

Question 7

How does Isoproterenol affect the BP?

Answer 7

lowers BP

Question 8

What is the onset of action after a bolus dose of epinephrine?

Answer 8

1 min - lasts 5-10 min

Question 9

How does epinehprine afftect blood glucose levels?

Answer 9

alpha-agonism&raquo_space; decreases insulin secretion, stimultes glycogenolysis + glucogenesis

beta-agonism&raquo_space; increases glucagon and ACTH (hence increased cortisol which decreases glucose tissue uptake)

Question 10

How do catecholamines affect coagulation?

Answer 10

increases shear-induced platelet reactivity

Question 11

Where is vasopressin released?

Answer 11

pars nervosa of the posterior pituitary

Question 12

What are the 4 vasopressin receptors?

Answer 12

V1R
V2R
V3R
oxytocin receptor

Question 13

List triggers for vasopressin release

Answer 13

Increased plasma osmolality
decreased blood pressure
decreased circulating volume

also:
* pain
* nausea
* hypoxia
* hypercarbia
* pharyngeal stimuli
* glycopenia
* certain tumors
* mechanical ventilation

Question 14

List drugs or chemicals that can cause vasopressin release

Answer 14

• opioids (high-dose)
• acetylcholine
• dopamine
• angiotensin II
• prostaglandins
• glutamine
• histamine

Question 15

What inhibits vasopressin release?

Answer 15

• glycocorticoid
• low-dose opioids
• atrial natriuretic factor
• GABA

Question 16

What receptors determine vasopressin release and where are they located?

Answer 16

central osmoreceptors
* third ventricle

peripheral osmoreceptors
* portal veins and mesenteric veins

Magnocellular neurons of the hypothalamus
* depolarized by hypertonicity

Baroreceptors
* Aortic arch and carotid sinus

Volureceptors
* left atrium

Question 17

How does Vasopressin cause vasoconstriction?

Answer 17

via V1R - G-protein coupled receptor

activates phospholipase C
conversion of PIP2 (phosphatidylinositol biphosphat) to IP3 (inositol triphosphate)&raquo_space; causes release of Ca from the sarcoplasmic reticulum&raquo_space; constriction

via depolarization

causes inactivation of potassium-ATPase channel
» less negative membrane potential&raquo_space; depolarization&raquo_space; opens Ca channels&raquo_space; constriction

Question 18

How does vasopressin affect hemostasis?

Answer 18

• activates platelets and stimulates thrombosis due to increased IC Ca++

Question 19

How does vasopressin affect renal blood flow and GFR?

Answer 19

decreased RBF in the inner medulla only
increased GFR (efferent renal arteriolar vasoconstriction)

Question 20

What are the effects of V2R stimulation?

Answer 20

Kidneys:
* G-coupled receptor&raquo_space; increaed cAMP&raquo_space; fusion of aquaporine-2 bearing vesicles with the apical cell membrane
* stimulating synthesis of RNA production for AQP-2 production

Hemostasis
* Platelet release from bone marrow
* vWF and FVIII release from endothelial cells and PLT

Vascular endothelium
* vasodilation

Question 21

What is the action of V3R receptors?

Answer 21

ACTH release

Question 22

What are the vasoactive effects of low levels of AVP?

Answer 22

vaodilation of the cerebral, pulmonary, mesenteric and renal vessels

Question 23

Wht is the half-life of vasopressin?

Answer 23

16-24 minutes

Question 24

What are Terlipressin and Selepressin?

Answer 24

Terlipressin
* synthetic protdrug, converted to lysine vasopressin
* greater V1R selectivity
* longer duration of action - 6 hours half-life

Selepressin
* novel selective V1R agonist

Question 25

What is the recommendation for vasopressin use in CPR from the RECOVER guidelines?

Answer 25

can be considered as an acceptable alternative to epinephrine during CPR

Question 26

What could be potential benefits of vasorpessin over epinephrine in CPR?

Answer 26

works well in acidemic and hypoxic environments

Question 27

What are potential causes for decreased vasopressin levels in prolonged vasodilatory shock?

Answer 27

• depletion of neurohypophyseal stores
• AVP degradation
• impaired autonomic reflexes from sepsis&raquo_space; impaired dysinhibition from baroreceptors
• volume loading/MV&raquo_space; atrial stretch receptors&raquo_space; inhibits release
• NO and norepinephrine&raquo_space; inhibit release

Question 28

Why does vasopressin administration improve urine output in sepsis?

Answer 28

• increased GFR from efferent arteriolar vasoconstriction
• improved hemodynamics and BP
• natriuresis from oxytocin receptor stimulation
• increase in strial natriuretic peptides

Question 29

List potential adverse effects of vasopressin

Answer 29

• high dose only: excessive coronary and splanchnic vasoconstriction
• hypercoaguable state
• local skin necrosis from extravasation
• irritation from conjunctival DDAVP
• GI/liver: gallbladder contraction, increased peristalsis, decreased gastric secretions, increased gastric sphincter tone
• contraction of urinary bladder