Vasopressors Flashcards
Fill in the blanks
Why could norepinephrine be containdicated in patients that are hypovolemic?
usually already in a state of increased vascular tone from endogenous catecholamine release - could impede venous return and decreased CO if exacerbated by norepinephrine
What are the dopaminergic receptros affected by dopamine?
D1 - postsynaptic - cause vasodilation
D2 - presynaptic - inhibit norepinephrine release, indirectly promoting vasodilation
List the different dose dependent effects of dopamine
Low dose - dopaminergic receptors (D1 and D2)»_space; vasodilation
Medium dose - beta adrenergic receptors»_space; increased HR, contractility, some vasodilation
High dose - alpha adrenergic receptors»_space; vasoconstriction
How does dobutamine affect the BP?
usually unchanged
How does ephedrine work?
Actually not a direct catecholamine
Sympathomimetic amin»_space; increases norepinephrine release from sympathetic nerve endings
can lead to tachyphylaxis with prolonged use - i.e., depleting norepi stores of the body
How does Isoproterenol affect the BP?
lowers BP
What is the onset of action after a bolus dose of epinephrine?
1 min - lasts 5-10 min
How does epinehprine afftect blood glucose levels?
alpha-agonism»_space; decreases insulin secretion, stimultes glycogenolysis + glucogenesis
beta-agonism»_space; increases glucagon and ACTH (hence increased cortisol which decreases glucose tissue uptake)
How do catecholamines affect coagulation?
increases shear-induced platelet reactivity
Where is vasopressin released?
pars nervosa of the posterior pituitary
What are the 4 vasopressin receptors?
V1R
V2R
V3R
oxytocin receptor
List triggers for vasopressin release
Increased plasma osmolality
decreased blood pressure
decreased circulating volume
also:
* pain
* nausea
* hypoxia
* hypercarbia
* pharyngeal stimuli
* glycopenia
* certain tumors
* mechanical ventilation
List drugs or chemicals that can cause vasopressin release
- opioids (high-dose)
- acetylcholine
- dopamine
- angiotensin II
- prostaglandins
- glutamine
- histamine
What inhibits vasopressin release?
- glycocorticoid
- low-dose opioids
- atrial natriuretic factor
- GABA
What receptors determine vasopressin release and where are they located?
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
How does Vasopressin cause vasoconstriction?
via V1R - G-protein coupled receptor
activates phospholipase C
conversion of PIP2 (phosphatidylinositol biphosphat) to IP3 (inositol triphosphate)»_space; causes release of Ca from the sarcoplasmic reticulum»_space; constriction
via depolarization
causes inactivation of potassium-ATPase channel
» less negative membrane potential»_space; depolarization»_space; opens Ca channels»_space; constriction
How does vasopressin affect hemostasis?
- activates platelets and stimulates thrombosis due to increased IC Ca++
How does vasopressin affect renal blood flow and GFR?
decreased RBF in the inner medulla only
increased GFR (efferent renal arteriolar vasoconstriction)
What are the effects of V2R stimulation?
Kidneys:
* G-coupled receptor»_space; increaed cAMP»_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
What is the action of V3R receptors?
ACTH release
What are the vasoactive effects of low levels of AVP?
vaodilation of the cerebral, pulmonary, mesenteric and renal vessels
Wht is the half-life of vasopressin?
16-24 minutes
What are Terlipressin and Selepressin?
Terlipressin
* synthetic protdrug, converted to lysine vasopressin
* greater V1R selectivity
* longer duration of action - 6 hours half-life
Selepressin
* novel selective V1R agonist
What is the recommendation for vasopressin use in CPR from the RECOVER guidelines?
can be considered as an acceptable alternative to epinephrine during CPR
What could be potential benefits of vasorpessin over epinephrine in CPR?
works well in acidemic and hypoxic environments
What are potential causes for decreased vasopressin levels in prolonged vasodilatory shock?
- depletion of neurohypophyseal stores
- AVP degradation
- impaired autonomic reflexes from sepsis»_space; impaired dysinhibition from baroreceptors
- volume loading/MV»_space; atrial stretch receptors»_space; inhibits release
- NO and norepinephrine»_space; inhibit release
Why does vasopressin administration improve urine output in sepsis?
- increased GFR from efferent arteriolar vasoconstriction
- improved hemodynamics and BP
- natriuresis from oxytocin receptor stimulation
- increase in strial natriuretic peptides
List potential adverse effects of vasopressin
- 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
