Vasopressors Flashcards
End organ damage occurs when map is below 50 for ___
1 minute
End organ damage occurs when MAP is below 65 for ____
13-28 minutes
What is the difference between autonomic and somatic ANS?
Somatic does not involve ganglia, ACH goes directly to the nicotinic receptor
Sympathetic innervation of the adrenal medulla
ACH binds to the nicotinic receptor on the adrenal medulla (instead of the post ganglionic neuron), then epinepherine is released into the blood to bind on to adrenergic receptors
Sympathetic innervation
ACH binds to the nicotinic receptor on the post ganglionic neuron which releases norepinepherine to bind to adrenergic receptors
Parasympathetic innervation
ACH binds to the nicotinic receptor on the post ganglionic neuron which releases ACH to bind to muscuranic receptors
Sympathetic nervous system origin
T1-L2
Preganglia near spinal cord
Postganglia secrete norepinepherine
What converts dopamine to norepinephrine?
Beta Hydroxylase
What releases NE from the synaptic vessel?
Action potential
Signal termination of NE
Reuptake
Metabolism by MAO and COMT
Dilution by diffusion
Location of adrenergic receptors
A1- periphery
A2- Presynaptic in the PNS, postsynaptic in the CNS
B1- heart
B2- smooth muscle
A1 receptor works by __
Increase intracellular Ca++
Smooth muscle contraction
Peripheral vasoconstriction
Bronchoconstriction
- insulin
+glycogenolysis
+gluconeogenesis
Mydriasis
GI relaxation
A2 works in the presynaptic PNS by ____
Decreases Ca++ into cell
Limits release of NE
A2 in the postsynaptic CNS
Sedation
Decreases BP
Decreases sympathetic outflow
Platelet aggregation
B-1 works to __
Increases chronotropy
Increases dromotropy
Increases inotropy
B2 works by __
Smooth muscle relaxation
Peripheral vasodilation
Decreases BP
+ insulin
+ glycogenolysis
+ gluconeogenesis
Decreases GI mobility
Parasympathetic nervous system origins
Craniosacral origin (3,7,9,10)
ACH
Activates BOTH arms of ANS
Ca++ mediated action potential
Formed by choline and acetyltransferase
Deactivated by acetylcholinesterase
SNS effect on GI system and bladder
Decreases motility
Constricts sphincter
Relaxes smooth muscle in bladder, but contracts sphincter
ANS effect on GI and bladder
Increases motility, relaxes sphincter
Contracts bladder smooth muscle, relaxes sphincter
Down regulation
Long process of destruction of receptors
Extended exposure to agonists will reduce the number of receptors
Tachyphylaxis
Up regulation
Chronic depletion of catecholamines or beta blockers will increase the amount of receptors but not their sensitivity
Tachyphylaxis
Decreased effectiveness due to chronic exposure
Happens with down regulation
Receptor uncoupling
Rapid inability of the receptor to bind to the G protein
Sequestration
Slowly move receptors inside the cell
Pheocromocytoma
Uncontrolled release of catecholamines due to adrenal gland dysfunction
Uses of sympathomimetics
Positive inotropy
Elevate blood pressure
Treat bronchospasms
Manage anaphylaxis
Arrhythmia management
Addition to LA to slow systemic absorbtion
Types of sympathomimetics
Naturally occurring catecholamines (direct)
Synthetic catecholamines
Synthetic non catecholamines (direct and indirect)
What are sympathomimetics derived from?
B Phenylethlamine
Catecholamines vs synthetic non catecholamines
Sympathomimetics (synthetic non catecholamines) do not have the hydroxyl group in the 3 and 4 position of benzene ring
Indirect acting
Synthetic non catecholamines
Direct acting
synthetic non catecholamines
catecholamines
How are catecholamines metabolized or rided?
COMT-
MAO- present in liver, kidneys, gi tract
Reuptake
How are synthetic non catecholamines metabolized?
MAO only
NO COMT
How are phenylepherine and catecholamines metabolized?
Sulfoconjugation reactions- SULT1A3 and SULT1A4
Via sulfate?
Vasoconstrictor non cardiac effects
Bronchodilation
Glycogenolysis
Increased insulin
Increased renin
Increased CNS stimulation
Increased pituitary hormone
Vasoconstrictor contraindications
LV failure can be worsened
RV failure can be exacerbated
Poor renal blood flow can be decreased more
Hypovolemia can be masked
What are the natural catecholamines
Epi
Dopamine
Norepi
What receptor does Epi work on?
A1, B1, B2
“all of them”
Most potent A1 activator
2-10x more potent than norepi
Epi works by __ and for ___
Asthma, anaphylaxis, cardiac arrest, bleeding, LA to stop absorbtion
Increases lipolysis
Increases glycogenolysis
Decreases insulin
Stimulated renin and decreases renal blood flow
Epi at low doses
1-2mcg/min
B-2
Decreases SVR but holds BP
NE
Catecholamine
Increases systolic, diastolic, and MAP
Maintains BP by adjusting SVR
Epi at moderate doses
4mcg/min
B1 effects
Epi at high doses
10mcg/min
A1 masks all other receptors
Reflex bradycardia can occur
No significant effect on cerebral arteries
Racemic epi
Levo and dextrorotatory isomers
Used for croup and airway edema
Treatment lasts for 30-60 minutes
2 hours later can experience rebound edema
Epi side effects
Little CNS effect
Hyperglycemia
mydriasis
Platelet aggregation
Sweating
Headache nausea
Skin tissue damage
NE side effects
Renal injury
Mesenteric infart
Gangrene of digits
NE receptors it affects
A1
B1 small and overshadowed by A1
NE effect on CO
Increase but may decrease at higher doses due to reflex bradycardia
Refractory hypotension
Dopamine receptor sites
Endogenous catecholamine
D at low doses
Beta at moderate doses 5mcg/kg/min
Alpha at high doses 10-20mcg/kg/min
Endogenous dopamine in the CNS
Low- schizophrenia
High- manic
Ephederine
Synthetic non catecholamine
Indirect and direct but mostly indirect
A1 and B receptors to increase inotropy
Venoconstriction is greater than arterioconstriction
Increases Sys and diastolic BP
Can lead to tachyphylaxis
Increase uterine blood flow
Smooth muscle relaxant
Ephederine dose
2.5-25mg IV or
25-50mg PO
How does ephederine compare to epinepherine
Ephderine is less intense but lasts longer
Ephedrine SE
Insomnia/ headache/ psychosis
Palpatations/ HTN/ tremor
Cocaine and amphetamines will exaggerate HTN due to the reuptake blockade
Phenyl
Synthetic non catecholamine
A1 agonist
Inreases preload more than afterload
Can improve coronary perfusion pressure without increasing chronotropy
Ok for pregnancies
Other used for phenyl
Priapism
Mydriatic
Decongestant
Phenyl SE
Reflex Bradycardia
Decreases renal and schplanic blood flow
Increases PA resistance and PAP
Phenyl dose and onset
50-200mcg
Onset 1-2 minutes
Duration- 5-10 minutes
Phenyl vs NE
Phenyl less effective but longer lasting
Onset of Epi, NE, Ephed, and Phenyl
Immediate
Immediate
1-3 minutes
1-3 minutes
Duration of Epi, NE, Ephed, and Phenyl
5-15
5-15
15-20
15-20
Synthetic catecholamines
Isoproterenol
Dobutamine
Synthetic non catecholamines
Ephedrine
Phenylepherine
Vasoconstrictor SE
Dysrhythmias
Reflex bradycardia
Antihypertensives may decrease pressor response to indirect acting drugs
OR they may increase to direct acting drugs
Vasoconstrictors and TCA / MAOI
TCA and MAOI can stop the breakdown and lead to a higher pressor effect
Exaggerated response with indirect acting
Worse in first 1-2 weeks of therapy (then a down regulation occurs)
Ok to continue perioperatively
Use decreased dose of direct activing drugs
Vasopressors and cocaine
Cocaine stops the reuptake
Enhances pressor effect
Weight loss products
May contain ephedra
Stop atleast 24h prior to surgery
Can lead to tachyphylaxis and perioperative cardiovascular collapse
Phentolamine
A1 and A2 antagonist
Treatment for necrosis from epi, NE, and dopamine
5-10mg injected at site
Peripheral vasodilator
DDAVP vs vaso
DDAVP no pressor affect 1200:0
Vaso 100:100 ADH:pressor effect
Posterior pituitary hormones
Vasopressin 100:100
Oxytocin (Pictocin) 1:1
adh/pressor effect
When to use vaso
Advanced vasodilitory shock
For pt who are resistance
Effects of vaso are preserved in hypoxia and severe acidosis
Vaso receptors
V1intense arterial constriction
V2 renal collecting ducts increase reabsorption of water
Vasopressin advantages of epi
Vaso does not increase myocardial O2 consumption
Vaso has no effect on heart
Epi may not work well in acidic and hypoxic patients
How does oxytocin work
Increases Ca++ in myometrium to increase uterine contraction strength
Oxytocin receptors increase in pregnancy
Used for uterine contractions and to reduce post partum hemorrhaging
