What are the endogenous catecholamines?
Epinephrine
Norepinephrine
Dopamine
What are the synthetic catecholamines?
Isoproterenol
Dobutamine
What are the two types of synthetic non-catecholamines?
What are some of these drugs?
-
Indirect acting- increases the endogenous NE release from post-ganglionic SNS nerves which then activate the GCPR
- Ephedrine, mephentermine, amphetamines
-
Direct Acting- interact directly with the G-protein coupled receptor.
- Phenylephrine, Methoxamine
What are the selective Alpha-2 agonists?
Clonidine
dexmedetomidine
What are the selective Beta-2 adrenergic agonists?
Albuterol
terbutaline
ritodrine
When will you use sympathomimetic drugs as a CRNA?
- to improve arterial blood pressure and contractility after administering an anesthetic with myocardial depressant/vasodilating properties
- to improve bronchodilation in susceptible pts with bronchoconstriction caused by airway instrumentation
- anaphylaxis treatment
- ACLS protocols
- as an additive to LAs
- sedation and analgesia (alpha 2)
What is a sympathomimetic?
What is the chemical makeup?
- “mimics” the Sympathetic nervous system
-
Beta-phenylethylamine derivatives
- an amine group side chain (NH2)
- Hydroxyl group on the 3.4 carbons of a benzene ring (catechol)
- catecol-amine……duh
Sympathomimetic Mechanism of Action
- Activates a G-protein, either directly or indirectly
- G protein will either be Gq, Gi, or Gs coupled
- usually this cascade with result in either increased or decreased intracellular Ca2+
- Specific effect will depend on:
- the type of receptor stimulated
- receptor density in given tissue
- what the second messenger activates at a molecular level
- Receptors will up or down regulate based upon plasma concentrations of sympathomimetic
How are Catecholamines terminated/metabolized?
- Reuptake
- Uptake 1- neuronal reuptake into presynaptic terminal
- Uptake 2- extraneuronal uptake- into other cells in the area
- MAO- Enzyme that catalyzes oxidation of monoamines. Found in lots of places.
- COMT- Enzyme that degrades things with catechol structure. primarily in Liver.
- Lungs ??
How are Non-catecholamines terminated/metabolized?
- MAO
- urinary excretion (unchanged)
What drug should you NOT give to a person on an MAOI?
Why?
Ephedrine
Ephedrine is indirectly acting, so it causes the release of all the stored NE. If somebody has been taking a medication the prevents the metabolism/breakdown of the NE, they will have a large amount stored and an abundant amount of NE would be released.
Receptor selectivity for:
phenylephrine
a1 > a2 >>>>> B
Receptor selectivity for:
Clonidine
a2 > a1 >>>>>B
Receptor selectivity for:
Norepinephrine
a1 = a2; B1 >>>>> B2
Receptor selectivity for
Epinephrine
a1 = a2; B1 = B2
Receptor selectivity for:
Dobutamine
B1 >B2>>>>a
**can get alpha effects at higher end of dosing range
Receptor selectivity for:
Fenoldopam
D1 >> D2
In the peri-op period, do IDDM patients require more or less insulin? Why?
More, because they have increased glycogenolysis from B2 receptors
Alpha 1 receptors effect _____
- Heart (increase contractility and HR)
- Vasoconstriction
- Iris- dilation
- pylomotor contraction
- prostate/uterus contraction
- pancrease (decreased insulin production)
Alpha 2 receptors effect ______
- Inhibits adrenergic release *
- GI relaxation *
- CNS decrease*
- Vascular smooth muscle dilation*
- vascular smooth muscle contraction
- Platelet aggregation
* presynaptic
Beta 1 receptors effect _______
- Heart (increase HR and contraction)
- Kidney (release renin)
Beta 2 receptors effect_______
- Smooth muscle relaxation
- skeletal muscle increased contraction
- Mast cells decrease histamine release
- Liver increase glycogenolysis
- pancrease increase insulin secretion
- increase adrenergic NE release
D1 receptor affects ______
Post synaptic; smooth muscle
dilates renal, mesenteric, coronary, cerebral blood vessels
D2 receptor affects
Pre synaptic; nerve endings
modulates neurotransmitter release, N/V