Sympathomimetics part 2 Flashcards
NOREPI is __ to epi at β1, very little β2 actions.
Potent α1 producing intense vasoconstriction in arterial and venous vascular beds
Because is has ver little B2 = no bronchodilating effects!
equal
Norepi Increases BP by increasing __ , May trigger the baroreceptor reflex, increased __ can elicit a reflex bradycardia.
SVR
SVR
NE released during stress in brain stem’s __ ___, which is the origin of most NE pathways in the brain.
Noradrenergic neurons project from __ __ to the cerebral cortex, limbic system, and spinal cord.
Locus ceruleus
Locus ceruleus
NE is a catecholamine & phenethylamine derivative.
Stereoisomer - we use the dextro or levo form?
LEVOphed
NE is synthesized in adrenal medulla from the amino acid __, then oxidated to __, then de-carboxylated to __
tyrosine
L-DOPA
Dopamine
NE action is followed by signal termination - either by degradation of NE or by NE uptake by surrounding cells.
degradation OR uptake
What are the two major urinary metabolites of catecholamine metabolism?
VMA and MOPEG
Zach rode his mopeg to the vma’s to get an award for the best skiing wreck of the winter break.
Again, does NE activate B2?
No, no bronchodilating properties
Again, how do NE increase BP?
Alpha 1 and 2 agonist causing increased SVR
Dopamine is a Phenethylamine derivative that is released by hypothalamus, stimulates the __.
Stimulates the CTZ
Of all the dopamine receptors, only d1 and d_ have clinical significance
d1 and d2
D1receptor works post synaptically to __
vasodilation of renal, mesenteric, coronary, and cerebral blood vessels
D2 receptor works pre synaptically to __
inhibits the release of NE, (post-synaptic) weak vasoconstriction
Dopamine acts @
β1 receptors with 3-10mcg/kg/min doses,
α1 @ >10mcg/kg/min doses
A portion of dopamine’s + inotrope effect is from release of endogenous NE (indirect actions!)
“Renal Dose Dopamine” 1-3 mcg/kg/min implies dopamine only works at kidneys at this level
NOT TRUE
Dopamine inactivated by reuptake via dopamine transporter DAT
Enzymatic breakdown by catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO) contributes to ending dopamine effects.
Dopamine may also simply diffuse away from the synapse, and help to regulate blood pressure
Dopamine doses
2 to 5 μg/kg/min:
binds D1 receptors, dilating blood vessels, increasing blood flow to renal, mesenteric, and coronary arteries
5 to 10 μg/kg/min:
Positive inotropic and chronotropic effects via increased β1 receptor activation. Used in patients with shock or heart failure to increase CO & BP.
10 to 20 μg/kg/min:
Dopamine causes vasoconstriction, increases SVR, and increases BP through α1 receptor activation.
ISOPROTERENOL is the Most potent activator of β adrenergic receptors due to substitution of isopropyl group at terminal amine of the beta-phenylethylamine
Has no α effects – no increases in SBP directly, increased SBP indirectly from greater CO
ISOPROTERENOL is used for greater HR, increased myocardial contractility, cardiac automaticity, bronchodilation, reductions in PVR
Use with post heart transplant patients due to de-innervation of the orthotopic heart transplant
Primary use is for bradycardia & heart block.
Isoproterenol causes + chrontropic, dromotropic, & inotropic effects (β1).
Isoproterenol activates all β receptors – not always desirable
Isoproterenol Uses/ Contraindications
Resistant bradyarrhythmias when pacing is not available
Pharmacologic pacing for torsade de pointes (polymorphic ventricular tachycardia)
Contraindications - angina, pre-existing arrhythmias, tachycardia or AV block caused by cardiac glycoside intoxication. Ventricular arrhythmias due to AV nodal block.
Usual effective dose 0.2-2 mcg/kg/minute
Dobutamine- direct stimulation B1 receptors.
Dobutamine not as useful in ischemic heart disease because it may increase HR, potentially increasing myocardial oxygen demand
DOBUTAMINE Selective β1 adrenergic agonist used to improve cardiac output
+ dromotrope… be careful with atrial fibrillation as HR may markedly increase.
Dobutamine is given as a racemic mixture of both + & - isomers.
The + isomer is a potent β1 agonist
The – isomer is an α1 agonist.
Dobutamine Dosing
rates typically 2-10 mcg/kg/min
PHENYLEPHRINE Synthetic non-catecholamine
Principally α1 direct effect with only a small part via indirect release of NE
Minimal if any β effect
Venoconstriction > arterial constriction
differing only by lacking a 4-hydroxyl group on the benzene ring from epi
Phenylephrine may impair LV global function when given rapidly to anesthetized patients (1mcg/kg)
Can be used to treat PSVT (500mcg bolus)
Dexmedetomidine - Like clonidine, agonist of α2 - adrenergic receptors in the brain.
imidazole compound
Dexmedetomidine has no absolute contraindications but —
Caution with boluses due to peripheral α2 -receptor stimulation with resulting hypertension and bradycardia
EPHEDRINE - Indirect acting synthetic noncatecholamine
Stimulates α and β adrenergic receptors
Endogenous release of NE (indirect) and direct stimulation of adrenergic receptors
takes 250X an ephedrine dose to equal an epi dose
good to know
Vasopressin stored in the posterior pituitary for release into the bloodstream or directly into the brain
Not an adrenergic agent
Works on Three arginine vasopressin receptor types
CRNA’s should like AVPR1A best!
