Adrenergic Agonists Flashcards
Sympathetic NS
More systemic in effects (functionally & anatomically) compared to PNS.
Thoracolumbar outflow T1-L2
Most pre-synaptic ganglion synapse with post-ganglion neurons in the paravetebral ganglia.
Cardiac Accelerator fibers T1-T4
Norepi & Epi are the primary endogenous NTs
Major adrenergic receptors alpha 1 & 2, beta 1 & 2
Pre-ganglionic SNS fibers- short, myelinated, release ACh
Sympathetic response- mydriasis, increased HR, decreased secretions, bronchodilation, decreased motility & tone of stomach intestines bladder, increased blood glucose.
Post-ganglionic fibers- long, non-myelinated, release norepi
Pathway of SNS fibers
Preganglionic SNS fibers exit through ventral root and ALL pass through the white ramus (myelinated) to the paravetebral ganglia.
- Some synapse there and then the post ganglionic fibers pass through the grey ramus & travel to effector organ
- Travel up/down the paravetebral ganglia before synapsing
- Pass through without synapsing and synapse with the postganglionc neurons in peripheral ganglia
Stellate Ganglion
Peripheral ganglia.
Block- injection into these nerves can relieve pain in the head neck upper arm and upper chest.
Can be unintentional from a brachial plexus block.
—> Horners syndrome
S/S: ipsilateral miosis, ptosis, enopthalamos, flushing, increased skin temp, anhydrosis, nasal congestion (Very Homely PAM)
Vasodilation, Horner, Ptosis, Anyhrosis, Miosis
Synthesis, Release, Termination Norepinephrine
Tyrosine —> dopa —> dopamine —> norepinephrine. Stored in presynaptic vesicles.
In adrenal medulla norepi is converted to epinephrine. Catecholamine pool=epi 20% and norepi 80%
AP travels axon of post ganglionic neuron. Depolarization = release of Ca2+, diffuses through channels into nerve terminal. Unites with Calmodulin = reactions to exocytosis. Spills into synaptic cleft.
Combines with adrenergic receptors. —> 1) ion channels open 2) activation of adenylate cyclase and intracellular production of cAMP.
Diffusion away from receptors. Either transported back to presynaptic nerve terminal (80%) or metabolized by MAO (in the synaptic cleft) or COMT (in the bloodstream)
Indirect acting sympathomimetics
Ephedrine and meperidine.
Work by displacing norepi from sympathetic nerve terminals as opposed to directly stimulating adrenergic receptors.
Avoid in patients on MAO inhibitors. The excess norepi can lead to severe hypertensive crisis.
alpha 1 adrenergic receptors
Gq linked. post-synaptic, located on smooth muscle - lungs, eyes, blood vessels, uterus, gut, GU. Increases intracellular Ca2+ = smooth muscle contraction. Myocardium A1 receptors = +inotropic effect. Most important CV effect is vasoconstriction = PVR, LV afterload & ABP
Alpha 2 Receptors
Gi linked. presynaptic and tissues on postsynaptic membranes in the brainstem & periphery.
primarily presynaptic, most responsible for the negative feedback loop - alpha 2 on post ganglion presynaptic nerve terminal inhibits adenylate cyclase which decreases Ca2+ ions and inhibits exocytosis of vesicles of norepinephrine.
postsynaptic A2 receptors in brainstem = sedation & decreased sympathetic outflow = peripheral vasodilation & decreased BP
Stimulation of alpha-2 in the substantia gelatinosa of spinal cord = analgesia
Beta 1 Adrenergic Receptors
Gs linked. Norepi potency = epi potency.
located on postsynaptic membranes of the heart and kidneys. Activates adenyl cyclase = ATP to cAMP. Results in + chronotropic, dromotropic, & inotropic effects. Also increases renin release.
B2 Adrenergic Receptors
Epi potency > norepinephrine.
GS linked.
located on post-synaptic smooth muscle, gland cells, ventricular myocytes. Adenyl cyclase activation here results in relaxation of smooth muscle = bronchodilation, vasodilation, & uterus/gut/bladder relaxation. Stimulates glycogenesis, , lipolysis, glucogenesis, & insulin release.
Dopaminergic Receptors
- D1 : vasodilation in kidneys, intestine, & heart
- D2: role in antiemetic action of droperidol
Epinephrine
Receptors: A1, A2, B1, B2. triggers G protein response to increase cAMP to increase Ca2+. but depends on the receptor stimulated.
Route: IV, IM, inhalation
Dose:
- cardiac arrest/shock: 1mg
- anaphylaxis: 100-500mcg
- infusion: 2-20mcg/min
- Mixed with local to decrease systemic absorption (1:200000, 5cg/ml)
Distribution:
- O: 1 min
- DOA: 5 min
- M: MAO& COMT
- E: Renal
Effect: Increased BP &CO Bronchial relaxation Mast cell stabilizer Dose dep: -Low – beta -Med – equal -High – alpha
Norepinephrine
- Agonizes alpha 1, 2 & weak beta 1.
- Triggers Gq protein response = Phospholipase C = IP3 & DAG = Ca++ = smooth muscle construction
Increases both S & D BP
Can decrease HR (baroreceptor reflex)
Decreases perfusion to splenic organs
Intense vasoconstriction of A & V vessels.
First line for shock* 1-20mcg/min
O: 1 min
DOA: 2 min
M: MAO & COMT
E: renal
-avoid in peripheral due to extravasation
Isoproterenol
Nonselective beta agonist.
B1: Increases HR, contractility & CO
B2: bronchodilation, decreased PVR & diastolic BP
Infusion: 0.015-0.15mcg/kg/min
0: 1 min
DOA: 1 min
M: COMT
E: renal 50% unchanged
Poor inotropic bc there is increased myocardial O2 demand with decreased supply (B1:B2)
Dopamine
direct & indirect acting sympathomimetic. acts on A, B, & D receptors in dose dep manner.
D: 2mcg/kg/min
B: 2-5 mcg/kg/min
A: >10mcg/kg/min
Renal: Increasd UOP via dilation of renal vasculature
Increased BP
Increased CO
O: 2 min DOA: 10 min M: COMT 75% inactive 25% norepi E: Renal
-Also inhibits aldosterone increases Na+ & urine excretion
Caution with MAOI &TCA –-> arrythmias
Extravasation
Dobutamine
Selective for beta 1. GS protein increases cAMP = Ca2+.
Minor activation of B2 and A1.
Increases contractility & CO
2-20 mcg/kg/min
Use: mild CHF, cariogenic/septic shock, cardiac stress test
O: 1 min
DOA: 10 min
M: MAO COMT
Ex: Renal
- decreases SVR and causes plt inhibition
