Lecture 20 Flashcards
What are SNS effects on eyes, heart, bronchi, GI tract, adrenal medulla, sweat glands?
Eyes: mydriasis and increase ocular fluid formation
Heart: Increase heart rate and force of contraction. Increase blood flow to coronary arteries. Overall increase in blood pressure.
Bronchi: Dilation of bronchi
GI tract: relaxation of GI tract, bladder. Constriction of urinary sphincter
Adrenal medulla: release of epinephrine
Sweat glands: increase sweating (although this is not an adrenergic receptor. It’s mAChR).
Which are the three main norepinephrine (NE) receptors?
Alpha 1, Alpha 2, and Beta 1.
What is the main ligand at the B2 receptor?
Epinephrine
What are the norepinephrine effects on the a1, a2, and b1 receptors? Where are these receptors located?
Alpha 2: decrease cAMP, GI relaxation, CNS effects (sedation, pain analgesia)
Alpha 1: GLASS-S (GI relaxation. Liver gluconeogenesis and glygenoysis. Arterial constriction to skin and viscera. Smooth muscle constriction of vas deferens, pupils, uterus, sphincters. Skin piloerector muscle contraction. Salivation.)
Beta 1: Heart- increased rate and force of contraction. Kidneys- renin release to increase BP. Fat- lipolysis.
Alpha 2 is located on the presynaptic cell and Alpha 1 and Beta 1 are located on post-synaptic cells.
In what respect is the a2 receptor different from the others?
It is on the presynaptic cell and it provides negative feedback to the release of norepinephrine. Activating it suppresses sympathetic tone.
How is norepinephrine action in the cleft terminated?
It is taken up by either the pre or post synaptic cell and metabolized by MAO or COMT.
What are catecholamines? Name 3 examples. What is their deitary precursor?
Catecholamines are molecules used as neurotransmitters by the sympathetic nervous system that all have catecholamines as their backbones.
Examples: dopamine, norepinephrine, and epinephrine.
Their common dietary precursor is Tyrosine.
How is norepinephrine broken down in the presynaptic versus the postsynaptic cell (2 enzymes)?
Presynaptic metabolism uses MAO and post synaptic metabolism uses COMT.
Which receptors will epinephrine mostly activate as an agonist and which less so?
Epinephrine is non-selective adrenergic agonist but it has a higher affinty for beta receptors than alpha receptors.
Why does epinephrine have a short half-life?
Because it is metabolized so quickly. The body breaks it down quickly because it has drastic effects on the cardiovascular system.
What are cardiovascular effects of epinephrine (by receptor)?
- B1 actionontheheartincreasesheartrateandforceofcontraction
- B2 actiononbloodvesselscausesvasodilationanddecreasesperipheralresistance
- A1 actiononbloodvesselscausesvasoconstrictionandincreasesperipheralresistance(bloodpressure). This A1 actioniswhatmakesepinephrinesuchapotentvasoconstrictionlocally.
What are dose-dependent affects of epinephrine on BP (low versus high concentrations)?
At low dose, epinephrine will activate beta receptors causing vasodilation to the skeletal muscle, coronary arteries, and renal arteries. This causes a decrease in BP.
At higher doses, alpha receptors are activated which cause perihperal constriction of blood vessels, leading to an increase in blood pressure.
What are 5 epinephrine effects on different smooth muscle tissues?
Relaxation of: bronchi, uterus, urinary bladder, GI tract.
Constriction of sphincters, pupils.
What are the effects of epinephrine on metabolism (think “flight and fight”)?
They increase lipolysis, glycogenolysis and gluconeogenesis. Also inhibits secretion of insulin and increases secretion of glucagon.
4 clinical applications for epinephrine
Increase heart rate and force of contraction in cardiac arrest.
Reduce bronchospasm
Treat allergic reactions (hypersensitivity reaction, anaphylactic shock)
Local vasoconstriction (w/local anesthetic, control hemorrhage, glaucoma)
What are possible adverse effects of epinephrine?
Potential for arrhythmia;
Excess vasoconstriction will cause hypertension;
Problems in circulation w/local anesthetics due to excessive vasoconstriction (tissue necrosis)
How does NE act on alpha and beta receptors to change BP and heart rate?
A1- constriction of perihperal blood vessels —>Increased blood pressure
B1 - accelerated heart but baroreceptor reflex slows heart (vagal activation) —> slows heart rate
Explain how the baroreceptor reflex regulates BP. Start out with BP being too high.
Increased BP—> activated stretch receptors (carotid sinus/aortic arch)—> increased afferent discharge to CNS —> decreased SNS, increased PNS output —> activation of M2 receptor —> decreased heart rate/peripheral resistance —> decreased BP
What are therapeutic uses of NE?
None
Dopamine acts on __ receptors, in high doses also on __ receptors and very high doses on __ receptors as well.
DA
B1
A1
What are dopamine effects on heart rate and (coronary heart) blood vessels?
Increases heart rate (positive ionotropic and chronotropic effects on heart via b-action)
Better perfusion of systems during shock (dilation of coronary arteries)
What are very high doses dopamine effects on BP and which receptors cause that?
Increase in blood pressure (a1 receptors activation (still activating DA receptors as well) —> increased perfusion of kidney, mesentey and heart —> useful in shock)
What are therapeutic uses of dopamine and what are its potential adverse effects?
Therapeutic uses: acute heart failure (cardiogenic and septic shock) ; stimulate heart (b1 effect) while dilating renal and coronary arteries
Adverse effects: possible tachycardia and ventricular arrhythmias ; BP effects potentially dangerous ; leakage of dopamine from vein can cause tissue necrosis
What is dobutatmine and how does it act on the heart and BP?
Dobutatmine is a synthetic compound that has mostly beta 1 effects.
Cardiovascular effects: stimulation of heart (increase HR) and SMALL changes in peripheral resistance (BP)
*Greater effect to increase contractility vs. heart rate compared to dopamine or epinephrine
