Adrenergic Agonists Flashcards
Synthesis of NE
- starts with tyrosine
- tyrosine transformed into DOPA in neuron, rate limiting step
- formed into dopamine in the neuron
- goes into vesicles
- turns into NE inside the vesicle
What is the rate limiting step in NE synthesis
Tyrosine into DOPA in the neuron
Where is NE formed?
Inside the vesicle
-from dopamine
Release of NE
- similar to Ach
- depolarize
- Ca2+ channels open
- Ca2+ rushes in
- vesicles go to membrane
- NE released into synapse
What are the fates of NE once it is released into the synapse?
- Bind to alpha or beta
- Metabolized by COMT
- NE reuptake into neuron
- Negative feedback binding to presynaptic
What does NE bind to
Alpha or beta
What is NE metabolized by
COMT
-turned into inactive metabolites, just like Ach is with acetylcholinesterase
NE reuptake into neuron
- very rapid
- goes back into the presynaptic neuron without being degraded (differnt for Ach)
- reason for short half life
- clears synapse even better than COMT
What is the major reason for short half life of NE
Rapid reuptake into the presynaptic neuron
What clears the synapse better, NE reuptake or COMT?
Reuptake
What receptor does NE bind to presynaptic ally for negative feedback on the neuron
A2
- low CAMP
- closes Ca2+ channels
- vesicle wont migrate
- wont release NE
Alpha 2 agonist
- stops NE release
- lowers BP
Alpha 2 antagonist
Increases NE release
Increases BP
COMT inhibitor
Increase NE in synapse
Cocaine and NE
Blocks reuptake
Blocks major pathway to clear NE
Stimulant effect
Na/K ATPase is what gets blocked by cocaine
TCA (tricyclic antidepressants) and NE
Work like cocaine
-block reuptake of NE
MAO
- Monamine oxidase inhibitor
- Metabolizes amines in the cytoplasm (dopamine, NE, dopamine safe from it in the vesicle)
- when there is reuptake of NE, MAO waits for it in the cytoplasm and limits NE in the neuron by degrading excess of it
MAOI (MAO inhibitor)
Increase recycling, increase NE
What is the enzyme responsible for the rate limiting step of NE synthesis
Tyrosine hydroxylase
-tyrosine into DOPA
there is one more step to NE synthesis that is not made int sympathetic nerves
NE into epi. This is done in adrenal medulla. Sympathetic nerves do not have the enzyme necessary to do this
A1 receptor
Gq
A2 receptors
Gi
B receptors
Gs
Tissues and receptor types
Different tissues have differnt receptors
Catecholamines
Epinephrine
NE
Dopamine
Duration of action of epi, NE, and dopamine
They are rapidly metabolized by COMT and MAO, so they have a short duration of action
Epi, NE, and dopamine given as drugs and the CNS
Not much penetration into the CNS
What type if receptors are found in most vascular smith muscle and what are the actions of it
A1
Contracts, vasconstricts, increase TPR, increase BP
What kind of receptors are in pupillary radial muscle and what is the action
A1
Contracts (mydriasis)
What kind of receptor is in the prostate and what does it do
A1a!!!!
Contracts and decreases urine output
What kind of drug should be given for BPH (benign prostate hyperplasia)
A1 antagonsit
What kind of drugs should be avoided in someone with BPH (benign prostate hyperplasia)
A1 agonist
M blockers
What kind of receptors are on adrenergic and cholinergic nerve terminals and what do they do
A2
Inhibits transmitter release via negative feedback
Don’t worry too much about the cholinergic part
What kind of receptors are on pancreatic Bcells and what do they do
A2
Inhibits insulin release
Want to use nutrients in fight or flight, not store them
What kind of receptors are on the heart and what do they do
B1
Stimulates rate and force
What kind of adrenoreceptors are on the juxtaglomerular cells and what do they do?
B1
Stimulates renin release
Activates RAAS
What drug can inhibit sympathetic induced renin release
B1 blocker
What kind of adrenorecptors are on respiratory, uterine, and vascular smooth muscle and what do they do?
B2 Relaxes -bronchodilate -can stop premature labor -vasodilator BV and decrease TPR and BP
What kind of drugs are good to give for asthma
B2 agonists and M antagonists
What is a good drug to give someone going into premature labor?
B2 agonist
What does a B2 agonist do to blood vessels and blood pressure
Vasodilate, decreases TPR and BP
Which adrenoreceptor is not innervated?
B2
What adrenorecptor is on the liver and what does it do
B2
Stimulates glycogenolysis
-need glucose quick for fight or flight
What adrenorecptor is on voluntary muscle and what does it do
B2
Causes tremor
-they dont do much because they are not innervated. We dont expect a tremor, but when someone takes a B2 agonist for asthma way more than they need, they get a tremor because of decreased BP. Usually systemic. A premature labor patient would have a tremor too
What adrenorecptors are found on fat cells and what do they do
B3
Stimulates lipolysis
What adrenoreceptors are found on renal and other splanchnic blood vessels and what do they do
D1
Relaxes (reduces resistance)
Vasodilate in renal BV
CNS effects of catecholamines
They do not enter the CNS effectively
-amphetamines are an example of sympathmimetics which do enter the CNS and can cause reduced fatigue, euphoria, and insomnia
What kind of sympathomimetic can get into the CNS
Amphetamines
Effects of adrenorecptors on the eye
The radial muscle responds to a1 agonists with mydriasis
Effects of adrenoreceptors on the bronchi
The smooth muscle of the bronchi relax in response to B2 agonists
GI tract effect of adrenorecptors
A1 and b2 both mediate smooth muscle relaxation
Effect of adrenorecptors on genitourinry tract
A1 receptors in the bladder mediate contraction of the sphincter, B3 agonists relax detrusor muscle
A1 agonists in the vascular system
Constrict skin and splanchnic blood vessels and increase peripheral vascular resistance nad venous pressure; since these drugs increase BP they evoke a compensatory reflex bradycardia
Response on heart is opposite of blood pressure
Increased BP=decreased HR
A2 agonists on the vascular system
When given orally, they accumulate in the CNS and reduce sympathetic outflow and blood pressure
-would get reflected tachycardia
