Adrenergic Agonists - Trachte Flashcards
What are the steps in norepinephrine synthesis?
-
Tyrosine →
- cytosol
-
DOPA →
- cytosol
-
Dopamine →
- leaves cytosol
-
Norepinephrine →
- vesicular
-
Epinephrine
- in adrenal medulla
What enzyme is the rate limiting step in the synthesis of adrenergic amines?
-
Tyrosine hydroxylase
- cystolic
- converts Tyrosine → DOPA
- blocked by Metyrosine
Where are adrenergic amines stored?
in granules with ATP-protein complex
What are the steps in the normal release of Adrenergic amines?
- Stimulation of nicotinic receptors on post-synaptic surface of the post-ganglionic nerve
- Depolarization (Na influx) and Ca influx
- Release of dopamine beta-hydroxylase, norepinephrine and ATP
- Norepinephrine inhibits its own release (alpha-2 receptors)
What neurotransmitter does the sympathetic preganglionic nerve release?
ACh
What kind of receptor on the sympathetic postganglionic cell body receives the neurotransmitter from the preganglionic?
Nicotinic Receptor
(via Na+ channel)
Once activated, what does a sympathetic postganglionic neuron release at its nerve terminal?
Norepinephrine
What receptor does NE interact with on the heart? Lungs?
- Heart = Beta-1
- only have one heart
- Lungs = Beta-2, Alpha-1
- have 2 lungs, thus Beta-2
If ACh is released on the adrenal gland, what receptor does it act on?
Nicotinic
What does the adrenal gland release in response to activation after receiving ACh?
NE & Epi
What happens in response to NE acting on Beta-1 receptors?
Increase HR, increase SV
What happens in response to NE acting on alpha-1 receptors?
Vasoconstriction, increased resistance
How is NE eliminated?
Axoplasmic pump transports NE back into synaptic terminal
What drugs act on the axoplasmic pump that brings NE back into the synaptic terminal?
- Cocaine
- stops reuptake of NE
- potentiate sympathetic responses
- Amphetamine
- reverse pump → spit out more NE
- increases BP
- Tricyclic antidepressents
- inhibits axoplasmic pump
What is the MOA of Reserpine (one of the first bp meds)?
- Inhibits the granular pump accumulating catecholamines in vesicles
- results in depletion of catecholamines (NE)
- also deplete serotonin, dopamine, and NE in brain = nasty side effects
- not used anymore
What two enzymes degrade adrenergic amines?
- COMT (catechole-O-methyl transferase)
- cytoplasm
- MAO (monoamine oxidase)
- mitochondria
What MAO inhibitor can potentiate the action of catecholamines and consequently lead to hypertensive crisis?
Pargyline
What compound found in cheese, wine, and beer releases catecholamines and is normally degraded by MAO?
Tyramine
(why patients on MAO inhibitors need to avoid these foods → can become hypertensive crisis → give alpha-1 blocker to treat)
What happens with activation of Beta-1 receptors?
- G-protein coupled receptor
- 7 transmembrane protein
- Adrenergic cardiac effects
- increase HR
- increase SV
- increase BP
What activates Beta-1 receptors?
isoproterenol > epinephrine = norepinephrine
What activates Beta-2 receptors?
isoproterenol > epinephrine >> norepinephrine
What happens with activation of Beta-2 receptors?
- found in lungs
- taken by asthmatics
- relaxation of smooth muscle & metabolic (glyogenolytic) effects
- primary site in CV system is blood vessels
- G-protein coupled receptor, increase cAMP
What happens with activation of alpha-1 receptors?
- mediates smooth muscle contraction
- primary CV system location is on blood vessels
- activates phospholipase C
- to increase intracellular calcium via inositol trisphosphate
What activates alpha-1 receptors?
epinephrine > norepinephrine >> isoproterenol
What activates Alpha-2 receptors?
epinephrine > norepinephrine >> isoproterenol
What happens with activation of Alpha-2 receptors?
- inhibition of neural norepinephrine release
- prejunctional nerve terminal, platelets, gut, medulla oblongata
- inhibit sympathetic activity
- acts to decrease cAMP or activate Na/H antiporter
What is the only Alpha-1 agonist that is used clinically?
Phenlyephrine
- used to reverse hypotension and paroxysmal atrial tachycardia
- vasoconstriction –> increases resistance
- doesn’t work if gave alpha-1 antagonist prior because all receptors are blocked
(also dilates pupils)
What does Albuterol do to blood pressure?
- lower pressure
- Beta-2 agonist
- action would be blocked if propanolol given prior (beta-2 antagonist)
What does Isoproterenol do to blood pressure?
- increase HR, SV → increase BP
- tachycardia (Beta-1)
- cardiac stimulant
- lower resistance → decrease BP
- vasodilate (Beta-2)
-
OVERALL = decrease BP!!!
- radius4
- will have no effect if enough Beta-blocker is given
- all beta receptors blocked
What does epinephrine do to blood pressure?
- Can do anything!
- Normal response = raise bp
- Increase HR, SV, resistance
- If alpha-blocker given (Terazosin), take away vascular effect
- no vasoconstrictor
- acts on Beta-2 → vasodilate
- decrease bp
What is the MOA of Imipramine?
potentiate sympathetics by blocking norepinephrine accumulation (block axoplasmic transporter)
(MOA similar to cocaine)
What is the MOA of Tyramine, Amphetamine, and Ephedrine?
reverse axoplasmic transporter → increase NE
(mimic sympathetic stimulation)
What is the MOA of Guanethidine and Guanadrel?
- induce release of NE from vesicle, probably via displacement
- depletes NE stores
- reduces responses to sympathetic stimulation
What receptors does Epinephrine activate?
- Alpha-1
- Alpha-2
- Beta-1
- Beta-2
What receptors does Norepinephrine activate?
- Alpha-1
- Alpha-2
- Beta-1
What receptors does Isoproterenol activate?
Beta-1 & Beta-2
What receptor(s) does Phenlyephrine activate?
Alpha-1
What receptor(s) does Clonidine activate?
alpha-2
What receptor(s) does alpha methyl Dopa activate?
alpha-2
What receptor(s) does Guanabenz activate?
alpha-2
What receptor(s) does Dobutamine activate?
Beta-1
What receptor(s) does Albuterol activate?
Beta-2
What receptor(s) does Metaproterenol activate?
Beta-2
What receptor(s) does Ritodrine activate?
Beta-2
What receptor(s) does Terbutaline activate?
beta-2
What receptor(s) does Salmeterol activate?
beta-2
What does Acetylcholine do to blood pressure and what blocks its effects?
- Reduce HR
- Vasodilation
- Decreased BP
- Blocked by anticholinergic meds (atropine)
