Chapter 9: Adrenegic Agonist Flashcards
Test 2
What NS does Adrenergic Agonist mimic?
SNS
SNS is largely mediated by which natural ligand?
NE
What is the main neurotransmitter in adrenergic agonists?
catecholamines
What are catecholamines derived from?
tyrosine
What type of adrenergic agonists do we have?
direct
indirect
What is a amine group?
NH(2)
What is a Catechol group?
Benzine ring with a -OH at carbon 3 and 4 (2x -OH)
What is a catecholamine?
A catechol group and a amine group combined
main adrenergic receptor neurotransmitter
T/F: Substitution in the catecholamine reduces potency
T
Can you take catecolamines orally? Why?
No
Instantly metabolized inactivated in the gut
What enzyme inactivates catecholaimes in the gut?
“COMT”
Catechol-O-methyltransferase
Is phenylephrine a catecholamine?
No. It does not have a catechol group
Lacks -OH at carbon 4
How do you count carbons?
Start at 3oclock —- Counter clockwise
Ex) 3oclock is carbon 1
Describe Non-catecholamines that lack a hydroxyl group
Longer half lives
Increased lipid solubility
increased oral bioavailability
Not inactivated by COMT
What is an hydroxyl group?
-OH
With catecholamines, what happens when you have a substitution at the Alpha carbon?
Prolonged action
Blocked oxidation by monoamine oxidase (MAO)
What is the Alpha Carbon?
The second carbon from the benzine ring in catecholamines
What is the beta carbon?
the 1st carbon from the benzine ring in catecholamines
Adrenergic receptors are all _______ receptors
GPCRs
T/F: No drug is specific for receptor subtype (only A2, only B1)
T
Epinephrine has the strongest affect on which receptor?
Alpha
Isoproterenol has the strongest affect on which receptor?
Beta
Beta-1 think
heart
Beta-2 think
lungs
T/F: B-1 has an equal affinity for epi and NE
T
B-2 has a greater affinty for _______
epi
Describe Clonidine
A2 agonist
G(i)
decrease bp
how many subtypes does Dopamine-R have?
Where are they found
5
Brain
Renal Vascular beds
NET =
NETransporter
Transport NE into Presynapse
DAT =
Dopamine Transporter
Transport Dopamine into presynapse
ST =
Serotonin Transporter
Transport Serotonin into presynapse
What does cocaine do NET at the synapse?
Blocks NET on the presynapse
Blocks NE reuptake
Prolonged NE at the synapse
What does amphetamines do at the synapse?
reverses NE through the NET
Increases/prolonged NE at synapse
Where is Beta-3 receptors?
Fat cells
Where are Alpha 2 receptors?
CNS
Many Adrenergic agonists are what type of drugs? What do they do?
Pressors
Increase BP
T/F: there are both Alpha and Beta receptors in the peripheries
T
Stimulation of B receptors does:
Increase CO
Decrease peripheral resistance
What is CO?
Cardiac Output
CO= SV x HR
What is normal CO?
5250 ml/min
What type of drug is phenylephrine?
Alpha agonist
T/F: There are more Beta receptors on skeletal muscles than smooth muscle
T
This allows them to dilate during fight or flight response
How do catecholamines affect the eye?
Alpha - dilates
Beta - no effect
Beta blockers - decrease production of aqueous humor
What catecholamines is useful in glaucoma?
Beta bloclers eye drops
decrease production of aqueous humor at the ciliary epithelium
How do catecholamines affect the lung?
Beta-2: Dilates
Ex) Albuterol
How do catecholamines affect the GI?
Alpha and Beta both relax
Can catecholamines cross the BBB? Why?
Most cant
2 positively charged -OH on the catechol
Why do non-catecholamines have an effect on the CNS?
They cross the BBB better because they have 1 less -OH group on the benzine ring making it less charged
Ex) Cocaine, Amphetamine
Drugs: Norepinephrine
Catecholamine
A1/B1 agonist
Increase SBP/DBP
vagus reflex overcomes chronotropic effects
Drugs: Epinephrine
Catecholamine
A1/B1/B2 agonist
increase in BP, HR, Contractility , dilation of bronchioles
Drugs: Isoproterenol
Beta agonist
Little to no Alpha effects
Increased CO
Fall in MAP slight decrease/increase in SBP
What does does low dose dopamine do?
DA-1 - induces diuresis
What does high doses of dopamine do?
Activates Alpha receptors
mimic epinephrine
vasoconstrictor
increases HR
What does medium doses of dopamine do?
Activate Beta-1 receptors
increase CO
Drugs: Dobutamine
Catecholamine
B1 selective agonist
Tx: Cardiac shock, Acute heart failure
Drugs: Phenylephrine
Non-Catecholamine
Pure Alpha agonist
Tx: Congestion; low BP
What is Tetralogy of Fallot?
- Overriding aorta
- Pulmonic stenosis
- Ventricular Septal Defect
- Right Ventricular Hypertrophy
All 4 of these causes mixing of oxygenated and deoxygenated blood in the heart.
What is Tx for Tetralogy of Fallot?
Phenylephrine
Squatting can temporarily fix if turning blue.
Drugs: Midodrine
Sympathomimetic
Alpha-1 selective agonist
Tx: Orthostatic hypotension (postural)
causes HTN in supine pt
Drugs: Ephedrine
NOT AVAILABLE IN US
Sympathomimetic
Direct – mimics epi (crosses BBB)
Indirect – releases stored catecholamines
Tx: Derivative Pseudoephedrine: nasal decongestant
What compound can you make meth from?
Ephedrine and pseudoephedrine
what fraction of people who try cocaine will get addicted vs meth?
2/5 for cocaine
4/5 for meth
Drugs: Methamphetamine
Sympathomimetic
crosses BBB
prone to addiction
Higher effects in CNS
Drugs: Amphetamine
Sympathomimetic
Crosses BBB - higher effects in CNS
Mood elevator
supresses appetite
Drugs: Cocaine
Indirect sympathomimetic
Crosses BBB – enters CNS
Inhibits NE and Dopamine reuptake by blocking DAT and NET
Cocaine has similar effects to _________
Amphetamine
T/F: Cocaine can cause fatal arrythmias
T
What is Tyramine?
Byproduct of tyrosine
Indirect sympathomimetic
High concentration in fermented foods
Releases stored catecholamines
Metabolized by MAOI
What will happen if you taking MAOI and eat fermented foods?
fermented foods are high in tyramine which releases catecholamines when metabolized by MAOIs
This will cause your BP to increase significantly
What are some examples of fermented foods?
Cheese
Wine
Yeast
Sausage
Smoked/Pickled Fish
Tx: Hypotensive Emergency
NE
Phenylephrine
Tx: Cardiogenic shock
Dobutamine
vasodilators
Tx: Septic shock
Volume
NE
Describe the use of Epi in local anesthesia
Alpha 2 receptors in the periperhies cause vasoconstriction which can help achieve hemostasis during Sx. usually mixed with lidocaine for numbing
Tx: Heart block
Atropine, dopamine, isoproterenol
Tx: Cardiac arrest
Epi…
Honestly everything.
What is the most effective way to treat a heart block?
Pacemaker
Tx: Asthma
B-2 selective agonists
Metaproterenol
Terbutaline
Tx: Asthma attack
B-2 selective agonists
Albuterol - rescue inhaler
Tx: Anaphylaxis
A1/B1/B2 agonist
IM Epi
Describe the overall effect of A2 agonists
Overall it lowers BP
decreases BP in CNS but Increases BP in peripheries
Name 2 Alpha-2 agonist
Clonidine
Precedex (Dexmedetomidine)
How do Alpha-2 agonist work?
- the drug binds to the receptor which is on the rostral ventral lateral medulla (RVLM)
- This increases firing of the vagus nerve
- this also decreases firing of the sympathetic nerves
- This leads to: Decreases HR/SV/VR/Overall BP
Symptoms of Sympathomimetic toxicity include:
Pressors: HTN, cerebral hemorrhage, pulmonary edema, Angina, Cardiac tamponade, MI
CNS (Cocaine/Amphetamines): Arrhythmias, MI, Seizures, cerebral hemorrhage
