Chapter 3: Adrenergic Pharmacology Flashcards
What is the main way NE leaves synaptic cleft?
through NE reuptake
What is the main transporter by which NE reuptaken?
through NaCl - NE co-transporter driven by the sodium gradient and maintained by Na+/K+ ATPase
Where are a1 receptors found and what do they do?
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Where are the a2 receptors located and what is the response?
Where are the B1 receptors located and what is their response?
Where are the B2 receptors located and what is their response?
Where are the B3 receptors located and what is their response?
Where are the D1 (peripheral) located and what is their response?
Which cells mediate release of renin from kidneys via B1 activation?
JG cells
Fenoldopam use and MOA.
D1 agonist used for severe hypertension
DA can affect which adrenergic receptors. (List from most affected by lower doses to higher doses)
D1
B1
a1
What G-protein coupled receptor pathway does a1 follow?
Gq > increased phospholipase C > IP3, DAG > inc. Ca 2+
What G protein coupled receptor pathway does a2 follow?
Gi coupled
Gi> dec adenylyl cyclase > dec. cAMP
What G-protein receptor pathway does B1 follow?
Gs
inc adenylyl cyclase > inc. cAMP
What G protein coupled receptor pathway does B2 follow?
inc adenylyl cyclase > inc. cAMP
What G protein coupled receptor pathway does D1 follow?
inc adenylyl cyclase > inc. cAMP
Clinical use of phenylephrine.
nasal decongestant and ophthalmologic use (mydriasis without cyclopegia), hypotensive states
MOA of phenylephrine.
a1 agonist
What are the prototype a2 agonist?
E=MC2
methyldopa
clonidine
What are the β agonist drugs we discussed?
- Isoproterenol (β1=β2)
- Dobutamine ( β1> β2) congestive heart failure CHF
- Selective β2 agonists: salmeterol, albuterol, terbutaline (asthma and premature labor)
- Selective β3 agonist: mirabegron (overactive bladder)
What are the mixed receptor acting adrenergic agonist neurotransmitters?
NE and Epi
Trick to remember some selective Beta2 agonists?
terol for B2 agonists
What are the effects of epinephrine on BP and HR?
depends on dose
low dose mimics isopreteronol
high dose mimics NE
How would you distinguish between isoproterenol and Epi on a trace diagram?
if gave more of the dose then graph would change unlike in isoproterenol in which it would not change
How do you differentiate between high dose Epi and NE.
Administer alpha blocker
In NE if do this the BP returns do baseline
In Epi BP won’t return to baseline because of B2 activity
Some metabolic effects of B2 agonists?
increased glycogenolysis (muscle and liver)
inc. gluconeogenesis
mobilization of fat
What are some major uses of NE and Epi?
- cardiac arrest because of B1 benefit
- adjunct to local anesthetics because of epi a1 benefit
- hypotension because of a1 benefit
- anaphylaxis (epi only) strong B2 benefit
- Asthma (mostly epi used) B2 benefit
Name some indirect acting adrenergic receptor agonists considered releasers.
tyramine
amphetamines
pseudoephedrine
Clinical use of pseudoephedrine?
cold medication
Clinical use amphetamines like methylphenidate?
narcolepsy and ADHD
If given an MAO-A inhibitor what should a patient not eat?
red wine, cheese
MAO type A found mainly where? What does it metabolize?
liver but Anywhere
NE, 5HT and tyramine
Where is MAO type B found? What does it metabolize?
Brain
Metabolizes DA
Name some reuptake inhibitors that are indirect-acting adrenergic receptor agonists?
cocaine
tricyclic antidepressants
Major uses of alpha receptor antagonist?
HTN
pheochromocytoma (use of nonselective a blocker to control BP before surgery)
BPH: selective a1 blocker
List drugs considered non-selective alpha receptor antagonist.
phentolamine (competitive inhibitor)
phenoxybenzamine (noncompetitive inhibitor)
List the drugs that are selective a1 blockers?
prazosin, doxazosin, terazosin, tamsulosin
Trick to remember the selective a1 blockers?
“zosins” mostly
MOA of tamsulosin? How does this pertain to clinical use? (benefits)
acts on alpha 1a receptor blockers; therefore only affects BPH not BP
Which has the longer half-life? Phentolamine or phenoxybenzamine?
phenoxybenzamine
B2 blockers have what metabolic effects?
block glycogenolysis, and gluconeogenesis
inc. LDLs, TGs
Reproduce this chart on Beta blockers
How do you remember the B1 selective blockers?
A-M olol B1 selective
N-Z olol B1 non selective
How do you remember what is a B blocker and something else?
olol B blocker only
ilol or alól B blocker and something else
Carvedilol and labetalol have what adrenergic blocking activities?
alpha - 1 and B-blocking activity
Clinical use of carvedilol and labetalol?
CHF and Hypertensive emergencies (respectively)
Benefit of labetalol over carvedilol?
consistent decrease in HR.
What is the mechanism of action of sotalol?
K+ channel blockade and B-blocking activity
What are some general uses of beta- blockers?
angina, HTN, post-MI
antiarrhythmics (class II: propranolol, acebutolol, esmolol)
glaucoma (timolol)
migraine, thyrotoxicosis, performance anxiety, essential tremor (propranolol)
Yohimbine MOA and clinical use.
a2 antagonist
postural hypotension
Mirtazapine MOA?
a2 antagonist
