Adrenergic Agents - Day 1 Flashcards
List three direct acting adrenergic receptor agonists
Dopamine (Intropin)
Norepinephrine (Levophed)
Epinephrine (Adrenalin)
Dopamine is an activator of ______ receptors.
Where in the body is dopamine especially important?
Beta adrenergic
Kidney
Dopamine is converted to NE by…
beta-hydroxylase
NE is an activator of _____ receptors.
alpha adrenergic receptors
also its okay at B1, but not so much B2
alpha1 receptors are especially important at what location?
Vascular System
alpha2 receptors are especially important at what location?
Presynaptic feedback
CV control in the brainstem
beta1 receptors are especially important at what location?
Heart
Kidney (For Renin Release)
beta2 receptors are especially important at what location?
Smooth muscle in BV of skeletal muscles
Direct agonists for alpha1 receptors (3)?
Phenylephrine (Neosynephrine)
Methoxamine (Vasoxyl)
Oxymetazoline (Visine)
Alpha1 receptors work by…
activation will trigger Gq to turn on PIP2. Leads to IP3 (which ups Ca) and DAG (which activated PKC)
Alpha2 receptors are directly activated by (5)…
Clonidine (Catapres) Methyldopa (Aldomet) Guanabenz (Wytensin) Guanfacine (Tenex) Tizanidine (Zanaflex)
How do alpha2 receptors work?
Turn on Gi, which inhibits Adenylate Cyclase (stopping cAMP signalling) and opens K channels to make cells more negative (and harder for nerves to fire)
Example of a non-selective beta receptor agonist?
Isoproterenol (Isuprel)
List two beta-1 adrenergic receptor agonists.
Dobutamine (Dobutrex)
Dopamine (Intropin)
List 5 beta2 adrenergic receptor agonists.
Metaproterenol (Metaprel, Alupent) Albuterol (Proventil, Ventolin) Salmeterol (Serevent) Terbutaline (Brethine, Bricanyl) Ritodrine (Yutopar)
How do beta adrenergic receptors work
Turn up Gs proteins, more AC, more cAMP
Alpha1 Adrenergic activation. Rank Phenylephrine, Epinephrine, Norepinephrine, and Isoproterenol from most potent to least potent.
PENI
Beta1 and Beta2 Adrenergic activation. Rank Phenylephrine, Epinephrine, Norepinephrine, and Isoproterenol from most potent to least potent.
IENP
Out of Phenylephrine, Epinephrine, Norepinephrine, and Isoproterenol, whose potency changes the most from beta 1 to beta 2.
Norepinephrine is much less potent in beta2
Cardiovascular effects of Norepinephrine. Tell me all about them.
NE is an alpha1 agonist, so it will trigger constriction of the vessels, increasing the BP. The increase in BP triggers the Vagus nerve to drop the pulse rate.
Cardiovascular effects of Epinephrine. Tell me about them.
E activates alpha1, beta1 and 2. Beta 1 stimulates the heart rate while causing a minor dilation of the vessels in the skeletal muscle. Beta2 and alpha 1 cancel out. Overall there is minimal BP change.
Cardiovascular effects of Isoproterenol. Tell me about them.
Beta1 will increase heart rate while beta2 will decrease peripheral resistance. This results in a drop in BP.
What is l-NE (Levophed)? What is it a substrate for? How is it dosed? What is it used for?
alpha and beta1 agonist.
Substrate for MAO and COMT.
Dosed Parenterally.
Used as a pressor.
What is Epinephrine (adrenaline)? What is it a substrate for? How is it dosed? What is it used for?
alpha, beta1, and beta2 agonist.
Substrate for MAO and COMT.
Dosed Parenterally.
Anaphylaxis, glaucoma, with local anasthetics.
Why use Epinephrine with anesthetics?
To diminish blood flow and keep the anasthetic at the site.
What is added to preparations of NE and E to prevent oxidation?
Sodium Bisulfite.
Phenylephrine activates what receptors?
alpha1
Phenylephrine is a substrate for…
MAO
Not COMT, so orally useable
Phenylephrine MO Administration?
Parenteral, Oral, Local
Basically – whatever the fuck you want.
Phenylephrine uses?
Mydriasis without cycloplegia
Glaucoma
Pressor
NASAL DECONGESTANT
The 2-aralkylimidazolines include which drugs?
Naphazoline
Tetrahydrozoline
Oxymetazoline
2-aralkylimidazolines activate which receptors?
alpha
2-aralkylimidazolines are administered how? why?
Locally/Topically
To promote vasoconstriction
Concerns with overuse of 2-aralkylimidazolines in a patient?
Tachyphylaxis (desensitization of receptors)
Uses for 2-aralkylimidazolines?
Nasal and ophthalmic decongestants
Clonidine is an activator of which receptors?
Alpha2
Significance of Clonidine’s dichlorophenyl ring?
Decreases the pKA from 13.6 to 8.0
Prevents charge, helps Clonidine get to target.
How is Clonidine administered?
Oral, parenteral, transdermal
Uses for Clonidine?
Hypertension, Opiate Withdrawl
How does Clonidine (or alpha2 adrenergic agonists in general) actually lower BP?
Clonidine turns off SNS –> decreased heart rate, decreased heart contractility, decreased renin release, and vasodilation.
What do Guanabenz and Guanfacine have in common?
They are open ring imidazolidines.
Guanabenz and Guanfacine act on which receptors?
alpha2
Guanabenz and Guanfacine. Whats important and unique about each.
Guanafacine – Can treat ADHD
Guanabenz – Short half life of 6 hours (half of the others)
Guanabenz and Guanfacine are typically prescribed to treat…
Hypertension
Methyldopa acts on which receptor type?
alpha2
What is Methyldopa?
A prodrug metabolized into its active form (1r,2s)-alpha-methylnorepinephrine
What does Methyldopa do for patients physiologically?
Acts on CNS alpha2s to decrease sympathetic outflow.
Why prescribe Methyldopa?
Hypertension
Non BP related use of apraclonidine?
Glaucoma (but not really anymore…the world is going in a more beta-blocker-y direction these days)
Non-BP related use of Tizanidine?
Muscle spasticity.
For example messed up reflex arcs of cerebral palsy. By increasing the activity of the alpha2 receptors in the spinal cord that control these arcs, spasticity goes down.
