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Flashcards in Adrenergic I Deck (20):
1

What is the role of sympathomimetic drugs?

Sympathomimetic drugs mimic the effects of stimulating the SNS.

1) Direct acting drugs => act on post-synaptic receptors (Epi/NE)

2) Indirect acting drugs =>
- Enhance the release of NE at synapse => Amphetamine, methamphetamine, MDMA (Ecstasy)

- Block the re- uptake of NE after release at the synapse => Cocaine, amitriptyline

- Block the degradation of NE => MAO-inhibitors like phenelzine

2

How is NE synthesized and stored by cells?

1) The amino acid Tyrosine is actively transported in the adrenergic neuron

2) Tyrosine is metabolized to DOPA, and then to Dopamine (by decarboxylation)

3) Dopamine is actively transported in vesicles and then converted to NE (by beta-hydroxylation)

3

How is NE released by the adrenergic neuron? (or any neurotransmitter released?)

NE is released by nerve action potential (pre-synaptic) 1) Action potential leads to influx of Ca ++ 2) This influx of Ca++ promotes fusion of vesicle with plasma membrane 3) Followed by exocytosis of NE from vesicle into synapse

4

How does NE interact with pre-synaptic/ post synaptic receptors? (How does any neurotransmitter interact with its receptors?)

1) NE diffuses to both post-synaptic and pre-synaptic receptors

2) NE in synapse is then recaptured by active transport back into the presynaptic terminal

3) NE can also diffuse away from the synapse

   - NE can then be metabolized to inactive compounds by MAO (monoamine oxidase) and COMT (catecholamine o-methyltransferase), with later conjugation to sulfates and glucuronates

   - MAO and COMT are abundant in the liver

4) Metabolized to inactive compounds

*The goal is to make sure that NE does not linger in the synapse*

5

How are neurotransmitters removed from their receptors/synapses?

1) Reuptake

2) NT can diffuse out of the synapse and be metabolized at an extra-neuronal site (via MAO and COMT)

6

Describe alpha-1 adrenergic receptor (alpha-1 AR) signaling.

PLC=> IP3 and DAG => activate PK(C)

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7

Describe β and α-2 AR signaling.

Adenyl cyclase => increase cAMP => R2C2 protein kinase => 2 C => enzymes => biological effect => activation => inhibit NE release

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8

Describe the general function of adrenergic receptors.

α1-AR⇒contraction and constriction blood vessels

α2-AR⇒↓NErelease

    - constrict blood vessels, relax GI smooth muscle

β1-AR⇒↑HR and contractility

   - Increase HR rate, force, AV node, conduction velocity

β2-AR ⇒ relax SM of airways, blood vessels,  and uterus

9

What is phenylphrine (Neosynephrine)?


-Synthetic alpha-receptor agonist, α1 > > α2
-Actions: vasoconstriction and venoconstriction by stimulating contraction of vascular smooth muscle cells
- Indications: nasal decongestant, mydriatic (dilate pupil for eye exam), increase BP in vasodilated state
- Other facts: less potent vasoconstrictor than NE, not inactivated by COMT, topical (eye, nose), intravenous infusion (increase BP)
 

10

What is clonidine (Catapres)?


-Synthetic and selective α2 receptor agonist
-Actions: Stimulate α2 receptors in brainstem, cause down-regulation of sympathetic nervous system
- Indications: treat HTN, treat or prevent migraine
-Other facts: may be given orally or patch, causes sedation and dry mouth, if given intravenously or OD can cause an increase in BP
 

11

What is isoproterenol (Isuprel)?


-Synthetic β1 and β2 receptor agonist
-Actions: Potent agonist at both beta receptors
Indications: Increase cardiac contractility, Increase HR, Increase cardiac conduction
Other facts: Given intravenously, no longer used as much in CCU, causes vasodilatation and tachyarrhythmias
 

12

What is Dobutamine (Dobutrex)?


-Synthetic β1 receptor agonist (with very little alpha simulation at high doses)
- Actions: Potent agonist at β1 receptors in heart (increase contractility) and blood vessels (dilates renal and mesenteric vessels); increases contractility more than HR
- Indications: useful in CCU for patients in cardiogenic shock
- Other facts: given as IV, side effects include unwanted tachycardia, hypertension, actopy
 

13

What is albuterol (Ventolin)?


Synthetic selective β2 receptor agonist 
- Actions: Potent agonist at β2 receptors on smooth muscle cells in airways (e.g. bronchioles)
- Indications: prompt-acting rescue inhaler for asthma, COPD (bronchodilator), inhibit premature labor (relaxes smooth muscle cells in uterus as well)
 -Side effects include anxiety, tachycardia and tremor
 

14

What is mirabegon (Myrbetriq)?


Synthetic selective β3 receptor agonist 
-Actions: Stimulation of β3 receptors in smooth muscle of bladder, reduces detrusor muscle tone
- Indications:
   -Treatment of patients with overactive bladder with features of urinary urgency/frequency
   -Increases bladder capacity
   -Does not produce bothersome anticholinergic symptoms like tolteridine
-Other facts:
   -Administered orally as extended release tablets
 

15

What is Dopamine (inotropin)?


 - Endogenous and now synthetic agonist at DA, β1, and α1 receptors
-Actions: DA agonist at low dose, β1 agonist at medium dose, α1 agonist at high dose
- Indications:
   -Shock 
   - Increased contractility (β1 stimulation), vasoconstriction (α1), and improved mesenteric and renal perfusion (DA)
-Other facts:
   -Given intravenously, preferably for short duration
 

16

What is Ephedrine?


Sympathomimetic drug => alkaloid obtained from plant (Ephedra)
-Actions: Acts indirectly to release NE from adrenergic nerve endings, also some direct agonism at receptors
-Indications:
   -Mild to moderate hypotension during surgery
   -Nasal congestion
- Other facts:
   -Potent CNS stimulant (NE)
   -Side effects include hypertension, insomnia

 

17

What is pseudoephedrine?


Sympathomimetic drug => Synthetic derivative of ephedrine
-Actions: Acts indirectly to release NE from adrenergic nerve endings, also some direct agonism at alpha- and beta-adrenergic receptors
-Indications:
   -Nasal and sinus decongestant
   -Less ability to dilate bronchioles than ephedrine

 

18

What is amphetamine?

Sympathomimetic drug => Synthetic compound similar to ephedrine

-Actions: Acts indirectly to release NE from adrenergic nerve endings
- Indications (none are FDA approved):
   -Obesity
   -Narcolepsy
   -ADHD
-Other facts:
   -FDA approval in 1939
   -Very high risk of dependence
   -Insomnia, restlessness, tremor
 

19

What is tyramine?

Sympathomimetic drug =>  Naturally occurring byproduct of tyrosine metabolism; present in many aged or fermented foods like red wine, smelly cheeses, pickled herring

-Actions: Acts indirectly to release NE from adrenergic nerve endings
-Indications (none are FDA approved):
   -Obesity
   -Narcolepsy
   -ADHD
-Other facts:
   -Metabolized in the liver by MAO
   -Watch out in patients on MAO inhibitor drugs (e.g. phenelzine)
   -Chance of food/drug interaction 
 

20

What is cocaine?

Sympathomimetic => Naturally occurring but purified alkaloid extracted from the coca plant

- Actions: Acts indirectly to block reuptake of NE (also Epi, DA) at the synapse, and can stimulate release of NE, Epi, and DA from neuron; also acts as a local anesthetic and CNS stimulant
- Indications:
   -Nose bleeds (anesthesia plus vasoconstriction)
   -Anesthesia for corneal surgery
-Other facts:
   -CNS stimulatioln more intense, shorter lasting than amphetamine
   -Can be smoked, snorted, or injected
   -Side effects hypertension, tachycardia, arrhythmias, seizures, MI
   -Controlled substance