Adrenergics Flashcards
Where do you find Alpha 1 receptors and what do they do?
Generally they CONSTRICT.
You find them in blood vessels and sphincters. They are also in charge of ejaculation and orgasm and the contractions of labor.
Where do you find Beta 2 receptors and what do they do?
Generally they DILATE.
You find them in blood vessels. They are also in charge of uterus relaxation and DECREASED GI motility and tone.
(decreased uterine motility/tone during labor)
Where to you find Beta 1 receptors and what do they do?
You find them in the heart (“B my number 1”)
They are in charge of the heart’s fight or flight response: increased heart rate (SA and AV nodes), increased contractility, increased renin release in the kidneys.
How are norepinephrine and epinephrine synthesized?
Dietary Tyrosine into sympathetic neuron transporter --> Dopa --> Dopamine into vesicle --> Norepinephrine --> Epinephrine (adrenal medulla only!)
How is Norepinephrine regulated?
Calcium entry –> NE release from neuron to synapse
Inhibited by Alpha 2 and Prostaglandin E2 receptors
Enhanced by Angiotensin II in its receptors
How are catecholamines metabolized?
MAO and COMT metabolize them in the liver, kidney and GI tract
MAO is also in the presynaptic terminals of noradrenergic neurons.
What happens to extra norepinephrine?
90% of extra NE in the synapse is taken up/recycled by the NE transporter (NET)
Extra NE in the cell is stored in vesicles for later or metabolized by MAO.
What do adrenergic agonists do, and name some examples
Short term: they activate alpha and beta receptors
Chronic: they desensitize/downregulate the receptors
Examples: phenylephrine, isoproterenol
What to adrenergic antagonists do, and name some examples
Short term: block alpha and beta receptors
Chronic: super-sensitize/up-regulate receptors
Examples: phentolamine, propranolol
What are four ways that the chemical structure of a drug can predict its action?
- Increasing SIZE of the amino group tail will increase Beta receptor affinity (eg: Isoproterenol)
- Hydroxyls at positions 3 and 4 will cause alpha and beta activity (eg: catecholamines)
- Removing hydroxyls will increase CNS penetration (eg: ephedrine, amphetamine)
- Noncatecholamines are NOT metabolized by COMT, and a substitution of the alpha carbon will also stop MAO metabolism (thereby increasing half-life)
Which catecholamine prefers alpha 1 and beta 1 receptors? (Which one “likes the 1s”?)
Norepinephrine
Which catecholamine prefers Beta 1 and Beta 2 receptors (“likes the betas”)?
Isoproterenol
Which catecholamine is nonselective/promiscuous for the alpha and beta receptors?
Epinephrine
Low doses: B1=B2>A1
Hi doses: B1=B2=A1
Which catecholamine is very promiscuous for all receptors at a high dose?
Dopamine
Low doses: DA>B1>B2
Hi doses: DA=B1=B2=A
Which drug is selective for contractility at low doses?
Dobutamine
Low doses: B1»>B2
Hi doses: B1»B2=A1
Which catecholamine will increase heart rate and decrease blood pressure at a low dose, but increase blood pressure at a high dose?
What is this used for?
Dopamine will increase heart rate (B1) and decrease blood pressure at a low dose (DA, B2), but increase blood pressure at a high dose (A1)
Used for shock, especially cardiogenic.
Which catecholamine will initially increase systolic BP but decrease diastolic BP?
What is this used for?
Epinephrine will initially increase systolic BP (B1 increases HR) but decrease diastolic BP (B2 vasodilation decreases total peripheral resistance and thus diastolic BP). Later A1 will “win” over B2, cause vasoconstriction and increases diastolic BP.
Used for anaphylaxis, asthma (bronchodilation), cardiac arrest (B1 stimulation), topical hemostasis (shrinks mucosa of nose/throat/larynx for surgery)(alpha 1 vasoconstriction)
Which catecholamine will increase heart contractility but not affect the heart rate?
What is this used for?
Dobutamine due to its selectivity for B1 at low dose (with some A1 and B2 at high dose).
Used for heart failure re open heart surgery, acute MI
Which catecholamine will cause a LOW blood pressure at LOW dose but a HIGH mean blood pressure at HIGH dose?
Epinephrine
Which catecholamine will increase heart rate and cardiac output and increases blood pressure without a dip in diastolic pressure?
What is it used for?
Norepinephrine
Sometimes used in ER for shock (neurogenic or spinal anesthesia) but not effective.
Which catecholamine will cause increased glycogen breakdown and free fatty acids and decreased glycogen synthase and insulin secretion?
Epinephrine
Which catecholamine will increase the heart rate, decrease blood pressure and increase bronchodilation?
What is it used for?
Isoproterenol was developed to be selective for Beta agonist to stimulate the heart. It will increase the heart rate (B1), decrease blood pressure (B2) and increase bronchodilation (B2)
It is used to stimulate the heart rate re heart block or re insertion of pacemaker.
Which catecholamine will increase HR and decrease BP at low dose but increase BP at high dose?
Dopamine will increase HR (B1) and decrease BP (DA, B2) at low dose but increase BP (A1) at high dose?
It is used for cardiogenic shock.
What is a non-catecholamine alpha 1 stimulant used as a decongestant and pupil dilator?
Phenylephrine
What is a non-catecholamine that is a weak alpha and beta agonist used as a nasal decongestant and as a pressor to increase blood pressure
Ephedrine
What is a beta 2 selective agonist that is the treatment of choice for acute asthma?
Albuterol
What is a selective beta 2 agonist sometimes used for asthma and to slow or stop labor?
Terbutaline
What drug is used to treat narcolepsy (CNS stimulation) and weight loss?
Amphetamine
What is Methylphenidate used for?
Treating ADHD
AKA: Concerta
Why is it that amphetamine, ephedrine and phenylephrine can give you a “buzz”?
The hydroxyl groups on the catechol nucleus are removed so they cross the blood brain barrier
What is the mechanism of action of Reserpine?
It enters the neuron freely (no transporter), blocks NE entrance into vesicles (VMAT).
Result: excess NE in the cell is then consumed by MAO.
What is the MOA of Guanethidine?
It enters the neuron via the NE transporter (NET), concentrates in the vesicles so there is no room for NE.
Result: “chemical sympathectomy”: decreased BP.
What is the mechanism of action of Tyramine and where is it found?
Found in aged cheese, beer, wine, fava beans
MOA: normally metabolized by MAO, but if taking an MAO inhibitor, it will displace NE in the vesicles, but the NE will not be consumed by MAO because of the inhibitor, so it will be released into the synapse.
Result: a hypertensive crisis.
What is the MOA of cocaine, imipramine and atomoxetine?
All three can block NE transporter so that extra NE cannot be recycled back in the neuron.
Result: a hypertensive crisis.
What is a non-catecholamine sympathomimetic amine?
A drug that is NOT a catecholamine, but stimulates alpha or beta receptors
What do non-catecholamine alpha stimulators do, and give some examples
Stimulate alpha 1: vasoconstriction
Used to shrink mucus membranes, increase blood pressure, dilate pupils.
Eg: phenylephrine and phenylpropanolamine
What do non-catecholamine beta stimulators do, and give some examples
Stimulate beta 2: bronchodilation and decreases mast cell degranulation
Used for asthma, anaphylaxis, to slow labor
Examples: ephedrine, albuterol, terbutaline, formoterol, ritodrine
What do non-catecholamine CNS stimulators do, and give some examples
Increase NE in synapse through facilitated exchange diffusion
Used to treat narcolepsy, cause weight loss, treat ADHD
Examples: amphetamine, methylphenidate
What is a xanthine, what does it do? Give some examples
Xanthines are sympathomimetics that do not bind adrenergic receptors. They mimic sympathetic responses by decreasing the breakdown of cAMP so more is available for bronchodilation and vasodilation.
Examples: Caffeine and theophylline
What is the MOA of caffeine?
It stimulates the cortex and sensitizes CO2 receptors increasing respiratory rate in high doses
What is the MOA of theophylline?
it increases heart rate and contractility, causes vasodilation and bronchodilation, but vasoconstriction in the CNS.
What is the MOA of an MOA inhibitor
They prevent MAO from metabolizing extra NE neuron, leading to extra NE in the synapse, causing increased BP and HR.
Which neurotransmitter do alpha 1 receptors “prefer”?
Epi>NE»Iso
Which neurotransmitter do beta 1 receptors “prefer”?
Iso>Epi=NE
Which neurotransmitter do beta 2 receptors “prefer”?
Iso>Epi»NE
