Adrenergic Agonist Eliud Flashcards

1
Q

What is the most common treatment of adrenergic drugs?

A

-Asthma
-Hypertension
-Common Cold Symptoms

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2
Q

Which neurotransmitter is at the terminus of the sympathetic nervous system?

A

Norepinephrine

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3
Q

Which neurotransmitter is synthesized mainly in the adrenal gland?

A

Epinephrine

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4
Q

Describe the Biosynthesis of Norepinephrine

A
  1. L-Tyrosine enters the presynaptic neurons via active transport and oxidize it though Tyrosine Hydroxylase to form L-DOPA (rate-limiting step).
  2. L-Dopa decarboxilation by Dopa decarboxylase to produce Dopamine which are stored in vesicles.
  3. Dopamine is oxidized by Dopamine-B-Hydroxylase to form Norepinephrine.
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5
Q

Storage and Release of Norepinephrine

A

-95% is reuptake through a transporter.
-Alpha 2 inhibits NE release
-NE can be metabolized through MAO or COMT

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6
Q

True or False: El metabolismo de Norepinefrina crea un metabolito inactivo bien hidrofilico para excretar.

A

True

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7
Q

Alpha 1 Receptors

A

Predominantly postsynaptic found in vascular smooth muscle and the CNS

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8
Q

Alpha 2 Receptors

A

Stimulation inhibits NE release

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9
Q

Beta 1 Receptors

A

Found in myocardial. Stimulation increase heart rate and force of contraction.

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10
Q

Beta 2 Receptors

A

Found in lungs, vascular smooth muscle, skeletal muscle, and uterus. Stimulation results in dilation or relaxation of these tissues.

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11
Q

Adrenergic Receptors: Asp 113

A

La más importante ya que está con carga negativa lo que ayuda a atraer el nitrógeno positivo de NE creando un enlace ionico.

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12
Q

Adrenergic Receptors: Ser204 and Ser207

A

Reconoce a los OH de anillo aromático

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13
Q

Adrenergic receptors: Phe290

A

Interactúa con el grupo fenol por van der waals

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14
Q

Adrenergic Receptors: Asn293

A

Puentes de hidrógeno con el OH del carbono B que tiene que está en conformación R para ser reconocido.

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15
Q

What is the base structure of Phenylethylamine Adrenergic Agonist?

A

Benzenediol structure. NH2 al final luego de dos carbonos entremedio.

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16
Q

R1 amine substituent (bind to NH)

A

Un grupo funcional voluminoso le dará mayor selectividad a los beta.

R1 Methyl: mayor selectividad a beta pero puede enlazarse a alpha

R1 i-propyl, t-butyl, or aralkyl: Too bulky for alpha receptor therefore high affinity for Beta. Butyl prefers B2

17
Q

R2 alpha-carbon substituent (en el carbono alpha)

A

Conformación S = acción directa
Confirmacjon R = acción indirecta

Vulnerable to MAO

R2 methyl: more selective to alpha 2 than 1

R2 ethyl: more selective to beta 2

18
Q

R3 Beta carbon substituent (en el carbono beta)

A

R3 OH: necessary for Beta receptor binding (Beta 2). A slow CNS penetration.

R3 H: Direct action decrease but indirect is maintained. Crosses BBB with no problem.

19
Q

Aromatic Substituents

A

3’ and 4’ OH: Catecol vulnerable to COMT therefore poor oral activity. Direct action to all adrenoreceptors and no cruza BBB

monophenol: OH in 3’ direct activity at alpha 1 receptors. OH in 4’ direct action at Beta receptors.

No substituents: cross BBB, direct action decrease. Mainly indirect action.

20
Q

Other patterns for aromatic substituents

A

A small H bonding in 3’ and an OH in 4’ plus t-butyl or bulky substitutes in R1 can have a Beta 2 affinity. Resistant to COMT.

An OH in 3’ and 5’ plus t-butyl or bulky substitutes in R1 can have a Beta 2 affinity. Resistant to COMT.

21
Q

Physicichemical Properties of Phenylethylamine Adrenergic Agonist

A

-Can be amphoteric (act as a base or acid)
-Different LogP
-Beta OH present and no Alpha CH3 is
more hydrophilic
-If no OH groups, more lipophilic

22
Q

Norepinephrine and Epinephrine Clinical Applications

A

-Non-Selective
-Alpha activity use for hypotension crisis
-Beta activity used for cardiac arrest
-Epinephrine is better for anaphylaxis because is a Beta 2 agonist.

23
Q

Selective Alpha 1 Adrenergic Agonist (La 1 PM)

A

Phenylphrine and Metaraminol have longer duration than NE and are vasoconstrictors for hypotensive crisis and nasal decongestant.

24
Q

Short acting Selective Beta 2 Adrenergic Agonist (TerMeLevPir)

A

Terbutaline, Metaproterenol, Levalbuterol, Pirbuterol

Bronchodilators for asthma and COPD

25
Q

Long acting Selective Beta 2 Adrenergic agonist (ay Fo Sal Ino Olo)

A

Al ser lipofilicos y tener grupo voluminosos, se ancla al receptor dándole el efecto de larga duración.

Formoterol: Faster onset than Salmeterol. Bulkiness makes both long acting
Salmeterol: treatment for severity of asthma attacks.

Indacaterol and Olodaterol are used as bronchodilators

26
Q

Arylimidazoline Adrenergic Agonist (SAR)

A

Estructura similar a phenylethanolamine pero tiene un anillo de imidazol.

En el carbono beta puede ser CH2 (selectivo alpha 2) or NH (selectivo Alpha 1)

Los grupos R voluminoso en el anillo fenol le da lipofilicidad y mayor afinidad a los receptores alpha pero si existe el grupo R3 es más selectivo a alpha 1

27
Q

Arylimidazoline Alpha 1 Agonist (carbono Beta = CH2)

A

Xylometazoline, Oxymetazoline, Tetrahydrozoline, and Naphazoline

28
Q

Clonidina

A

Arylimidazoline Alpha 2 Agonist
-Treat Antihypertensive, ADHD, Glaucoma, and Nicotine and opioid withdrawal.

-Ionizado es como se queda en la periferia y no ionizado cruza el BBB

29
Q

Arylimidazoline Alpha 2 Agonista

A

Apraclonidine: Glaucoma
Brinonidine: Glaucoma
Tizanidine: Espasmos muscular
Guanabenz (doble enlace de N) y Guanfacine (no doble enlace): Antihipertensivo
Methyldopa: prodroga antihipertensiva (metabolito no cruza BBB)