Drug targets: The adrenoceptors

Question 1

What are Adrenoceptors?

Answer 1

Adrenergic Receptors

GCPRs expressed thoughout the body - Different G-proteins affecting how they work, function and activate

Responsible for many physiological responses.

Both bind to ARs
Adrenaline-hormone produced in adrenal glands
Noradrenaline-CNS neurotransmitter produced in brain stem

Question 2

Where are alpha and beta receptors found and how good is NA as an agonist and what are they responsible for?

Answer 2

Coronary arteries, NA was the best out of the six agonists in contracting the arteries, alpha receptors, expressed in all the tissues listed on the slide, no effect in the heart

Heart: NA was the wort at contracting the heart, beta receptors, expressed somewhere else.

Alpha smooth muscle contraction
Beta smooth muscle relaxation, hear and lungs

Question 3

Where are alpha 1 and its subtypes found?

Answer 3

Smooth muscles, eyes, GIT, lungs, blood vessles, bladder etc.

Question 4

Where are alpha 2 found?

Answer 4

In the brain

Question 5

Where are beta 1 found?

Answer 5

Only expressed in the heart

Question 6

Where are beta 2 found?

Answer 6

Found in all smooth muscles

Question 7

What does Alpha 1 receptor activate?

Answer 7

Gq,phospholipase C, increasing IP3 and DAG, and ultimately increasing the intracellular calcium concentrations leading to smooth muscle contraction

Question 8

What does beta receptors activate?

Answer 8

Gs

Question 9

What does alpha 2 receptors activate?

Answer 9

Gi

Question 10

Give the pathway for Alpha-q for SM contraction?

Answer 10

PLC–>PIP2—>IP3–>Ca2+
—>DAG—>PKC

Question 11

Give the pathway for Alpha-s for SM relaxation contraction?

Answer 11

Adenylyl cyclase–>cAMP–>PKA
alpha i/o inhibits cyclase

Question 12

What is the potency/best agonist for alpha 1?

Answer 12

NA>A»ISO

Question 13

What is the potency/best agonist for alpha 2?

Answer 13

A>NA»ISO

Question 14

What is the potency/best agonist for beat 1?

Answer 14

ISO>NA>A
iso potent

Question 15

What is the potency/best agonist for Beta 2?

Answer 15

ISO>A>NA
iso most potent

Question 16

What is the potency/best agonist for Beta 3?

Answer 16

ISO>NA=A
iso most potent

Question 17

Non selective alpha receptor agonist

Answer 17

Decongestant: Oxymetazoline

Question 18

Alpha 1 receptor agonist (vasoconstrictor)

Answer 18

Anti-hypertensive: Phenylephrine

Question 19

Alpha 2 receptor agonist (subtype specific)

Answer 19

Antihypertensive: Clonidine
ADHD treatment: Guanfacine

They are interchangeable in use they can both do the same job same with the sedatives on the alpha 2 examples

Question 20

Non selective Beta receptor agonist

Answer 20

Brachycardia: Isoprenaline

Question 21

Beta 1 receptor Agonist

Answer 21

Cardiogenic shock: Dobutamine
Heart failure: Xamoterol (partial), cause it acts as a antagonist

Question 22

Beta 2 Receptor agonist

Answer 22

Bronchodilator: Salbutamol
Tocolytic: Terbutaline

Interchangable

Question 23

Beta 3 receptor agonists

Answer 23

Overactive bladder mirabegron
Vasodilator: Nebivolol (beta blocker)

Question 24

Non selective AR agonist

Answer 24

Decongestants: Pseudoephedrine, no preference for beta or alpha

Question 25

Non selective Alpha receptor Antagonist

Answer 25

Phenoxybenzamine: only used inadrenal gland tumour removal

Question 26

Alpha 1 receptor antagonist (sub-type dependent)

Answer 26

Anti hypertensive: Prazosin Enlarged prostate: Tamsulosin

Question 27

Alpha 2 recepotr antagonist

Answer 27

No clinical use: Yohimbine, Idozoxan (used in research by blocking recepotors

Question 28

Non-selective Beta receptor antagonist

Answer 28

Antihypertensive Propranolol Anti agina: Metoprolol interchangable

Question 29

Beta 2 receptor antagonists

Answer 29

No clinical use: Butoxamine

Question 30

Non selective adrenoceptor antagonist

Answer 30

Beta blocker: Carvedilol (inverse agonist?? stabalise HR by reducing it