- Adrenergic Receptors 22mars10

7/29/2019 - Adrenergic Receptors 22mars10

1/25

1

Adrenergic Receptor

Pharmacology


2/25

2

Learning Objectives

1. Describe the anatomy of the sympatheticnervous system.

2. Explain the actions of the transmitters of theautonomic nervous system.

3. Describe responses mediated by adrenergicreceptors.

4. Describe how adrenergic receptors regulatecardiovascular function.


3/25

3


4/25

4

SYMPATHETIC NEUROTRANSMITTERS

Preganglionic acetylcholine (nicotinic)

Postganglionic catecholamine (norepinephrine, epinephrine, dopamine)

Norepinephrine

primary transmitter released by sympathetic nerves Epinephrine

released by adrenal medulla,

circulating hormone

adrenal medulla is a nicotinic site

Dopamine released by nerve stimulation

precursor for norepinephrine

Storage of catecholamines in dense core vesicles in nerve terminal of adrenergic nerve

All released by adrenergic stimulation (exocytosis - calcium-dependentprocess).


5/25

Mar-10 5

Adrenergic Neurons

Na+

Tyrosine

Ca++

Receptor

MAO

Dopamine

Dopa

Dopamine is

converted to

epinephrine


6/25

Mar-10 6

EFFECTS ON RECEPTORS

Norepinephrine 1, 2, 1 >> 2

postganglionic neurotransmitter

activates receptors and causes vasoconstriction, mydriasis,constriction of pyloric, intestinal and bladder

sphincters

activates 1 receptors and increases heart rate, heart contractility - inotropic action, arrhythmias (ectopic beats,

etc.)

stored in dense core vesicles (97%) and in cytoplasmicpools (3%)

Epinephrine + effects effects occur at lower doses effects occur at higher doses


7/25Mar-10 7

SITE OF ACTION OF CATECHOLAMINES ADRENERGICRECEPTORS


8/25Mar-10 8


9/25Mar-10 9

The

Sympathetic

Nervous System


10/25Mar-10 10

Inactivation of noradrenaline

1. Reuptake

3.


11/25Mar-10 11

Adrenergic Receptors

Two Families:Alpha and Beta

Based on affinity toadrenergic agonists

Alpha affinity: epinephrinenorepinephrine>>

isoproteranol

Beta affinity: Isoproteranol>epinephrine>

norepinephrine

Epinephrine Norepinephrine Isoproteranol

Epinephrine NorepinephrineIsoproteranol


12/25Mar-10 12

Signaling properties of adrenergic receptors

Adrenergic receptors are G protein coupling receptors


13/25Mar-10 13

Direct-acting sympathomimetics

1. Adrenaline (epinephrine)2. Noradrenaline (norepinephrine)

3. Isoproterenol

4. Phenylephrine

5. Clonidine

6. Dobutamine7. Salbutamol

Indirect-acting sympathomimetics

1. Facilitate noradrenaline release (amphetamine),2. Block noradrenaline re-uptake (cocaine)

1, 2` 1, 21, 2` 1, 2

--------` 1, 2

1 --------

Presynaptic 2` -------

-------- 1-------- 2

Drugs Acting on the SympatheticNervous System


14/25Mar-10 14

Adrenergic Agonists

Direct Albuterol

Dobutamine

Dopamine

Isoproterenol

Indirect Amphetamine

Mixed Ephedrine

NB: SYMPATHOMIMETIC: Adrenergic drug which acts directly on

adrenergic receptor, activating it


15/25Mar-10 15


16/25Mar-10 16

Adrenergic Agonists

Direct acting: Epinephrine: interacts with both alpha and

beta

Low dose: mainly beta effects (vasodilation)

High dose: alpha effects (vasoconstriction)


17/25Mar-10 17

Adrenergic Agonists

Indirect:

Cause NE release only

Example: Amphetamine

CNS stimulant

Increases BP by alpha effect on vasculature, beta effect on heart


18/25Mar-10 18

Mixed-Action

Causes NE release AND stimulatesreceptor

Example:

Ephedrine: What type of drug?

Alpha and beta stimulant

Use: asthma, nasal sprays

slower action


19/25Mar-10 19

Adrenergic Antagonists

Alpha blockers Eg: Prazosin

Selective alpha 1 blocker

Tmt: hypertension

relaxes arterial and venous smooth muscle

Causes first dose response (what is this?)


20/25Mar-10 20


Beta Blockers Example:

Propranolol: Non-selective (blocks beta-1 and beta-2)

Effects: cardiac output, vasodilation, bronchoconstriction

Atenolol, Metoprolol: Selectively blocks beta-1 but nobeta-2 effects

(why is beta-1 selective good?)


21/25Mar-10 21

Adrenergic Antagonists with Intrinsic Sympathometic Activity

Adrenergic antagonists which also haveIntrinsic Sympathometic Activity, i.ethey as Partial Agonists too or weaklystimulate beta 1 and beta 2

Pindolol, acebutolol

Causes less bradycardia


22/25

Mar-10 22


Eg: Nadolol Nonselective beta blocker

Used for glaucoma

Eg: Labetolol

Alpha AND beta blocker

Used in treating Pregnancy InducedHypertension (Pre-eclampsia)


23/25

Mar-10 23

Drugs that Affect Uptake/Release

Eg: Cocaine Blocks Na+/K+ ATPase

Prevents reuptake ofepinephrine/norepinephrine


24/25

Mar-10 24

Assignement

Adrenaline andNoradrenaline

Synthesis

Release

Storage

And degradation


25/25

Documents

- Adrenergic Receptors 22mars10