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Adrenergic Receptor
Pharmacology
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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.
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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).
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Adrenergic Neurons
Na+
Tyrosine
Ca++
Receptor
MAO
Dopamine
Dopa
Dopamine is
converted to
epinephrine
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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
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SITE OF ACTION OF CATECHOLAMINES ADRENERGICRECEPTORS
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The
Sympathetic
Nervous System
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Inactivation of noradrenaline
1. Reuptake
3.
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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
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Signaling properties of adrenergic receptors
Adrenergic receptors are G protein coupling receptors
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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
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Adrenergic Agonists
Direct Albuterol
Dobutamine
Dopamine
Isoproterenol
Indirect Amphetamine
Mixed Ephedrine
NB: SYMPATHOMIMETIC: Adrenergic drug which acts directly on
adrenergic receptor, activating it
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Adrenergic Agonists
Direct acting: Epinephrine: interacts with both alpha and
beta
Low dose: mainly beta effects (vasodilation)
High dose: alpha effects (vasoconstriction)
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Adrenergic Agonists
Indirect:
Cause NE release only
Example: Amphetamine
CNS stimulant
Increases BP by alpha effect on vasculature, beta effect on heart
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Mixed-Action
Causes NE release AND stimulatesreceptor
Example:
Ephedrine: What type of drug?
Alpha and beta stimulant
Use: asthma, nasal sprays
slower action
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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?)
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Adrenergic Antagonists
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?)
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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
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Adrenergic Antagonists
Eg: Nadolol Nonselective beta blocker
Used for glaucoma
Eg: Labetolol
Alpha AND beta blocker
Used in treating Pregnancy InducedHypertension (Pre-eclampsia)
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Drugs that Affect Uptake/Release
Eg: Cocaine Blocks Na+/K+ ATPase
Prevents reuptake ofepinephrine/norepinephrine
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Assignement
Adrenaline andNoradrenaline
Synthesis
Release
Storage
And degradation
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