adrenergic pharmacology involves the study of agents that act on pathways mediated by ____
- endogenous catecholamines, norepinephrine and epinephrine
*SMS is a major source of endogenous catecholamine production and release
what are catecholamines synthesized by, what is the steps in their synthesis
- synthesized by chemical modifications of aa tyrosine
- Oxidation of tyrosine to dihydroxyphenylalanine (DOPA) mediated by enzyme tyrosine hydroxylase (TH)
- TH is the rae limiting enzyme in the synthesis
- DOPA is converted to dopamine by relatively nonspecific aromatic amino acid decarboxylase
- dopamine is taken up by aynaptic vesicles where it is hydroxylated by dopamine-β -hydroxylase to yeild norepinephrine
*in tissues that produce epinephrine, norepinephrine is them methylated on its amino group by phenylethanolaine N-methyltrasnferase (PNMT)
what is expresseion of PNMT dependent on?
- expression of PNMT in the adrenal medulla is largely dependent on high concentrations of the stress hormone cortisol that flows into the medulla via veins draining the adrenal cortex
*this is the enzyme methylates
what happens once a catecholamine has exerted its effect at a postsynaptic receptor
- the response is terminated by one of 3 mechanisms
1. reuptake of catacholamine into presynaptic neurons
2. metabolism of catacholamine to an inactive metabolite
*metabolism involves two enzymes: monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
- diffusion of cetacholamine away fromt he synaptic cleft
what are teh two main groups of adrenergic receptors
α (α1, α2) and β (β1, β2, β3),
- each receptor is a member of g-protein superfamilty
how are alpha adrenergic and β1 receptors activated
by both norepinephrine and epinephrine
how are β2 receptors activated
- much mor responsive to epinephrine
- β2 receptors often show in adrenergic synpase diagrams as responding to norepinephine but in reality has very little effect on them
what is the rate limiting step in the synthesis of catecholamines? What inhibits it?
- all synthesized from tyrosine
- rate limiting = oxidation of cytoplasmic tyrosine to dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosine hydroxylase (TH)
- inhibited by
hows does L-DOPA get converted to dopamine and put into vesicles
- aromatic L-amino acid decarboxylase converts L-DOPA into dopamine
- vesicular monoamine transporter (VMAT) translocated dopamine (and other monoamines) into synpatic vesicles
how is dopamine coverted to norepinephrine in adreneric neurons
- in adrenergic neurons, intravesicular dopamine-β-hydorxylase converts dopamine to norepinephrine
- norepinephrine is then stores in the vesicle until release
how is norepinephrine coverted to epinephrine
in adrenal mdullary cells
- norepinephrine (made form dopamine) returns to the sytosol where phenylethanolamine N-methyltransferae (PNMT) coverts norepinephrine to epinephrine
- epinephrine is then transported back into the vesicle for storage
what happens to norepinephrine that is released
- can stimulate postsynaptic α1-, β1-, or β2-adrenergic receptors or presynpatic α2-adrenergic autoreceptors
- can also be taken up into presynpatic terminals by the selective NE transporter
- ME in the cytoplasm of presynpatic neuron can be futher taken up into synpatic vesicles by VMAT or degraded to 3,4- dihydoxyphenylglycoaldehyde (DOPGAL) by mitochondrion-associated monoamine oxidase (MAO)
location and actions of the α1 receptor
- Smooth muscle cells (vessels in skin, mucosa and abdominal organs)
Intestinal and urinary sphincters: contraction - Eye: pupil dilation
- Liver: glycogenesis and glucognesis
*inc IP3/DAG = excitatory, activate PKC and calcium dependent potein kinase
locations and actions of the α2 receptor
- Pancreatic β-cells: decreased insulin secretion
- Platelets: aggregation
- Nerve: decreased norepinephrine release
- Smooth muscle: contraction
- decrease cAMP: inhibitory, prevent phosphorylation of enzymes
What are the locations and action of the β1 receptor
- Heart: increased rate/force of contraction
- Juxtaglomerular cells: increased renin secretion
*inc cAMP: excitatory
Locations and actions of β2 receptor
- Smooth muscle (most organs and blood vessels supplying skeletal muscle): relaxation
- Liver: Glycogenesis and glycogenesis
- Skeletal muscle: Glycogenesis and K+ uptake
Locations and actions of β3 receptor
adipose: lipolysis
*inc cAMP: excitatory
impact of receptor agonists on the heart
M2 → decrease heart rate
β1 → increase heart rate
impacts of agonists on (most) blood vessels
M3 →vasodilation
α1 →vasoconstriction
impact of agonists on skeletal muscle blood vessels
β2 →vasodilation
impact of receptor agonists on most organ systems/glands
M3 → contraction → increase activity
→ increase secretion
β2 → relaxation of smooth muscle
α1 → constriction of sphincters
how are autonomic drugs used in ophthamology and optometry
- contraction of sphincter M3 = constriction of pupil
- contraction of dilator α1 = dilation of pupil
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Pharmacokinetics55
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Clinical applications of Pharmacokinetics22
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Pharmacodynamics26
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Unit 3: divisions of the NS20
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Cholinergic Transmission19
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Adrenergic Transmission22
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Cholinergic Drugs53
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Agrenergic Drugs64
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Unit 04: Antihypertensives49
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Unit 4: drugs22
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Unit 0.4: Treatment of Heart Failure27
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Unit 04: Treatment of Angina39
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Unit 05: Pharmacology31
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unit 5 drugs28
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Unit 05: Physchosis and mood31
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Unit 05: Depression and Anxiety29
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Unit 05L abused drugs33
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Unit 06: premedications34
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Unit 06: drugs35
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Unit 06: IV Anesthetics23
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Unit 06: inhalant Anesthetics19
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Unit 06: Neuromuscular Blockers35
