Physiology of Sympathomimetics - Week 1 Flashcards
Sympathetic NS branches from what region the spinal cord?
Thoracolumbar (T1-L2)
Where are the sympNS preganglia located?
Near the spinal cord
SympNS postglaglia secrete ________
Norepinephrine (adrenergic fibers)
What converts dopamine into NE after it enters the synaptic vessel?
Dopamine beta hydroxylase
What releases NE from the synaptic vessel?
an action potential
3 modes of signal termination from NE
- Reuptake
- Dilution by diffusion
- Metabolism by
- Monamine oxidase (MAO)
- Catechol-o-methyltransferase (COMT)
Primary sites of action for the adrenergic receptors:
- Alpha 1
- Alpha 2
- Beta 1
- Beta 2
- Alpha 1: periphery (and some organs)
- Alpha 2: central (negative feedback loops)
- Beta 1: heart
- Beta 2: other smooth muscle (throughout the body; counterbalances A1)
Functions of the alpha 1 postsynaptic receptor
- activation increases intracellular Ca (important for both release of NT’s and for must contraction)
- smooth muscle contraction
- peripheral vasoconstriction
- bronchoconstriction
- inhibits insulin secretion
- stimulates glycogenolysis and gluconeogenesis
- mydriasis (pupils dilate)
- GI relaxation
Functions of the alpha 2 PREsynaptic receptors in the PNS:
- decreases entry of Ca into the cell
- limits the release of NE
Functions of the alpha 2 POSTsynaptic receptors in the CNS:
- sedation
- decreased symp outflow
- decreased BP
- plt aggregation
Functions of the beta 1 postsynaptic receptor:
- Increases HR
- Increases conduction velocity (SA and AV nodes)
- Increases myocardial contractility
Functions of beta 2 postsynaptic receptor:
- smooth muscle relaxation
- peripheral vasodilation (esp sk musc)
- decreases BP
- Bronchodilation (overrides a1)
- increases insulin secretion
- increases glycogenolysis and gluconeogenesis
- Decreases GI motility
ParasympNS (PSNS) originates from what region of the spinal cord?
Craniosacral
What cranial nerves and what sacral nerves specifically are associated w the PSNS?
Cranial nerves III, VII, IX, and X
Sacral nerves 2,3,4
Where are the PSNS pre ganglia located?
near their organs of innervation
What do the post ganglia of the PSNS secrete?
Each (cholinergic fibers)
Anticholinergic = ________
Antiparasympathetic
What enzyme catalyzes the conversion of choline and Acetyl CoA into acetylcholine
Choline acetyltransferase
What mediates an ACh action potential?
Calcium
Each is deactivated by __________ into _________ and __________
Acetylcholinesterase
Choline and acetate
Up regulation and down regulation are controlled by?
Effector cell receptors
What is down regulation?
What does down regulation result in?
decrease in number but not response of effector cell receptors
results in tachyphylaxis
What is up regulation?
What is a possible result of up regulation?
increase in number but not sensitivity of receptors (d/t chronic depletion of catecholamines or use of antagonists
May account for withdrawal syndrome w B-blockers
The reduction in a physiologic response to a stimulus that is constant over time
desensitization
Type of desensitization/down regulation which
- occurs over seconds to minutes
- the receptor is unable to bind to the G protein (therefore the fx of the receptor is altered)
- caused by phosphorylation of the receptor and possibly the G protein
Uncoupling
Type of desensitization/down regulation which:
- occurs over minutes to hours but is still reversible
- moves receptors from the cell surface to intracellular compartments
- the receptors are therefore not accessible to ________?
Sequestration
receptors inaccessible to hydrophilic ligands
Type of receptor desensitization/down regulation which
- is the slowest process
- occurs over hours to days
- receptors are moved from cell surface to intracellular compartments, and then destroyed
Down regulation
during down regulation, are receptors available for recycling to the cell surface
No. A new receptor protein must be made from RNA to replace the lost receptors
What is autonomic tone?
Residual basal activity of the autonomic nervous system
What is pheochromocytoma?
uncontrolled release of catecholamines due to an adrenal gland tumor; constant SympNS stimulation
True or False: Catecholamines are both neurotransmitters and hormones
True
What are sympathomimetics?
Compounds that resemble catecholamines except that hydroxyl groups are not present in both the 3 and 4 positions of the benzene ring
How are sympathomimetics classified?
according to their selectivity for simulating alpha and/or beta receptors
Do synthetic non-catecholamines act directly or indirectly? Why?
Both
indirectly - cause the release of NE (an endogenous NT) from postganglionic sympathetic nerve endings
directly - activate the adrenergic receptors directly
Indirect-acting sympathomimetics are characterized mostly by ______ and _______ adrenergic effects because NE is a weak _______ agonist
Alpha and Beta 1
Beta 2
Does denervation or depletion of NT, as w repeated doses of sympathomimetic, blunt the pharmacologic responses normally evoked by an indirect-acting sympathomimetic drug?
yes
Name 2 direct-acting synthetic noncatecholamines
phenylephrine and methoxamine
T/F: Synthetic noncatecholamines are less potent than catecholamines
True
Does denervation or depletion of NT prevent the activity of direct-acting sympathomimetics?
no
T/F: Most direct sympathomimetics activate alpha and beta receptors, but the magnitude of alpha and beta activity varies greatly from pure alpha agonist phenylephrine to pure beta agonist isoproterenol.
True
3 types of sympathomimetics
- Naturally occurring catecholamines
- Synthetic catecholamines
- synthetic non-catecholamines (indirect and direct acting)
All Sympathomimetics are derived from:
beta phenylethylamine
Presence of hydroxyl groups on the 3 and 4 position of the benzene ring of the B phenylethylamine creates a _________. Drugs with this composition are ________.
catechol
catecholamines
CV/resp pharmacologic effects of sympathomimetics
- vasoconstriction - cutaneous and renal circulations
- vasodilation - skeletal muscle
- bronchodilation
- cardiac stimulation
- increased HR
- increased contractility
- vulnerability to dysrhythmias
Other pharmacologic effects of sympathomimetics (hepatic, metab, endocrine, CNS)
- Hepatic - Glycogenolysis
- Liberation of free fatty acids from adipose tissue
- Endocrine - modulation of insulin, renin, and pituitary secretion
- CNS - stimulation
What is the only time a vasopressor should be used?
When a pt’s BP must be increased immediately to avoid pressure-dependent reductions in organ perfusion w subsequent ischemia
The pharmacologic response caused by a sympathomimetic is related to:
The density of the alpha and beta receptors in the tissues
T/F: An inverse relationship exists b/t the conc’n of available sympathomimetic and the number of receptors.
True
For example, increased plasma conc’n’s of NE results in a decrease in the density of B-adrenergic receptors in cell membranes
The response evoked by a sympathomimetic is influenced by:
The anatomical distribution of a and B receptors
Why does NE have minimal effects on airway resistance
Because adrenergic receptors in bronchial smooth muscle are mostly B2 and thus not stimulated by this catecholamine
Why are epidural and isoproterenol potent bronchodilators?
because they are able to activate B2 receptors
What structure must a drug have to be rabidly inactivated by both MAO and COMT?
3,4 dihydroxybenzene (catecholamine)
Name the enzyme present in liver, kidneys, and GI tract that catalyzes oxidative deamination
Monoamine oxidase (MAO)
Name the enzyme that methylates the hydroxyl group of catecholamines
Catechol-o-transferase (COMT)
Name 2 ways to potentiate the effects of epinephrine
- inhibition of reuptake
- inhibition of COMT or MAO
completeness of this reuptake mechanism and metab is evidenced by:
minimal presence of unchanged catecholamines in the urine
Name some ways the metabolism of synthetic non-catecholamines differs from the metab of catecholamines
synthetic non-catecholamines:
- lack a 3-hydroxyl group
- aren’t metab by COMT
- depend of MAO for metab
- are metabolized more slowly than catechols
- duration of action is prolonged by inhibition of MAO
How may pts on MAOI’s respond when treated w synthetic non-catecholamines?
they may manifest exaggerated responses
