Introduction Into Autonomic Pharmacology Flashcards
Compounds associated with the parasympathetic system?
Acetylcholine
Muscarine
Nicotine
Compounds associated with the sympathetic system?
Norepinephrine/Noradrenaline
Epinephrine (Adrenaline)
Cholinergic drugs influence….
Adrenergic drugs influence…
Parasympathetic
Sympathetic
The receptors of the PANS are named after exogenous agents. What are they
Muscarine and Nicotine
Sympathetic preganglionic fibers leave the CNS through which spinal nerves?
Thoracic and Lumbar
Parasympathetic preganglionic fibers leave the CNS through which spinal nerves?
Cranial Nerves
Sacral
All preganglionic nerves release _____ into post ganglioncic nerves expressing ____ receptors
Acetylcholine
Nicotinic Cholinergic Receptors
Somatic motor neurons release _____ directly onto _______ receptors
Acetylcholine
Nicotinic cholinergic receptors
Parasympathetic postganglionic nerves release _____ onto organs with _____ receptors
Acetylcholine
Muscarinic
Sympathetic postgangionic nerves primarily release _____ that can bind to _____ receptors
Norepinephrine
Adrenergic
Sympathetic postganglionic nerves acting on skin release ____ onto _____ receptors
Acetylcholine
Muscarinic Receptors of Thermoregulatory Sweat Glands
Sympathetic postganglionic nerves acting on the kidneys release ____ to bind ______ receptors
Dopamine
Dopamine D1 to cause vasodilation
Postganglionic sympathetics acting on the adrenals cause….
Epi and a little bit of NE release into the bloodstream
Which muscarinic receptors are found postsynaptically?
Presynaptically?
Post – 1, 3, 4, 5
Pre – 2, 4
Why have muscarinic receptors presynaptically?
Inhibitory autoreceptors
ACh in the synapse is quickly metabolized by ______ and ______
Acetylcholinesterase
Butylcholineesterase
ACh metabolism generates…
Acetate and Choline
What does ChAT do?
Choline AcetylTransferase transfers an acetyl to choline from AcCoA to remake ACh.
ACh is taken back into synaptic vesicles by…
Acetylcholine transporter (vAchT)
Sympathetic receptors found post synaptically?
Pre synaptically?
Post – alpha1, beta1, beta2
Pre – alpha2, beta2
How is NE made?
Tyrosine turned to DOPA by tyrosine hydroxylase
DOPA to Dopamine by Aromatic Acid Decarboxylase
Dopamine to NE by dopamine beta-hydroxylase
After release, NE is returned by ____
NET (NorEpinephrine Transporter)
What two fates may occur for NE after its reuptake?
MAOs could turn it into dihydroxyphenylglycol
Taken into vesicles by VMAT (vesicular monamine transporter)
Postsynaptically, NE is metabolized by ______ into ______
COMT (catechl-0-methyltransferase
Normetanephrine
How do Methylphenidate (Ritalin) and amphetamines (adderall) increase NE/DA release?
Blocking VMAT
Indirect activation of SANS
Classification of drugs that mimic acetylcholine? Block acetylcholine?
Parasympathomimetic
Parasympatholytic
Classification of drugs that mimic NE? Block NE?
Sympathetomimetic
Sympatholytic
Three sites you might look for Nicotinic Cholinergic receptors?
Ganglionic
Skeletal Muscle
Neronal
Nicotinic cholinergic receptors consist of ___ subunits
5
Nicotinic cholinergic receptors – why should be care about their subunits?
The arrangement decides on function and affinity
ex. the pentameric alpha7 homomeric Ach receptor can bind 5 ACh molecules
Gq coupled Muscarinic receptors include…
M1, M3, M5
Gi coupled Muscarinic receptors include…
M2, M4
In PANS, the most important presynaptic muscarinic receptor is _____ and the most important postsynaptic receptors is _____.
M2
M3
M2 is primarily located where?
Heart and Bladder
Also, Certain brain regions
Which muscarinic receptors are usually found in the brain?
M1, M4, M5
Function of M5 receptors?
Vasodilation of cerebral blood vessels
Describe the structure of muscarinic receptors?
GPCRS
7 transmembrane
Effects of M3 activation?
Increases in calcium
Neuronal activation through a PLC mechanism
Effects of M2 activation?
Inhibit NT release by activating GIRK and inhibiting VGCC via AC inhibition
Adrenergic receptors are invited into ____ subtypes with three isoforms each
alpha1, alpha2, and beta
G couplings for alpha1, alpha2, and beta subtypes
Alpha1 – Gq-coupled
Alpha2 – Gi-coupled
beta – Gs-coupled
Which adrenergic receptors are primarily responsible for SANS responses?
alpha1 and beta
Where are alpha2 receptors at?
Mostly CNS
also GI tract and pancreas
The radial muscles of the iris contain ____ receptors
alpha1
aka. THE DILATOR
The circular muscles of the iris contain _____ receptors
M3
Cause consriction, Miosis
The ciliary muscles contain ___ receptors
M3R
Why should we care about the M3R on ciliary muscles?
Contraction changes accommodation
Stretches trabecular meshwork, may reduce open angle glaucoma
Beta receptors are also present on the ciliary endothelium. Why?
They increase the secretion of aqueous humor
Blockage for glaucoma treatment
Blood Pressure is driven by what two factors
Flow (Q)
Resistance (R)
Flow is driven by what two factors
Stroke Volume (SV) Heart Rate (HR)
How can the autonomic nervous system control Bloodpressure?
Control R with Vasodilation/Vasoconstriction
Control SV by changing force of contraction
Control HR by changing frequency
ANS triggered vasoconstriction uses ____ receptors in vascular smooth muscles
alpha1
Activation of Beta2 receptors in vessels cause…
Relaxation of the smooth muscle
Vasodilation
What vessels are exposed to both alpha and beta stimulation, who wins?
Alpha
How are alpha1 and alpha2 receptors in vessel walls activated? What do they do?
Activated by Ep in the blood stream
Cause vasoconstriction
What is the significance of non-innervated M3 receptors in the endothelial lining?
They respond to exogenous cholinergic drugs
Activation of endothelial M3s causes….
Release of NO
Vasodilation by relaxation of the vascular smooth muscle
Trumps the vasoconstriction response of smooth muscle M3
ANS responses in the heart are primarily mediated by ____ and ____
M2 and beta1
The beta receptors in the heart cause…
Increase in HR and force of contraction
M2 receptors in the heart cause…
Slowed HR and decreased force of contraction
parasympathetic receptors in the lung are mostly ______. They are located on ______.
M3
Smooth muscle cells and mucosal glands
Activation of M3 in the lungs causes…
Bronchoconstriction
Release of Mucous
Sympathetic receptors in the lungs are primarily…. and located on…..
beta2
Smooth muscle cells
Activation of beta2 in the lungs causes
Muscle relaxation and Bronchodilation
Apocrine sweat glands (stress induced), Piloerection, and erector muscles use….
alpha 1 receptors
Where are apocrine sweat glands usually found
Armpits, Genatalia, Palms
What receptors are responsible for eccrine (thermoregulatory) sweating?
M3s
Parasympathetic and Sympathetic receptor and response.
Salivary Glands.
Both increase secretion – alpha1, M3
Parasympathetic and Sympathetic receptor and response.
Smooth Muscle Sphincters.
S = Contraction (alpha1) P = Relaxation (M2)
Parasympathetic and Sympathetic receptor and response.
Smooth muscle walls
S = Relaxation (alpha2, beta2) P = Contraction (M3)
Parasympathetic and Sympathetic receptor and response.
GI secretions.
S = Inhibition (alpha2) P = Increased (M1,M3)
Parasympathetic and Sympathetic receptor and response. Bladder Wall.
S = Relaxation (beta3) P = Contraction (M3)
Sympathetic receptor and response. Ureter and sphincter.
Contraction (alpha1)
Sympathetic receptor and response. Uterus.
Relaxation (beta2)
Contraction (alpha1)
Sympathetic receptor and response. Penis
Ejaculation (alpha1)
Sympathetic receptor and response. Liver.
Gluconeogenesis, Glycogenolysis (alpha1, beta2)
Sympathetic receptor and response. Fat cells.
Lipolysis (alpha1, beta1-3)
Sympathetic receptor and response. Kidney.
Increased renin secretion (beta1)
Sympathetic receptor and response. Pancreas.
Decreased Insulin release (alpha2)
Activation of M3 receptor on the bladder causes…
Contraction of the bladder wall
urge to urinate
Beta3 activition on the detrusor wall causes…
relaxation
Activation of alpha1 on the urethra causes…
contraction
