Autonomic Pharmacology Flashcards
What are the two main neurotransmitters for the efferent neurons?
Acetylcholine Norepinephrine
What is the origin of the sympathetic nervous system?
Thoracolumbar (T1-L3) in the sympathetic chain ganglion
What are the fiber lengths of the pre and post ganglionic neurons of the SNS?
Short pre-ganglionic Long post ganglionic
What is the origin of the parasympathetic nervous system?
Cranial Sacral (originate via cranial nerves)
Where are the ganglia located in the SNS?
Paravertebrial chain
How are is the SNS distributed throughout the body?
Widely distributed, post-ganglionic neurons may innervate more than one organ
What are the fiber lengths of the pre and post ganglionic neurons of the PSNS?
Long pre-ganglionicShort post ganglionic
Where are the ganglia located in the PSNS?
Near the effector tissue
What is the typical response of the SNS?
Flight of fight
How is the PSNS distributed throughout the body?
Discrete, post-ganglionic neurons are not branched and are directed to a specific organ
What is the primary response of the PSNS?
Rest and digest
What are the two types of nicotinic receptors?
Nicotinic neural (Nn)Nicotinic muscular (Nm)
How does the SNS and the PSNS react to each other?
Opposing, antagonistic effects
What type of receptors and neurotransmitter are at all preganglionic junctions?
Nn receptors agonized by Ach
What type of receptor and neurotransmitter are at the sweat glands?
Muscarinic receptors agonized by Ach (sweat glands are innervated by the SNS)
What type of receptors and neurotransmitters are at adrenergic tissues?
Alpha and beta receptors are agonized by Norepinephrine
The term adrenergic is used to describe which type of drugs?
Epinephrine
Norepinephrine
Dopamine
What dopamine receptor is predominately peripheral?
D1 (D2 more important for the brain)
What are nonadrenergic/noncholinergic neurotransmitters?
Neurotransmitters and or co-transmitters that function in the PNS, unsure of exact role currently
What are the criteria for a neurotransmitter?
- Synthesis2. Storage3. Release 4. Action at receptor5. Termination
What two components make up an acetylcholine molecule?
Acetyl CoACholine
What enzyme breaks down acetylcholine?
Acetylcholinesterase, choline is recycled by transporter
What is unique about the choline transporter?
It is rate limiting
How many subtypes are there of muscarinic acetylcholine receptors?
M1-M5
What distinguishes the two subgroups of muscarinic Ach receptors?
The two subgroups are stimulatory and inhibitory, the difference is the second messenger
What type of receptor is the muscarinic Ach receptor?
G-protein coupled receptor
What type of receptor is the nicotinic Ach receptor?
Ligand-gated Na and K depolarizing channel
Where are muscarinic Ach receptors located?
Parasympathetic effector tissues (heart, endothelium, smooth muscle and glands)
Where are nicotinic Ach receptors located?
Autonomic ganglia-NnCNS-NnSkeletal muscle innervated by somatic nerves-Nm
How are blood vessels affected by the PSNS?
Blood vessels are only innervated by the SNS, but M2 receptors on endothelium can cause vasodilation
How is norepinephrine synthesized?
Tyrosine –> DOPA –> Dopamine –> NE
What two enzymes break down Norepinephrine?
MAOCOMT
How is the action of Norepinephrine terminated?
Re-uptake
What type of receptors are alpha and beta?
G-protein coupled receptors
What is the difference between the two alpha receptors?
A1 is excitatory (increased Ca)A2 is inhibitory (decreased cAMP)
What are the ligands for the alpha and beta receptors?
Epinephrine
Norepinephrine
Dopamine (at high doses)
Which adrenergic receptor is most susceptible to change?
Betas are susceptible to adaptive changes (up or down regulate)
What are the autonomic effector tissues?
Hear, Kidney, Liver, Smooth muscle, Somatic motor, and Fat cells
What adrenergic receptor causes the release of renin?
Beta1
What effects does the beta2 receptor have on the liver?
Glycogenolysis and gluconeogenesis
Why might a beta2 agonist be given to a patient in preterm labor?
It causes uterine relaxation
How does the SNS effect the eye?
Contracts radial muscle –> pupil dilationEye Ciliary –> increased secretion of aqueous humor
What muscarinic receptor is agonized for the GI/GU and eyes?
M3
What receptors are on the sweat glands?
Thermoregulatory-MuscarinicApocrine (stress)-Alpha
What effect does the B3 receptor exhibit?
Lipolysis
Why don’t we use ganglionic blocking drugs?
Blocks ALL autonomic output
What is the chemical composition of Acetylcholine?
Quaternary ammonium that works on both Nn and Nm ach receptors
Why aren’t other cholinergic agents able to be broken down by AchE?
Other cholinergic agents do not have an ester like Ach and cannot be broken down by AchE
How does AchE break down Ach?
AchE hydrolyzes Ach
What type of AchE inhibitor is Neostigmine?
Carbamate, it is reversible
What type of AchE inhibitor is Edrophonium?
Alcohol, it is reversible
What is the only type of irreversible AchE inhibitors?
Organophosphates
What is the prototype muscarinic antagonist?
Atropine
What were ganglionic blockers used for?
Hypertensive emergency
Why don’t catecholamines cross the BBB?
They are Quaternary Amines, charged particles
What adrenergic receptors does Epinephrine agonize?
A1 A2 B1 B2 B3
Why do we used Epinephrine with local anesthetics?
It constricts the blood vessels and keeps the LA in the area for a longer period of time
What adrenergic receptors does Norepinephrine agonize?
A1 A2 B1 (little effect on B2) more alpha effects
What type of drug is isoproterenol?
Non-selective beta agonist (B1 & B2)
What adrenergic receptor does Dobutamine agonize?
B1
What adrenergic agent has the highest affinity for Alpha receptors?
Epinephrine > Norepinephrine > Isoproterenol
What adrenergic agent has the highest affinity for Beta receptors?
Isoproterenol > Epinephrine > Norepinephrine
What are some side effects of an Alpha1 specific antagonist?
Nasal congestionOrthostatic HoTNTachycardia
Why isn’t there a Beta2 specific antagonist?
We do not want to cause bronchoconstriction
What is the chemical structure of catecholamines?
Benzene ring with two HO
What is the function of COMT?
An enzyme that deactivates the catecholamine dopa, dopamine, epinephrine and norepinephrine
What is the function of MAO?
An enzyme that catalyzes the oxidation of amines
What cholinergic antagonist treats profound bradycardia most effectively?
Atropine > Glycopyrolate > Scopolamine
What are additional benefits of using anti-muscarinic agents?
Prevents salivationPost-op N/VSedation
What is the only anti-muscarinic agent that doesn’t cross the BBB?
Glycopyrolate
What is the concentration of Atropine?
0.4mg/mL
What is the does of Atropine?
15-70mcg/kg
What is the onset, peak and duration of Atropine?
Onset: 15-30sPeak: 2minDuration: 1-2hrs
What is the concentration of Glycopyrolate?
0.2mg/mL
What is the dose of Glycopyrolate?
10-20mgc/kg
What is the onset, peak and duration of Glycopyrolate?
Onset: 1minPeak: 5minDuration: 2-4hrs
What is the concentration of Edrophonium?
10mg/mL
What is the dose of Edrophonium?
0.5-1mg/kg
What is the onset, peak and duration of Edrophonium?
Onset:30-60 secsPeak: 1-5minDuration: 5-20min
What is the concentration of neostigmine?
0.5-1mg/mL
What is the dose of Neostigmine?
0.04-0.08mg/kg
What is the onset peak and duration of Neostigmine?
Onset: 1-3minsPeak: 5-7minsDuration: 40-60mins
What are the three types of indirect acting adrenergic agonists?
NT releaseRe-uptake inhibitorsMAOI
What is the prototype beta2 agonist?
Albuterol
What is the prototype alpha1 antagonist?
Prazosin
What are the three mechanisms of neurotransmitter termination?
ReuptakeEnzyme degradationDiffusion
How does the botulinum toxin affect neurotransmission?
Prevents the release of Ach from the vesicle
What are the muscarinic receptor ligands?
AchMuscarine
What are the nicotinic receptor ligands?
AchNicotineSucs
What enzyme breaks down cGMP?
PDE5, phosphodiesterase 5
What enzyme makes NO for L-arginine in the muscarinic receptor mediated vasodilation?
Nitric oxide synthase
What types of drugs are indirect acting cholinergic agonists?
AchE inhibitors
What mechanism causes vasoconstriction with alpha1 agonists?
Once agonized there is an increase in Ca causing calmodulin activation and increases actin myosin interaction
