Autonomic (Cholinergic/Adrenergic) Drugs Flashcards
Compare the transmission of signals from the CNS to the target via the SNS and PSNS pathways
SNS signals are from the spinal cord. Sent via the short pre-ganglionic axon. Transmission to the longer post ganglionic axon is done via the nicotinic receptor and acetylcholine release. At the target organ, norepinephrine (or Ach or dopamine) bind to adrenergic receptors.
PSNS signals come from the brainstem or sacrum via a long pre-ganglionic axon. Signal transmitted via a nicotinic receptor and Ach to the shorter post-ganglionic axon. At the target organ, Ach is released and interacts with muscarinic (aka. cholinergic) receptors.
What are the steps of signal transmission at the ganglion level
- Acetyl-CoA + choline result in acetylcholine formation. In vesicles.
- Depolarization (influx of Na+) via an action potential.
- The Ca voltage gated ion channel open resulting in increased Ca2+. Influx results in vesicle fusion and release Ach.
- Ach binds nicotinic receptors via ligand gated ion channels which bind and depolarize the post synapse axon.
- Ach also binds the pre-synaptic nicotinic receptor. Negative feedback due to binding results in less Ach release
- Acetylcholinesterase degrades Ach in synaptic cleft
- Acetyl-CoA and choline resorbed
What are the steps of signal transmission from the SNS at the target tissue
- The post-ganglionic action potential causes release of norepinephrine
- NE bind the post-synaptic adrenergic receptor which is a G protein coupled receptor. This causes signal transduction and sympathetic effect.
- NE will also bind the pre-synaptic adrenergic receptor. Negative feedback will ensue resulting in less NE release and increased degradation.
How is norepinephrine degraded in neurons
Metabolism is done via catechol-o-methyltransferase (COMT). After absorption into the neuron it can be degraded in the mitochondria by monoamine oxidase (MAO). It could also diffuse away and be metabolism in plasma, liver, or kidneys.
What are the steps of signal transmission from the PSNS at the target tissue
- The post-ganglionic action potential causes release of Ach
- Ach bind the post-synaptic muscarinic/cholinergic receptor which is a G protein coupled receptor. This causes signal transduction and parasympathetic effect.
- Ach will also bind the pre-synaptic adrenergic receptor. Negative feedback will ensue resulting in less Ach release and increased degradation by AchE.
What is the structure of adrenal glands and the associated function?
There are 3 zones in the cortex.
1. zona glomeerulosa: salt - mineralocorticoids
2. zona fasiculata: sugar - glucocorticoid
3. zona reticularis: sex - androgens
Medulla: stress - cortisol
What is the function of the adrenal gland in the context of autonomic stimulation
The adrenal gland is a modified sympathetic ganglion. The chromaffin cells release NE which target alpha receptors resulting in a vascular effect. They can also release epinephrine which bind both alpha and beta receptors which results ini vasodilation of skeletal muscle, skin, and kidney. It also increases cardiac output. It may vasoconstrict some other vasculature.
If you have excess epinephrine it will have an preference for alpha receptors causing more vasoconstriction which increases blood pressure.
What are the consequences of PSNS overstimulation
DUMBBELLS
diarrhea
urination
miosis
bradycardia
bronchorrhea
emesis
lacrimation
lethargy
salvate/sweat
Compare the target organs of SNS and PSNS stimulation
SNS targets the radial smooth muscle around eye, salivary glands, arterioles, lung, heart,stomach, GI, kidney, and bladder.
PSNS targets the constricting circular muscle in eye, lacrimal gland, salivary gland, heart, lung, GI, bladder, penis, prostate. PSNS has no direct effects on vascular smooth muscle.
What are the factors impacting adrenergic activation
It depends on receptor subtype and the tissue it is expressed on. The effect of NT depends on what receptors are expressed and activated
How does autonomic innervation impact cardiovascular structures.
Heart is subject to PSNS and SNS impacts
Vasculature is only impacted by SNS. Vasoconstriction and dilation is controlled by the amount or frequency of SNS stimulation
What type of drug is a sympathomimetic?
adrenergic agonist
What are the potential mechanisms of action for adrenergic agonists?
It can be direct via endogenous catecholamines like norepi and epi or via specific adrenergic receptor agonists (dobutamine)
It could also be from indirect mechanisms like making them release more catecholamines or reducing catecholamine metabolism by inhibiting MAO/COMT or reducing reuptake
Drugs can act via both mechanisms
Discuss the pros and cons of alpha 2 agonists
It is a good pre-med and effective for large animal standing procedures
Some negative effects include
- reduced cardiac output which is independent of the dose (a reduction in dose will result in the same magnitude of effect and but for a shorter duration)
- it can cause persistent bradycardia
- it can cause paradoxical excitation
it is important to use it in healthy animals
What are the contraindications for uses of alpha 2 agonist
- shock
- cardiovascular disease
What is the mechanism of action for alpha 2 agonists
It causes sedation via inhibiting norepi release a the brainstem (initially acts as norepi resulting in reduced subsequent release)
It causes analgesia via reduced neurotransmitter release in afferent pathways
It reduces cardiac output via initial vasoconstriction causing increased blood pressure, this is followed by reflex bradycardia. The pre-synaptic effect is bradycardia
How is the sedation and analgesia effect of alpha 2 agonists enhanced
If it is paired with an opiod
What type of drugs are parasympathomimetics?
either cholinergics or cholinoreceptor stimulants
What is the mechanism of action for cholinergic drugs
either
Muscarinic receptors that target nerves/heart/glands
nicotinic receptors which target ganglions which is also neuromuscular but under somatic control
What is the mechanism of action for cholinoreceptor stimulant drugs
It can act either directly or indirectly
Directly it can act as an agonist via alkaloid or choline esters
Indirectly it can act as a reversible or irreversible AchE inhibitor that can affect both muscarinic or nicotinic receptors
What type of drug is xylazine?
alpha2 agonist
What species is xylazine used in primarily?
horses and ruminants
What are the negative effects and potential contraindications of xylazine?
It is an alpha 2 agonist and so it has the associated impacts
- AV block
- reduced GI motility
- increased sweating
- increased uterine tone resulting in a risk of birth in pregnant animals
Compare the use of xylazine in horses and ruminants
Ruminants require 1/10th the dose when compared to a horse dose
