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
How is xylazine enhanced for sedation and analgesia?
It is usually combined with an opioid like butorphanol to increase its sedation and pain control effects
The analgesia effect is much shorter than the sedative effect
What drug class is detomidine
alpha 2 agonist
What species is detomidine used in primarily?
horses mainly and also ruminants
How is detomidine reversed?
atipamezole an alpha 2 antagonist
Compare detomidine to xylazine
they are both alpha 2 agonists but detomidine is 50-100x more potent and it also offers better pain control and sedation with a reduced likelihood of inducing birth
How is xylazine reversed?
atipamezole or yohimbine
What type of drug is romifidine and how does it compare to detomidine?
It is another alpha2 agonist and it will cause effects for a longer duration and result in less ataxia
What drug class is dexmedetomidine
alpha 2 agonist
What species is dexmedetomidine primarily used in
small animal sedation
What is/are the adverse effect(s) of dexmedetomidine
50% of cats vomit
How to reverse dexmedetomidine
atipamezole
Compare the effect of Dexmedetomidine and Metomadine and why is there a difference?
Metomadine contains both isomers of the drug but only one isomer is the active one
Dexmedetomidine contains only the active isomer of the drug
They are essentially the same but dexmedetomidine is more potent
What drug class is dobutamine
beta 1 agonist
What are the adverse effects of dobutamine
It precipitates with bicarbonate
At high doses it can cause tachycardia
It must be given as a CRI
in cats it can induce seizures
What is the mechanism of action of dobutamine? How does this impact its use?
It is a positive inotrope and there is no change in heart rate at a normal dose
It is important to fix any hypovolemia before administration
What is the drug class of clenbuterol
beta 2 agonist
What species is clenbuterol used in
horses
What species is clenbuterol not used in
production animals
How is clenbuterol used? in what scenario?
as a treatment for equine asthma but now there are newer treatments like steroids, albuterol, and ciclesonide that are better
What drug class is epinephrine?
It is a non selective adrenergic agonist
When is epinephrine used in veterinary medicine and what is its mechanism of action
Low dose epinephrine is used for CPR to increase coronary perfusion and increase arterial blood pressure
- increasing cardiac output will also increase cardiac oxygen demands
It is used to treat anaphylaxis by inducing vasoconstriction
What route of administration is epinephrine given
IM
SC
IV
IT
What class of drug is prazosin
alpha 1 antagonist
What species is prazosin used in
small animals
What is prazosin used for primarily?
It was used for blocked cats but it isnt anymore
It now may increase the risk of these cats re-blocking
What is the mechanism of action for prazosin?
It causes vasodilation which reduced arterial and venous blood pressure
97% of it is protein bound
What drug class is atipamezole?
alpha 2 antagonist
What species is atipamezole used in?
small animals and horses
What is atipamezole used for and how is it administered?
It is used to reverse sedation and analgesia
It is administered IM
- in horses you can administer half the dose IM and the other half IV (inject slowly)
What should you consider/be aware of when reversing dexmedetomidine, ketamine, and butorphanol after a cat neuter (for example)? How would you reverse these drugs?
an alpha 2 antagonist like atipamezole
Ensure that you wait long enough for the ketamine to wear off
Also consider that when you are reversing sedation you are also reversing the analgesic effects as well
What drug class is esmolol?
beta 1 antagonist
What species is esmolol used in?
Cats
What is esmolol used for?
Primarily used in CPR and anesthesia of cats
What is the mechanism of action for esmolol and what are the associated adverse effects?
It acts to reduce heart rate and contractility (chronotropy and inotropy) resulting in reduced myocardial oxygen demand and reduced systolic and diastolic blood pressure
The adverse effects are hypotension and bradycardia
What drug class is neostigmine?
cholinergic
What is the mechanism of action of neostigmine?
It is a reversible acetylcholinesterase inhibitor which results in the reduced breakdown of Ach
What is neostigmine used for?
Used to treat myasthenia gravis but pyridostigmine is now the preferred treatment because it has less impact on the GI
It increases GI motility
What toxins is neostigmine similar to? How is it different?
It is similar to organophosphates and sarin gas
They both bind AchE receptors
Neostigmine reversibly binds these receptors and the toxins irreversibly bind them
What drug class is atropine?
anticholinergic
What drug class is glycopyrrolate?
anticholinergic
What is the mechanism of action of both atropine and glycopyrrolate? What are the effects?
They are competitive muscarinic antagonists resulting in
increased chronotropy
mydriasis
reduced secretions
bronchodilation
The effects are dose dependent
What are the adverse effects of atropine and glycopyrrolate?
tachyarrhythmias
ileus in horses
If used in combination with an alpha 2 agonist it increases the risk for myocardial hypoxia (increases cardiac work)
high doses of atropine are associated with mania
What is atropine and glycopyrrolate used for?
It is an emergency treatment for bradyarrhythmias
Treats equine recurrent uveitis and acute recurrent airway obstruction (RAO)
Used for opthalmic exam
When you need to increase heart rate
- when there is a risk for vagal bradycardia (eye sx)
- opioid use
- brachycephalic breeds with high vagal tone
How does atropine compare to glycopyrrolate?
Atropine does cross the BBB and glycopyrrolate does not
There are more neurologic effects associated with atropine vs glycopyrrolate
What is another name(s) for N-butylscopolammorium bromide? What drug class is it?
Hyoscine butylbromide aka buscopan
anticholinergic
What species is N-butylscopolammonium bromide used in?
horses only
What is the mechanism of action of hyoscine butylbromide? What are its effects?
It is similar to atropine
It is a competitive muscarinic antagonist
- increase chronotropy
- mydriasis
- reduced secretion
- bronchodialation
What is hyoscine butylbromide used for?
To treat spasmodic or gas colic
To treat choke
- relaxes the smooth muscle in the intestines and esophagus
To treat acute equine asthma
- bronchodilation
After administration of buscopan you ascult the horse to monitor heart rate. The heart rate is notably increased. What does this mean?
It it a normal response to the drug
You cannot use heart rate as a measure of pain when administering buscopan/hyoscine butylbromide/N-butylscopoammonium bromide
List 2 cholinergics commonly used in vet med
neostigmine
pyridistigmine
List 3 anticholinergics commonly used in vet med
atropine
glycopyrrolate
N-butylscopoammonium bromide/hyoscine butylbromide
List 3 alpha 1 antagonists commonly used in vet med
prazosin
acepromazine
carvedilol
List 5 alpha 2 agonists commonly used in vet med
xylazine
detomidine
dexmedeomidine
medetomidine
romifidine
List 1 beta 1 agonist commonly used in vet med
dobutamine
List 1 beta 1 antagonist commonly used in vet med
esmolol
List 2 beta 2 agonists commonly used in vet med
clenbuterol
albuterol
List the primary non selective adrenergic agonist used in vet med
epinephrine
What is the overall impact of alpha 1 receptors on the body
No impact on the heart
vasoconstriction systemically
reduced GI motility
increased muscle tone in the GI, bladder, uterus
What is the overall impact of alpha 2 receptor stimulation on the body
Initially:
vasoconstriction of the viscera and the muscle
reduced motility and secretion in GI
increased smooth muscle tone in the uterus
There is a pre-synaptic effect of alpha 2 receptors that reverse the initial effects resulting in sedation and analgesia
What are the overall effects of beta 1 receptor stimulation on the body
increased chronotropy and inotropy of the heart
What are the overall effects of beta 2 receptor stimulation on the body
Vasodilation of the viscera and muscles
reduced GI motility
increase lung secretion
Reduced tone in bronchioles, bladder, and uterus
What is the effect of stimulating dopamine receptors on the body?
vasodilation of the viscera and kidneys
What is the effects of muscarinic receptor stimulation on the body
Reduced chronotropy and inotropy
Increased GI motility and secretion
Reduced tone in GI sphincters
Increased tone in the bladder, uterus. and bronchioles
Increased lung secretion
