14b - Autonomic NS Flashcards
Direct-acting cholinergic agonist: non-selective cholinergic (N=M) examples
- Acetylcholine
- Carbachol: more metabolically stable, don’t use systemically=danger in stopping the heart (ex. used in the eyes)
Carbachol in the eyes
- Pupillary constriction
- Aqueous humor production effected
Direct-acting cholinergic agonist: nicotinic selective (N»M) example
- Nicotine
- *mix of PS and S effects
- *muscle twitching=stimulates skeletal muscle
Direct-acting cholinergic agonist: muscarinic selective (M»N) example
- Muscarine
- Bethanechol
- Pilocarpine
- *can still affect the heart (be careful if use systemically)
- *ophthalmically OR systemically for stimulating urination
Indirect-acting IRREVERSIBLE agonist (AChE inhibitors) examples
- Organophosphate/carbamate
- Insecticides
- *non-selective cholinergic (N=M)
- *accumulation of ACh
- **double stimulation in PS (ganglion and effector organs)
o SLUD
Indirect-acting REVERSIBLE agonist (AChE inhibitors) examples
- Edrophonium
- Neostigmine
- *non-selective cholinergic (N=M)
- *used after a paralysis drug (specifically in skeletal muscle)
Cholinergic antagonists: muscarinic selective (M»N) examples
- Atropine: competitive
- Ipratropium
- *need to add A LOT of it to get a N effect
Cholinergic antagonists: Nn, ganglionic blocker (Nn>Nm»MM) examples
- Hexamethonium
- Trimethaphan
- don’t use in a conscious animal
- *controlled HYPOTENSION: stops firing of S and PS system=stops baroreceptor reflex=HR will remain low
Cholinergic antagonists: Nm, neuromuscular blocker (Nm>Nn»M) examples
- Tubocurarine
- Pancuronium
- Succinyl choline (initially an agonist, then antagonizes receptor)
o Ex. rapidly intubate and animal
*if add a lot of the drugs=will start to antagonize the next receptor
Dose effects in this course
- Assume all effects are possible
Atropine low dose: what do you see?
- Salivation: reduced
- Minor effect on inhibiting urination
- No HR increase or accommodation of vision
Atropine moderate dose: what do you see?
- Inhibits urination more
- Reduced salivation significantly
- Increased HR
- Decreased accommodation of vision
Atropine high dose: what do you see?
- Complete inhibition of salivation
- Max out HR
- Max decrease of accommodation of vision
ACh low to moderate dose IV
- No affect on activity at autonomic ganglia (nicotinic): not as highly perfused
- Decrease in diastolic BP=vasodilation (muscarinic)
- Decrease HR (muscarinic)
- Increase GI motility(muscarinic)
- *transient effects
Atropine given IV and then give ACh low to moderate dose again
- Atropine acts for many hours!
o Give it once and it persists - *muscarinic antagonists
- No change in gut motility
- Slight drop in diastolic BP (minor vasodilation)
10x dose of ACh: does atropine still antagonize?
- Yes
o Effect in gut - *autonomic ganglion=more firing (now seeing more prominent S effects)
o Increase in HR
o Increase in diastolic pressure (vasoconstriction) (atropine already reduced the vasodilation response)
Give alpha+beta blockers after atropine and then give high dose ACh: what would happen?
- Beta receptors in heart: no HR change
- Alpha receptors in arterials: no change in diastolic pressure
- NO effect in gut
- Autonomic ganglia stimulation is not effected (due to them being nicotinic)
o Would need an Nn blocker (ex. hexamethonium)
Give hexamethonium after atropine and then give high dose ACh: what would happen?
- No gut effect
- No HR or blood pressure response
- No increase in autonomic ganglion activity (maybe even below baseline firing)
Adrenergic agonists: E receptor selectivity
- Alpha 1 and 2
- Beta 1 and 2
- *EQUALLY
Adrenergic agonists: NE receptor selectivity
- Alpha 1 and 2
- Beta 1 > beta 2
Adrenergic agonists: Isopreterenol receptor selectivity
- *cardiac support in an emergency
- Beta 1=2»_space;alpha
Adrenergic agonists: dopamine
- D1>beta1>beta2>alpha
- NT but effects outside of CNS
- Really high doses=loses selectivity (stimulates D1
D1 receptors:
- vasculature (especially renal vasculature)
- stimulated=dilates
Ex. use in a shocked animal to prevent irreversible kidney damage due to lack of blood flow
Dobutatmine
- Less peripheral dilation
- More pure cardiac stimulation
- *beta1>beta2>alpha
Phenylephrine
- Predominantly vasoconstriction
o Support BP in crashing animal OR decongestion - *alpha1>alpha2»beta
Clonidine; xylazine
- Cause sedation
- *alpha2>alpha1»beta
Terbutaline, clenbuterol, salbutamol
- Beta 2 agonists
- *bronchodilate (ASTHMA)
- Too high dose=beta 1 receptors (monitor)
- *beta 2>beta1»alpha
Humans: beta-3 agonists are used for (ex. mirabegron)
- Overactive bladder treatment
- Target detrusor muscle=relaxes it=less likely to urinate
- *selection for beta-3 may not actually be that good (still needs improvement!)
Glaucoma (cause and effects of muscarinic and beta-adrenergic stimulation)
- High intraocular pressure
o Too much aqueous humor production
o Impair aqueous humour outflow - Muscarinic receptor stimulation increases aqueous humour outflow
- Beta-adrenergic stimulation increases aqueous humour production
Alpha antagonists examples
- Prazosin
- Phenoxybenzamine
- Phentolamine
- Tolazone, atipamezole
Prazosin
- Alpha COMPETITIVE antagonist
- Alpha1»»>alpha2
o Old school ANTI-HYPERTENSIVE - *works too good so not used in human med anymore
Phenoxybenzamine
- Alpha IRREVERSIBLE antagonist
- Alpha1>alpha2
Phentolamine
- Alpha antagonist
- Alpha1=alpha2
Tolazine, atipamezole
- Alpha antagonist
- Alpha2»alpha1
- *used to REVERSE the alpha 2 agonists used for sedation
Mixed antagonists examples
- Labetalol, carvedilol
- *less selective
Labetalol, carvediol
- Mixed antagonist
- Beta1=beta2>alpha1>alpha2
- *for HEART FAILURE
o Beta1 antagonism: lower HR
o Beta 2 antagonism: tolerated
o Alpha 1 antagonism: reverse excess vasoconstriction
Beta antagonists examples
- Metoprolol, acebutolol, atenolol
- Propranolol, timolol
Metoprolol, acebutolol, atenolol
- Beta antagonists
- Beta1»>beta2
o Heart: anti-arrhythmic (slow down heart)
o Juxtaglomerular apparatus: prevent renin release - *anti-hypertensive
Propranolol, timolol
- Beta antagonists
- Beta1=beta2
o non-selective - *preferred beta blocker to use ophthalmic (to control aqueous humour production)
- Can be a problem in asthmatics (would want to use a beta1 selective antagonist to reduce risk of triggering an asthma attack)
Give NE: effects on CV system
- *alpha1, alpha2, beta 1
- HR: increase stretch increases firing of baroreceptors=cause decrease in S firing, and increase in vagal firing=decrease HR (*due to large increase in TPR)
o *still increase in cardiac output (increased pulse pressure!) - BP: increase in TPR, increases diastolic P
- TPR: pure alpha2 response=vasoconstriction=LARGE increase in TPR
- CRASHING ANIMAL: if give NE=increased TPR could slow the heart down
o Maybe if really high dose of NE=override the baroreceptors and get increased HR
How can you have increased CO when HR is lower?
- Increased SV: due to strong beta1 stimulation in heart muscle cells
o increased contractility
Give E: effects on CV system
- Alpha1, alpha2, beta1, beta2
- CRASHING ANIMAL: E preferred
- HR: less stretch of baroreceptor=stimulate S and inhibit PS=NET effect is to increase HR (NOT fighting the direct stimulation of E on the heart=further support stimulator effect)
o HR and SV increased=CO increased! - BP: diastolic P decreased due to decreased TPR
- TPR: beta2=vasodilate=decrease slightly
Give Isoproterenol: effects on CV system
- Beta1=beta 2, little to no alpha stimulation
- HR: increased (CO increased!)
- BP: more decreased diastolic pressure
- TPR: large decreased due to beta2=vasodilation (add to stimulator effects on the pacemakers, baroreceptor not firing as much)
Give Dopamine (higher dose): effects on CV system
- D1>beta1>beta2>alpha
- Renal vascular dilation
- HR: increased (decreased stretch and the beta1 effects)
- BP: slight decrease in diastolic and increase in systolic
- TPR: slight decrease vasodilation (not as high receptor affinity for beta2)
o Dilation in renal vasculature
o Minor dilation in peripheral skeletal muscle vascular beds - *VERY DESIRABLE IN AN EMERGENCY
