ANS cont'd Flashcards
Phospholipase C system in heart
- Agonist activates alpha 1 and M3 receptors in smooth muscle
- Leads to activation of phospholipase C
3.Activates Ca release
- Activates Protein kinase
Adenylyl cyclase system in heart
1.Agonist activates either beta receptors OR alpha 2 and M2 receptors
(Alpha 2 and M2 inhibit; beta excites pathway)
- Leads to activation of adenylyl cyclase
3.Activates cAMP which then activates protein kinase
- REsults in further activation of enzymes leading to increased contraction in heart (beta 1) and bronchodilation (beta 2)
What deactivates cAMP?
Phosphodiesterase (PDE3)
-will convert cAMP to AMP which is the inactive form
M3 of vascular endothelium
- Activated M3 on vascular endothelium, results in Ca Calmodolin release which acts on NO synthase to produce NO
- NO activates Guanylyl cyclase. Increasing cGMP causing relaxation
**deactivated by Phosphodiesterase converting cGMP into GMP
M3 of vascular smooth muscle activation
M3 receptor activation leads to Ca released in muscle, resulting in contraction
Viagra (sildenafil) as a phosphodiesterase inhibitor
-Works on vascular smooth muscle leading to the vasodilation of pulmonary arteries in pulmonary hypertension
Black widow spider venom
-Causes an increase in Ach release due to increased leakiness of vesicles into synapse
-will cause mild SLUD, and muscle twitching
*not usually deadly…usually from an allergy
Botulinum toxin
-Blocks exocytosis (release) of Ach vesicles= anticholinergic effect
**no systemic application! Many side effects!
Acetylcholinesterase
Acetylcholinesterase= OFF SIGNAL
-Cholinesterase inhibitors prevent off signal from occurring. Results in high levels of Ach present in the synapse= Cholinergic receptors are heavily acitivated
What occurs with high levels of Ach that cannot be removed due to acetylcholinesterase?
- SLUD
salivation, lacrimation, urination, defecation - Blue- extremely low heart rate
- Twitching
Cholinergic receptor agonists or antagonists
Either increase or decrease cholinergic receptors
Adrenergic Neurotransmission
Associated with NE release into synapse which will bind to alpha and beta receptors
Metyrosine
Prevents the synthesis of NE
Amphetamine
Causes NE to leak out of nerve terminals
Results in excitation/stimulation (proadrenergic or indirect adrenergic agonist)
Bretylium
Prevents NE release
Cocaine
Blocks NE reuptake into the pre-synaptic neuron, resulting in accumulation of NE into the synaptic cleft
Increase HR, vasoconstriction, activated fight or flight response
Adrenergic receptor agonists or antagonists
-Either increase or decrease adrenergic alpha or beta receptors
Monoamine oxidase
Enzyme used to convert NE into metabolites
-antidepressants used to prevent it because increase serotonin production BUT will also result in higher levels of NE resulting in side effects
Neuromuscular junctions
Ach acts on Na channels
-Off signal=acetylcholinesterase
Acetylcholinesterase inhibitors
- Irreversible= insecticides
2.Reversible
- edrophonium
Tubocurarine or Pancuronium
Competitive antagonists for Ach at junction, preventing Ach effects on receptors
-Used when need flaccid paralysis (eg. orthopaedic procedures)
Non selective (N=M) direct acting cholinergic
Acetylcholine
Carbachol
Non selective (equal at N and M receptors)
Direct acting agonist nicotinic selective
Nicotine
-skeletal muscles and ganglion
-sympathetic and parasympathetic effects
-muscle twitching
Direct acting agonists muscarinic selective
-muscarine (least used)
-bethanechol
-pilocarpine
Muscarinic selective
-used opthalmically or systemically for stimulating urination
Non-selective cholinergic indirect acting agonists
Irreversible:
-organophosphate/carbamate insecticides
Reversible:
-edrophonium
-neostigmine
Equal between nicotinic and muscarinic
-accumulation of Ach; both parasympathetic and sympathetic stimulation
-SLUD
Muscarinic selective cholinergic antagonists
-atropine
-ipratropium
-competes for Ach binding at muscarinic receptors. Used as preanesthetic drug to prevent secretions/drooling, treat insecticide poisoning
Nicotinic neuronal blocker cholinergic antagonists
-hexamethonium
-trimethaphan
-block nicotinic neuronal more than nicotinic muscle receptors
-both parasympathetic and sympathetic systems.
-used in surgeries- cardiovascular for controlled hypotension
-cuts out baroreceptor keeping HR low
Nicotinic M blocker cholinergic antagonists
-tubocurarine
-pancuronium
-succinyl choline
-Selects for muscle nicotinic receptors over neural nicotinic receptors, and then muscarinic
Amount of atropine dose impact on various effects
At low dose:
-first see reduced salivation and low effect on urination inhibition
Moderate dose:
-higher effect resulting in decrease in salivation and urination
-increases HR
-Causes a decrease in eye accommodation (ability to see close)
High dose:
-max effect on decreased salivation, urination, and increased HR and accommodation
Dose dependent effects of Ach SLIDE
Nicotinic receptors in autonomic ganglia
Low dose: not enough to cause much of an effect
High dose: effect on nicotinic autonomic ganglion
Muscarinic receptors in heart and GI
Low dose: Ach causes vasorelaxation, drop peripheral resistance, drop diastolic pressure. Will increase GI motility
High dose: Ach cannot antagonize effects from previously given atropine. Can see an increase in HR and BP showing sympathetic effects BECAUSE parasympathetic effects are being blocked by Atropine
**give atropine: long lasting. Antagonize muscarinic responses/parasympathetic effects
alpha and beta blockers: block alpha 1 in arterioles, beta in heart
-no effect on GI and autonomic ganglia nicotinic, but blocks muscarinic in heart
Hexamethonium- blocks nicotinic receptors so see decrease in autonomic ganglia
Receptor selectivity of Epi
alpha1=alpha2
beta1=beta 2
Receptor selectivity of NE
alpha 1=alpha 2
beta 1 more than beta 2
receptor selectivity of Isopreterenol
beta1=beta2»_space;alpha
receptor selectivity of Dopamine
D1 (renal vasculature=dilation) > beta 1> beta 2> alpha
receptor selectivity of Dobutamine
Beta1>beta 2> alpha
receptor selectivity of Phenylephrine
alpha1 > alpha 2»_space;beta
**predominantly vasoconstriction
receptor selectivity of clonidine; xylazine
alpha2>alpha1»_space;beta
receptor selectivity of terbutaline
beta 2>beta 1»_space;alpha
-predominantly bronchodilate= asthma
receptor selectivity of Clenbuterol, salbutamol
beta 2 > beta 1» alpha
-predominantly bronchodilate= asthma
receptor selectivity of Mirabegron
beta 3> beta 1»_space;beta 2»_space; alpha
**common in humans for overactive bladder treatment. Selective for detrusor muscle to relax body wall and make it harder to urinate
NOT efficient for animal use because beta 3 more equal to beta 1(side effects)
Glaucoma
Condition of high intraocular pressure
-too much aqueous humour production
-impaired aqueous humour outflow
Glaucoma Receptor involvement
-Muscarinic receptor stimulation increases aqueous humour outflow
-Beta adrenergic stimulation increases aqueous humour production
Prazosin
-alpha antagonists
-alpha 1»_space;»> alpha 2
Phenoxybenzamine
-alpha antagonists
alpha 1 greater than alpha 2
Phentolamine
-alpha antagonists
alpha 1=alpha 2
Tolazoline, atipamezole
-alpha antagonists
alpha 2»_space;alpha 1
-reversal agents
Labetalol, carvedilol
-mixed antagonists
beta 1=beta 2 > alpha 1 > alpha 2
-used mostly in heart failure. Beta 1 antagonism to reduce heart issues. Alpha 1 receptor antagonism helps to reverse vasoconstriction
Metoprolol, acebutolol, atenolol
beta antagonists
beta 1»> beta 2
-block effects in heart, and kidney (prevents renin release)
Propranolol, timolol
-beta antagonists
beta 1=beta 2
-preferred beta blocker for controlling aqueous humour production, anti hypertension and anti arrhythmic
-Be careful!! Need beta 2 for asthmatics (need to prevent aggravation)
NE on Heart
Peripheral Resistance:
-vasoconstriction
-large increase in peripheral resistance
Blood pressure:
-increase in diastolic pressure (due to increase in peripheral resistance)
Heart Rate:
Increase stretch from increase BP, increases baroreceptors: decrease sympathetic, increase vagal= total decrease in HR
Epi on Heart
Peripheral Resistance:
-vasoconstriction, leading to increase in vasodilation to balance= decrease in peripheral resistance
BP:
-peripheral resistance decreased so diastolic decreases
HR:
Less stretch with baroreceptor=increase heart rate
Isoproterenol on heart
Peripheral Resistance: vasodilation, leading to decreased resistance
BP:
HR:
-decreased baroreceptor stretch= increase sympathetic= increase in HR
Dopamine on Heart
Peripheral Resistance: vasodilation leading to decreased resistance
BP: Increase systolic pressure, slight decrease in diastolic resistance
HR: decreased stretch=increase sympathetic= increase heart rate
Succinylcholine
Competes with acetylcholine. Initially causes twitching and then muscle paralysis
-good for intubation
