Exam 3 - ANS & Cholinergic Agonists Flashcards
Two nervous divisions
- PNS: between periphery and CNS
- CNS: brain/spinal cord
CNS components
- Brain: process input/output
- Spinal cord: conduit between body and brain
PNS divisions
- Efferent: carry away from CNS
- Afferent: carry sensory to CNS
- Sensory = afferent
- Motor = efferent
Afferent division
- sensory
- reflex arcs
- provide sensory signals for efferent to respond to
Efferent division
- divides into ANS and SNS
- ANS: autonomic control
- SNS: conscious control
Somatic Nervous System (SNS)
- voluntary
- sensory and motor neurons
- sensory: signals to CNS
- motor: can only stimulate, not inhibit
Neuromuscular junction
- Ach is neurotransmitter
- ionotropic: excites skeletal muscles
- AChE degrades Ach in the junction
ANS vs Endocrine
- ANS: electrical impulses and neurotransmitters
- Endocrine: hormonal signals
ANS divisions
- Enteric: brain of gut
- Parasympathetic: rest/digest
- Sympathetic: fight/flight
ANS motor division paths
Preganglionic - cell body in CNS Postganglionic: -cell body in middle ganglion -terminates at effector organ
Neurotransmitter substances
- BOTH preganglionic: Ach
- Para post: Ach
- MOST symp post: NE
Parasympathetic neurons arise from:
Cranial and sacral regions
Sympathetic neurons arise from
Thoracic and lumbar regions
Fiber lengths
- Symp pre: short
- Symp post: long
- Para pre: long
- Para post: short
Nicotinic receptor
- binds to Ach
- in between pre and postganglionic fibers
- aka presynaptic junction
Enteric system
- part of ANS
- GI / pancreas / gallbladder
- made up of myenteric and submucosal
Sympathetic nervous system
- continually active: vascular tone
- adjusts to stressful situations
- up HR/BP/Blood flow to skeletal and heart
- dilation of pupils/bronchioles
- diffuse response: all at same time
- adrenal medulla releases Epi and NE
Parasympathetic nervous system
- maintain homeostasis
- drop HR
- constrict bronchioles/pupils
- Discrete response: not all at same time
- SLUDD
- salivate/lacrimate/urinate/digest/defecate
Location of ganglia in symp vs para
- Symp: near spinal cord
- Para: in or near organ
Distribution of symp vs para
- Symp: wide
- Para: limited
Glands with only sympathetic innervation
- sweat glands
- adrenal medulla
- kidney
- pilomotor muscles
BP is controlled by
Sympathetic nervous system
CNS and the ANS
- reflex arcs
- emotions can influence ANS
Signaling between cells
- hormones
- local mediators (don’t enter blood)
- neurotransmitters (Ach and NE)
- all bind to receptors
- too hydrophilic to pass through
Inotropic
Ion channel opens
Metabotropic
Binding + 2nd messenger system
Ach
- cholinergic neurons used for: - somatic system - preganglionic of ANS - postganglionic of para
Cholinergic receptors
- nicotinic
- muscarinic
NE and Epi
- adrenergic neurons
Used in: - postganglionic of symp (all except sweat)
Adrenergic receptors
- Alpha 1 and 2
- Beta 1 and 2
Midbrain and medulla
- important processing part of brain
- integrates ANS/sensory input/endocrine system
Primary controlled variable in CV function
- MAP
- autonomic drugs can really affect MAP
Effects of slow infusion of NE
- adrenergic
- vasoconstrictor
- positive chronotrope (up HR)
- positive ionotrpe (up contractility)
- MAP and HR should go way up…..but…
- increase in SVR and MAP….but decrease in HR
- due to integration of cerebral cortex (response mech)
- mech is barroreceptors
- not true for transplant patients (no innervation of vagus)
Autoreceptor
- Neuron responds to chemical it releases
- inhibitory
- like NE
- presynaptic
Heteroreceptor
- neuron responds to chemicals released from other neurons that synapse with nerve ending
- inhibitory
- some vagal nerve fibers inhibit NE release
- presynaptic
Postsynaptic regulation
- can up or down regulate receptors
- receptors can be desensitized to previous activity
- transmitter can act on more than one type of receptor:
- one may inhibit
- one may excite
- means of regulation
Ach sites of action
- Preganglionic adrenal medulla
- Preganglionic symp and parasympth
- postganglionic para
- postganglionic sweat glands
- skeletal muscles of somatic
Step 1 of cholinergic neurotransmission
- Choline into neuron via Na cotransport
- choline + acetyl coenzyme A = Ach
- Choline acetyltransferase does this
- uptake of choline is rate limiting step
Step 2 of cholinergic neurotransmission
- Ach packed into vesicles via active transport Vesicles contain: - Ach - ATP - proteoglycan
Step 3 of cholinergic neurotransmission
- release of Ach into cleft
- voltage gated Ca channels open when action potential arrives….Ca moves in…vessicle fuses with membrane….Ach released
Step 4 of cholinergic neurotransmission
- Ach binds to target receptors to get response
- Ach also binds to pre-synaptic membrane to prevent over-release
Step 5 of cholinergic neurotransmission
- Ach degraded in cleft via AchE
- Ach cut into choline and acetate
Step 6 of cholinergic neurotransmission
- Na cotransport brings choline back into neuron
Muscarinic receptors
- high affinity for muscarine
- G protein coupled
Innervates: - smooth muscle
- cardiac muscle
- glandular tissue
- mimics effect of parasympathetic
- aka parasympathomimetic
Muscarinic subtypes
- 5 exist and all 5 on neuron
- other locations besides neuron:
- M1: gastric
- M2: cardiac and smooth muscle
- M3: bladder and smooth muscle
Muscarinic activation
- rest and digest responses
- constrict at high dose
- dilate vessels at low dose
Nicotinic receptors
- high affinity for nicotine
- ligand gated ion channels (ionotropic)
- low [ ]: stimulates receptor
- high [ ]: inhibits receptor
Located in:
-CNS
-adrenal medulla
-autonomic ganglia
-NMJ muscles
Direct acting drug
- bind to receptor
Indirect acting drug
- Blocks AChE
- provoke response at ALL cholinoreceptors
- short acting
Nicotine
- direct acting nicotinic agonist
- easily absorbed / lipophilic
Carbachol aka Miostat
- direct acting muscarinic AND nicotinic agonist
- non selective… so can’t be used systemically
- otherwise too broad of effect
- produces constriction of eye during surgery
- reduce pressure in glaucoma or post surgery
Bethanechol / Urecholine
- direct acting muscarinic agonist
- produces urination
- short action
- acts on smooth muscle of bladder
Pilocarpine / Salagen
- direct acting muscarinic agonist
- less potent but can penetrate CNS
- used on eye for miosis and reduce pressure
- stimulates sweat, tears, saliva
- research for Alzheimer’s
- For Sjögren’s syndrome (dry mouth/no tears)
Edrophonium / Enlon
- indirect acting reversible cholinergic agonist
- acts for 10-20 min
- diagnoses myasthenia gravis
- chronic neuromuscular disease
- negative effect on nicotinic receptors ion NMJ
- not long term treatment
Physostigmine
- indirect acting reversible cholinergic agonist
- acts for 30 min - 2 hours
- treats glaucoma / anticholinergic overdose
Neostigmine
- indirect acting reversible cholinergic agonist
- like physostigmine but cannot enter CNS
- greater effect on skeletal
- antidote for NMJ blockers
- management of myasthenia gravis
Pyridostigmine
- indirect acting reversible cholinergic agonist
- chronic management for myasthenia gravis
- lasts for 4-6 hours
Organophospahtes
- indirect acting IRREVERSIBLE cholinergic agonist
- permanently deactivates AchE
Actions: - cholinergic stimulation
- paralysis
- convulsions
- breathing difficulties
- once used topically for glaucoma
Organophosphate poisoning
SLUDGE
-salivation/lacrimation/urination/diarrhea/GI upset/emesis
Example:
- Sarin gas:
-eye pain/drooling/SOB/SLUDGE/weakness/headache
Organophosphate poison therapy
Pralidoxime / 2-PAM
- reactivate AchE
- no CNS entering
Atropine
- competitively binds to muscarinic receptor
- can get into CNS
- no direct effect on AchE
