autonomics and cholergenics Flashcards
NS divisions
ANS
- INVOLUNTARY
- SYMPATHETIC (SANS) ANDPARASYMPATHETIC (PANS)
- HANDLES VISCERAL FUNCTIONS
- 2 NEURONS IN SERIES
- PRE- AND POST-GANGLIONIC
- ALL PREGANGLIONIC FIBERS RELEASE ACH
SYMPATHETIC (SANS)
- FIGHT OR FLIGHT
- RUNS ON NOREPINEPHRINE
- INCREASES CO, BP, RR, BLOOD FLOW, BG
- DECREASES RBF, DIGESTIVE PROCESSES
- FIRES AT ONCE
- SHORT PRE-, LONG POST
PARASYMPATHETIC (PANS)
- NORMAL MAINTENANCE AND ANABOLIC METABOLISM
- INCREMENTAL ACTIVATION
- VAGAL STIMULATION
- LONG PRE-, SHORT POST
SOMATIC NERVOUS SYSTEM
- VOLUNTARY
- CONTROLS MOVEMENT, RESPIRATION, POSTURE
- ALWAYS EXCITATORY
- NO GANGLIA
CHOLINERGIC FIBERS
- SYNTHESIZE AND RELEASE ACH
- ALL PREGANGLIONIC EFFERENT AND SOMATIC MOTOR FIBERS TO SKELETAL MUSCLE
- MOST PARASYMPATHETIC POSTGANGLIONIC FIBERS
ADRENERGIC FIBERS
- RELEASE NOREPINEPHRINE
- MOST SYMPATHETIC POSTGANGLIONIC FIBERS
somatic NS fiber diagram
SNS fiber diagram
SNS function at adrenal medulla diagram
parasym nn diagram
CHOLINERGIC
TRANSMISSION mechanism
andregenic transmission mechanism
same as cholergenic except Tyr converted to Dopamine then to NE
NE stored and released via Ca
NO NE BREAKDOWN in synapse (NET reuptake)
AUTONOMIC RECEPTORS classes
- CHOLINERGIC RECEPTORS:
NICOTINIC (GANGLIONIC)
MUSCARINIC - ADRENERGIC RECEPTORS:
ALPHA
BETA
DOPAMINE
NICOTINIC RECEPTORS
classes?
excitatory or inhibitory?
- 3 MAIN CLASSES:
1. MUSCLE
2. GANGLIONIC
3. CNS - EXCITATORY: Ach binds for Na influx
MUSCARINIC RECEPTORS classes
M1-5
M1
- M1 – NEURAL; CNS EXCITATION, GASTRIC SECRETION
M2
M2 – ATRIAL; CARDIAC AND NEURAL
INHIBITION
decreases HR and CO
M3
- M3 – GLANDULAR/SMOOTH MUSCLE; GASTRIC ACID, SALIVARY SECRETION, GI CONTRACTION, OCULAR ACCOMMODATION, VASODILATION
ADRENERGIC RECEPTORS
where/types?
- POST-GANGLIONIC SYMPATHETIC SYSTEM ONLY
- Α1, Α2
- Β1, Β2, Β3
- DOPAMINE
CHOLINERGIC DRUGS
types?
muscarinic agonists
* PARASYMPATHOMIMETIC
- DIRECT ACTING: BINDS DIRECTLY TO NACH(OS) AND MACH(OS)
- INDIRECT ACTING: INHIBITS ACETYLCHOLINESTERASE, AMPLIFIERS OF ENDOGENOUS ACH
DIRECT ACTING CHOLINERGICS names
- PILOCARPINE
- BETHANECHOL
- CEVIMILINE
- PILOCARPINE (SALAGEN®)
tx of what usually? how does it help this?
dental use?
- GLAUCOMA TX
- CAUSES MIOSIS, LOWERS IOP
- DENTAL USE – RADIATION-INDUCED XEROSTOMIA TX
- BETHANECHOL (URECHOLINE®)
tx of?
most resistant of?
- POST-OPERATIVE URINARY RETENTION TX
- MOST RESISTANT TO CHOLINESTERASE
- CEVIMILINE (EVOXAC®)
selective for?
tx of?
- SELECTIVE FOR M3
- MORE SELECTIVE FOR EXOCRINE GLANDS
- RADIATION-INDUCED XEROSTOMIA; SJOGREN’S SYNDROME
INDIRECT ACTING CHOLINERGICS
types?
- ACETYLCHOLINESTERASE INHIBITORS
- REVERSIBLE: ‘-STIGMINE’ AGENTS, DONEPEZIL (ARICEPT®), GALANTAMINE (RAZADYNE®)
- IRREVERSIBLE: ORGANOPHOSHPATES
INDIRECT ACTING CHOLINERGICS
* USED FOR TREATMENT OF:
- MYASTHENIA GRAVIS
- GLAUCOMA
- GI MOTILITY
- REVERSAL OF NEUROMUSCULAR BLOCKADE
- ANTICHOLINERGIC TOXICITY
- ALZHEIMER
REVERSIBLE ACHE INHIBITORS names
Pyridostigmine (Regonol®)
indications?
1st line for?
duration?
indications:
*Myasthenia gravis
*Nerve agent prophylaxis
notes:
1st line for MG
4-6h duration
Neostigmine (Prostigmin®)
indications?
does not?
indications:
*Myasthenia gravis
*Post-op ileus / urinary retention
*Neuromuscular blockade reversal
Doesn’t enter CNS (quaternary amine)
Physostigmine (Antilirium®)
indication?
enters? why not routinely used?
*Anticholinergic toxicity
Enters CNS (tertiary amine): Not routinely used due to CNS activity, ADRs
Edrophonium (Tensilon®)
used for? why?
*Diagnosis of myasthenia gravis
Doesn’t enter CNS (quaternary amine)
Not routinely used for treatment, short t ½ (5 min)
Galantamine, rivastigmine, donepezil
indication?
why?
*Mild-to-moderate Alzheimer’s disease
More selective AChE for management of cognitive dysfunction.
Modest clinical benefits
ORGANOPHOSPHATES
bind?
Insecticides?
nerve agents?
Irreversible AChE
Long lasting
Insecticides: Parathion (more dangerous), malathion (safer)
Nerve agents: Sarin, soman, tabun, VX
Novichok Agents (binary, req mixture)
NORMAL PROCESS - ACHE
cleavage to inactivate Ach
ORGANOPHOSPHATE
MECHANISM
Phosphorous (+) attracted to serine (-)
OP attaches to AChE, prevents ACh binding= excess Ach
outcomes of AchE with OP
Cholinesterase is now blocked, 1 of 3 things can happen
1. Hydrolyze to original state (slow)
2. Regenerate with an oxime (fast)
3. Age (cannot regenerate)
aged bond of AchE
cholergenic toxicity signs progression
usually muscarinic signs followed by nicotinic
Muscarinic S/S of Chol toxicity
SLUDGE:
salivation
lacrimation
urination
Diarrhea
GI discomfort
Emesis
OR
DUMBBELLS :
Diarrhea
Urination
Miosis/muscles weak
Bronchorrhea
Bradycardia
Emesis
Lacrimation
Salivation/sweating
nicotinic S/S of toxicity
M T W T F
Muscle cramps
Tachycardia
Weakness
Twitching
Fasciculations