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
how much time do we have with these agents at play?
possible abbreviations
- PRALIDOXIME (2-PAM)
- REGENERATES ACHE
must use before bond ages to prevent AchE inhibitors from binding
- ATROPINE with Ach toxicity, issues with this?
REQUIRES HUGE AMOUNTS
* MUSCARINIC ANTAGONISM ONLY, WON’T CORRECT NICOTINIC SX (PARALYSIS)
- PYRIDOSTIGMINE for Ach toxicity?
- PROPHYLAXIS ONLY, when exposure possible, acts as a cholergenic agent but binds AchE to prevent binidng of others
possible otpions for Ach toxicity tx
- PRALIDOXIME (2-PAM)
- ATROPINE
- PYRIDOSTIGMINE
ANTICHOLINERGICS/ MUSCARINIC
ANTAGONISTS
- BINDS MUSCARINIC RECEPTORS, BLOCKS ACH
classes of M antagonists and anticholergenics
dif of the classes
- TERTIARY AMINES HAVE CENTRAL EFFECTS
- QUATERNARY AMINES – PERIPHERAL EFFECTS
- TERTIARY AMINES anticholergenics
names?
- TERTIARY AMINES HAVE CENTRAL EFFECTS
- ATROPINE, SCOPOLAMINE, BENZTROPINE , DICYCLOMINE
- QUATERNARY AMINES anticholergenics
- QUATERNARY AMINES – PERIPHERAL EFFECTS
- GLYCOPYRROLATE, TIOTROPIUM
ATROPINE
* PROTOTYPICAL?
* SELECTIVITY?
* NO EFFECT in pts with hx of?
* INDICATIONS?
* DON’T USE what dose in adults. why?
- PROTOTYPICAL ANTICHOLINERGIC
- MUSCARINIC SELECTIVITY
- NO EFFECT S/P HEART TRANSPLANT (vagal transection)
- INDICATIONS:
- BRADYCARDIA
- OP TOXICITY – HUGE AMOUNTS NEEDED
- DON’T USE < 0.5MG IN ADULTS= PARADOXICAL BRADYCARDIA
atropine mechanism
binds M2 to prevent Ach binding
increased HR with no effect on sympathetics or BP, improves AV conduction
SCOPOLAMINE
* FOUND IN?
* AMINE?
* PRIMARY USE?
results of use?
- FOUND IN HYOSCYAMUS NIGER (HENBANE)
- TERTIARY AMINE
can be used to prevent short term mem formation/ increase suggestability - PRIMARY USE:
- MOTION SICKNESS
- VOODOO ZOMBIFICATION
GLYCOPYRROLATE
* AMINE structure?
* USED TO?
* ADJUNCT FOR REVERSAL OF?
anticholergenic
* QUATERNARY AMINE, FEWER CENTRAL EFFECTS
- USED TO DRY SECRETIONS:
- SURGERY
- KETAMINE TREATMENT
- ADJUNCT FOR REVERSAL OF NEUROMUSCULAR BLOCKERS
ANTICHOLINERGIC USES
* OPHTHALMOLOGY
- INDUCE MYDRIASIS, INDUCE CYCLOPLEGIA, REDUCE IOP
ANTICHOLINERGIC USES GI
- ANTISPASMODIC, ANTIDIARRHEAL, URINARY INCONTINENCE
ANTICHOLINERGIC USEs CV
- VAGOLYTIC (INCREASES HEART RATE)
ANTICHOLINERGIC USES secretions
DECREASES ALL; SURGERY AND DENTAL USES
ANTICHOLINERGIC USES as ANTIDOTE
REVERSAL OF CHOLINERGIC TOXICITY (ORGANOPHOSPHATE POISONING)
ANTICHOLINERGIC USES PULMONARY
- COPD / ASTHMA TREATMENT (BRONCHODILATION)
ANTICHOLINERGIC TOXICITY EFFECTS
CNS:
Eye:
CV:
Respiratory:
GI:
CNS: Drowsiness, amnesia, agitation, hallucinations, coma (scopolamine > atropine)
Eye: Mydriasis, cycloplegia, reduced lacrimal secretion
CV: Tachycardia (vagal inhibition)
Respiratory: Bronchodilation, reduced airway secretions
GI: Decreased motility, xerostomia
amt liquid nic to be fatal?
signs?
40MG (1 DROP PURE LIQUID) = FATAL
signs: Seizure, Respiratory arrest, Coma, Paralysis
*VARENICLINE (CHANTIX®)
* mechanism
* T½ AND AFFINITY
* INHIBITS:
common side effect
- PARTIAL AGONIST/ ANTAGONIST of nicotine
- LONG T½ AND HIGH AFFINITY FOR NACH(OS)
- INHIBITS:
- NICOTINE BINDING
- WITHDRAWAL SYMPTOMS
- DOPAMINE RELEASE
people cease due to vivid nightmares
NEUROMUSCULAR
BLOCKERS classes/ names
- DEPOLARIZING: SUCCINYLCHOLINE
- NONDEPOLARIZING: ROCURONIUM, VECURONIUM, PANCURONIUM, CISATRICURIUM
NEUROMUSCULAR
BLOCKERS main action
general action of both classes
- INHIBIT BINDING OF ACH AT NMJ
SUCCINYLCHOLINE
* mechanism
* ONSET
* DURATION
* higher dose if pt is?
* CAUTION FOR?
depolarizing NM blocker
* OPENS SODIUM CHANNELS
* ONSET ~ 60 SECONDS
* DURATION ~ 5 MINUTES
* MORE IF HYPOTENSIVE
* CAUTION: HYPERKALEMIA! due to DENERVATION SUPERSENSITIVITY
denervation supersensitivity, implication with succinylcholine
occurs with injury, can allow a denervated mm fiber to increase AchR over days post injury
when suc administered the K outflux would be much greater (Potassium Increase 5 – 10 mEq/L)
ROCURONIUM
* ONSET?
* DURATION?
* ADR?
* REVERSAL?
NONDEPOLARIZING
* ONSET ~60 SECONDS
* DURATION ~ 45 MINUTES, not broken down by AchE like Succ
* NO SIGNIFICANT ADR
* REVERSAL AGENT can be given to ensure proper sedation
Vecuronium
onset/duration
ADR?
2 min / 45 min
Few ADRs
Pancuronium
onset/duration
causes?
3 min / > 2 hrs
Causes tachycardia
Cisatracurium
onset/duration?
used as?
2 min / 1 hr
Few ADRs, used as continuous infusion in therapeutic temperature management
Rocuronium
onset/duration?
excellent for?
1 min / 45 min
Excellent intubating conditions, no sig. ADRs
- PILOCARPINE (SALAGEN)
- BETHANECHOL (URECHOLINE)
- CEVIMILINE (EVOXAC)
DIRECT ACTING CHOLINERGICS names
- GLAUCOMA TX
- CAUSES MIOSIS, LOWERS IOP
- DENTAL USE – RADIATION-INDUCED XEROSTOMIA TX
- PILOCARPINE (SALAGEN®)
tx of?
causes?
dental use?
- POST-OPERATIVE URINARY RETENTION TX
- MOST RESISTANT TO CHOLINESTERASE
- BETHANECHOL (URECHOLINE®)
tx of?
most resistant of?
- SELECTIVE FOR M3
- MORE SELECTIVE FOR EXOCRINE GLANDS
- RADIATION-INDUCED XEROSTOMIA; SJOGREN’S SYNDROME
- CEVIMILINE (EVOXAC®)
selective for?
tx of?
- REVERSIBLE: ‘-STIGMINE’ AGENTS, DONEPEZIL (ARICEPT®), GALANTAMINE (RAZADYNE®)
- IRREVERSIBLE: ORGANOPHOSHPATES
INDIRECT ACTING CHOLINERGICS
* ACETYLCHOLINESTERASE INHIBITORS
types?
- MYASTHENIA GRAVIS
- GLAUCOMA
- GI MOTILITY
- REVERSAL OF NEUROMUSCULAR BLOCKADE
- ANTICHOLINERGIC TOXICITY
- ALZHEIMER
INDIRECT ACTING CHOLINERGICS
* USED FOR TREATMENT OF:
REVERSIBLE ACHE INHIBITORS names
indications:
*Myasthenia gravis
*Nerve agent prophylaxis
notes:
1st line for MG
4-6h duration
Pyridostigmine (Regonol®)
indications?
1st line for?
duration?
AchE inhibitor indicated for:
*Myasthenia gravis
*Post-op ileus / urinary retention
*Neuromuscular blockade reversal
Doesn’t enter CNS (quaternary amine)
Neostigmine (Prostigmin®)
indications?
does not?
indication:
*Anticholinergic toxicity tx via AchE inhibition
Enters CNS (tertiary amine)
Not routinely used due to CNS activity, ADRs
Physostigmine (Antilirium®)
indication?
enters? why not routinely used?
indication:
*Diagnosis of myasthenia gravis
Doesn’t enter CNS (quaternary amine)
Not routinely used for treatment,
short t ½ (5 min)
Edrophonium (Tensilon®)
used for? why?
*Mild-to-moderate Alzheimer’s disease
More selective AChE for management of cognitive dysfunction with Modest clinical benefits
Galantamine, rivastigmine, donepezil
all 3amine AchE inhibitors
Irreversible AChE
Long lasting
Insecticides: Parathion (more dangerous), malathion (safer)
Nerve agents: Sarin, soman, tabun, VX
Novichok Agents (binary, req mixture)
ORGANOPHOSPHATES
bind?
Insecticides?
nerve agents?
- REGENERATES ACHE
must use before bond ages to prevent AchE inhibitors from binding
- PRALIDOXIME (2-PAM)
REQUIRES HUGE AMOUNTS
* MUSCARINIC ANTAGONISM ONLY, WON’T CORRECT NICOTINIC SX (PARALYSIS)
- ATROPINE with Ach toxicity
- PROPHYLAXIS ONLY, when exposure possible, acts as a cholergenic agent but binds AchE to prevent binidng of others
- PYRIDOSTIGMINE for Ach toxicity?
- PROTOTYPICAL ANTICHOLINERGIC
- MUSCARINIC SELECTIVITY
- NO EFFECT S/P HEART TRANSPLANT
- INDICATIONS:
- BRADYCARDIA
- OP TOXICITY – HUGE AMOUNTS NEEDED
- DON’T USE < 0.5MG IN ADULTS= PARADOXICAL BRADYCARDIA
ATROPINE
* PROTOTYPICAL?
* SELECTIVITY?
* NO EFFECT in?
* INDICATIONS?
* DON’T USE what dose in adults. why?
- FOUND IN HYOSCYAMUS NIGER (HENBANE)
- TERTIARY AMINE
can be used to prevent short term mem formation/ increase suggestability - PRIMARY USE:
- MOTION SICKNESS
- VOODOO ZOMBIFICATION
SCOPOLAMINE
* FOUND IN?
* AMINE?
* PRIMARY USE?
results of use?
- QUATERNARY AMINE, FEWER CENTRAL EFFECTS
- USED TO DRY SECRETIONS:
- SURGERY
- KETAMINE TREATMENT
- ADJUNCT FOR REVERSAL OF NEUROMUSCULAR BLOCKERS
GLYCOPYRROLATE
* AMINE structure?
* USED TO?
* ADJUNCT FOR REVERSAL OF?
- PARTIAL AGONIST/ ANTAGONIST of nicotine
- LONG T½ AND HIGH AFFINITY FOR NACH(OS)
- INHIBITS:
- NICOTINE BINDING
- WITHDRAWAL SYMPTOMS
- DOPAMINE RELEASE
people cease due to vivid nightmares
*VARENICLINE (CHANTIX®)
* mechanism
* T½ AND AFFINITY
* INHIBITS:
common side effect
depolarizing NM blocker
* OPENS SODIUM CHANNELS
* ONSET ~ 60 SECONDS
* DURATION ~ 5 MINUTES
* MORE IF HYPOTENSIVE
* CAUTION: HYPERKALEMIA! due to DENERVATION SUPERSENSITIVITY
SUCCINYLCHOLINE
* mechanism
* ONSET
* DURATION
* higher dose if pt is?
* CAUTION FOR?
NONDEPOLARIZING
* ONSET ~60 SECONDS
* DURATION ~ 45 MINUTES, not broken down by AchE like Succ
* NO SIGNIFICANT ADR
* REVERSAL AGENT can be given to ensure proper sedation
ROCURONIUM
* ONSET?
* DURATION?
* ADR?
* REVERSAL?
2 min / 45 min
Few ADRs
Vecuronium
onset/duration
ADR?
3 min / > 2 hrs
Causes tachycardia
Pancuronium
onset/duration
causes?
2 min / 1 hr
Few ADRs, used as continuous infusion in therapeutic temperature management
Cisatracurium
onset/duration?
used as?
1 min / 45 min
Excellent intubating conditions, no sig. ADRs
Rocuronium
onset/duration?
excellent for?
- ATROPINE, SCOPOLAMINE (SCOPACE®), BENZTROPINE (COGENTIN®), DICYCLOMINE (BENTYL®
- TERTIARY AMINES anticholergenics
- TERTIARY AMINES HAVE CENTRAL EFFECTS
- GLYCOPYRROLATE (ROBINUL®), TIOTROPIUM (SPIRIVA®)
- QUATERNARY AMINES anticholergenics
- QUATERNARY AMINES – PERIPHERAL EFFECTS
depolarizing NM blockers
succinylcholine
nondepolarizing NM blockers
ROCURONIUM, VECURONIUM, PANCURONIUM, CISATRICURIUM
ROCURONIUM, VECURONIUM, PANCURONIUM, CISATRICURIUM
nondepolarizing NM blockers
