Ex4 Reversal Agents Flashcards
Ganglia
group of nerve cells forming a nerve center, especially one outside brain/spinal cord
in both spine + brain, back (posterior) is always
sensory
in both spine + brain, front (anterior) is always
motor
mnemonic for PNS
SAME DAVE sensory-dorsal afferent-afferent motor-ventral efferent-efferent
site of action for NMBAs
NMJ in skeletal muscle (somatic/voluntary) portion of efferent peripheral pathways
thoracolumbar ANS
sympathetic
craniosacral ANS
parasympathetic
effects of thoracolumbar NS
fight/flight/fright
- redistribution of blood flow from vicera to skeletal muscle
- increased cardiac fxn
- decreased salivation
- pupillary dilation (mydriasis)
effects of craniosacral NS
rest + digest (maintenance of fxns)
- digestive fxns (increased salivation/mucus secretion, GI motility)
- GU fxns
receptors in ANS are classified by
- neurotransmitters with which they react
2. described in terms of location (pre/post-synaptic)
adrenergic receptors react with
NE or Epi
adrenergic receptors are subdivided into
alpha1, alpha2, beta1, beta2
also dopaminergic receptors (D1-D5)
cholinergic receptors react with
ACh
cholinergic receptors subdivided into
muscarinic, nicotinic
Cholinergic nerves include
-all motor nerves that innervate skeletal muscle (somatic)
- all preganglionic para/symp neurons
- all postganglionic parasymp neurons
- some postgangl symp neurons: sweat glands/certain blood vessels
- preganglionic symp neurons that originate from grtr splanchnic nerve + innervate adrenal medulla
- central cholinergic neurons
most organs have _____ innervation
dual (symp + parasymp)
anticholinergic Rx combine _____ with ____ receptors to compete with _____
combine reversibly with
muscarinic receptors
to compete with ACh
antimuscarinic Rx may enhance _____ activity
sympathetic
antimuscarinic Rx block all ______ effects
muscarinic
DOC - tx of reflex bradycardia
Atropine
tx of anticholinergic syndrome
physostigmine 15-60 mcg/kg IV
causes of anticholinergic syndrome
scopolamine
atropine
s/s anticholinergic syndrome
restlessness, somnolence, hallucinations, unconsciousness
atropine - caution in patients with
narrow angle glaucoma
prost hypertrophy
bladder neck obstruction
atropine uses
premedication- antisialogogue
tx for bradyarrhythmias
minimize effects of anticholinesterases
potent effects on heart/bronchial smooth muscle
how to minimize effects of anticholinesterases
add atropine, scopolamine, or glycopyrrolate
atropine premedication dosage
0.01-0.04 mg IM
max dose atropine
up to 0.4-0.6 mg total (adults)
max dose atropine w/ edrophonium
10mcg/kg
scopolamine premedication dose
0.4-0.6 mg IM
scopolamine - caution in
patients with:
narrow (closed) angle glaucoma, prost hypertrophy, bladder neck obstruction
additional use for scopolamine
prevention of PONV + motion sickness
glycopyrrolate premedication dose
up to 0.3mg IM
glycopyrrolate DOA
2-4 hours after IV adm
glycopyrrolate effects
increased HR
glycopyrrolate max dose
up to 0.01-0.012 mg/kg IV
with neostigmine or pyridostigmine
effect of anticholinesterase administration
massive parasympathetic response
actual s/s of anticholinesterase administration
salivation weeping wheezing vomiting urinating defecating seizing
only endogenous compound that causes simultaneous bradycardia/hypotension
ACh
muscarinic effects of ACh are similar to
vagal stimulation
effects of ACh
- generalized vasodilation (including cor/pulm circ)
- negative chrono/dromotropic effects
- inhibition of NE release from adrenergic nerves
- smooth muscle contraction (bronch/int/gu)
- relaxation of sphincters
- contraction of iris
- lacrimal, trach/bronch, salivary, dig, exocrine secretion
primarily used for reversal of residual NMB by NDMRs
anticholinesterases (or cholinesterase inhibitors)
goal of anticholinesterases
inhibition of AChE (“true cholinesterase”)
when is reversal appropriate?
SAFE - only after evidence of spontaneous recovery from NDMRs
what must be present in order to reverse with anticholinesterases?
a single twitch on TOF
2/4 TOF = better
in absence of NDMRs, what can anticholinesterases produce?
- fasciculations of skeletal muscles
- excess ACh may cause desensitization after admin
cholinergic crisis/anticholinesterase OD
often by organophosphate insecticides
cholinergic crisis/anticholinesterase OD s/s
bradycardia, miosis, abdominal cramps loss of bowel/bladder control weakness, confusion, ataxia coma, seizures, vent depression SLUDGE
SLUDGE mnemonic
Salivation, Lacrimation, Urination, Defacation, GI upset, emesis
Tx: cholinergic crisis
supportive (intubate/mech vent)
anticholinergic rx
administration of AChE reactivator (pralidoxime)
MOA Pralidoxime
antagonizes CNS effects of excessive ACh
effects of anticholinesterases
primarily reflect muscarinic effects
- bradycardia/decreased SVR
- salivation/hyperperistalsis
- bronchial secretions/bronchoconstriction
- miosis
antimuscarinic drugs are not effective where?
NMJ
neostigmine dosage
up to 0.07mg/kg (no more than 5mg total)
who should not receive neostigmine?
patient with profound NMB
pt with no twitches but + tetanic facilitation
no reversal
neostigmine peak
10 minutes
neostigmine DOA
> 1 hour
prolonged in CRI/CRF
if incomplete reversal at peak of neostigmine
you MUST wait for full recovery prior to extubation (take patient to PACU intubated)
preferred antimuscarinic given with neostigmine
glycopyrrolate d/t slower time to onset
neostigmine effect on elderly/peds
more sensitive to effects, rapid onset, smaller dose
elderly only: prolonged DOA
pyridostigmine is ______ as potent as neostigmine
20%
pyridostigmine dosage
up to 0.35 mg/kg
up to 20mg in adults
pyridostigmine onset
10-15 minutes
pyridostigmine DOA
> 2 hours
prolonged in CRI/CRF
Endrophonium dosage
up to 1mg/kg
Endrophonium onset
1-2min
*fastest in class
Endrophonium + atropine
co-administered
Endrophonium + glycopyrrolate
glyco administered several minutes prior
Endrophonium DOA
> 1 hour in large doses
prolonged in CRI/CRF
tx for anticholinergic toxicity caused by atropine/scopolamine
Physostigmine
unique for physostigmine
tertiary amine group
*lipid soluble = only anticholinesterase that can access CNS
large doses of physostigmine may cause
central cholinergic crisis
physostigmine dosage
up to 0.03 mg/kg
what should be available with physostigmine administration?
atropine + glco d/t bradycardia (infrequent)
physostigmine onset
5 minutes
physostigmine DOA
30-300 minutes
physostigmine metabolism
plasma esterases
*unique for class
physostigmine AEs
salivation, vomiting, convulsions
echothiophate is used for
eye gtt
combines irreversibly w/ AChE
inhibits plasma cholinesterase, may prolong DOA SCh
Sugammadex characteristics
- modified gaba-cyclodextrin
- 3d, hollow cone shape
- hydrophobic cavity, hydrophylic exterior (drugs go in but not back out)
Sugammadex MOA
encapsulates steroidal NMBA
Roc>Vec>Pan
sugammadex is biologically _____
inactive
sugammadex metabolism
biologically inactive, rapid excretion, does not bind to plasma proteins
75% eliminated thru urine
~70% excreted w/in 6h, > 90% in 24h
sugammadex is capable of reversing _____ depth of NMBA induced by ____ or _____ to a TOF ratio of _____ within ____ (time)
any depth
roc/vec
> or = 0.9
within 3 minutes
sugammadex is ineffective against
Sux Benzylisoquinolinium NMBAs (miva/atra/cistracurium)
Sugammadex dosage: RSI wtih Roc
16mg/kg
Sugammadex dosage: TOF 0/4
4mg/kg
Sugammadex dosage: TOF 2/4
2mg/kg
Sugammadex AEs
Anaphylaxis Marked bradycardia Residual blockade Risk of coagulopathy not recommended - severe renal impairment (CrCl < 30mL/min)
