2 - Neuromuscular and Ganglionic Blockers Flashcards
Ganglionic blockers =
Nicotinic receptor antagonists
Ganglionic blockers block what reflexes?
Baroreceptor
Pupillary
____ is a ganglionic blocker for HoTN for surgery
Trimethaphan
For tourettes, smoking cessation, and severe HTN
Mecamylamine
endogenous tone of vascular smooth muscle
mild vasoconstriction
Endogenous tone of all other ANS functions
P>S
Mild bradycardia
blockage = tachycardia
Blockage of Ach transmission can occur either…
presyn or postsyn
Drugs that block nicotinic receptors on skeletal muscle have ______
They are ______
Quaternary amine
peripherally restricted
First clinically used NM blocker
Curare
D-tubocurarine = active alkaloid
What is TOF ratio
the response of 4th twitch relative to the first
TOF ratio = ____= 75% of receptors blocked
but…
0.25
but still near full muscular response
Recovery to __ needed for extubation, ___ for full recovery
- 7
- 9
____ twitch properly sedated
1-2
What level of twich can be rapidly reversed when monitoring NM blockade
1 twitch
Done redose if _____
no twitch
Sequence of paralysis by NM block
- Eye/speech
- DIgits
- Limbs
- Intercostals
- Diaphragm
What happens as a result of persistent depolarizaiton of the muscle fiber?
Makes it more resistant to further stimulation by Ach
- Succinylcholine duration
- metabolized to
- Use?
- CI’s?
- 5-10 m
- Metabolized to choline by BuChE
- Used in trauma care, (intubation), electroconvulsant therapy
- Avoid in HyperKalemia, cause of cardiac arrest
Binding of SUX to receptor allows ____
Na influx
Non-depolaizing NM blocker (curare-like)
Pancuronium (long acting, 180m)
Vecuronium + Atracurium (intermediate, 30m)
Trimethaphan (short acting i.v.)
Benefit of curare like NMBs
Easily reversible
Reversal agents for Non-depolarizing NMB’s
Neostigmine (interacts with Ach)
Sugammadex (interacts with pancoronium)
AChe degrades Ach to
Choline and acetate
Enyme that makes Ach
ChAT
substrates for Ach production
AcetylCoA + Choline
Plasmacholinesterase =
Where?
What molecules?
Butyrylcholinesterase (BuChE)
In plasma
SUX, Local anesthetics (procaine)
AChE inhibitors =
Have what groups?
Mechanism?
- Carbamates
- quaternary or tertiary amine groups
- Temporary covalent modification to AChE
=Reversible
Tertiry amine AchE that enters CNS?
Use?
Physostigmine
used for ATROPINE OD, glaucoma, Alzheimers
Neostigmine and Pyridostygmine properties
Uses
Peripherally restricted, Quaternary amine
M. gravis, NMB reversal, post-op ileus, bladder distension
Quaternary amine that’s orally available, has fewer sides and longer duration
Pyridostygmine
Irreversible Covalently bonding Ach inhibitors
Length of duration
Use?
Organophosphates
>week in duration
Treatment for glaucoma
Other Irrev. covalent Ach Inhibitors
Nerve gases = Soman/Sarin
Insecticides = Malathion (prodrug), Parathion, Diazinon
Insecticides are _______
rapidly inactivated in mammals
Antidote for ACHE poisioning
(antidote for…)
Pralidoxime Chloride (2-PAM)
(antidote for pesticide or nerve gas poisoning)
*should give within 2-3 hours of exposure
Symptomatic treatment of ACHE poisioning (as opposed to antidote)
benefit of using this?
Atropine
fast onset
Treatment of ACHE poisoning involves ________
combination of Pralidoxime + Atropine
Symptoms of ACHEI poisoning
DUMBBELLS
M3 = Diarrhea, Urination, Miosis, Bronchospasms…Lacrimation, Sweating, Salivation
M2 = Bradycardia
Nm = Permanent depol of diaphragm is fatal (atropine wont help)
ACHEI poisoning is more frequent with ______
farmers
Edrophonium (Tensilon)
Binding
DoA
Use?
Binds non-covalently
Short acting (5-10 minutes)
Used to Dx Myasthenia Gravis
M. gravis etiology
ABs block Nicotinic Ach receptors at the postsynaptic junction (NMJ)
In M. gravis, Edrophonium improves _____
Treatment includes
Muscle strength
Tx = neostigmine/pyridostigmine
Lambert Eaton Mg etiology
Treatment?
ABs against vg Calcium channels
Excercise improves muscle strength
Edrophonium has NO EFFECT
Edrophonium is good at determining the difference between ___ and ___
Cholinergic crisis and MG
CC = no effect, small decrease in muscle strength
CI’s to using Parasympathomimetic drugs?
- Asthma and COPD (bronchoconstrict)
- Coronary deficiency (lower HR)
- Peptic ulcer (acid secretion increased)
- Obstruction of UT or GIT
- Epilepsy (M1Rs, CNS penetrable drugs like pilocarpine)
Parkinsons etiology
- Reduction in ___ and____
Dementia with lewy bodies
- Reduction in neocortical choline acetyltransferase (ChAT)
- Rediuction in AchE activity in posterior regions and thalamus
Other region implicated in Parkinson’s
Nucleus Basalis of Meynert
Alzheimers = ____ of brain,
___ of sulci/____ of gyri
Improper proccessing of ___ leads to what??
Atrophy
wide sulci, narrow gyri
Improper processing of Beta amyloid precursor protein (b-APP) leads to toxic form that promotes apoptosis
Toxic form of beta amyloid
b-A42
Alzheimers Tx
- MOA
- Binding
- but…
Donepezil (aricept)
- Bind to anionic site and block ACh binding
- Reversible, non-covalent
- Does NOT SLOW PROGRESSION of the disease
Rivastigmine MOA
Function
Sides
Replacement?
Reversible carbamate ACHEI
increases cholinergic function
Sides = Nausea, vomit, anorexia, weight loss.
Replacement = Eptastigmine
Galamthamine MOA
From where?
May be a ____
Pharmacokinetics?
Reversible Competitive ACHEI
From daffodil
May be a nicotinic receptor agonist
Inhibits P450 (3A4, 2D6)
Rivastigmine and Galanthamine caveat
Lost effectiveness as disease progresses
