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21 Cards in this Set

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Drugs that mess with Ach biosynthesis and release? (3)
Hemicholinium (HC-3) - blocks Choline trans into Nerve

Vesamicol - blocks Ach packaging into vesicles

Botulinus Toxin
From Clostridium botulinum
blocks vesicle fusion at terminal (cleaves Synaptobrevin)
Death by Flaccid Paralysis
1 of most potent toxins - 3 micrograms will kill a human
Synthetic Parasympathomimetic Drugs (4)
Acetylcholine (not used)
Metacholine (Musc, Brady/HypoBP)
Carbamylcholine / 'Cabachol' (Musc and Nic - Glaucoma Tx)
Bethanecol / Myotonachol (Musc - test Panc, Tx urinary retention)
Naturally Occurring Parasympathomimetic Drugs (3)
Pilocarpine
Arecoline
Muscarine
Pilocarpine
Pilocarpus shrub
100x Ach potency
MUSCARINIC > nicotinic
Increases Salivation and Sweating

*Stims Miosis ----> lower IO pressure
~may cause tachycardia/hypertension
Arecoline
from Betel Nut of Areca catechu
Muscarinic AND Nicotinic
~addictive/stimulant like Nicotine

*Not currently used
(was a vermifuge, is a taenicide in China)
Muscarine
from Amantia muscarina mushrooms

MUSHROOM POISIONING:
SLUD, GI Pain, CV Collpase, vertigo-confusion-coma-DEATH

onset under 1 hour - Death w/in hours

*Antidote = ATROPINE
Anti-Muscarinic Agents (5)
Homoatropine (fast/less potent)
Scopolamine (Tx Motion Sickness)
Propantheline (no BBB, decrease spasm - Tx diarrhea or choke)
Tropicamide aka Mydriacil - (short acting mydriasis)
Atropine
Atropine
from Deadly Nightshade (Atropa belladona)
competitive Muscarinic

^HR, bronchoDilate, v-resp secretions, v-GI motile, MYDRIASIS

Tx - Pre-Op Med, AntiAsthmatic, OTC Lacrimal/Nasal Glands
Glaucoma Tx
Muscarinic Agonists
(miosis -> ^drainage -> low IO press)

B-Blockers - TIMOLOL - decrease aq. humor production
Nicotinic Ganglionic Agonists (4)
Lobeline (Lobelia - the patch, the gum)
DMPP (3x Nicotine potency, always on)
TMA (always on - no dose dep. off)

NICOTINE
complex, unpredictable - high doses may INHIBIT N-R's. Effects at Nn (ganglionic) therefore hits SYMP and PARASYMP - who knows what will happen!?
Nicotinic Ganglionic Blockers (2)
Trimethaphan (Vet Med - Lower BP in Sx)

Hexamethonium aka C6
Ganglionic blocker, therefore blocks both SYMP and PARASYMP... therefore very limited uses.
3 Classes of Anti-AchE
1. Reversible - N binds Anionic AchE site temporarily

2. Carbamylating - substrate binds Active AchE site for extended period

3. Phosphorylation of AchE - Covalent bind, IRREVERSIBLE inactivation of AchE enzyme)
Reversible Anti-AchE Drug (1)
Edrophonium aka Tensilon

M.Gravis - Immune Mediated Ach-R defect

Tx M.Gravis - Transient Improvement
Tx Cholinergic Crisis - Transient Worsening
Carbamylating Anti-AchE Drugs (5)
Physostigmine aka Eserine
Neostigmine aka Prostigmin
Pyridostigmine
Demeserium
Carbaril aka Sevin
1. Eserine / Physostigmine
2. .Prostigmin / Neostigmine
3. Pyridostsimgine
4. Demeserium
5. Carbaril / Sevin
1. well absorbed, x-BBB (Glaucoma, Atropine poisoning)
2. not well absorbed, no x-BBB (M.Gravis)
3. shorter half life (nerve gas prophylactic)
4. more potent, longer duration
5. Insecticide
Phosphorylating Anti-AchE Drugs (4)
1. DFP - must make new AchE to recover
profound toxic effects - cumulative over reasonable amt time
2. Sarin (GB) - quick, less persistent
3. VX - more toxic, very persistent, normally liquid form which can stick
4. OrganoPhosphates - insecticides
What will Nerve Gas or OrganoPhosphate insecticides do to you?
Irreversibly bind your AchE... therefore you will not break down your Ach.
Initially - Increase Ach --> muscle twitching --> fasciculations
...Eventually, you exhaust your Ach (no recycling) and your Ach-R's --> Paralysis and Death
How do you defend yourself from that Nerve Gas?
2 ways... 1. Pyridostigmine

2. Inject yourself with Pralidoxime (2-PAM) and Atropine

Pralidoxime will dephosphorlyate and thus RECOVER AchE

Atropine will block Ach-R's at MUSCARINIC sites, therefore protecting you against overflow of Ach
NEUROMUSCULAR BLOCKERS
ie - No Longer Parasympathetic ANS
Competitive Blockers at NMJ (3)
CURARE - Arrow Poison
d-Tubocuranine
Pancuronium (Pavulon)
Atracurium (Tracrium)

short onset, long acting, no x-BBB

**RECOVER w/ Anti-AchE
Depolarizing Blockers at NMJ (1)
Succinylcholine (Anectine)

ultra short onset, short duration
(longer in dog than other animals)
Desensitizes Ach-R's at NMJ

*NO RECOVERY - just time