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24 terms

Indirect acting cholinergic agonists

Actions of an Indirect cholinergic agonist?
1. inhibit ACHE, thus increasing ACH in synapse at all locations where ACH is released
2. stimulate Muscarinic receptors on autonomic organs
3. stimulate then desensitize ganglia and skeletal muscle
Reversible indirect cholinergic agonists include?
1. carbamates,
2. Quaternary ammoniums
reverse in minutes to hours
Irreversible indirect cholinergic agonists include?
1. Nerve gas
2. organophosphates
Tx uses for indirect cholinergic agonists
1. paralytic ileus-->stimulate urinary bladder
2. glaucoma
3. myasthenia gravis
4. anticholinergic poisoning
5. alzheimer's disease
6. reversal of neruomuscular blockade
7.prophylaxsis of cholinesterase poisoning
physostigmine tx dosage form?
orally active but only available as injection
crosses BBB
physostigmine tx uses and side effects
1. mitotic in glaucoma
2. atropine toxicity
1.muscarinic: SLUD
neostigmine dosage form
-P.O and injection
-doesnt cross bbb(no cns actions
only use for peripheral effects
neostigmine tx uses
1. paralytic ileus
2.urinary retention
3. myasthenia gravis-short t1/2 so needs multiple doses
4. reverse neuromuscular blockade
Pyridostigmine dosage form
-P.O/ injection
-slower onset
-longer dura of action
pyridostigmine tx. uses
1. myasthenia gravis
2. prophylactic for nerve gases-only inhibit 20-30% enzyme activity so protecting ACHE
3. reverse neuromuscular blockade
Ambenonium dosage form
-longer DOA than neostigmine
fewer side effects
ambenonium tx. uses
1. myasthenia gravis
2. some muscle activation***Partial agonist activation
3. Narrow therapeutic index
Edrophonium DF and TX uses
1. Injection--short DOA(10mins)
--lacks carbamoyl group, blocks anionic site
2.diagnosis of Myasthenia gravis
Tacrine place of action
1. CNS selective-no carbamoyl, reversible inhibitor
Tacrine TX uses
1. Alzheimers disease (15-30% patients)
does not slow disease
need to be give QID
hepatotoxicity limits its use but it is reversible so DC
Donepezil Tx. indications
1. Alzheimers disease
--QD, no hepatotoxicity
--Effective in 80% patients
--may slightly slow disease (55wks) but not alter
2. Muscarinic SE (SLUD)
Galantamine TX use and Side effects
1. Alzheimers disease
2. SE: liver, GI tract, Bronchoconstriction, drowsiness
**less effective than aricept(donepezil)
**reversible inhibitor (ACHE)
Rivastigmine TX uses and Side effects
1. Alzheimers (newest agent)
-P.O bid (DOA: 10hrs)
-may slow progression
--selective for G1 isoform mostly in brain, slowly dissociates
2. Muscarinic(SLUD) hallucinations
These structural features help organophosphates have good cns penetration?
1. high lipid solubility
2. low molecular weight
3. transdermal absorption
Prophylaxis treatment of organophosphates
1. pyridostigmine-->reversible indirect agonist (will bind to ACHE reversibly)
Treatment of organophosphate poisoning
1. Atropine-antagonist at muscarinic receptors
2. Pralidoxime(2PAM)
-chem. rxn w/ organophosphate bound to ACHE
Example of Organophosphates
1. Tabun
2. Sarin
3. soman
4. Paration
5. Diazinon, dimpylate
6. malathion
once this process occurs 2PAM is no longer able to bind with the organophosphate and reverse the binding
EFFECTS of organophosphate/nerve gas treatment
SLUD (at muscarinic effects)
diaphragm contraction-->muscle contraction so can't breathe (DIE)