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54 Cards in this Set
- Front
- Back
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acetylcholinesterase (AChE)is found where?
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throughout the body
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two primary forms of AChE
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1) ture AChE
2) pseudocholinesterase (or plasma cholinesterase or butyrylcholinesterase) |
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true AChE is found on?
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on RBC and on the pre and post synaptic memb. of cholinergic transmission sites
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pseudocholinesterase is found in?
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in the plasma and many other sites throughout the body
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function of AChE?
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to destroy Ach and prevent overstimulation of cholinergic receptors
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acetylcholinesterase inhibitors (AChE-I's)
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blodk this enzymatic degradation of Ach by AchE
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How AChE-I act in the ANS?
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as parasympathomimetics
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How AChE-I act in the somatic system?
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as neuromuscular stimulants
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use of AChE-I
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insecticides
military "war gas" agents |
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2 classifications of AChE-I
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1) reversible agents
2) irreversible agents |
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reversible agents
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do not permanently bind to AChE
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irreversible agents
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organophosphates (OP)
form long-term or permanent covalent bonds to the serine esteratic site very toxic |
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aging process
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the covalent bond is further strengthened with time as an 'R' group on the phosphoryl group splits off
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half-aging times
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different OP's have different half-aging times
most toxic compound - minutes less toxic compound - days |
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tx for OP poisoning
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Atropine
Pralodoxime (2-PAM, Protopam)if the attached OP has not yet 'aged' |
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symptomology of AChE-I toxicity
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salivation
lacrimation urination defecation (SLUD) sweating miosis |
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irriversible agents
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1) Echothiophate (Phospholine)
2) Malathion (Ovide) |
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Echothiophate
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Phospholine
member of OP class |
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use of Echothiophate
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ophthalmic miotic agent used for glaucoma and dx
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Echothiophate; great care must be used in?
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asthmatic and cardiac pt
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long-term use of Echothiophate may lead to?
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cataract formation
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Malathion
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Ovide
member of OP class, but least human toxic very potent insecticide |
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use of Malathion
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as topical agent (lotion, shampoo) for the tx of external parasites, including head lice
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Malaoxon
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active form of Malathion
toxic if ingested or pulmonary aspirated |
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Malathion poisoning is treated with?
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atropine and pralidoxime
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Reversible agents
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1) Physostigmine
2) Neostigmine 3) Pyridostigmine 4) Edrophonium 5) Tacrine 6) Donepezil 7) Rivastigmine 8) Galantamine |
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Physostigmine
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Eserine, Antilirium
reversible isolated from the Calabar bean, used as an ordeal poison tertiary compounds - cross BBB better than neostigmine (guat) |
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use of Physostigmine
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open-angle glaucoma
Alzheimer's diseases with limited success |
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action of Physostigmine
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potentiates the effects of Ach at peripheral nicotinic and muscarinic sites, and in the CNS mainly at muscarinic sites
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normal response to parenteral administration of Physostigmine
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increased skeletal muscle tone
increased GI tone and motility bradycardia sweat and salivary gland stimulation bronchoconstriction miosis decreased IOP |
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How Physostigmine decrease IOP?
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by widening the trabecular network, which allows increased outflow of aqueous humor
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Physostigmine at high doses
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acts directly at neuromuscular and ganglionic nicotinic receptors as a depolarizing blocker
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Neostigmine
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Prostigmine
quat |
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use of Neostigmine
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treat acute episodes of MG and dx of MG (edrophonium is preferred for dx due to short half life)
antagonizing the effects of non-depo. NMB tx of post-op urinary retention and abd. distention |
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Pyridostigmine
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Mestinon
quat poor oral absorption |
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use of Pyridostigmine
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tx of MG
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Edrophonium
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Tensilon
only parenteral form available due to *very short duration* onset of effect is very rapid quat |
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use of Edrophonium
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drug of choice for dx of MG
for accessing potential benefits/risks of AChE-I therapy post-op non-depo. reversal |
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Edrophonium with Atropine
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used to tx the respiratory depression seen following curare poisoning
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Edrophonium; muscarinic effect?
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few muscarinic effects are seen in challenge dosing due to the short duration of action
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Tacrine
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Cognex
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use of Tacrine
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1st drug approved to treat Alz. disease to improve cognitive function, but no proof that use will show the progression of the disease
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actions of Tacrine
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similar to donepezil, but there are more peripheral effects seen
potential for hepatotoxicity |
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Tacrine inhibits
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both true AChE and pseudo ChE almost equally
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oral administration of Tacrine
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high first pass metabolism seen orally (up to 95 %)
food can decrease absorption 30% (give on an empty stomach) |
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Donepezil
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Aricept
piperidine type reversible ChE-I high affinity for CNS cholinesterase |
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use of Donepezil
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for mild to moderate Alz. disease
not prolong the course of the disease |
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Donepezil; hepatotoxicity?
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not possess the hepatotoxicity risk seen with Tacrine, and it has fewer peripheral effects
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selectivity of Donepezil
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more selective for true AChE than Tacrine
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oral absorption of Donepezil
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well absorbed (100%)
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metabolism of Donepezil
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via P450 system, which converts Donepezil into two active and two inactive metabolites
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half life of effect of the parent compound and active metabolites combined
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approximately 70 hrs
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Rivastigmine
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Exelon
reversible treat Alz. disease improve thinking adn memory |
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Galantamine
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Reminyl
treat cognitive loss due to Alz. disease acts as reversible, competitive antagonist of AChE |
