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cholinergic drugs
CVM
91
Medical
Graduate
03/14/2010

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Term
what is the MOA for cholinergic drugs?
Definition
produce the same physiological response as the neurotransmitter acetylcholine (Ach) by either directly activating the receptor or indirectly activating the system by interfering with an enzyme (such as blocking cholinesterase, a catalytic enzyme - reduces biotransformation)
Term
what is a nicotinic recptor?
Definition
an Ach receptor that forms a ligand-gated ion channel in the plasma membrane of certain neurons/postsynaptic side of the neuromuscular junction
Term
what is a muscarinic receptor?
Definition
G-protein coupled Ach receptors found in the plasma membranes of certain neurons/other cells
Term
what is the usefulness of Ach as a drug?
Definition
minimal, it has a short duration (rapid hydrolysis), and is nonspecific (affects all cholinergic receptors)
Term
what is miochol? what does it do?
Definition
Ach for intraocular use, it produces rapid, complete miosis for ocular sx. it contracts the smooth muscle of the iris sphincter, constricting the pupil and contracting ciliary muscles (accomodation for near vision)
Term
what is the length of action of miochol? ADRs?
Definition
miochol is active for 10-20 min and ADRs include burning, itching, and headache
Term
what are the 2 main direct-acting synthetic cholinomimetic agents?
Definition
carbachol and bethanechol
Term
what are the two forms of carbachol?
Definition
miostat, administrated intraocularly for pupillary miosis during sx and isopto carbachol, administered topically for chornic tx of open-angle glaucoma and faciliates outflow of aqueous humor.
Term
what is the most potent direct-acting cholinergic drug?
Definition
carbachol
Term
what is the onset of miosis for carbachol? duration?
Definition
onset of misos: 2-5 min, duration: up to 8 hrs (slow hydrolysis)
Term
what are ADRs for carbachol?
Definition
headache, hyperemia of conjunctival vessels, ciliary spasm with decreased vision
Term
what are some systemic effects that can occur with carbachol (even after just opthalmic use)?
Definition
flushing, sweating, cramping, urinary urgency, severe headache
Term
what are contraindications for carbachol?
Definition
corneal abrasions, acute iritis (precautions include asthma, pepti ulcer, GI/urinary distress, and parkinsons)
Term
what drugs interact with carbachol?
Definition
carbachol's mitotic effects can be reversed by anticholinergics such as atropine
Term
what kind of cholinergic receptor does the direct acting, synthetic choline ester bethanechol activate? what are its affects?
Definition
muscarinic. it increases GI peristalsis and defecation. *it has a methyl group which makes it more specific
Term
what is bethanechol used for?
Definition
treatment of *nonobstructive urinary retention, neurogenic atony of urinary bladder, and postop abdominal distention/paralytic ileus
Term
what are some ADRs for bethanechol?
Definition
sweating, flushing, salivation, abdominal discomfort, nausa, diarrhea, GI pain/cramping, headache, urinary urgency, hypotension, and asthma-like attacks
Term
what are contraindications for bethanechol?
Definition
peptic ulcer, bronchial asthma, * coronary artery disease, *disturbances in AV conduction, urinary obstruction, parkinsons, pregnancy
Term
what drugs may interact with bethanechol?
Definition
quinidine and procainamide may antagonize bethanechol activity
Term
why is parkinsons a precaution for administration of cholinergic drugs?
Definition
with parkinson's, dopamin is low. in the brain, dopamine and Ach levels should be balanced, so adding more Ach will cause this imbalance to be even more exaggerated
Term
what are the two forms of bethanechol?
Definition
duvoid and urecholine
Term
what are the 2 naturally found Ach cholinomimetic alkaloids?
Definition
pilocarpine and nicotine
Term
what is pilocarpine? what does it do?
Definition
a cholinomimetic alkaloid that directly activates cholinergic receptors, contracting ciliary muscles and ciliary bodies, allowing increased outflow of aqueous humor from the anterior chamber
Term
what are systemic effects of pilocarpine?
Definition
salivation, sweating, bradycardia, vasodilation, bronchoconstriction, and increased GI motility
Term
what is pilocarpine indicated for?
Definition
open angle glaucoma and narrow angle glaucoma (prior to sx)
Term
since pilocarpine is absorbed by melanin, what does this mean for its administration to pts with dark eyes?
Definition
they may require higher doses
Term
what is the onset and duration of pilocarpine?
Definition
onset within 10-20 min and duration is 4-8 hrs (residual effects can be up to 24 hrs)
Term
what are contraindications for pilocarpine?
Definition
acute iritis and inflammatory conditions of the anterior chamber
Term
what is the pilocarpine ocular therapeutic system (ocusert pilo)?
Definition
a depo-like continuous release system for pilocarpine placed in the lower conjunctival cul-de-sac that is used primarily for continuous therapy for pts w/open angle glaucoma. its release rate is not affected by the prescence of other locally acting drugs and myopia can occur for several hours following insertion of the system. it should be used cautiously in the presence of infectious conjunctivitis or keratitis
Term
what is nicotine? where does it have an effect?
Definition
the principal alkaloid in tobacco, which activates cholinergic receptors in the autonomic ganglia, NMJ, adrenal medulla, and brain
Term
how does nicotine affect the brain?
Definition
nicotine stimulates the cerebral cortex via locus ceruleus and increases alertness and cognitive performance. it also stimulates the limbic system and increases the reward & pleasure action
Term
how does nicotine affect the CV system?
Definition
it peripherally vasoconstricts, increases blood pressure and causes tachycardia
Term
what is nicotine used for medically?
Definition
it can aid in smoking habit elimination, transdermally as habitrol or nicoderm
Term
what are ADRs for nicotine?
Definition
HTN, diarrhea, constipation (compensation), CNS, nausa/vomiting, headache, insomnia, dizziness, paresthesia, erythema, prutitis, dysmenorrhea. increased risk with CV hx of MI or buerger's disease
Term
how do indirect-acting cholinergic drugs basically work?
Definition
inhibition of cholinesterase via competetive blockade, slowing inactivation of ACh, increasing its presence at postsynaptic receptors and prolonging its action
Term
what are the reversible indirect acting cholinergic drugs? what are they used for?
Definition
ambenonium, demecarium, donepezil, edrophonium, galantamine, neostigmine, physostigomine, pyridostigmine, antilirium, rivastigma, and tacrine. these are used primarily for opthalmic use and dx/tx of myasthenia gravis. they can also be used as antidotes to cuariform and atropine-like drugs, to relieve postoperative urinary bladder atony, and to suppress paroxysmal atrial tachycardia
Term
what is physostigmine? what are its 2 forms?
Definition
a reversible indirect cholinergic drug which can be used topically as eserine and systemically as antilirium
Term
what is eserine used for?
Definition
eserine, a topical form of physostigmine, is used for tx of open-angle glaucoma (alt to pilocarpine). it can also reverse cycloplegia (paralysis of the ciliary muscle of the eye) and mydriasis caused by anticholinergics
Term
what is the time to peak effect with eserine and duration?
Definition
time to peak effect is 1-2 hrs and duration of effect is 12-14 hrs for eserine
Term
what are ADRs for eserine?
Definition
decreased visual acuitiy, eyelid twitching, increased tearing, mild headache, and dermatitis
Term
what are contraindications for eserine?
Definition
inflammation of the iris or ciliary body, narrow angle glaucoma
Term
what is the systemic form of physostigme? what is it used for?
Definition
antilirium, which is used as an antidote to toxic neurologic effects caused by drugs having central anticholinergic activity (scopolamine, tricyclic antidepressants). it has been investigated as possible tx for alzheimer's
Term
is antilirium lipid soluble?
Definition
yes it readily penetrates the CNS
Term
how long until effects of antilirium are seen, how long is its duration?
Definition
effects can be seen within 5 min, and antilirium can last up to 4 hrs (systemic doses are rapidly metabolized by cholinesterase)
Term
what are ADRs for antilirium?
Definition
sweating, nausea, urinary urgency, cramping, salivation, vomiting, diarrhea, muscle weakness, hypotension, bradycardia, bronchospasm, convulsions, respiratory paralysis
Term
what are contraindications for antilirium?
Definition
CV disease, bladder/intestine obstruction. cautions for pts with epilepsy, parkinsons, and bradycardia
Term
what are possible interactions for antilirium?
Definition
antilirium can be potentiated by depolarizing neuromuscular blovking agents (such as succinylcholine) and choline esters
Term
what indirect cholinergic is for topical use only?
Definition
demecarium, which is a powerful miotic; a reversible cholinesterase inhibitor with a duration of action significantly longer than that of other reversible inhibitors. miosis is developed w/in 30 min, and can last up to 1 wk
Term
what is demecarium used for?
Definition
glaucoma tx
Term
what are ADRs for demecarium?
Definition
blurred vision, eyelid twitching, brow pain, lacrimation, photophobia, elevated intraocular pressure, lens opacities. (systemically, demecarium can produce symptoms of cholinergic OD)
Term
what should done immediately after instillation of demecarium?
Definition
compression of lacrimal sac to decrease drainage into nasal chamber and decrease systemic absorption
Term
what are contraindications for demecarium?
Definition
narrow-angle glaucoma, inflammatory eye conditions (cautions for pts w/asthma, ulcers and other GI disorders, and parkinsons)
Term
what are potential drug interactions associated with demecarium?
Definition
demecarium may potentiate succinylcholine and anticholinesterase drugs used in tx of mysthenia gravis
Term
what are the 4 systemic reversible cholinesterase inhibitors? how are they administered? what is the time to onset of action? how long is the duration of action?
Definition
neostigmine, pyridostigmine, ambenonium, and edrophonium. these are administered by injection, have rapid onset and short duration of action (~20 min)
Term
what is the primary use for reversible systemic cholinesterase inhibitors?
Definition
dx/tx of myasthenia gravis
Term
what is the intended effect of reversible systemic cholinesterase inhibitors?
Definition
increased cholinergic neurotransmittion at NK junction leading to improved muscle strength and delayed fatigue
Term
why would used of a reversible cholinesterase inhibitor possibly require a muscarinic antagonist?
Definition
b/c muscarinic cholinergic responses occur at the onset of therapy and an antagonist may be required to minimize ADRs. *however, tolerance to muscarinic ADRs frequently develops and penetration to the CNS is minimal
Term
what are CNS, resp, ocular, CV, GI, GU and other ADRs associated with reversible systemic cholinergic inhibitors?
Definition
CNS: restlessness, convulsions. resp: increased bronchial secretions, laryngospasm, bronchoconstriction, resp paralysis. ocular: miosis, cycloplegia, diplopia, lacrimation. CV: bradycardia, arrhythmia, hyptension. GI: increased salivary, gastric, intestinal secretions, nausea/vomiting. GU: urinary frequency, incontinence. other: sweating, muscle twitching, muscle weakness
Term
what can an OD in a reversible systemic cholinesterase inhibitor lead to?
Definition
a cholinergic crisis: nausea, diarrhea, sweating, increased bronchial/salivary secretions, bradycardia, and muscle weakness. there is a narrow margin between first appearance of side effects and serious toxicity
Term
what are signed of CNS toxicity associated with reversible systemic cholinesterase inhibitors?
Definition
jitteriness, confusion, and dizziness. death can occur due to bronchial airway obstruction and respiratory paralysis
Term
what should be done in the case of a reversible systemic cholinesterase inhibitor OD?
Definition
discontinue rx and administer atropine IV
Term
what are contraindications for reversible systemic cholinesterase inhibitors?
Definition
intestinal or urinary obstruction
Term
what is amebenonium, a reversible systemic cholinesterase inhibitor used for?
Definition
tx of myasthenia gravis. (also used to test for underdosage or OD of cholinergic agents in patients with myasthenia)
Term
what is edrophonium, a reversible systemic cholinesterase inhibitor used for?
Definition
dx of myasthenia gravis, tx of poisoning with nondepolarizing skeletal muscle relaxants. (also used to test for underdosage or OD of cholinergic agents in patients with myasthenia)
Term
what is neostigmine, a reversible systemic cholinesterase inhibitor used for?
Definition
tx of myasthenia gravis, tx of poisoning with nondepolarizing skeletal muscle relaxants. *it may also increase release of presynaptic stores of ACh and have some direct Ach action b/c its molecular structure (quaternary) is analogous to the Ach molecule. it is also used to reverse skeletal blockade after sx
Term
what is pyridostigme, a reversible systemic cholinesterase inhibitor used for?
Definition
treatment of myasthenia gravis and poisoning with nondepolarizing skeletal muscle relaxants (as well as nerve gas)
Term
what is a caution for use of neostigmine and pyridostigmine?
Definition
neostigmine and pyridostigmine are bromide salts; contraindicated in pts with bromide hypersensitivity
Term
what are the irreversible indirect acting cholinergic drugs? what are they mainly used for?
Definition
echothiphate and isoflurophate which are organo-phosphorus compounds that phosphorylate cholinesterase, causing permanent inactivation. enzymatic activity remains impaired until additional enzyme can be synthesized; usually requires weeks or months for full restoration. originally developed as chemical warfare agents; now extensively used as pesticides and insecticides. **major clinical application is in eye for production of prolonged miosis in treatment of glaucoma.
Term
what are the uses of echothiophate (phospholine iodide)? how fast is onset? effects? can tolerance occur?
Definition
glaucoma tx (chronic open-angle and angle-closure following iridectomy), dx/tx of accommodative convergent strabismus. onset of miosis in 10 min, intraocular pressure reduced within 6 hrs, effects may last up to several weeks. tolerance may occur w/prolonged use
Term
what are ADRs for echothiophate?
Definition
stinging/burning in the eye, temporary blurred vision, lid twitching, hyperemia, browache, iris cysts, lens opacityies, iritis. systemic aborbtion may produce symptoms of cholinergic crisis (discontinue id signs of which appear)
Term
what are contraindications for echothiophate?
Definition
narrow angle glaucoma prior to sx, inflammatory conditions of the eye. cautious use in patients with asthma, ulcers, hypotension, epilepsy, parkinsonism, CV disease.
Term
what is different between the irreversible cholinesterase inhibitors echothiophate and isoflurophate?
Definition
isoflurophate is similar to echothiophate, but it is insoluble in water and is only available as an opthalmic ointment. its potency is reduced if the ointment contacts moisture (unstable in water). or maintenance therapy, drug may be applied once every 8 to 72 hours.
Term
what is pralidoxime (protopam)? what is it used for?
Definition
this cholinesterase inhibitor antidote disrupts the bond between the phosphorus group of enzyme inhibitor & esteratic site of cholinesterase enzyme; then displaces cholinesterase inhibitor from enzymatic binding sites. this is usually used for ODs of organophosphorus cholinesterase inhibitors; usually occurring due to insecticide poisoning (can also be used to lessen effect of reversible cholinesterase inhibitors).
Term
why should pralidoxime be administered asap following poisoning?
Definition
the cholinesterase inhibitors can become extremely stable and resistant to pralidoxime fairly quickly
Term
how quickly does pralidoxime work?
Definition
peak plasma levels: IV - 5 to 10 min; IM - 10 to 20 min
Term
what are ADRs for pralidoxime?
Definition
dizziness, blurred vision, headache, drowsiness, nausea, hyperventilation, muscle weakness. (tachycardia/muscle rigidity/laryngospasm may occur if infusion is too rapid, excitement/hypomania may follow recovery of consciousness)
Term
what is guanidine, and what is it used for?
Definition
this is a unique cholinergic agent that alleviates muscle weakness in myasthenic eaton-lambert syndrome (a myopathy related to cancer that prevents acetylcholine from being released) by enhancing release of acetylcholine after nerve impulse.
Term
what are ADRs for guanidine?
Definition
GI: diarrhea, abdominal cramping, N/V, CNS: paresthesias, trembling, tremor, lightheadedness, nervousness, confusion, hallucinations. heme: bone marrow depression, anemia, leukopenia, thrombocytopenia, sore throat, skin rash, fever, mucosal ulceraation/dyscrasia. renal: nephritis, renal tubular necrosis. CV: tachycardia, atrial fibrillation, hypotension. derm: rash, petechiae, purpura, ecchymoses, skin eruptions
Term
what is the most common form of dementia? how is the ACh system affected?
Definition
alzheimer's, featuring poor cognition, functional ability, behavior, and mood. there is reduced activity of choline ACh transferase, reduced sythesis of ACh, reduced responsiveness of post-synaptic M1 receptors in the frontal cortex and hippocampus, and loss of cortical neurons. other effects include increased deposition of beta-amyloid protein, reduced number of synapses, and reduced activity of ACh (possible compensation for reduced ACh synthesis)
Term
what are some probable causes of alzheimer's?
Definition
genetic, aging, trauma, aluminum exposure
Term
how does lecithin (phosphatidylcholine) help with alzheimer's?
Definition
it increases ACh synthesis, b/c it is an ACh precursor. it increases ACh levels in central synapses (e.g., lecithin reduces tardive dyskinesias), but therapeutic effects are oberved only when combined with physostigmine or tacrine.
Term
how does 4-aminopyridine help with alzheimer's?
Definition
this is an investigational K+ channel blocker that reduces K+ efflux and increases ACh release (longer time to repolarize = increased Ca++ influx = increased release of ACh). it has shown some improvement with memory improvememnt. ADRs include xerostomia, disorientation, and confusion
Term
what drugs can be given to reduce catabolism of ACh in alzheimer's?
Definition
physostigmine (antilirium), tacrine (tetrahydroaminoacridine; THA; cognex), donepezil (aricept), galantamine (razadyne), rivastigmine (exelon)
Term
how does physostigmine (antilirum) help with alzheimer's?
Definition
this is a centrally-acting reversible anticholinesterase agent w/a short half life that has shown slight increases in memory performance. ADRs include bradycardia, dizziness, headace, N/V/diarrhea, and diaphoresis
Term
how does tacrine help with alzheimer's?
Definition
this centrally-acting reversible anticholinesterase agent has shown significant increase in cognitive performance, ADRs include N/V/diarrhea, abdominal pain, skin rash, and **hepatotoxicity
Term
of the newer agents (donepezil, galantamine, rivastigmine) designed to enhance ACh activity in alzheimer's pts which is favored?
Definition
donepezil (aricept), which is a centrally-acting reversible anticholinesterase agent, *not hepatotoxic, and the 1st product approved by FDA for tx of all degrees of dementia of the alzheimer's type: mild, moderate, & severe. there is some degree of improvement occurs in cognitive performance - disappears when drug therapy withdrawn. ADRs include N/V/diarrhea, anorexia, muscle cramps, and insomnia
Term
what is unique about the action of rivastigmine (exelon)?
Definition
this drug inhibits both anticholinesterase AND butyrylcholinesterase - which both biostransform central ACh
Term
what was a problem with galantamine's name? what does it do uniquely?
Definition
this centrally-acting reversible anticholinesterase agent was originally named something that got it confused with drug for diabetics. it also stimulates the nicotinic receptors at sites different from those of acetylcholine and nicotine; enhances action of nicotinic receptors in presence of acetylcholine and stimulates central cholinergic sites without causing concomitant desensitization
Term
what is memantine (NAMENDA)?
Definition
pathological overactivation of NMDA (N-methyl-D-aspartate) receptors may be an etiologic factor in alzheimer’s disease; such effects promote excessive Ca2+ influx which may initiate synaptic or dendritic damage, necrosis or apoptosis - memantine binds to NMDA receptor: noncompetitive blockade, possibly slowing of progression of AD
Term
can reduction of systemic aluminum help with alzheimer's?
Definition
aluminum levels found in central neurons of AD pts can be 5x to 9x higher than in normal age-matched subjects and geographic areas with high aluminum concentrations in water have higher frequency of residents with cognitive impairment. deferoxamine (DESFERAL) is a iron chelator that can also be used to reduce aluminum levels in: bones of pts presenting with renal failure and pts with dialysis-induced encephalopathy. use of this has been shown to slow cognitive deterioration. ADRs include hearing loss, impaired vision, diarrhea, leg cramps, and tachycardia.
Term
what is deprenyl (SELEGILINE)?
Definition
an irreversible MAO-B inhibitor, AD may be caused by increased production of oxygen free radicals which promote degeneration of neurons, and deprenyl combined with tacrine or physostigmine has shown improvement in cognition in both AD and parkinson's pts
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