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
|
|
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
|
|
Term
| what are the 2 naturally found Ach cholinomimetic alkaloids? |
|
Definition
|
|
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
|
|
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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