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21 Cards in this Set
- Front
- Back
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Acetlycholine
Agonist/AChE inbhib? Duration? Stimulates which receptors? Clinical use? |
Agonist
Very short acting <20 sec, rapidly destroyed by ChE Stimulates BOTH muscarinic & nicotinic receptors Used in when rapid stimulation/degradation is required ex. cataract surgery |
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Bethanechol
Agonist/ChE inhib? Duration? Receptor? |
Agonist
Long acting-NOT hydrolyzed by ChEs Only stimulates muscarinic |
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Carbachol
Agonist/ChE inhib? Duration? Receptors? Action? |
Agonist
Long acting-NOT hydrolyzed by ChEs Stimulates BOTH muscarinic & nicotinic Causes release of ACh from synapses |
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Pilocarpine
Agonist/ChE inhib? Derivation? Effect? |
Agonist
Plant alkaloid Muscarinic effects |
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Cevimeline
Agonist/ChE inhib? Receptors? |
Agonist
Selective agonist for M3 receptors -esp. lacrimal & salivary glands -well absorbed orally |
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Edrophonium & Ambenonium
Agonist/ChE inhib? Durations? Binding mechanism? Reversible or Irreversible? Which crosses the BBB? |
ChE inhibitor
Brief duration: Edrophonium (min) Ambenonium (hrs) Electrostatic forces & H-bonding Reversible Neither cross BBB |
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Neostigmine, Physostigmine, Pyridostigmine
Agonist/ChE inhib? Binding mechanism? Which cross the BBB? |
ChE inhibitor
All have binding mechanism similar to ACh but removed MORE SLOWLY (.5-6 hrs) Only Physostigmine crosses BBB, others have poor lipid solubility & only target peripheral cholinergic receptors. |
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Isoflurophate & Echothiophate
Agonist/ChE inhib? Class? Mech of action? Reversible? Bonding? Which crosses the BBB? |
ChE inhibitor
Organophosphates (Insecticides & nerve gases) Binds NON-COMPETITIVELY to ChE by phosphoryl-ChE bond VERY SLOW REVERSE (100's of hrs) Bond strength increases with age becoming irreversible Overcome by synthesizing new enzyme ChE Isoflurophate is uncharged & easily crosses BBB -Echothiophate is charged & not lipid soluble |
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Cholinomimetric Agents
1)Definition? 2)Function? 3)Mechanism of Action? 4)Inactivation? |
1)Agents that increase stimulation of cholinergic receptors = Muscarinic or Nicotinic
2)Increase stimulation of post-synaptic ACh receptors 3)Cholinergic agonists: directly stimulate postsynaptic ACh receptors Cholinesterase inhibitors: Block the destruction of ACh by inhibiting ChE & prolong the time of effective receptor stimulation of endogenously secreted ACh, indirectly producing similar effects. 4)Enzymatic degradation by cholinesterases |
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Cholinergic Receptors
What are the 3 types? Cholinomimetic agonists & anticholinesterases act on which ones? |
Muscarinic (M1-M5): Peripheral effector end organs, cardiac muscle, glands(M2,M3)
-Parasympathetic Nervous system Nicotinic-neural (Nn): Peripheral ganglia (BOTH sympathetic & parasympathetic), Brain Nicotinic muscular (Nm): Neuromuscular junction of striated, somatic muscle Cholinomimetic agonists & anticholinesterases act on ALL receptors. |
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Peripheral Effects of Cholinomimetics
Peripheral effects? Clinical use? |
Peripheral effects similar to Prasympathetic Nervous System (PSNS) or Sketletal muscle (nicotinic) stimulation
Clinical goal is local increase in post-ganglionic, post-synaptic receptor activation. |
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CNS Cholinergic System
95% Muscarinic receptors & 5% Nicotinic Effects of CNS cholinergic stimulation? |
Peripheral sympathetic Activation
Cognitive effects: Confusion, coma, altered memory. Motor responses: Tremors followed by convulsion. |
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Therapeutic Considerations for muscarinic-cholinomimetic agents
Specificity? How is widespread effect overcome? What class of drugs are most effective in high tone organs? |
Little receptor specificity, acting on M1-M5
Both M2 & M3 are present in most peripheral organs -Produces response in multiple organs Local admin-strategy for specific responses(ex. Pilocarpine topically to eye) Anticholinesterases: most effective -ex. eye, GI tract, salivary glands |
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Myasthenia gravis
Problem? Results? Diagnosis? Therapeutic Goal? Treatment? |
Autoimmune response decreasing number, blocking, &/or dilutes functional Nm receptors.
Results in weak & fragile skeletal muscle Administer Edrophonium IV/atropine & see brief improvement in skeletal muscle strength Increase muscle strenght by increasing synaptic [ ] & duration of action of ACh ChE Inhibitor: Moderate duration NOT crossing BBB (Neostigmine, Pyridostigmine, Ambenonium) |
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Glaucoma
Problem? Cause? Diagnosis? Therapeutic goal? Treatment? |
Increased intraocular pressure
blockage of the drainage by dilated iris measure intraocular pressure directly Increase aqueous humor drainage to reduce pressure Cholinomimetic agonist or ChE inhibitor: topical(pilocarpine, carbachol) or (echothiophate) |
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Xerostomia
Cause? Therapeutic goal? Treatment? |
Dry mouth: head irradiation, diabetes, meds, aging, stress
Increase saliva production Cholinomimetic: -Pilocarpine -Cevimeline: M3 specific, longer lasting, fewer side effects |
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Urinary bladder Atonia(doesn't empty)
Cause? Diagnosis? Therapeutic goal? Treatment? |
Lack of muscular tone: Anesthesia induced, Neural injury, Spinal Shock
Full bladder that doesn't empty Increase muscle tone in detrusor muscle(bladder wall) & decrease sphincter tone in bladder Cholinomimetic or ChE inhibitor: Bethanecol-M3 selective/neostigmine-short duration(2-4hrs) |
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Neuromuscular blockade during surgery
Why? Therapeutic Goal? Treatment? |
Nm antagonist given to reduce muscle mvmt-tone
Post Surgery restoration of muscle mvmt & tone IV Neostigmine: inhibits ChE in muscle & overcomes saturable block of Nm receptors on muscle cells |
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Intoxication by Antimuscarinic Agents
Cause? Therapeutic Goal? Treatment? |
Poisoning with atropine, antihistamines, tricyclic antidepressants=>CNS & peripheral effects
Increase ACh [ ]/duration of action to overcome competitive blockade Physostigmine: Passes BBB, treats BOTH CNS & peripheral effects. Can cause seizures |
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Alzheimer's Disease
Cause? Therapeutic goal? Treatment? |
Progressive dementia: loss of Ach neurons in parts of CNS
Enhance [ ] of ACh in CNS to enhance memory ChE inhibitors to SLOW disease progression -Tacrine:Not widely used, reversible liver damage -Donepezil: more selective to CNS ChE, less toxic, long duration of action. 1x/day -Rivastigmine & Galantamine: 2x/day, long-acting, less toxic similar to donepezil, but still get nausea, vomiting, diarrhea, & insomnia |
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Contraindiations
Asthma? Coronary Insufficiency? Peptic Ulcers? |
Asthma: broncho-constriction & secretion
Coronary insufficiency: hypotension, ↓ heart rate, arteriolar dilation. Peptic Ulcers: ↑ gastric acid |
