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82 Cards in this Set
- Front
- Back
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Parasympathetic outflow from the CNS
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Craniosacral
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Parasympathetic ganglia location
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Terminal
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Parasympathetic response to stimuli
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Localized
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Parasympathetic postganglionic fiber length
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Short
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Distribution of parasympathetic neurotransmittors
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Confined
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Parasympathetic Preganglionic fiber length
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Long
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Parasympathetic Neurotransmitter
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Acetylcholine
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Parasympathetic Action
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Bradycardia, negative inotropic effect
Constrict Bronchiols, Increase secretion Increase gastric motility and secretion Constrict bladder, relax sphincters Increase secretions, salivation, sweating, and lacrimation Constrict pupil (miosis) Accomodation |
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What would we use cholinergic agents to do?
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Lower HR
Increase GI motility Cause Urination ..... |
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Precursor molecule for ACH from diet
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choline
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Converting enzyme in Ach synthesis
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Choline Acetyltransferase (CAT)
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Where does the acetyl Coa come from for Ach synthesis?
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Kreb Cycle
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How is Ach metabolized?
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In the synapse by acetylcholinesterase into choline and acetate. Choline is returned to terminal and acetate is returned to krebs cycle
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How many sites on the acetylcholinesterase interact with Ach
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Two
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Location of Nicotine Nm receptors
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skeletal muscle
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Effects caused by the activation of Nm receptors
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Open (Na) ion channel
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What does activation of Nm receptors cause in the body?
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Contract muscle
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Where are Nn receptors located?
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Neural
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Cellular effects caused by Nnreceptor activation
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Open (Na) ion channel
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What are the functional effects on the body from the activation of Nn receptors?
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Ganglia
CNS Adrenal Medulla |
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Where are M1 receptors located?
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CNS
Ganglia Paracrine cells |
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What cellular effects does activation of M1,3,5 receptor cause?
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Activation of second messanger system Gq, which increase IP3 and DAG
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What functional body response is due to M1 receptor activation?
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Excite
increase CNS Gastric Increase Acid Motility |
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Where are M2 receptors located?
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Atria
Neurons Presynaptic CNS |
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What cellular effects does activation of M2,4 receptors casue?
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Activation of Gi second messanger system which decreases cAMP and opens potassium channels
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What bodily functions does M2 receptor activation cause?
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Inhibit heart
Inhibit presynaptic release Neuronal Inhibition |
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Where are the M3 receptors located?
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Glands
Smooth muscle CNS |
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What bodily functions are effected by M3 receptor activation?
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Increase secretions
Contract smooth muscle Increase NO Vasodilation |
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Where are M4 receptors located?
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Glands
Smooth muscles CNS |
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What bodily functions are effected by M4 receptor activation?
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CNS, Forebrain
Autoreceptors Increase DA release |
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Where are M5 receptors located?
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Glands
Smooth Muscle CNS |
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What bodily functions does the activation of M5 receptors effect?
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CNS learning and memory
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Nicotinic receptors are stimulated by what and inhibited by what?
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Stimulated: Nicotine
Inhibited: Curare, Trimethaphan |
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What are the 5 subunits of the nicotine receptors in:
Muscle Neural Ganglia |
Muscle: 2alpha, 1beta, 1 gama, 1 delta
Neural: 2 alpha3, 3 beta4 Ganglia: 2 alpha4, 3 beta4 |
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Muscarinic receptors are activated by what and inhibited by what?
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Activate: Muscarine
Inhibit: Atropine |
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Acetylcholine (Miochol)
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Direct Cholinergic Agonist
Topical use for Miosis Short acting (10mins) Both N and M agonist |
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Nicotine
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Direct cholinergic agonist
Stimulates Nn and Nm receptors Over stimulation shuts down receptors TU: Nicotine withdrawal, Ulcerative colitis SE: Tremors, convulsing, respiratory paralysis, and CTZ stimulant (vomit) |
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Methacholine (Provocholine)
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Direct cholinergic agonists
Potent M3 stimulator Used to test airway responsivenss |
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Carbachol (Carbastat, Carboptic)
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Direct cholinergic agonist
N and M effects Resistant to AchE Stimulates GI and Bladder Used in: Urinary retention, glaucoma (can stretch), miosis |
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Bethanechol (Urecholine)
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Direct Cholinergic Agonist
Selective muscarinic Resistant to AchE Bowel and bladder stimulant Urinary stimulant SE: Sweating, salivation, bronchospasm, accommodation problems |
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Arecholine
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Direct Cholinerigic Agonist
Natural Alkaloid-betelnut N and M activity No AchE activity Looked at for Alzheimer's |
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Muscarine
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Direct Cholinergic Agonist
Amantia Muscarine-mushroom M activity No AchE activity |
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Pilicarpine (ocusert, pilocar, salagen)
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Direct Cholinergic Agonist
Natural alkaloid M actions Stimulates sweat glands, salivary glands, and gastric glands, crosses BBB Uses: glaucoma, GI, Xerostomia (dry mouth), looked at for Alzheimer's |
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What are the general toxicities of direct cholinergic agonists?
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Salivation
Lacrimation Urination Defecation Sweating Visual Problems Miosis Bradycardia, hypotension |
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What are the contraindications for direct cholinergic agonists?
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Asthmatics
Hyperthyroid patients (atrial fibrillation) Myocardial ischemia Peptic Ulcer |
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What is the general action of indirect acting cholinergic agonists?
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Inhibit AchE which increase Ach in the synapse at all locations where Ach is released.
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What effects do indirect acting cholinergic agents have on muscarinic receptors?
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Stimulate muscarinic receptors on autonomic organs
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What effects do indirect acting cholinergic agents have on nicotinic receptors?
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Stimulate and then desensitize ganglia and skeletal muscle.
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T/F Indirect acting cholinergic agonists directly activate the receptors
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F- They inhibit AchE which prevents the breakdown of Ach in the synapse leading to increased loads of Ach. The Ach directly activates the receptors
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What are the two types of indirect acting cholinergic agonists?
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Reversible
Irreversible |
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What is found on the reversible indirect acting cholinergic agonists to cause them to disassociate from the enzyme?
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Carbamoly group
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What are some therapeutic uses for indirect acting cholinergic agonists?
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Paralytic ileus, stimulate urinary bladder
Glaucoma Myasthenia Gravis Anticholinergic poisoning Alzheimer's Disease |
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Physostigmine (esereine, antilirum)
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Indirect Acting Cholinergic Agonist
Natural alkaloid in calabar bean Orally active, only available as an injection, crosses the BBB Uses: Mitotic in Glaucoma, Atropine toxicity (competitive inhibition) SE: Muscarinic |
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Neostigmine (Prostigmine)
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Indirect Acting Cholinergic Agonist
Doesn't enter CNS, oral and injection Uses: Paralytic ileus, Urinary retention, Myasthenia Gravis, Reverse Neuromuscular blockade. |
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Pyridostigmine (mestinon, regonol)
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Indirect Acting Cholinergic Agonist
Similar to neostigmine Slower onset, longer duration of action, orally, injection Uses: Myasthenia Gravis, Prophylactic for nerve gases, Reverse Neuromuscular blockade |
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Edrophonium (Tensilon, Reversol, Enlon)
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Indirect Acting Cholinergic Agonist
Lacks carbamoyl group, blocks anionic site Very short duration of action (10mins) Injection Used in the diagnosis of Myasthenia Gravis |
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Tacrine (Cognex)
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Indirect Acting Cholinergic Agonist
CNS Selective- no carbamoyl group, reversible inhibitor Use: Mild-moderate Alzheimer's disease Does not slow disease Problems:Take 4 times a day, Hepatotoxixity |
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Donepezil (Aricept)
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Indirect Acting cholinergic Agonist
Used in treating Alzheimer's disease (works best in mild-moderate) Once daily dosing, no liver disease Effective in up to 80% May slightly slow progression by about 6 months, but does not alter underlying disease Muscarinic SE (diarrhea, salivation, tearing) |
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Galantamine (Reminyl)
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Indirect Acting Cholinergic Agonist
Used in Alzheimer's disease 2x oral dose Natural alkaloid form daffodil plant, reversible inhbitor SE: liver, GI tract, bronchonstriction, drowsiness |
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Rivastigmine (Exelon)
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Indirect Acting Cholinergic Agonist
Newest inhibitor for Alzheimer's Long lasting (10hrs) 2x day oral dose May slow progression of disease better than aricept Selective for G1 isoform found mainly in brain, slowly dissociates SE: Muscarinic, hallucinations |
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Irreversible Indirect Acting Cholinergic Agonists
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Organophosphates
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What are the characteristics of Irreversible Indirect Acting Cholinergic Agonists?
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High lipid solubility
Low molecular weight Transdermal absorption CNS penetration |
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What are the uses of Organophosphates?
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Insecticides
Nerve gases |
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How do organophosphate work?
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Bind to AchE at the methyl group on the histamine. Very quickly side group cleave leaving the phosphate permantly bound to the enzyme deactivating it.
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What is pralidoxime (2-pam) and how does it work?
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It helps prevent insecticide poisoning after exposure. It does so by binding to and removing the organophospate before it cleaves the phosphate.
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Name some Insecticides and Nerve gases
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Insecticides: Parthion, Diazinon, Malathion
Nerve Gas: Tabun, Sarin, Soman |
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What are the main actions of muscarinic antagonists?
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Mydriasis, blurred vision
Tachycaridia Decreased sweating, increased temperature, flushing Bronchodilation, decreased secretions Decreased GI Motility, decreased secretions Urine retention, decreased tone CNS- ataxia (in-coordination), hallucinations, delirium, coma |
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Atropine (Atripisol, Ocu-tropin, Sal-tropin)
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Non-selective Muscarinic Antagonist
Belladonna Alkaloid Uses: Mydriasis, Bradycardia, GI hyperactivity, Bronchodilation Homatropin (-OH shorter duration) Main use: eye exams |
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What is used to stop atropine poisoning?
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Indirect Acting Cholinergic Agonist- act as competitive antagonists
Specifically: physostigmine |
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Describe the symptoms of atropine overdose
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Dry as bone: decreased secretions
Red as a beet: increasing temperature, decreasing sweating, increasing flushing Blind as a bat: blockade of accommodation Mad as a hatter: hallucinations, dellirium from blockade of muscarinic receptors with in the CNS Fever-in children |
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Scopolamine (scopace, isoptohyoscine, Tranderm Scop)
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Choloniergic Antagonist
Natural alkaloid-henbane shrub Effective prophylaxis of motion sickeness Mydriasis Can cause Amnesia CNS depression "Twilight Sleep"- morphine and scopolamine (used in delivery in the 50s and 60s) |
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Ipratropium (Atrovent)
Tiotropium (Spiriva) |
Quaternary ammonium doesn't cross BBB, inhilation
Developed for bronchial relaxation Less paralytic effect than atropine on cilia Used in COPD and asthma SE come from muscarinic blockade in the circulation Ipratropium not selective in muscarinic receptors. |
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Tolterodine (Detrol)
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Cholinergic Antagonist
Selective for Bladder Used in Overactive Bladder Causes Dry mouth in 40% of patients |
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Oxybutynin (Ditropan)
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Cholinergic Antagonist
Used for urinary incontinence Causes dry mouth and dry eyes Oxytrol- transdermal formulation which has less SE. |
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Solifenacin (Vesicare)
Darfenacin (Enablex) |
Selective M3 antagonist
slightly more selective for bladder than other drugs Less SE Drug interactions: Solifenacin CYP3A4 and Daribenacin CYP3A4, CYP2D6 |
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Benztropin (Cogentin)
Trihexyphenidyl (Artane) |
Cholinergic Antagonist
Used to control CNS effects (tremor) in Parkinson's disease Balance DA release, doesn't stop progression of disease Effects only last for 10 years therefore it is saved for later treatment |
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Pirenzipine (Gastrozepin)
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Not on Market
M1 ganglia blocker Blocks acid secretion in GI Could be used for nocturnal increased acid secrtion prevention but not ideal for meal acid increase prevention. |
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What are the effects and mechanism of action for : Botulinus toxin, Metacholine, and Mg++
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Effect: Anticholinergic
MOA: Prevent release of Ach Causes flacid paraylasis |
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What are the effects and mechanism of action for: Hemicholinium?
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Effect: blocks choline uptake
MOA: interferes with synthesis of Ach Causes paralysis of muscle |
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What are the effects and mechanism of action for: Beta Bungarotoxin (snake venom), and black widow venom?
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Effect: muscle constriction
MOA: Enhances release of Ach |
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What are the effects and mechanism of action for: Atropine, D-tubocurarie, hexamethonium, and alpha Bungarotoxin?
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Effect:Antimuscarinic paralysis
MOA: Blocks postsynaptic receptors Prevents muscle contraction |
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What are the effects and mechanism of action for: Physostigmine
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Effects: Enhances cholinergic function
MOA: Inhibits AchE |
