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42 Cards in this Set
- Front
- Back
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Hemicholinum |
INHIBITOR OF ACETYLCHOLINE BIOSYNTHESIS Synthetic compound that blocks uptake of choline into nerve terminal Limits the synthesis of ACh in terminal and therefore the amount of ACh stored for release |
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Vesamicol |
INHIBITOR OF ACETYLCHOLINE STORAGE Blocks the transport of ACh into nerve terminal vesicles thereby decreasing the amount of ACh stored for subsequent release. |
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Botulinum Toxin |
INHIBITOR OF ACETYLCHOLINE RELEASE Blocks the fusion of vesicles with plasma membrane, thereby blocking transmission Toxins are derived from the bacterium Clostridium botulinum, bind to the cell membrane and are internalized. One of the subunits is a protease which cleaves synaptobrevin, a protein involved in vesicle fusion Causes flaccid paralysis of muscles Death by paralysis of respiratory muscles (very potent!) |
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Acetylcholinesterase |
ENZYME THAT CATALYZES THE HYDROLYSIS OF CHOLINE ESTERS Terminates action ACh at nerve terminals Attached to collagen-like filaments on presynaptic and post-synaptic membrane Very rapid degradation of ACh (VERY EFFICIENT!) Ensures rapid termination of ACh action and helps prevent receptor desensitization. |
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Pseudocholinesterase |
ENZYME THAT CATALYZES THE HYDROLYSIS OF CHOLINE ESTERS Function of this form not clear Synthesized in the liver and primarily found in plasma Not specific for Acetylcholine |
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Where are Nicotinic Cholinergic receptors located? |
All autonomic ganglia Adrenal Medulla NMJ Spinal cord, optic tracts, and other areas of the brain |
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Where are Muscarinic Cholinergic receptors located? |
Parasympathetic effector cells (smooth muscle, cardiac muscle, exocrine glands) Brain (esp. cortex and midbrain) |
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Main effects of Nicotinic receptors |
ANS ganglion stimulation Contraction of skeletal muscle Stimulated adrenal gland discharge CNS effects |
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Main effects of Muscarinic receptors |
Gland secretion stimulation Contraction of smooth muscle Pupilary constriction via contraction of iris muscles Relaxation of sphincters Slowing of heart (SLUD--salivation, lacrimation, urination, defecation) |
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Acetylcholine |
PARASYMPATHOMIMETIC DRUG >>>No therapeutic applications<<< Short duration of action (hydrolysis in GI tract, *metabolism by acetylcholinesterase* and pseudo AChE) Does not cross BB |
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Methacholine |
PARASYMPATHOMIMETIC DRUG--SYNTHETIC ACh ANALOG Methylated on Beta-carbon *Somewhat resistant to AChE* Selective Muscarinic activity Used for GI and urinary stimulation CV effects limit clinical use (Causes bradycardia, hypotension) |
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Carbachol (Carbamylcholine) |
PARASYMPATHOMIMETIC DRUG--SYNTHETIC ACh ANALOG Carbamylated ACh *Resistant to AChE* Muscarinic and Nicotinic activity Selectively stimulates urinary and GI tracts Limited clinical use due to ganglionic stimulation Used to induce miosis Used in treatment of glaucoma to increase aqueous humor outflow |
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Bethanecol (Myotonachol) |
PARASYMPATHOMIMETIC DRUG--SYNTHETIC ACh ANALOG Carbamylated and methylated ACh *Resistant to AChE* Selective Muscarinic Activity Used clinically to test pancreatic function since it increases secretions Used to treat urinary retention by stimulating contraction of bladder. |
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Pilocarpine |
PARASYMPATHOMIMETIC DRUG--NATURALLY OCCURRING CHOLINERGIC ALKALOID Mainly Muscarinic agonist properties but some Nicotinic Has pronounced action on sweat and salivary glands (inc. salivation and induce sweating) Ophthalmological uses: induce miosis, decreases intraocular pressure, counteract mydriasis of atropine Stimulates ganglia to small degree |
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Arecoline |
PARASYMPATHOMIMETIC DRUG--NATURALLY OCCURRING CHOLINERGIC ALKALOID Acts at Nicotinic and Muscarinic Receptors Derived from the 'Betel Nut' (West Indies) No current therapeutic uses Was used in vet med as a vermifuge to induce the expulsion of worms from horses |
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Muscarine |
PARASYMPATHOMIMETIC DRUG--NATURALLY OCCURRING CHOLINERGIC ALKALOID Acts at Muscarinic Cholinergic Receptors Derived from mushroom Amantia muscaria No current therapeutic uses Symptoms of Mycetismus (Mushroom poisoning): lacrimation, salivation, sweating, miosis, abdominal pain, watery/painful diarrhea, CV collapse, vertigo, weakness confusion, coma, convulsions, death Antidote= Muscarinic receptor antagonist (aka ATROPINE) |
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Atropine |
ANTIMUSCARINIC AGENT Naturally-Occurring alkaloid found in deadly nightshade High affinity competitive Muscarinic receptor antagonist Pharmacological effects= tachycardia, dec. intestinal contraction and motility, bronchodilation, pupillary dilation, tremor, CNS delusion, excitement, life-like dreams Therapeutic uses= Preanesthetic to decrease resp. secretions, anti asthmatic medication, ophthalmology (mydriasis), cold medications to decrease lacrimal and nasal gland secretions. |
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Homoatropine |
ANTIMUSCARINIC AGENT More rapid onset and shorter duration than atropine Less potent than atropine |
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Scopolamine |
ANTIMUSCARINIC AGENT Therapeutic uses: Preanesthetic to decrease respiratory secretions associated with intubation and inhalant anesthetics Over-the-counter medications dec for motion sickness Same peripheral actions as atropine but has pronounced sedative action/ euphoria Used to sedate mentally ill patients |
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Propantheline |
SYNTHETIC ANTIMUSCARINIC AGENT Synthetic quaternary ammonium compound No blood barrier (BBB) penetration therefore no CNS effects except at high doses Used to mitigate GI spasm and secretions, decrease diarrhea (treats spasmodic colic in horses) Used for preparation of rectal exams Used to treat "choke" in horses by reducing spasm and promote relaxation of the esophagus |
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Tropicamide (mydriacyl) |
SYNTHETIC ANTIMUSCARINIC AGENT Synthetic quaternary ammonium compound Short duration of action Used in Ophthalmology to induce mydriasis Preferred over atropine due to recovery time (hours vs 7-12 days w/ atropine) |
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Nicotine |
NICOTINIC AGENT--GANGLIONIC STIMULANT Can stimulate then eventually inhibit nicotinic receptor-mediated events (dose-dependent: initial stimulation followed by dominant blocking action) By modifying the ganglion activity you can affect sympathetic and parasympathetic outflow CNS effects Stimulates the Adrenal Medulla to release NE and EPI into the blood Can also act on the nicotinic receptor in skeletal muscle No therapeutic uses |
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1) Lobeline 2) DMPP 3) TMA |
NICOTINIC AGENTS--GANGLIONIC STIMULANT 1) derived from the Lobelia plant, used at one time to ameliorate nicotine withdrawal symptoms 2) 3x more potent than nicotine 2 and 3) Initial stimulation is NOT followed by dominant blocking action (unlike Nicotine) |
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Hexamethonium (C6) |
NICOTINIC AGENT--GANGLIONIC BLOCKER Specifically blocks ganglionic Nicotinic receptors (Nn) (not active against Nm) Therapeutic use limited since it blocks sympathetic and parasympathetic ganglia |
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Trimethoprim |
NICOTINIC AGENT--GANGLIONIC BLOCKER Has been used in veterinary medicine to lower blood pressure during surgery |
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What are the effects of AChE Inhibitors on Transmission? |
Nerve depolarization Voltage-gated Na+ and Ca2+ channels Ca2+-dependent vesicle fusion and exocytosis Diffusion into synaptic cleft Receptor binding and activation Transmitter breakdown |
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What are the side effects of AChE Inhibitors? |
Muscarinic actions at autonomic effector organs Nicotinic actions at ANS ganglia Nicotinic stimulation at NMJ CNS effects |
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What are the three mechanisms of action of AChE inhibitors? |
Reversible AChE inhibition: Quarternary nitrogen binds reversible to the anionic site on AChE Carbamylation of AChE: Substrate for AChE and occupy active site for extended time Phosphorylation of AChE: Covalently bind to and irreversibly inactivate enzyme |
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Edrophonium (Tensilon) |
AChE INHIBITOR--REVERSIBLE Simple competitive inhibitor that binds to the anionic site on AChE No covalent attachment Rapidly reversible and short acting (3-4 minutes) Used as a tool to diagnose Myasthenia Gravis (a myasthenia patient will show transient improvement, while a patient in cholinergic crisis will show transient worsening) |
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Myasthenia Gravis |
A neuromuscular disease characterized by weakness of skeletal muscle. Caused by an ACh receptor defect at the NMJ. Antibodies bind to the ACh receptor and cause it to be cleared from the surface of the muscle. Decreased ACh receptor density yields decreased muscle contraction in the presence of the same amount of ACh. |
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Physostigmine (Eserine) |
AChE INHIBITOR--CARBAMYLATION OF AChE >>>Absorbed well from GI tract and crosses BBB<<< Originally used in therapy of Myasthenia Gravis (to increase ACh at the NMJ) Used in treatment of Glaucoma Used in treatment of Atropine poisoning (resultant increase in ACh counteracts the action of Muscarinic blocking agents) |
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Neostigmine (Prostigmin) |
AChE INHIBITOR--CARBAMYLATION OF AChE Contains a quarternary N >>>Not well absorbed orally and does not cross the BBB<<< Only peripheral effects--Used for the treatment of Myasthenia Gravis |
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Pyridostigmine |
AChE INHIBITOR--CARBAMYLATION OF AChE Similar action to Physostigmine and Neostigmine but has shorter half life Used prophylactically by US soldiers in 1990 in anticipation of "nerve gas" exposure |
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Demecarium |
AChE INHIBITOR--CARBAMYLATION OF AChE Linking two quaternary ammonium nuclei yields increased potency and duration of action |
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What is the action of carbamylating insecticides? And what is the name of a common carbamylating insecticide? |
Carbamylating insecticides inhibit AChE by acting as a substrate of AChE and occupying the active site for an extended time. Carbaril (Sevin) is a common Carbmylating Insecticide. It is effective against a wide range of insect pests of forage crops, fruit, and vegetables; ticks, lice, and fleas |
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What is the mechanism of action of Organophosphates? |
Organophosphates are AChE inhibitors covalently bind and irreversibly inactivate the enzyme via phosphorylation Recovery of enzymatic activity requires synthesis of new AChE protein. Enzyme replenishment process takes weeks. Physiological excess of AChE exists in the body, therefore profound toxic effects occur when 80-90% of enzyme is inactivated. Exposure over reasonable time period is cumulative. |
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Nerve Gas |
AChE INHIBITOR--ORGANOPHOSPHATE Originally developed by the Germans then by British and US military establishments |
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Sarin (GB) |
AChE INHIBITOR--ORGANOPHOSPHATE Also known as Isopropyl methylphosphonofluoridate Disperses quickly and is considered non-persistent |
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VX Gas |
AChE INHIBITOR--ORGANOPHOSPHATE More toxic than GB Long persistence Normally a liquid and has been formulated to stick to any surface it comes in contact with |
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Toxicology of OP Poisoning |
Effects are due to Muscarinic and Nicotinic receptor stimulation and CNS effects (SLUD, Miosis) Nicotinic actions at NMJ of skeletal muscle (depolarization block, muscle relaxes but will not contract, leading to paralysis) Paralysis of diaphragm and thoracic muscles leads to respiratory failure CNS effects |
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Pralidoxime (2-PAM) |
ORGANOPHOSPHATE POISONING ANTIDOTE Phosphate acceptor Can remove phosphate group from the protein to regenerate native enzyme Only effective before aging process takes place (will only bind to non-aged complex) Does not cross BBB Does not work with carbamylating AChE inhibitors |
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Therapeutic Uses of AChE Inhibitors |
Glaucoma (reduce IOP) Anesthesia (reverse non-depolarizing neuromuscular blockers) Myasthenia Gravis (inc. ACh at NMJ) Atropine Poisoning |
