Term
Muscarinic pharmacological effects of primary interest (Heart)
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Definition
•Heart (direct effects)
–SA node - Reduced rate of firing (Bradycardia)
–AV node - Slow conduction, increase refractory period
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Term
Muscarinic pharmacological effects of primary interest Blood vessels |
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Definition
•Blood vessels - Vasodilator; blood vessels contain muscarinic receptors but are not innervated by cholinergic nerves
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Term
Muscarinic pharmacological effects of primary interest :Gastrointestinal tract and Urinary Bladder
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Definition
•Gastrointestinal tract
–Stomach and intestines - Increase tone and motility
–Sphincters – Relaxation
•Urinary bladder - Contraction of detrusor and relaxation of sphincter
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Term
Muscarinic pharmacological effects of primary interest Eye
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Definition
•Eye
–Pupil- Contraction (miosis)
–Ciliary muscle - Contraction (fixed for near vision)
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Term
Muscarinic pharmacological effects of primary interest Bronchi of lungs and endocrine glands |
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Definition
•Bronchi of lungs - Constriction, can precipitate asthmatic attack
•Exocrine glands - Stimulation of secretion, e.g. tears, sweat, saliva, rhinorrhea, mucus, stomach acid and pepsin and other digestive enzymes
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Term
Nicotinic pharmacological effects of primary interest
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Definition
•Autonomic Ganglia - Stimulation of both sympathetic and parasympathetic
–requires high dose
•Adrenal Medulla - Release of epinephrine and norepinephrine
–(requires high dose)
•Skeletal Muscle - Depolarization of skeletal muscle end-plate and contraction
–Requires intra-arterial injection into muscle and usually an anticholinesterase drug
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Term
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Definition
–synthetic analogues - less susceptible to inactivation by cholinesterase enzymes - longer duration of action
•therapeutic uses for choline esters
•relief of postoperative GI atony and urinary retention
•wide-angle glaucoma (topical)
•contraindications for choline esters
–peptic ulcer
–asthma
–hyperthyroidism
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Term
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Definition
•therapeutic uses
–open angle glaucoma
–antiemetic agents in cancer chemotherapy
–diagnostic and research tools
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Term
Cholinesterase Inhibitors
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Definition
-Function and structure of acetylcholinesterase (AChE)
–the enzyme is regenerated
•one of the most efficient enzymes know
•This enzyme has two functional binding sites: an anionic subsite and an esteratic subsite
–choline portion of ACh (with quaternary amine group attached) binds at the anionic (negative) sub-site and choline is cleaved from the molecule
–acetic acid portion of ACh binds to the esteratic sub-site, forms an acetyl enzyme-conjugate intermediate and the subsequent release of choline through hydrolysis
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Term
Reversible cholinesterase inhibitors |
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Definition
–physostigmine
–neostigmine
–edrophonium
–carbamate insecticides
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Term
Irreversible cholinesterase inhibitors
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Definition
–isoflurophate (DFP)
–organophosphate insecticides
–nerve gases
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Term
Cholinesterase Inhibitors Mechanism of action
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Definition
–prevents metabolism of ACh in the synapse which is the major means of inactivation of the neurotransmitter
–this results in an increased concentration of ACh in the synapse due to inhibition of AChE
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Term
Cholinesterase Inhibitors Therapeutic Uses
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Definition
–Topically in eye for glaucoma (narrow and wide-angle glaucoma)
–Post operative GI atony and urine retention
–Myasthenia gravis
–Reverse effects of neuromuscular blockers
–Atropinic poisonings
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Term
Treatment - specific antidotes for Organophosphorus toxicity
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Definition
•Treatment - specific antidotes for Organophosphorus toxicity
•Knowledge of signs and symptoms critical for rapid diagnosis
–termination of exposure
–artificial respiration
–atropine, 2-4 mg IV - repeat every 5-10 minutes until signs of atropinization
–2-PAM (pyridine-2-aldoxime methyl chloride; pralidoxime), 1 g slowly IV
•reactivation of enzyme
–decontamination
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